|
1
|
Kim JE, Park J, Jang Y, Kang E, Kim YC, Kim DK, Joo KW, Kim YS, Lee H. Oral phosphate binders and incident osteoporotic fracture in patients on dialysis. Nephrol Dial Transplant 2025; 40:329-340. [PMID: 38886108 DOI: 10.1093/ndt/gfae139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients. METHODS We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both CBPB and NCBPB (mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality. RESULTS Out of 69 368 incident dialysis patients, 22 326, 5020, 2853 and 39 169 were included in the CBPB, NCBPB, mixed and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared with non-users. Specifically, only the CBPB group showed a reduced risk of vertebral [adjusted hazard ratio (aHR) 0.83 (0.76-0.92)], hip [aHR 0.81 (0.74-0.89)] and distal radius [aHR 0.88 (0.78-0.99)] fractures compared with non-users. This relationship presented in a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months [aHR 0.9 (0.83-0.99)] and ≥6 months [aHR 0.83 (0.78-0.89)], compared with those using CBPB for <3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared with non-users. CONCLUSIONS Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared with non-users.
Collapse
Affiliation(s)
- Ji Eun Kim
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea
| | - Jina Park
- Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yunyoung Jang
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Eunjeong Kang
- Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| |
Collapse
|
|
2
|
Nakano T. Atherosclerotic Diseases in Chronic Kidney Disease. J Atheroscler Thromb 2025; 32:111-119. [PMID: 39551490 PMCID: PMC11802252 DOI: 10.5551/jat.rv22030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 10/15/2024] [Indexed: 11/19/2024] Open
Abstract
Patients with chronic kidney disease (CKD) have a high incidence of atherosclerotic diseases, such as ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. To prevent the incidence of atherosclerotic cardiovascular disease in patients with CKD, the pathology of arteriosclerosis should be determined. Vascular calcification is a characteristic of arteriosclerosis in patients with CKD. Recent studies have reported that coronary artery calcification is associated with acute coronary syndromes. CKD is frequently associated with heart failure. Furthermore, recent evidence suggests that coronary artery calcification affects asymptomatic myocardial ischemia. Hyperphosphatemia and calciprotein particles may be involved in the pathology of vascular calcification. Controlling the progression of vascular calcification and classical atherosclerotic risk factors is important to prevent the occurrence of atherosclerotic diseases in CKD.
Collapse
Affiliation(s)
- Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| |
Collapse
|
|
3
|
Henner DE, Drambarean B, Gerbeling TM, Kendrick JB, Kendrick WT, Koester-Wiedemann L, Nickolas TL, Rastogi A, Rauf AA, Dyson B, Singer MC, Desai P, Fox KM, Cheng S, Goodman W. Practice patterns on the management of secondary hyperparathyroidism in the United States: Results from a modified Delphi panel. PLoS One 2025; 20:e0266281. [PMID: 39888902 PMCID: PMC11785329 DOI: 10.1371/journal.pone.0266281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Accepted: 03/17/2022] [Indexed: 02/02/2025] Open
Abstract
BACKGROUND Secondary hyperparathyroidism (SHPT) is common in patients with chronic kidney disease (CKD). Many recommendations in the Kidney Disease Improving Global Outcomes (KDIGO) CKD-mineral and bone disorder guidelines are supported by modest evidence and predate the approval of newer agents. Therefore, an expert panel defined consensus SHPT practice patterns in the United States with real-world context from the nephrology community. METHODS Ten US healthcare providers and one patient participated in a modified Delphi method comprising three phases. Consensus was determined via iterative responses to a questionnaire based on the 2009 and 2017 KDIGO guidelines and published literature on the identification, evaluation, monitoring, and interventional strategies for patients with SHPT. The threshold for consensus was 66% agreement. RESULTS Panelists generally agreed with KDIGO recommendations, with some differences. Consensus was reached on 42/105 (40%), 95/105 (90.5%), and 105/105 (100%) questions after phases 1, 2, and 3, respectively. Panelists unanimously agreed that SHPT treatment is often started late. There was a preference for serum phosphate level <4.6 mg/dL, and consensus to maintain serum calcium levels <9.5 mg/dL. There was unanimous agreement for vitamin D analogues as first-line options in patients not on dialysis with severe, progressive SHPT and unanimous preference for intravenous calcimimetic, etelcalcetide, in appropriate in-center dialysis patients. Factors such as formularies, dialysis center protocols, and insurance were recognized to influence therapeutic strategies. CONCLUSIONS Expert consensus was reached on SHPT management, further defining therapeutic strategies and medication use and emphasizing need for treatment early. Despite evidence-based treatment preferences supported by clinical experience, factors other than scientific evidence influence decision making, particularly with medications.
Collapse
Affiliation(s)
- David E. Henner
- Division of Nephrology, Berkshire Medical Center, Pittsfield, MA, United States of America
| | - Beatrice Drambarean
- University of Illinois Hospital & Health Sciences System, Chicago, IL, United States of America
| | | | - Jessica B. Kendrick
- Division of Renal Diseases and Hypertension, University of Colorado, Aurora, CO, United States of America
| | | | - Lisa Koester-Wiedemann
- Division of Nephrology, Washington University School of Medicine, St Louis, MO, United States of America
| | - Thomas L. Nickolas
- Division of Nephrology, Columbia University Irving Medical Center, New York, NY, United States of America
| | - Anjay Rastogi
- Division of Nephrology, UCLA School of Medicine, Los Angeles, CA, United States of America
| | - Anis A. Rauf
- Nephrology Associates of Northern Illinois, Oakbrook, IL, United States of America
| | | | - Michael C. Singer
- Department of Otolaryngology–Head and Neck Surgery, Henry Ford Hospital, Detroit, MI, United States of America
| | - Pooja Desai
- Amgen, Inc., Thousand Oaks, CA, United States of America
| | | | - Sunfa Cheng
- Amgen, Inc., Thousand Oaks, CA, United States of America
| | | |
Collapse
|
|
4
|
Salera D, Bellasi A, Del Vecchio L, Locatelli F. Update on current and emerging treatment paradigms for hyperphosphatemia in chronic kidney disease. Expert Opin Pharmacother 2025; 26:85-100. [PMID: 39676576 DOI: 10.1080/14656566.2024.2441328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/09/2024] [Indexed: 12/17/2024]
Abstract
INTRODUCTION Hyperphosphatemia in advanced CKD often accompanies high PTH and FGF23 levels, impaired bone mineralization, ectopic calcifications, and increased cardiovascular risks. Novel treatments are now available to lower serum phosphorus effectively. However, safety, tolerability, and patient adherence must be evaluated to determine the best therapeutic option for hyperphosphatemia. AREAS COVERED This review examines available treatment strategies for hyperphosphatemia in CKD patients and new emerging treatments, emphasizing the latest inhibitors of active phosphate absorption. EXPERT OPINION Despite the numerous compounds available, managing hyperphosphatemia in CKD remains challenging. While many phosphate binders exist, they often have limitations and side effects. Aluminum carries significant toxicity risks. Calcium-based binders are effective but can cause hypercalcemia and vascular calcification. Lanthanum is absorbed in the gut, but its long-term tissue deposition appears clinically irrelevant. Sevelamer reduces vascular calcification but has inconclusive data and gastrointestinal side effects. Iron-based binders are effective but may cause gastrointestinal discomfort and lack long-term outcome data. New inhibitors of intestinal phosphate absorption show promise with low pill burden but need more clinical validation. Although these newer compounds might eventually improve phosphate management in CKD patients, enhancing adherence and reducing pill burden, future studies are required to elucidate the best treatment for hyperphosphatemia.
Collapse
Affiliation(s)
- Davide Salera
- Service of Nephrology, Ospedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero Cantonale, Lugano, Switzerland
| | - Antonio Bellasi
- Service of Nephrology, Ospedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero Cantonale, Lugano, Switzerland
- Faculty of Biomedical Sciences, Università della Svizzera italiana (USi), Lugano, Switzerland
| | - Lucia Del Vecchio
- Department of Nephrology and Dialysis, Sant'Anna Hospital, ASST Lariana, Como, Italy
| | - Francesco Locatelli
- Department of Nephrology and Dialysis, Past Director, Alessandro Manzoni Hospital, ASST Lecco, Lecco, Italy
| |
Collapse
|
|
5
|
Georgopoulos C, Duni A, Stamellou E, Kitsos A, Gouva C, Dounousi E. Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: A systematic review and meta-analysis. Hemodial Int 2025; 29:6-16. [PMID: 39422162 PMCID: PMC11730771 DOI: 10.1111/hdi.13187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 09/24/2024] [Accepted: 10/05/2024] [Indexed: 10/19/2024]
Abstract
INTRODUCTION Phosphate binders are commonly used in patients receiving kidney replacement therapy (KRT), aiming to reduce and maintain serum phosphorus. Chronic kidney disease-mineral and bone disorder has been linked to reduced lifespan and worsened quality of life. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving KRT. METHODS The data sources examined were MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with a search deadline of October 2023. We examined randomized controlled trials that compared sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving KRT. We performed a meta-analysis combining the data from trials, using R-studio. FINDINGS Inclusion criteria were met by five randomized trials. There was no statistically significant difference in the reduction of serum phosphorus between the two groups (MD: -0.07 mmol/L, 95% CI-random effects: -0.15 to 0.02). In the same line, a non-statistically significant difference was observed in serum i-PTH reduction between the two drugs (MD = -1.53 mg/dL, 95% CI = (-4.45, 1.4), p = 0.26, random effects model). No statistically significant difference was observed in all adverse events between the two groups (odds ratio: 1.11, 95% CI: 0.65-1.88, random effects model). Further analysis of gastrointestinal adverse events revealed that sevelamer carbonate increases gastrointestinal adverse events by up to 60% (odds ratio: 1.60, 95% CI: 1.31-1.97, common (fixed) effect model). DISCUSSION This meta-analysis of randomized trials showed that both drugs, sucroferric oxyhydroxide and sevelamer equally and effectively controlled serum phosphorus levels, whereas sucroferric oxyhydroxide revealed a better profile in terms of gastrointestinal adverse events. Sucroferric oxyhydroxide is a valuable option for patients receiving KRT when sevelamer carbonate is more difficult to tolerate.
Collapse
Affiliation(s)
| | - Anila Duni
- Department of NephrologyUniversity Hospital of IoanninaIoanninaGreece
| | - Eleni Stamellou
- Department of NephrologyUniversity Hospital of IoanninaIoanninaGreece
- Department of Nephrology and Clinical ImmunologyRWTH Aachen University HospitalAachenGermany
| | - Athanasios Kitsos
- Department of NephrologyUniversity Hospital of IoanninaIoanninaGreece
| | | | | |
Collapse
|
|
6
|
Macias-Cervantes HE, Ocampo-Apolonio MA, Guardado-Mendoza R, Baron-Manzo M, Pereyra-Nobara TA, Hinojosa-Gutiérrez LR, Escalante-Gutiérrez SE, Castillo-Velázquez MA, Aguilar-Guerrero R. Effect of vitamin K1 supplementation on coronary calcifications in hemodialysis patients: a randomized controlled trial. J Nephrol 2024:10.1007/s40620-024-02154-9. [PMID: 39680321 DOI: 10.1007/s40620-024-02154-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Accepted: 11/05/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Chronic kidney disease (CKD) is associated with several adverse cardiovascular outcomes, including coronary heart disease, heart failure, and arrhythmias. The severity of arterial calcifications predicts the risk of coronary heart disease and increases the risk of premature cardiovascular death. In experimental models, vitamin K1 supplementation appears to reduce coronary artery calcifications. METHODS In this single-center clinical trial (NCT04247087 on 07/09/2019), we randomized 60 Mexican patients on chronic hemodialysis and a coronary calcification score > 10 Agatston units to receive 10 mg intravenous vitamin K1 or placebo at the end of the hemodialysis session thrice weekly for 12 months. The primary outcome was the progression of coronary artery calcifications as assessed by the absolute change in Agatston and coronary calcium volume scores. RESULTS The baseline coronary calcium score was 112.50 (14-2027) Agatston units in the vitamin K1 group and 177 (10-2843); Agatston units in the placebo group (p = 0.71), and after 12 months, the coronary calcium score in the vitamin K1 group was 78.50 (10-1915) Agatston units in the vitamin K1 group versus 344 (10-3323); Agatston units (p = 0.05) in the placebo group. Progression of coronary calcification was 20.8% in the vitamin K1 group versus 44% in the placebo group, with a relative risk (RR) of 0.45 (CI 95% 0.18-1.15). CONCLUSIONS In the Mexican hemodialysis cohort enrolled in this study intravenous vitamin K1 supplementation reduced the progression of coronary artery calcifications by 55% compared with placebo over a 12-month follow-up period.
Collapse
Affiliation(s)
- Hilda Elizabeth Macias-Cervantes
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México.
| | - Marco Antonio Ocampo-Apolonio
- Nephrology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | | | - Miguel Baron-Manzo
- Radiology Departament, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Texar Alfonso Pereyra-Nobara
- Director of Health Education and Research, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Luis Ricardo Hinojosa-Gutiérrez
- Radiology Departament, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Sergio Edgardo Escalante-Gutiérrez
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Mario Alberto Castillo-Velázquez
- Cardiology Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| | - Rodolfo Aguilar-Guerrero
- Internal Medicine Department, Unidad Medica de Alta Especialidad, Hospital de Especialidades No. 1, Centro Médico Nacional del Bajío, León, Guanajuato, México
| |
Collapse
|
|
7
|
Marando M, Tamburello A, Salera D, Di Lullo L, Bellasi A. Phosphorous metabolism and manipulation in chronic kidney disease. Nephrology (Carlton) 2024; 29:791-800. [PMID: 39433296 PMCID: PMC11579558 DOI: 10.1111/nep.14407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 09/13/2024] [Accepted: 10/05/2024] [Indexed: 10/23/2024]
Abstract
Chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome commonly observed in subjects with impaired renal function. Phosphate metabolism has been implicated in the pathogenesis of CKD-MBD and according to the phosphorocentric hypothesis may be the key player in the pathogenesis of these abnormalities. As phosphorous is an essential component for life, absorption from the bowel, accumulation and release from the bones, and elimination through the kidneys are all homeostatic mechanisms that maintain phosphate balance through very sophisticated feedback mechanisms, which comprise as main actors: vitamin D (VD), parathyroid hormone (PTH), calciproteins particles (CPPs), fibroblast growth factor-23 (FGF-23) and other phosphatonins and klotho. Indeed, as the renal function declines, factors such as FGF-23 and PTH prevent phosphate accumulation and hyperphosphatemia. However, these factors per se may be responsible for the organ damages associated with CKD-MBD, such as bone osteodystrophy and vascular calcification. We herein review the current understanding of the CKD-MBD focusing on phosphorous metabolism and the impact of phosphate manipulation on surrogate and hard outcomes.
Collapse
Affiliation(s)
- Marco Marando
- Service of PneumologyHôpitaux Universitaires de GenèveGenevaSwitzerland
| | | | - Davide Salera
- Department of Internal MedicineOspedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero CantonaleLuganoSwitzerland
| | - Luca Di Lullo
- UOC Nephrology and Dialysis UnitAzienda USL Roma 6Albano LazialeItaly
| | - Antonio Bellasi
- Service of NephrologyOspedale Regionale di Lugano, Ospedale Civico, Ente Ospedaliero CantonaleLuganoSwitzerland
- Faculty of Biomedical SciencesUniversità della Svizzera italianaLuganoSwitzerland
| |
Collapse
|
|
8
|
Li P, Li Q, Tang M, Hu X, Tian J, Zhang J, Yang C, Zhu B. Associations of phosphorus concentrations with medial arterial calcification in lower-extremity arteries and diabetic foot in people with diabetes: a retrospective cross-sectional study. Cardiovasc Diabetol 2024; 23:275. [PMID: 39061014 PMCID: PMC11282733 DOI: 10.1186/s12933-024-02361-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. METHODS We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. CONCLUSIONS Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.
Collapse
Affiliation(s)
- Peishan Li
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Qingxian Li
- Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China
| | - Mingyu Tang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Xingyun Hu
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Jing Tian
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Jianbin Zhang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China
| | - Chuan Yang
- Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
| | - Baile Zhu
- Zhongshan People's Hospital, Zhongshan, 528403, China.
| |
Collapse
|
|
9
|
Disthabanchong S, Kasempin P, Srisuwarn P, Chansomboon P, Buachum N. The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data. PLoS One 2024; 19:e0304649. [PMID: 38820324 PMCID: PMC11142503 DOI: 10.1371/journal.pone.0304649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Accepted: 05/06/2024] [Indexed: 06/02/2024] Open
Abstract
INTRODUCTION Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics. METHODS This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model. RESULTS 714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant. CONCLUSION Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.
Collapse
Affiliation(s)
- Sinee Disthabanchong
- Faculty of Medicine, Department of Medicine, Division of Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Panhathai Kasempin
- Faculty of Medicine, Department of Medicine, Division of Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Praopilad Srisuwarn
- Faculty of Medicine, Department of Medicine, Division of Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Payupol Chansomboon
- Faculty of Medicine, Department of Medicine, Division of Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Nuchcha Buachum
- Faculty of Medicine, Department of Medicine, Division of Nephrology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| |
Collapse
|
|
10
|
Le D, Crews DC, Grams ME, Coresh J, Shin JI. Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis. Am J Nephrol 2024; 55:450-462. [PMID: 38555633 PMCID: PMC11614033 DOI: 10.1159/000538253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 03/05/2024] [Indexed: 04/02/2024]
Abstract
INTRODUCTION Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association. METHODS Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (vs. non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups. RESULTS Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91-1.06) or all-cause mortality (220 vs. 224 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.93-1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization. CONCLUSION Among patients requiring hemodialysis, sevelamer (vs. non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.
Collapse
Affiliation(s)
- Dustin Le
- Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Deidra C. Crews
- Division of Nephrology, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Morgan E. Grams
- Division of Precision Medicine, Department of Medicine, New York University, New York, NY
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| | - Jung-Im Shin
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
| |
Collapse
|
|
11
|
Haruyama N, Nakayama M, Yamada S, Tanaka S, Hiyamuta H, Taniguchi M, Tokumoto M, Tsuruya K, Kitazono T, Nakano T. History of fragility fracture is associated with cardiovascular mortality in hemodialysis patients: the Q-Cohort study. J Bone Miner Metab 2024; 42:253-263. [PMID: 38509305 DOI: 10.1007/s00774-024-01501-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 02/08/2024] [Indexed: 03/22/2024]
Abstract
INTRODUCTION In patients undergoing dialysis, major bone fracture is associated with a high risk of mortality, including death of cardiovascular (CV) origin. In the present study, we aimed to determine whether a history of fragility fracture is a predictor of CV death in patients undergoing hemodialysis with long-term follow-up. MATERIALS AND METHODS In total, 3499 patients undergoing hemodialysis were analyzed for 10 years. We evaluated the history of fragility fracture in each patient at enrollment. The primary outcome was CV death. A Cox proportional hazard model and a competing risk approach were applied to determine the association between a history of fragility fracture and CV death. RESULTS A total of 346 patients had a history of fragility fracture at enrollment. During a median follow-up of 8.8 years, 1730 (49.4%) patients died. Among them, 621 patients experienced CV death. Multivariable Cox analyses after adjustment for confounding variables showed that a history of fragility fracture was associated with CV death (hazard ratio, 1.47; 95% confidence interval, 1.16-1.85). In the Fine-Gray regression model, a history of fragility fracture was an independent risk factor for CV death (subdistribution hazard ratio, 1.36; 95% confidence interval, 1.07-1.72). CONCLUSION In a large cohort of patients undergoing hemodialysis, a history of fragility fracture was an independent predictor of CV death.
Collapse
Affiliation(s)
- Naoki Haruyama
- Division of Nephrology, Department of Internal Medicine, NHO Kyushu Medical Center, Fukuoka, Japan
| | - Masaru Nakayama
- Division of Nephrology, Department of Internal Medicine, NHO Kyushu Medical Center, Fukuoka, Japan
| | - Shunsuke Yamada
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shigeru Tanaka
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroto Hiyamuta
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | | | - Masanori Tokumoto
- Division of Nephrology and Dialysis Center, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan
| | - Kazuhiko Tsuruya
- Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
| |
Collapse
|
|
12
|
Molina P, Molina MD, Carrero JJ, Escudero V, Torralba J, Castro-Alonso C, Beltrán S, Vizcaíno B, González-Moya M, Kanter J, Sancho-Calabuig A, Bover J, Górriz JL. Sevelamer Use and Mortality in People with Chronic Kidney Disease Stages 4 and 5 Not on Dialysis. J Clin Med 2023; 12:7631. [PMID: 38137700 PMCID: PMC10743559 DOI: 10.3390/jcm12247631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 11/27/2023] [Accepted: 12/07/2023] [Indexed: 12/24/2023] Open
Abstract
Rationale and objective: Data suggest that non-calcium-based binders, and specifically sevelamer, may lead to lower rates of death when compared with calcium-based binders in end-stage renal disease (ESRD) patients. However, the association between sevelamer use and mortality for those with non-dialysis-dependent chronic kidney disease (NDD-CKD) patients has been uncertain. Study design: Our research is presented in a prospective cohort study. Setting and participants: A total of 966 participants with NDD-CKD stages 4-5 were enrolled in the PECERA study from 12 centers in Spain. Exposure: The participants were treated with sevelamer. Outcome: This study yielded all-cause and cardiovascular mortality outcomes. Analytical approach: We conducted an association analysis between mortality and sevelamer use with time-dependent Cox proportional hazards models. Results: After a median follow-up of 29 months (IQR: 13-36 months), death occurred in 181 participants (19%), with cardiovascular (n = 95, 53%) being the leading cause of death. In a multivariable model, the adjusted hazard ratios (HRs) for patients under sevelamer treatment were 0.44 (95% CI, 0.22 to 0.88) and 0.37 (95% CI, 0.18 to 0.75) for all-cause and cardiovascular mortality, respectively, compared with those of untreated patients. Limitations: Some limitations include potential confusion via indication bias; causal statements about these associations cannot be made due to the observational nature of this study. Conclusions: In this prospective NDD-CKD cohort study, the administration of sevelamer was independently associated with lower all-cause and cardiovascular mortality, suggesting that non-calcium-based phosphate binders might be the first-line therapy for phosphate lowering in this population. Further interventional studies clarifying the risks and benefits of phosphate binders in NDD-CKD are warranted.
Collapse
Affiliation(s)
- Pablo Molina
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Mariola D. Molina
- Department of Mathematics, Universidad de Alicante, 03690 Sant Vicent del Raspeig, Spain;
| | - Juan J. Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden;
| | - Verónica Escudero
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Javier Torralba
- Department of Nephrology, Hospital General Universitario, 03010 Alicante, Spain;
| | - Cristina Castro-Alonso
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Sandra Beltrán
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Belén Vizcaíno
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Mercedes González-Moya
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Julia Kanter
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
| | - Asunción Sancho-Calabuig
- Department of Nephrology, Hospital Universitari Dr. Peset, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, 46017 Valencia, Spain; (V.E.); (C.C.-A.); (S.B.); (B.V.); (M.G.-M.); (J.K.); (A.S.-C.)
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
| | - Jordi Bover
- Nephrology Department, University Hospital Germans Trias i Pujol, 08916 Badalona, Spain;
| | - José L. Górriz
- Department of Medicine, Universitat de València, 46010 Valencia, Spain;
- Department of Nephrology, Hospital Clínico Universitario, Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana, 46010 Valencia, Spain
| |
Collapse
|
|
13
|
Cao Q, Yang F, Lian X, Li X, Li Z. Analysis of risk factors for abdominal aortic calcification in dialysis patients and its influence on long-term recovery. J Investig Med 2023; 71:845-853. [PMID: 37485956 DOI: 10.1177/10815589231190565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
This study investigated the risk factors of abdominal aortic calcification (AAC) in patients with stage 5 chronic kidney disease (CKD) and the effects of AAC and different dialysis methods on the 3-year survival rate of patients with stage 5 CKD. A retrospective cohort study was conducted on stage 5 CKD patients who received dialysis treatment. The general data were collected, and all fasting venous blood samples were harvested before the first dialysis to detect biochemical markers. The AAC was evaluated by lateral abdominal X-ray. The patients were followed up with a cut-off date of March 31, 2022, with all-cause mortality as the endpoint event. A total of 205 patients were included. multivariable Cox regression analysis confirmed that AAC (hazard ratio (HR) = 2.173, 95% CI 1.029-4.588, p = 0.042), advanced age (HR = 1.061, 95% CI 1.031-1.093, p < 0.001), duration of dialysis (HR = 1.015, 95% CI 1.007-1.032, p < 0.001), diabetes (HR = 3.966, 95% CI 2.164-7.269, p < 0.001), and hypertension (HR = 1.897, 95% CI 1.089-3.303, p = 0.024) were independent risk factors for 3-year mortality. However, peritoneal dialysis (HR = 0.366, 95% CI 0.165-0.812, p = 0.013), high albumin (HR = 0.882, 95% CI 0.819-0.950, p = 0.001), and high hemoglobin (HR = 0.969, 95% CI 0.942-0.997, p = 0.031) were protective factors for 3-year mortality in stage 5 CKD patients. Increased age, long-term dialysis, high level of intact parathyroid hormone, diabetes, and hypertension are closely related to the occurrence of AAC in patients with stage 5 CKD. In addition, AAC is an independent risk factor for all-cause mortality in patients with stage 5 CKD.
Collapse
Affiliation(s)
- Qianying Cao
- Department of Nephrology, Beiiing Luhe Hospital, Capital Medical University, Beijing, China
| | - Fan Yang
- Department of Nephrology, Beiiing Luhe Hospital, Capital Medical University, Beijing, China
| | - Xiaoying Lian
- Department of Nephrology, Beiiing Luhe Hospital, Capital Medical University, Beijing, China
| | - Xiangnan Li
- Department of Geriatrics, Aerospace Center Hospital (ASCH), Beijing, China
| | - Zhongxin Li
- Department of Nephrology, Beiiing Luhe Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
14
|
Torregrosa JV, Bover J, Rodríguez Portillo M, González Parra E, Dolores Arenas M, Caravaca F, González Casaus ML, Martín-Malo A, Navarro-González JF, Lorenzo V, Molina P, Rodríguez M, Cannata Andia J. Recommendations of the Spanish Society of Nephrology for the management of mineral and bone metabolism disorders in patients with chronic kidney disease: 2021 (SEN-MM). Nefrologia 2023; 43 Suppl 1:1-36. [PMID: 37202281 DOI: 10.1016/j.nefroe.2023.03.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 03/26/2022] [Indexed: 05/20/2023] Open
Abstract
As in 2011, when the Spanish Society of Nephrology (SEN) published the Spanish adaptation to the Kidney Disease: Improving Global Outcomes (KDIGO) universal Guideline on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), this document contains an update and an adaptation of the 2017 KDIGO guidelines to our setting. In this field, as in many other areas of nephrology, it has been impossible to irrefutably answer many questions, which remain pending. However, there is no doubt that the close relationship between the CKD-MBD/cardiovascular disease/morbidity and mortality complex and new randomised clinical trials in some areas and the development of new drugs have yielded significant advances in this field and created the need for this update. We would therefore highlight the slight divergences that we propose in the ideal objectives for biochemical abnormalities in the CKD-MBD complex compared to the KDIGO suggestions (for example, in relation to parathyroid hormone or phosphate), the role of native vitamin D and analogues in the control of secondary hyperparathyroidism and the contribution of new phosphate binders and calcimimetics. Attention should also be drawn to the adoption of important new developments in the diagnosis of bone abnormalities in patients with kidney disease and to the need to be more proactive in treating them. In any event, the current speed at which innovations are taking place, while perhaps slower than we might like, globally drives the need for more frequent updates (for example, through Nefrología al día).
Collapse
Affiliation(s)
| | - Jordi Bover
- Hospital Germans Trias i Pujol, Badalona, Spain
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Ohtake T, Mitomo A, Yamano M, Shimizu T, Mochida Y, Ishioka K, Oka M, Maesato K, Moriya H, Hidaka S, Mwanatambwe M, Kobayashi S. Impact of Arterial Calcification of the Lower Limbs on Long-Term Clinical Outcomes in Patients on Hemodialysis. J Clin Med 2023; 12:jcm12041299. [PMID: 36835836 PMCID: PMC9967859 DOI: 10.3390/jcm12041299] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/06/2023] [Accepted: 02/03/2023] [Indexed: 02/10/2023] Open
Abstract
Lower limbs' arterial calcification is significantly associated with the clinical severity of lower extremity artery disease (LEAD) in patients undergoing hemodialysis (HD). However, the association between arterial calcification of the lower limbs and long-term clinical outcomes in patients on HD has not been elucidated. Calcification scores of the superficial femoral artery (SFACS) and below-knee arteries (BKACS) were quantitatively evaluated in 97 HD patients who were followed for 10 years. Clinical outcomes, including all-cause and cardiovascular mortality, cardiovascular events, and limb amputation were evaluated. Risk factors for clinical outcomes were evaluated using univariate and multivariate Cox proportional hazard analyses. Furthermore, SFACS and BKACS were divided into three groups (low, middle, and high), and their associations with clinical outcomes were evaluated using Kaplan-Meier analysis. SFACS, BKACS, C-reactive protein, serum albumin, age, diabetes, presence of ischemic heart disease, and critical limb-threatening ischemia were significantly associated with 3-year and 10-year clinical outcomes in the univariate analysis. Multivariate analysis showed that SFACS was an independent factor associated with 10-year cardiovascular events and limb amputations. Kaplan-Meier life table analysis showed that higher SFACS and BKACS levels were significantly associated with cardiovascular events and mortality. In conclusion, long-term clinical outcomes and the risk factors in patients undergoing HD were evaluated. Arterial calcification of the lower limbs was strongly associated with 10-year cardiovascular events and mortality in patients undergoing HD.
Collapse
Affiliation(s)
- Takayasu Ohtake
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
- Regenerative Medicine, The Center for Cell Therapy & Regenerative Medicine, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura 247-8533, Japan
- Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura 247-8533, Japan
- Correspondence: ; Tel.: +81-467-46-1717; Fax: +81-467-45-0190
| | - Ayaka Mitomo
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Mizuki Yamano
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Toshihiro Shimizu
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Yasuhiro Mochida
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Kunihiro Ishioka
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Machiko Oka
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Kyoko Maesato
- Department of Nephrology, Tokyo Nishi Tokushukai Hospital, Tokyo 196-0003, Japan
| | - Hidekazu Moriya
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
| | - Sumi Hidaka
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
- Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura 247-8533, Japan
| | - Milanga Mwanatambwe
- Department of Pathology, University of Mbuji Mayi, Mbujimayi 433, Congo
- International Division of Tokushukai of Medical Corporation, Tokushukai, Tokyo 188-0013, Japan
| | - Shuzo Kobayashi
- Department of Kidney and Transplant Center, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan
- Shonan Research Institute of Innovative Medicine (sRIIM), Kamakura 247-8533, Japan
| |
Collapse
|
|
16
|
Rhee CM, Zhou M, Woznick R, Mullon C, Anger MS, Ficociello LH. A real-world analysis of the influence of age on maintenance hemodialysis patients: managing serum phosphorus with sucroferric oxyhydroxide as part of routine clinical care. Int Urol Nephrol 2023; 55:377-387. [PMID: 35953565 PMCID: PMC9859895 DOI: 10.1007/s11255-022-03327-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 07/25/2022] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Despite the growing number of elderly hemodialysis patients, the influence of age on nutritional parameters, serum phosphorus (sP), and use of phosphate-binder (PB) medications has not been well characterized. We aimed to describe age-related differences in patient characteristics in a large, real-world cohort of maintenance hemodialysis patients, and to examine the impact of age on sP management with sucroferric oxyhydroxide (SO). METHODS We retrospectively analyzed de-identified data from 2017 adult, in-center hemodialysis patients who switched from another PB to SO monotherapy as part of routine clinical care. Changes in baseline PB pill burden, sP levels, and nutritional and dialytic clearance parameters were assessed across varying age groups through 6 months. RESULTS At baseline, older patients had lower mean sP, serum albumin, and pre-dialysis weights compared with younger patients. Prescription of SO was associated with a 62% increase in the proportion of patients achieving sP ≤ 5.5 mg/dl and a 42% reduction in daily pill burden. The proportion of patients achieving sP ≤ 5.5 mg/dl after transitioning to SO increased by 113, 96, 68, 77, 61, 37 and 40% among those aged 19-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years, respectively. CONCLUSIONS Older patients had worse nutritional parameters, lower pill burden, and lower sP at baseline versus younger counterparts. Prescription of SO was associated with improved sP control and reduced pill burden across all ages.
Collapse
Affiliation(s)
- Connie M. Rhee
- grid.266093.80000 0001 0668 7243Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, University of California Irvine, Orange, CA USA
| | - Meijiao Zhou
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | | | - Claudy Mullon
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | - Michael S. Anger
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| | - Linda H. Ficociello
- grid.419076.d0000 0004 0603 5159Global Medical Office, Fresenius Medical Care, 920 Winter Street, Waltham, MA 02451 USA
| |
Collapse
|
|
17
|
Hu L, Napoletano A, Provenzano M, Garofalo C, Bini C, Comai G, La Manna G. Mineral Bone Disorders in Kidney Disease Patients: The Ever-Current Topic. Int J Mol Sci 2022; 23:12223. [PMID: 36293076 PMCID: PMC9603742 DOI: 10.3390/ijms232012223] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/07/2022] [Accepted: 10/10/2022] [Indexed: 02/08/2023] Open
Abstract
Chronic kidney disease (CKD) is a complex and multifactorial disease, and one of the most prevalent worldwide. Chronic kidney disease-mineral bone disorders (CKD-MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD. Pathophysiology of CKD-MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH) which are discussed in this review. We therefore examine the prognostic association between CKD-MBD and the increased risk for cardiovascular events, mortality, and CKD progression to end-stage kidney disease (ESKD). Lastly, we present specific treatments acting on CKD to prevent and treat the complications associated with secondary hyperparathyroidism (SHPT): control of hyperphosphatemia (with dietary restriction, intestinal phosphate binders, and adequate dialysis), the use of calcimimetic agents, vitamin D, and analogues, and the use of bisphosphonates or denosumab in patients with osteoporosis.
Collapse
Affiliation(s)
- Lilio Hu
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Angelodaniele Napoletano
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Michele Provenzano
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Carlo Garofalo
- Renal Unit, University of Campania “L. Vanvitelli’’, 80138 Naples, Italy
| | - Claudia Bini
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Giorgia Comai
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| | - Gaetano La Manna
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS—Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
| |
Collapse
|
|
18
|
Colombijn JMT, Vonk S, Cornelis T, Boorsma S, Krekels MME, Abrahams AC, van Jaarsveld BC. Impact of phosphate binders on quality of life in dialysis patients: Results from the prospective Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes study. Nephrology (Carlton) 2022; 27:834-844. [PMID: 36122909 PMCID: PMC9826474 DOI: 10.1111/nep.14088] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Revised: 06/29/2022] [Accepted: 07/14/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Phosphate binders cause high pill burden for dialysis patients, complicate medication regimens, and have unpleasant taste and large size which may affect patients' quality of life. This study explores the association between phosphate binder pill burden and health-related quality of life (HRQoL) in dialysis patients. METHODS We conducted a cross-sectional multi-centre cohort study in 21 Dutch dialysis centres. Phosphate binder pill burden was extracted from electronic patient records. Primary outcome was HRQoL measured with the Short Form 12 physical and mental component summary scores (PCS and MCS). Secondary endpoints were severity of gastro-intestinal symptoms, itching, dry mouth, and mental health symptoms, measured with the Dialysis Symptom Index. RESULTS Of 388 included patients, aged 62 ± 16 years, 77% underwent haemodialysis. PCS scores were comparable for patients with and without phosphate binders. Patients using 1-3 pills reported lower scores for decreased appetite (β -0.5; 95%CI -0.9 to -0.2), implying better appetite, than patients without phosphate binders. Patients using 4-6 pills also reported lower scores for decreased appetite (β -0.5; 95%CI -0.8 to -0.1) and for itching (β -0.5; 95%CI -0.9 to -0.1). Patients using >6 pills reported lower MCS (β -2.9; 95%CI -6.2-0.4) and higher scores for feeling nervous (β 0.6; 95%CI 0.1-1.1) and feeling sad (β 0.4; 95%CI 0.0-0.9). CONCLUSION Phosphate binder pill burden is not associated with physical quality of life. A higher pill burden is associated with better appetite and less itching. Patients using >6 pills per day report lower mental quality of life and felt nervous and sad more often.
Collapse
Affiliation(s)
- Julia M. T. Colombijn
- Department of Nephrology, Amsterdam Cardiovascular SciencesAmsterdam UMC, Vrije Universiteit AmsterdamAmsterdamThe Netherlands,Department Nephrology and HypertensionUniversity Medical Centre UtrechtUtrechtThe Netherlands,Julius Centre for Health Sciences and Primary Care, University Medical Centre UtrechtUtrecht UniversityUtrechtThe Netherlands
| | - Sanne Vonk
- Department Nephrology and HypertensionUniversity Medical Centre UtrechtUtrechtThe Netherlands
| | - Tom Cornelis
- Department of NephrologyJessa HospitalHasseltBelgium
| | - Siska Boorsma
- Department of NephrologyLaurentius HospitalRoermondThe Netherlands
| | | | - Alferso C. Abrahams
- Department Nephrology and HypertensionUniversity Medical Centre UtrechtUtrechtThe Netherlands
| | - Brigit C. van Jaarsveld
- Department of Nephrology, Amsterdam Cardiovascular SciencesAmsterdam UMC, Vrije Universiteit AmsterdamAmsterdamThe Netherlands,Diapriva Dialysis CentreAmsterdamThe Netherlands
| |
Collapse
|
|
19
|
Ogata H, Fukagawa M, Hirakata H, Kagimura T, Akizawa T. Effect of lanthanum carbonate and calcium carbonate on the progression of coronary artery calcification among hemodialysis patients with vascular calcification risk: a randomized controlled trial. Clin Exp Nephrol 2022; 26:1223-1232. [PMID: 36064876 DOI: 10.1007/s10157-022-02270-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Accepted: 08/23/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Coronary artery calcification (CAC) is predictive of cardiovascular events. We assessed whether a non-calcium-based phosphate binder, lanthanum carbonate (LC), could delay CAC progression compared with a calcium-based phosphate binder, calcium carbonate (CC), in hemodialysis patients. METHODS This was a subsidiary of the LANDMARK study, which is a multicenter, open-label, randomized control study comparing LC and CC for cardiovascular events among Japanese hemodialysis patients with hyperphosphatemia who were at risk of vascular calcification. Participants were randomly assigned (1:1) to receive LC or CC. The changes in the total Agatston score of CAC 2 years from baseline were the primary outcome. Secondary outcomes included the changes in the total Agatston score at 1 year from baseline and the changes in serum phosphate, corrected calcium, and intact parathyroid hormone concentrations. RESULTS Of 239 patients, 123 comprised the full analysis set. The median daily drug dose (mg) was 750 [interquartile range (IQR), 750‒1500] in the LC group and 3000 (IQR, 3000‒3000) in the CC group; it remained constant throughout the study period. There was no significant difference in the change in total Agatston score from baseline to 2 years between the LC and CC groups [368 (95% confidence interval, 57-680) in the LC group vs. 611 (105-1118) in the CC group; difference, 243 (- 352-838)]. CONCLUSIONS LC-based treatment for hyperphosphatemia did not delay CAC for 2 years compared with CC-based treatment in hemodialysis patients with at least one risk factor for vascular calcification.
Collapse
Affiliation(s)
- Hiroaki Ogata
- Division of Nephrology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Chigasaki-chuo 35-1, Tsuzuki, Yokohama, Kanagawa, 224-8503, Japan.
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | | | - Tatsuo Kagimura
- The Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Chuo-ku, Kobe, Hyogo, Japan
| | - Tadao Akizawa
- Division of Nephrology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan
| | | |
Collapse
|
|
20
|
Hashimoto A, Gao J, Kanome Y, Ogawa Y, Nakatsu M, Kohno M, Fukui K. Evaluation of cerium oxide as a phosphate binder using 5/6 nephrectomy model rat. BMC Nephrol 2022; 23:277. [PMID: 35941569 PMCID: PMC9358871 DOI: 10.1186/s12882-022-02904-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 08/02/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The number of chronic kidney disease (CKD) patients continues to increase worldwide. CKD patients need to take phosphate binders to manage serum phosphorus concentrations. Currently, several types of phosphate binder, including lanthanum carbonate, are used. However, they each have disadvantages. METHODS In this study, we evaluated cerium oxide as a new phosphate binder in vitro and in vivo. First, cerium oxide was mixed with phosphoric acid at pH 2.5 or 7.0, and residual phosphoric acid was measured by absorption photometry using colorimetric reagent. Second, cerium oxide was fed to 5/6 nephrectomy model rats (5/6Nx), a well-known renal damage model. All rats were measured food intake, water intake, feces volume, and urine volume, and collected serum and urine were analyzed for biochemical markers. RESULTS Cerium oxide can adsorb phosphate at acidic and neutral pH, while lanthanum carbonate, which is a one of popular phosphate binder, does not dissolve at neutral pH. Cerium oxide-treatment reduced serum phosphate concentrations of 5/6Nx rats without an increase in serum alanine transaminase levels that would indicate hepatotoxicity, and cerium oxide-treatment maintained serum creatinine and blood urea nitrogen levels, while those of normal 5/6Nx rats increased slightly. CONCLUSIONS These results suggest that cerium oxide can be a potential phosphate binder. Decreased body weight gain and increased water intake and urine volume in 5/6Nx rats were thought to be an effect of nephrectomy because these changes did not occur in sham operation rats. Additional investigations are needed to evaluate the longer-term safety and possible accumulation of cerium oxide in the body.
Collapse
Affiliation(s)
- Akiko Hashimoto
- applause Company Limited, Biko building 4F, Shinkawa 2-24-2, Chuo-ku, Tokyo, 104-0033, Japan.,Molecular Cell Biology Laboratory, Department of Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan
| | - Jiaqi Gao
- Molecular Cell Biology Laboratory, Department of Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan
| | - Yuki Kanome
- Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, College of System Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan
| | - Yukihiro Ogawa
- applause Company Limited, Biko building 4F, Shinkawa 2-24-2, Chuo-ku, Tokyo, 104-0033, Japan
| | - Masaharu Nakatsu
- applause Company Limited, Biko building 4F, Shinkawa 2-24-2, Chuo-ku, Tokyo, 104-0033, Japan
| | - Masahiro Kohno
- SIT Research Institute, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan
| | - Koji Fukui
- Molecular Cell Biology Laboratory, Department of Systems Engineering and Science, Graduate School of Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan. .,Molecular Cell Biology Laboratory, Department of Bioscience and Engineering, College of System Engineering and Science, Shibaura Institute of Technology, Fukasaku 307, Minuma-ku, Saitama, 337-8570, Japan.
| |
Collapse
|
|
21
|
A Comparison Between the Effects of Calcium Acetate and Sevelamer Carbonate on Progression of Aortic Vascular Calcification in Patients with Chronic Kidney Disease Stages 4 and 5. Nephrourol Mon 2022. [DOI: 10.5812/numonthly-120721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Calcium-based and non-calcium-based phosphate binders are frequently used to treat hyperphosphatemia in patients with chronic kidney disease (CKD). Objectives: This study aimed to compare the effects of calcium acetate and sevelamer carbonate on the progression of aortic vascular calcification in patients with CKD stages 4 and 5. Methods: This was an open-label randomized prospective comparative study, in which the participants encompassed both male and female patients with ambulatory hyperphosphatemic CKD stages 4 and 5 aged above 18 years. One hundred fifty patients with CKD stages 4 and 5 were screened for Aortic vascular calcification using digital X-ray lumbar spine and multi-slice CT scan, of whom fifty patients with vascular calcification were selected and randomly assigned into two groups. The participants were then serially studied for the effects of phosphate binders on the progression of vascular calcification over one year. One group was prescribed calcium acetate, and the other group was prescribed sevelamer carbonate. Results: Fifty hyperphosphatemic CKD patients with a mean age of 57 years were randomly assigned into two groups. There was no statistically significant difference between the two groups; however, the patients assigned to the sevelamer group were older and higher aortic calcification index (ACI) (P = 0.035) and Kauppila scores (P = 0.04), and elevated serum calcium (P = 0.04), Ca X PO4 (P = 0.006), and vitamin D. In calcium acetate-treated patients, the mean ACI increased significantly during six months and one year; however, the increase was not significant in the sevelamer group. Serum cholesterol, serum triglycerides, serum iPTH level, and the inflammatory markers of atherosclerosis high sensitivity of C-reactive protein (hs-CRP), interleukin-6 (IL-6) (hs-CRP, IL-6) decreased significantly in the sevelamer group. Conclusions: The prevalence of vascular (abdominal aortic) calcification in pre-ESRD (CKD stage 4 and 5) patients was 75%. Abdominal aortic calcification increased significantly in calcium acetate-treated patients during six months and one year; however, the progression was not significant regarding sevelamer. Because of its pleiotropic properties, sevelamer is more effective and consistent in retarding the progression of vascular calcification than calcium acetate in patients with CKD stages 4 and 5.
Collapse
|
|
22
|
Ulaya G, İla HB. In vitro cytogenetic analysis of two different anti-phosphates (sevelamer hydrochloride and calcium carbonate) agents used by patients with hyperphosphatemia. Drug Chem Toxicol 2022:1-9. [DOI: 10.1080/01480545.2022.2083150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Goulzar Ulaya
- Department of Biology, Faculty of Science and Letters, Çukurova University, Adana, Turkey
| | - Hasan Basri İla
- Department of Biology, Faculty of Science and Letters, Çukurova University, Adana, Turkey
| |
Collapse
|
|
23
|
Oka Y, Miyazaki M, Takatsu S, Matsuda H. Calcium-Based Phosphate Binders and Plasma Oxalate Concentration in Dialysis Patients. J Am Soc Nephrol 2022; 33:1427. [PMID: 35500940 PMCID: PMC9257817 DOI: 10.1681/asn.2022030248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Affiliation(s)
- Yoshinari Oka
- Department of Surgery, Saiwaicho Memorial Hospital, Okayama City, Japan
| | - Masashi Miyazaki
- Department of Surgery, Saiwaicho Memorial Hospital, Okayama City, Japan
| | - Shigeko Takatsu
- Department of Internal Medicine, Saiwaicho Memorial Hospital, Okayama City, Japan
| | - Hiroaki Matsuda
- Department of Surgery, Saiwaicho Memorial Hospital, Okayama City, Japan
| |
Collapse
|
|
24
|
Jadav PR, Husain SA, Mohan S, Crew R. Non calcium phosphate binders - Is there any evidence of benefit. Curr Opin Nephrol Hypertens 2022; 31:288-296. [PMID: 35266882 DOI: 10.1097/mnh.0000000000000796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes. RECENT FINDINGS Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies. SUMMARY There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality.
Collapse
Affiliation(s)
- Paresh R Jadav
- Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY
| | - S Ali Husain
- Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY
- The Columbia University Renal Epidemiology (CURE) Group
| | - Sumit Mohan
- Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY
- The Columbia University Renal Epidemiology (CURE) Group
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA
| | - Russell Crew
- Department of Medicine, Division of Nephrology, Columbia University Medical Center, New York, NY
| |
Collapse
|
|
25
|
Rudloff S, Jahnen-Dechent W, Huynh-Do U. Tissue chaperoning—the expanded functions of fetuin-A beyond inhibition of systemic calcification. Pflugers Arch 2022; 474:949-962. [PMID: 35403906 PMCID: PMC8995415 DOI: 10.1007/s00424-022-02688-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/29/2022] [Accepted: 03/31/2022] [Indexed: 02/06/2023]
Abstract
AbstractTraditionally, fetuin-A embodies the prototype anti-calcification protein in the blood, preventing cardiovascular calcification. Low serum fetuin-A is generally associated with mineralization dysbalance and enhanced mortality in end stage renal disease. Recent evidence indicates that fetuin-A is a crucial factor moderating tissue inflammation and fibrosis, as well as a systemic indicator of acute inflammatory disease. Here, the expanded function of fetuin-A is discussed in the context of mineralization and inflammation biology. Unbalanced depletion of fetuin-A in this context may be the critical event, triggering a vicious cycle of progressive calcification, inflammation, and tissue injury. Hence, we designate fetuin-A as tissue chaperone and propose the potential use of exogenous fetuin-A as prophylactic agent or emergency treatment in conditions that are associated with acute depletion of endogenous protein.
Collapse
Affiliation(s)
- Stefan Rudloff
- Department of Nephrology and Hypertension, Bern University Hospital, Freiburgstrasse 15, 3010, Bern, Switzerland
- Department of Biomedical Research, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland
| | - Willi Jahnen-Dechent
- Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen, University Medical Faculty, Pauwelsstrasse 30, 52074, Aachen, Germany
| | - Uyen Huynh-Do
- Department of Nephrology and Hypertension, Bern University Hospital, Freiburgstrasse 15, 3010, Bern, Switzerland.
- Department of Biomedical Research, University of Bern, Freiburgstrasse 15, 3010, Bern, Switzerland.
| |
Collapse
|
|
26
|
Xu C, Smith ER, Tiong MK, Ruderman I, Toussaint ND. Interventions to Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials. J Am Soc Nephrol 2022; 33:1011-1032. [PMID: 35232774 PMCID: PMC9063901 DOI: 10.1681/asn.2021101327] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 02/16/2022] [Indexed: 11/03/2022] Open
Abstract
Background Vascular calcification is associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Evidence-based interventions that may attenuate its progression in CKD remain uncertain.
Methods We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compare with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiological methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) method.
Results There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.
Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
Collapse
Affiliation(s)
- Chelsea Xu
- Department of Medicine, University of Melbourne, Parkville, Australia
| | - Edward R Smith
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Mark K Tiong
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Irene Ruderman
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| | - Nigel D Toussaint
- Department of Medicine, University of Melbourne, Parkville, Australia
- Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia
| |
Collapse
|
|
27
|
New evidence of direct oral anticoagulation therapy on cardiac valve calcifications, renal preservation and inflammatory modulation. Int J Cardiol 2021; 345:90-97. [PMID: 34688719 DOI: 10.1016/j.ijcard.2021.10.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 09/25/2021] [Accepted: 10/15/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b - 4. METHODS This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b - 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months. RESULTS Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value <0.001). CONCLUSIONS Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.
Collapse
|
|
28
|
Xu JP, Zeng RX, Liao PD, Zhang MZ. Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: A meta-analysis of randomized controlled trials. Hemodial Int 2021; 26:223-233. [PMID: 34897963 DOI: 10.1111/hdi.12988] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 08/19/2021] [Accepted: 11/30/2021] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium-based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. METHODS RCTs comparing lanthanum carbonate with calcium-based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. FINDINGS Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium-based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: -74.28, 95% CI: -149.89, 1.33), change in coronary artery calcium scores (WMD: -105.18, 95% CI: -113.83, -96.53), and left ventricular mass index (WMD: -29.95, 95% CI: -54.25, -7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: -0.18, 95% CI: -0.26, -0.10), calcium (WMD: -0.22, 95% CI: -0.25, -0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: -3.78, 95% CI: -5.60, -1.96) but not intact parathyroid hormone (WMD: -4.23, 95% CI: -64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10-0.97) but not all-cause mortality (OR: 1.08, 95% CI: 0.39-3.01) in lanthanum carbonate therapy was observed. DISCUSSION In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium-based phosphate binders. However, more well-designed RCTs are required for confirmation.
Collapse
Affiliation(s)
- Jun-Peng Xu
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Rui-Xiang Zeng
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Peng-Da Liao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| | - Min-Zhou Zhang
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
| |
Collapse
|
|
29
|
Bonato FOB, Karohl C, Canziani MEF. Diagnosis of vascular calcification related to mineral and bone metabolism disorders in chronic kidney disease. J Bras Nefrol 2021; 43:628-631. [PMID: 34910796 PMCID: PMC8823916 DOI: 10.1590/2175-8239-jbn-2021-s104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 06/24/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
| | - Cristina Karohl
- Universidade Federal do Rio Grande do Sul, Porto Alegre, RS,
Brazil
| | | |
Collapse
|
|
30
|
Kim JS, Hwang HS. Vascular Calcification in Chronic Kidney Disease: Distinct Features of Pathogenesis and Clinical Implication. Korean Circ J 2021; 51:961-982. [PMID: 34854578 PMCID: PMC8636761 DOI: 10.4070/kcj.2021.0995] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/27/2021] [Accepted: 10/13/2021] [Indexed: 01/10/2023] Open
Abstract
Chronic kidney disease (CKD) is associated with a higher prevalence of vascular calcification (VC) and cardiovascular disease. VC in CKD patients showed different pathophysiological features from those of the general population. The pathogenesis of VC in CKD is a highly organized process, and prior studies have suggested that patients with CKD have their own specific contributors to the phenotypic change of vascular smooth muscle cells (VSMCs), including uremic toxins, CKD-mineral and bone disease (CKD-MBD), inflammation, and oxidative stress. For the diagnosis and monitoring of VC in CKD, several imaging modalities, including plain radiography, ultrasound, and computed tomography have been utilized. VC in CKD patients has distinct clinical features and implications. CKD patients revealed a more intense and more prevalent calcification on the intimal and medial layers, whereas intimal calcification is predominantly observed in the general population. While a higher VC score is clearly associated with a higher risk of all-cause mortality and cardiovascular events, a greater VC score in CKD patients does not fully reflect the burden of atherosclerosis, because they have more calcification at equal volumes of atheromatous plaques. The primary goal of VC treatment in CKD is the prevention of VC progression, and the main management is to control the biochemical components of CKD-MBD. Cinacalcet and non-calcium-containing phosphate binders are the mainstay of VC prevention in CKD-MBD management. VC in patients with CKD is an ongoing area of research and is expected to advance soon.
Collapse
Affiliation(s)
- Jin Sug Kim
- Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Korea
| | - Hyeon Seok Hwang
- Division of Nephrology, Department of Internal Medicine, Kyung Hee University, Seoul, Korea.
| |
Collapse
|
|
31
|
Peix A. Choosing between anatomy and function is not always evident for the heart of end-stage renal disease patients. How low can we go? J Nucl Cardiol 2021; 28:2671-2675. [PMID: 32342299 DOI: 10.1007/s12350-020-02118-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 10/24/2022]
Abstract
Patients with chronic kidney disease (CKD) are at a very high risk of adverse cardiovascular events. In CKD patients, vascular calcification is more prevalent, appears at an earlier age, and is more severe than in the general population. CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease in these patients. Considering the significant morbidity and mortality attributable to cardiovascular disease in the CKD population, risk stratification remains an important challenge. Topics such as function vs anatomy to properly risk stratify these patients, as well as future perspectives on non-invasive techniques, will be addressed.
Collapse
Affiliation(s)
- Amalia Peix
- Nuclear Medicine Department, Institute of Cardiology, 17 No. 702, Vedado, CP 10 400, La Habana, Cuba.
| |
Collapse
|
|
32
|
Wang AYM, Pasch A, Wong CK, Chu IMT, Tang TK, Chu J, Cheuk-Ying Fong C, Yau YY, Lo WK. Long-Term Effects of Sevelamer on Vascular Calcification, Arterial Stiffness, and Calcification Propensity in Patients Receiving Peritoneal Dialysis: The Randomized Pilot SERENE (Sevelamer on Vascular Calcification, Arterial Stiffness) Trial. Kidney Med 2021; 4:100384. [PMID: 35243302 PMCID: PMC8861951 DOI: 10.1016/j.xkme.2021.10.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Rationale & Objective There is a concern regarding increased risk of vascular calcification with the use of calcium-based phosphorus binders. This study aimed to compare the effects of sevelamer used as a second-line, low-dose therapy with calcium-based phosphorus binders with those of sevelamer used as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity over 2 years in patients with hyperphosphatemia receiving peritoneal dialysis (PD). Study Design A 2-year-long prospective, multicenter, open-label, randomized pilot study. Setting & Participants Prevalent patients with hyperphosphatemia receiving PD from 2 university-affiliated hospitals in Hong Kong. Interventions The patients were randomized to receive sevelamer either as a first-line therapy at a high dose of 800 mg thrice daily (can titrate up to 1,200 mg thrice daily as required) or a second-line therapy at a low dose of 400 mg thrice daily with calcium carbonate to achieve a serum phosphorus target of ≤5.5 mg/dL. Outcomes The primary endpoints were changes in coronary artery calcium score and aortic PWV over 104 weeks. The secondary endpoints were changes in heart valve calcium scores, calcification propensity measure, and biochemical parameters of chronic kidney disease–mineral bone disease over 104 weeks. Results Among 60 prevalent patients receiving PD, with a mean age of 53 ± 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; P = 0.21), aortic PWV (mean ± standard error, 0.3 ± 0.1 vs 0.8 ± 0.2 m/s, respectively; P = 0.31), heart valve calcium score, maturation or transformation time, serum calcium levels, and phosphorus levels over 104 weeks were similar for the second-line, low-dose and first-line, high-dose sevelamer groups. Alkaline phosphatase and intact parathyroid hormone levels increased and low-density lipoprotein cholesterol decreased in both the groups, with no significant between-group differences. Limitations The sample size was small, and the dropout rates were relatively high. Conclusions Low-dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with a calcium-based phosphorus binder had similar effects on vascular calcification, valvular calcification, and arterial stiffness compared with high-dose sevelamer used as a first-line therapy. This approach may be considered in resource-constrained countries to minimize calcium loading. Funding The study was supported by a competitive grant from SK Yee Medical Foundation. T50 assays and other biochemical assays were funded by a research grant from Sanofi Renal Corporation. Trial Registration NCT00745589.
Collapse
|
|
33
|
Association between Serum Phosphate Levels and the Development of Aortic Stenosis in Patients Undergoing Hemodialysis. J Clin Med 2021; 10:jcm10194385. [PMID: 34640403 PMCID: PMC8509227 DOI: 10.3390/jcm10194385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 11/25/2022] Open
Abstract
We aimed to investigate the factors associated with the development of aortic stenosis (AS) in patients undergoing hemodialysis (HD), and to elucidate the prognosis of HD patients with AS. Patients on HD that had also undergone echocardiography at Nagasaki Renal Center between July 2011 and June 2012 were included. Patients with AS at the time of inclusion were excluded. The diagnosis of AS was based on an annual routine or additional echocardiography. The patients were followed up until June 2021. The association between patient background and AS was also evaluated. Of the 302 patients (mean age, 67.4 ± 13.3 years; male, 58%; median dialysis history, 4.7 years), 60 developed AS and 10 underwent aortic valve replacement. A Cox proportional hazards model revealed that age (hazard ratio (HR), 1.07; 95% confidential interval (CI), 1.04–1.10; p < 0.001) and serum phosphate levels (HR, 1.40; 95%CI, 1.16–1.67, p < 0.001) were independent risk factors for developing AS. Incidentally, there was no significant mortality difference between patients with AS and those without (p = 0.53). Serum phosphate levels are a risk factor for developing AS and should be controlled. Annual echocardiography may contribute to the early detection of AS and improves the prognosis of patients undergoing HD.
Collapse
|
|
34
|
Jandaghi E, Yarmohammadi M, Ghorbani R, Jalali T, Salehani AK, Khani PM. Comparison of Sevelamer and Calcium Carbonate in Prevention of Hypomagnesemia in Hemodialysis Patients. Int J Prev Med 2021; 12:104. [PMID: 34729138 PMCID: PMC8505683 DOI: 10.4103/ijpvm.ijpvm_464_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/07/2020] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a life-threatening disease with numerous complications. Hemodialysis (HD) patients are prone to magnesium deficiency due to malnutrition, which can cause cardiovascular complications and increase mortality. The present study aimed to investigate the effects of sevelamer and calcium carbonate, as phosphate binders, on serum levels of magnesium, calcium, and phosphorus in HD patients. METHODS A parallel clinical trial was conducted on 54 patients undergoing HD at Kosar Hospital of Semnan. The inclusion criteria were end-stage renal disease (ESRD), alternative HD treatment for at least 3 months 3 times a week, and serum phosphate levels greater than 4.5 mg/dL. The participants were randomly assigned to two groups of sevelamer (n = 27) and calcium carbonate (n = 27). If the participants were taking a phosphate binder, they were asked to stop it for 3 weeks. Participants in the sevelamer group received 800 mg of sevelamer at most three times a day and those in the calcium carbonate group were treated with 500 mg of calcium carbonate at most 3 times a day. Before and 3 months after the intervention, the serum levels of calcium, magnesium, and phosphorus were measured through the Arsenazo method using the Pars Azmun kit in the Selectra auto-analyzer. Twenty-one patients in the sevelamer group and 22 patients in the calcium carbonate group finished the study. RESULTS The results showed that calcium carbonate and sevelamer increased serum magnesium level by 0.20 (P = 0.028) and 0.26 (P = 0.002), on average, which were statistically significant. The administration of calcium carbonate did not significantly change serum calcium levels (P = 0.53), whereas sevelamer reduced serum calcium levels by 0.23 (P = 0.017), on average. This reduction was statistically significant. The results also indicated that none of the calcium carbonate (P = 0.099) and sevelamer (P = 0.543) caused significant changes in serum phosphorus levels. The study findings showed no significant difference between the two groups in terms of changes in the serum levels of magnesium (0.590), calcium (0.116), and phosphorus (0.113). CONCLUSIONS Both drugs (Sevelamer and calcium carbonate) prevented hypomagnesemia and increased serum magnesium levels, but no significant differences were found in blood levels of calcium, phosphorus, and magnesium compared to the two drugs. Considering the effect of magnesium on cardiovascular diseases, increasing the serum magnesium levels through the administration of calcium carbonate and sevelamer can prevent the likelihood of cardiovascular diseases. However, none of the studied drugs was superior to the other in this regard.
Collapse
Affiliation(s)
- Elahe Jandaghi
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Tehran, Iran
| | - Maliheh Yarmohammadi
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Tehran, Iran
| | - Raheb Ghorbani
- Social Determinant of Health Research Center, Semnan University of Medical Sciences, Semnan, Tehran, Iran
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Tehran, Iran
| | - Tahereh Jalali
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Khadjeh Salehani
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Tehran, Iran
| | - Peiman Mohammad Khani
- Department of Internal Medicine, Semnan University of Medical Sciences, Semnan, Tehran, Iran
| |
Collapse
|
|
35
|
Edmonston DL, Isakova T, Dember LM, Brunelli S, Young A, Brosch R, Beddhu S, Chakraborty H, Wolf M. Design and Rationale of HiLo: A Pragmatic, Randomized Trial of Phosphate Management for Patients Receiving Maintenance Hemodialysis. Am J Kidney Dis 2021; 77:920-930.e1. [PMID: 33279558 PMCID: PMC9933919 DOI: 10.1053/j.ajkd.2020.10.008] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 10/01/2020] [Indexed: 12/16/2022]
Abstract
RATIONALE & OBJECTIVE Hyperphosphatemia is a risk factor for poor clinical outcomes in patients with kidney failure receiving maintenance dialysis. Opinion-based clinical practice guidelines recommend the use of phosphate binders and dietary phosphate restriction to lower serum phosphate levels toward the normal range in patients receiving maintenance dialysis, but the benefits of these approaches and the optimal serum phosphate target have not been tested in randomized trials. It is also unknown if aggressive treatment that achieves unnecessarily low serum phosphate levels worsens outcomes. STUDY DESIGN Multicenter, pragmatic, cluster-randomized clinical trial. SETTING & PARTICIPANTS HiLo will randomize 80-120 dialysis facilities operated by DaVita Inc and the University of Utah to enroll 4,400 patients undergoing 3-times-weekly, in-center hemodialysis. INTERVENTION Phosphate binder prescriptions and dietary recommendations to achieve the "Hi" serum phosphate target (≥6.5 mg/dL) or the "Lo" serum phosphate target (<5.5 mg/dL). OUTCOMES Primary outcome: Hierarchical composite outcome of all-cause mortality and all-cause hospitalization. Main secondary outcomes: Individual components of the primary outcome. RESULTS The trial is currently enrolling. LIMITATIONS HiLo will not adjudicate causes of hospitalizations or mortality and does not protocolize use of specific phosphate binder classes. CONCLUSIONS HiLo aims to address an important clinical question while more generally advancing methods for pragmatic clinical trials in nephrology by introducing multiple innovative features including stakeholder engagement in the study design, liberal eligibility criteria, use of electronic informed consent, engagement of dietitians to implement the interventions in real-world practice, leveraging electronic health records to eliminate dedicated study visits, remote monitoring of serum phosphate separation between trial arms, and use of a novel hierarchical composite outcome. TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT04095039.
Collapse
Affiliation(s)
- Daniel L. Edmonston
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC,Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC
| | - Tamara Isakova
- Division of Nephrology, Department of Medicine, and Center for Translational Metabolism and Health, Institute of Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Laura M. Dember
- Renal, Electrolyte and Hypertension Division, Department of Medicine, and Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | | | - Amy Young
- DaVita Clinical Research, DaVita Inc, Minneapolis, MN
| | | | - Srinivasan Beddhu
- Division of Nephrology, Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT
| | | | - Myles Wolf
- Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
| |
Collapse
|
|
36
|
Ogata H, Fukagawa M, Hirakata H, Kagimura T, Fukushima M, Akizawa T. Effect of Treating Hyperphosphatemia With Lanthanum Carbonate vs Calcium Carbonate on Cardiovascular Events in Patients With Chronic Kidney Disease Undergoing Hemodialysis: The LANDMARK Randomized Clinical Trial. JAMA 2021; 325:1946-1954. [PMID: 34003226 PMCID: PMC8132143 DOI: 10.1001/jama.2021.4807] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 03/12/2021] [Indexed: 11/14/2022]
Abstract
Importance Among patients with hyperphosphatemia undergoing dialysis, it is unclear whether non-calcium-based phosphate binders are more effective than calcium-based binders for reducing cardiovascular events. Objective To determine whether lanthanum carbonate reduces cardiovascular events compared with calcium carbonate in patients with hyperphosphatemia at risk of vascular calcification undergoing hemodialysis. Design, Setting, and Participants Open-label, randomized, parallel-group clinical trial with blinded end point adjudication performed in 2374 patients with chronic kidney disease from 273 hemodialysis facilities in Japan. Eligible patients had hyperphosphatemia and 1 or more risk factors for vascular calcification (ie, ≥65 years, postmenopausal, diabetes). Enrollment occurred from November 2011 to July 2014; follow-up ended June 2018. Interventions Patients were randomized to receive either lanthanum carbonate (n = 1154) or calcium carbonate (n = 1155) and titrated to achieve serum phosphate levels of between 3.5 mg/dL and 6.0 mg/dL. Main Outcomes and Measures The primary outcome was a composite cardiovascular event (cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, transient ischemic attack, or hospitalization for heart failure or ventricular arrhythmia). Secondary outcomes included overall survival, secondary hyperparathyroidism-free survival, hip fracture-free survival, and adverse events. Results Among 2309 randomized patients (median age, 69 years; 40.5% women), 1851 (80.2%) completed the trial. After a median follow-up of 3.16 years, cardiovascular events occurred in 147 of 1063 patients in the lanthanum calcium group and 134 of 1072 patients in the calcium carbonate group (incidence rate, 4.80 vs 4.30 per 100 person-years; difference 0.50 per 100 person-years [95% CI, -0.57 to 1.56]; hazard ratio [HR], 1.11 [95%, CI, 0.88 to 1.41], P = .37). There were no significant differences in all-cause death (difference, 0.43 per 100 person-years [95% CI, -0.63 to 1.49]; HR, 1.10 [95% CI, 0.88 to 1.37]; P = .42) or hip fracture (difference, 0.10 per 100 person-years [95% CI, -0.26 to 0.47]; HR, 1.21 [95% CI, 0.62 to 2.35]; P = .58). The lanthanum carbonate group had an increased risk of cardiovascular death (difference, 0.61 per 100 person-years [95% CI, 0.02 to 1.21]; HR, 1.51 [95% CI, 1.01 to 2.27]; P = .045) and secondary hyperparathyroidism (difference, 1.34 [95% CI, 0.49 to 2.19]; HR, 1.62 [95% CI, 1.19 to 2.20]; P = .002). Adverse events occurred in 282 (25.7%) in the lanthanum carbonate group and 259 (23.4%) in the calcium carbonate groups. Conclusions and Relevance Among patients undergoing hemodialysis with hyperphosphatemia and at least 1 vascular calcification risk factor, treatment of hyperphosphatemia with lanthanum carbonate compared with calcium carbonate did not result in a significant difference in composite cardiovascular events. However, the event rate was low, and the findings may not apply to patients at higher risk. Trial Registration ClinicalTrials.gov Identifier: NCT01578200; UMIN Clinical Trial Registry Identifier: UMIN000006815.
Collapse
Affiliation(s)
- Hiroaki Ogata
- Division of Nephrology, Department of Internal Medicine, Showa University Northern Yokohama Hospital, Tsuzuki, Yokohama, Kanagawa, Japan
| | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan
| | | | - Tatsuo Kagimura
- The Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Chuo-ku, Kobe, Hyogo, Japan
| | - Masanori Fukushima
- The Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, Chuo-ku, Kobe, Hyogo, Japan
| | - Tadao Akizawa
- Division of Nephrology, Department of Medicine, Showa University School of Medicine, Shinagawa, Tokyo, Japan
| |
Collapse
|
|
37
|
Vascular Calcification Progression Modulates the Risk Associated with Vascular Calcification Burden in Incident to Dialysis Patients. Cells 2021; 10:cells10051091. [PMID: 34063597 PMCID: PMC8147653 DOI: 10.3390/cells10051091] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 04/24/2021] [Accepted: 04/25/2021] [Indexed: 12/26/2022] Open
Abstract
Background: It is estimated that chronic kidney disease (CKD) accounts globally for 5 to 10 million deaths annually, mainly due to cardiovascular (CV) diseases. Traditional as well as non-traditional CV risk factors such as vascular calcification are believed to drive this disproportionate risk burden. We aimed to investigate the association of coronary artery calcification (CAC) progression with all-cause mortality in patients new to hemodialysis (HD). Methods: Post hoc analysis of the Independent study (NCT00710788). At study inception and after 12 months of follow-up, 414 patients underwent computed tomography imaging for quantification of CAC via the Agatston methods. The square root method was used to assess CAC progression (CACP), and survival analyses were used to test its association with mortality. Results: Over a median follow-up of 36 months, 106 patients died from all causes. Expired patients were older, more likely to be diabetic or to have experienced an atherosclerotic CV event, and exhibited a significantly greater CAC burden (p = 0.002). Survival analyses confirmed an independent association of CAC burden (hazard ratio: 1.29; 95% confidence interval: 1.17-1.44) and CACP (HR: 5.16; 2.61-10.21) with all-cause mortality. CACP mitigated the risk associated with CAC burden (p = 0.002), and adjustment for calcium-free phosphate binder attenuated the strength of the link between CACP and mortality. Conclusions: CAC burden and CACP predict mortality in incident to dialysis patients. However, CACP reduced the risk associated with baseline CAC, and calcium-free phosphate binders attenuated the association of CACP and outcomes, suggesting that CACP modulation may improve survival in this population. Future endeavors are needed to confirm whether drugs or kidney transplantation may attenuate CACP and improve survival in HD patients.
Collapse
|
|
38
|
Pudil J, Steyerová P, Macová I, Zemánek D, Král A, Pad'our M, Chen Z, Daneš J, Kovárník T. Coronary artery disease prediction based on breast arterial calcification in women undergoing mammography as a screening for breast cancer. Menopause 2021; 28:787-791. [PMID: 33760780 DOI: 10.1097/gme.0000000000001765] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of the study was to test the potential role of breast arterial calcification (BAC) in the prediction of coronary artery disease (CAD) in women. The criterion standard for CAD diagnostics was coronary angiography. METHODS This retrospective study enrolled 163 consecutive women, who underwent digital mammography and coronary angiography in our hospital. We assessed the presence and severity of BAC, and tested whether the presence and/or extent of BAC could be a predictor for CAD, quantified by Gensini score. RESULTS BAC was presented in 34 patients (21%). Neither the presence of CAD (17 patients, 50%, vs 55 42.6%, P = 0.44), nor the Gensini score (20.5 ± 29.7 vs 15.4 ± 24.1, P = 0.3) differed significantly between BAC-present and BAC-absent patients.A finding of triple-vessel disease, however, more frequently occurred in the BAC-present (seven patients, 20.6%) than in the BAC-absent (nine patients, 7%) group, odds ratio (OR) 3.1, 95% CI 1-9.5, P = 0.049. The presence of BAC did not significantly increase the odds for the presence of CAD (OR = 1.29, P = 0.54). Among the subgroup of patients with CAD, BAC presence was associated with triple vessel disease (OR = 3.34, P = 0.049). CONCLUSIONS We did not confirm BAC as a predictor of CAD. However, BAC showed association with more severe forms of coronary atherosclerosis (triple vessel disease).
Collapse
Affiliation(s)
- Jan Pudil
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Petra Steyerová
- Department of Radiology, Breast Cancer Screening and Diagnostic center, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Iva Macová
- Department of Radiology, Breast Cancer Screening and Diagnostic center, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - David Zemánek
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Aleš Král
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Michal Pad'our
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Zhi Chen
- Department of Electrical and Computer Engineering and Iowa Institute for Biomedical Imaging, The University of Iowa, Iowa City, IA
| | - Jan Daneš
- Department of Radiology, Breast Cancer Screening and Diagnostic center, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Tomáš Kovárník
- 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| |
Collapse
|
|
39
|
Wald R, Walsh MW. In Search of the Optimal Target for Phosphate Control: Episode 1. J Am Soc Nephrol 2021; 32:526-528. [PMID: 33547217 PMCID: PMC7920181 DOI: 10.1681/asn.2021010027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
- Ron Wald
- Division of Nephrology, St. Michael’s Hospital, Toronto, Ontario, Canada,Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada,Department of Medicine and the Institute for Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
| | - Michael W. Walsh
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada,Department of Health Research Methods, Evaluation and Impact, McMaster University, Hamilton, Ontario, Canada,Population Health Research Institute, Hamilton Health Sciences/McMaster University, Hamilton, Ontario, Canada,Division of Nephrology, St. Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
| |
Collapse
|
|
40
|
Isaka Y, Hamano T, Fujii H, Tsujimoto Y, Koiwa F, Sakaguchi Y, Tanaka R, Tomiyama N, Tatsugami F, Teramukai S. Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients. J Am Soc Nephrol 2021; 32:723-735. [PMID: 33547218 PMCID: PMC7920180 DOI: 10.1681/asn.2020050598] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 11/28/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.
Collapse
Affiliation(s)
- Yoshitaka Isaka
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takayuki Hamano
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
- Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Hideki Fujii
- Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine
| | - Yoshihiro Tsujimoto
- Division of Internal Medicine, Medical Corporation Aijinkai Inoue Hospital, Suita, Japan
| | - Fumihiko Koiwa
- Division of Nephrology, Department of Internal Medicine, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Yusuke Sakaguchi
- Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Ryoichi Tanaka
- Department of Radiology, Iwate Medical University School of Medicine, Shiwa, Japan
- Division of Dental Radiology, Department of Reconstructive Oral and Maxillofacial Surgery, Iwate Medical University School of Dentistry, Shiwa, Japan
| | - Noriyuki Tomiyama
- Department of Radiology, Osaka University Graduate School of Medicine, Suita, Japan
| | - Fuminari Tatsugami
- Department of Diagnostic Radiology, Hiroshima University, Hiroshima, Japan
| | - Satoshi Teramukai
- Department of Biostatistics, Kyoto Prefectural University of Medicine, Kyoto, Japan
| |
Collapse
|
|
41
|
Mizuiri S, Nishizawa Y, Doi T, Yamashita K, Shigemoto K, Usui K, Arita M, Naito T, Doi S, Masaki T. Iron, coronary artery calcification, and mortality in patients undergoing hemodialysis. Ren Fail 2021; 43:371-380. [PMID: 33596750 PMCID: PMC7894440 DOI: 10.1080/0886022x.2021.1880937] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Objective A high coronary artery calcification score (CACS) may be associated with high mortality in patients undergoing hemodialysis (HD). Recently, effects of iron on vascular smooth muscle cell calcification have been described. We aimed to investigate the relationships between iron, CACS, and mortality in HD patients. Methods We studied 173 consecutive patients who were undergoing maintenance HD. Laboratory data and Agatston’s CACS were obtained at baseline for two groups of patients: those with CACS ≥400 (n = 109) and those with CACS <400 (n = 64). Logistic regression analyses for CACS ≥400 and Cox proportional hazard analyses for mortality were conducted. Results The median (interquartile range) age and duration of dialysis of the participants were 67 (60–75) years and 73 (37–138) months, respectively. Serum iron (Fe) and transferrin saturation (TSAT) levels were significantly lower in participants with CACS ≥400 than in those with CACS <400, although the serum ferritin concentration did not differ between the groups. TSAT ≥21% was significantly associated with CACS ≥400 (odds ratio 0.46, p<0.05). TSAT ≥17%, Fe ≥63 µg/dL, and ferritin ≥200 ng/mL appear to protect against 5-year all-cause mortality in HD patients, independent of conventional risk factors of all-cause mortality (p < 0.05). Conclusion We have identified associations between iron, CACS, and mortality in HD patients. Lower TSAT was found to be an independent predictor of CACS ≥400, and iron deficiency (low TSAT, iron, or ferritin) was a significant predictor of 5-year all-cause mortality in HD patients.
Collapse
Affiliation(s)
- Sonoo Mizuiri
- Division of Nephrology, Ichiyokai Harada Hospital, Hiroshima, Japan
| | | | - Toshiki Doi
- Division of Nephrology, Ichiyokai Harada Hospital, Hiroshima, Japan.,Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | | | | | - Koji Usui
- Ichiyokai Ichiyokai Clinic, Hiroshima, Japan
| | | | | | - Shigehiro Doi
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| | - Takao Masaki
- Department of Nephrology, Hiroshima University Hospital, Hiroshima, Japan
| |
Collapse
|
|
42
|
Hsu BG, Tsai JP. Vascular calcification of chronic kidney disease: A brief review. Tzu Chi Med J 2021; 33:34-41. [PMID: 33505876 PMCID: PMC7821827 DOI: 10.4103/tcmj.tcmj_36_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/13/2020] [Accepted: 06/23/2020] [Indexed: 12/29/2022] Open
Abstract
Vascular calcification (VC) is highly prevalent among patients with chronic kidney disease (CKD). There is growing evidence that there is more underlying this condition than the histological presentation of atherosclerotic plaque and arteriosclerosis and that the risk of cardiovascular disease in the context of CKD might be explained by the presence of VC. While VC has been observed in the absence of overt abnormal mineral metabolism, this association is coupled to abnormal homeostasis of minerals in patients with CKD, due to hyperphosphatemia and hypercalcemia. Furthermore, recent studies have shown that the differentiation of vascular smooth muscle cells into an osteogenic phenotype is highly regulated by pro-calcifying and anti-calcifying factors. There are several imaging modalities currently used in clinical practice to evaluate the extent and severity of VC; each has different advantages and limitations. Although there is no universally accepted method for the treatment of VC, there is growing evidence of the beneficial effects of medical therapy for the condition. This study discusses the mechanism underlying VC, imaging modalities used for evaluation of the condition, and possible treatments.
Collapse
Affiliation(s)
- Bang-Gee Hsu
- School of Medicine, Tzu Chi University, Hualien, Taiwan.,Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | - Jen-Pi Tsai
- School of Medicine, Tzu Chi University, Hualien, Taiwan.,Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| |
Collapse
|
|
43
|
Bellasi A, Di Lullo L, Russo D, Ciarcia R, Magnocavallo M, Lavalle C, Ratti C, Fusaro M, Cozzolino M, Di Iorio BR. Predictive Value of Measures of Vascular Calcification Burden and Progression for Risk of Death in Incident to Dialysis Patients. J Clin Med 2021; 10:jcm10030376. [PMID: 33498192 PMCID: PMC7863918 DOI: 10.3390/jcm10030376] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 01/14/2021] [Accepted: 01/17/2021] [Indexed: 12/13/2022] Open
Abstract
Background: Vascular calcification (VC) is a marker of cardiovascular (CV) disease and various methods allow for presence and extension assessment in different arterial districts. Nevertheless, it is currently unclear which one of these methods for VC evaluation best predict outcome and if this piece of information adds to the predictive value of traditional CV risk factors in patients receiving hemodialysis (HD). Methods: data of 184 of the 466 patients followed in the Independent study (NCT00710788) were post hoc examined to assess the association three concurrent measures of vascular calcification and all-cause survival. Specifically, coronary artery calcification (CAC) was determined by the Agatston and the volume score while abdominal aorta calcification was determined by plain X-ray of the lumbar spine (Kauppila score (KS)). Survival and regression models as well as metrics of risk recalculation were used to test the association of VC and outcome beyond the Framingham risk score. Results: Middle-age (62.6(15.8) years) men (51%) and women (49%) starting HD were analyzed. Over 36 (median 36; interquartile range: 8–36) months of follow-up 69 patients expired. Each measure of VC (CAC or KS) predicted all-cause mortality independently factors commonly associated with all-cause survival (p < 0.001). Far more importantly, each measurement of VC significantly improved risk prediction and patient reclassification (p < 0.001) beyond traditional cardiovascular risk factors. Conclusions: Overall, presence and extension of VC, irrespective of the arterial site, predict risk of all-cause of death in patients starting hemodialysis. Of note, both CAC and KS increase risk stratification beyond traditional CV risk factors. However, future efforts are needed to assess whether a risk-based approach encompassing VC screening to guide HD patient management improves survival.
Collapse
Affiliation(s)
- Antonio Bellasi
- Department of Research, Innovation and Brand Reputation, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
- Correspondence:
| | - Luca Di Lullo
- Department of Nephrology and Dialysis, Ospedale Parodi, Delfino, 00034 Colleferro, Italy;
| | - Domenico Russo
- Department of Nephrology, School of Medicine, University “Federico II”, 80125 Napoli, Italy;
| | - Roberto Ciarcia
- Departments of Vetecerinary Medicine and Animal Productions, University of Naples Federico II, 80137 Naples, Italy;
| | - Michele Magnocavallo
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Policlinico Universitario Umberto I, Sapienza University of Rome, 00185 Roma, Italy; (M.M.); (C.L.)
| | - Carlo Lavalle
- Department of Clinical, Internal, Anesthesiology and Cardiovascular Sciences, Policlinico Universitario Umberto I, Sapienza University of Rome, 00185 Roma, Italy; (M.M.); (C.L.)
| | - Carlo Ratti
- Department of Cardiology, Ospedale Ramazzini, 41012 Carpi, Italy;
| | - Maria Fusaro
- National Research Council (CNR)–Institute of Clinical Physiology (IFC), 56124 Pisa, Italy;
- Department of Medicine, University of Padua, 35122 Padua, Italy
| | - Mario Cozzolino
- Renal Division, Department of Health Sciences, ASST Santi Paolo e Carlo, University of Milan, 20142 Milan, Italy;
| | | |
Collapse
|
|
44
|
Bellasi A, Raggi P, Bover J, Bushinsky DA, Chertow GM, Ketteler M, Rodriguez M, Sinha S, Salcedo C, Garg R, Gold A, Perelló J. Trial design and baseline characteristics of CaLIPSO: a randomized, double-blind placebo-controlled trial of SNF472 in patients receiving haemodialysis with cardiovascular calcification. Clin Kidney J 2021; 14:366-374. [PMID: 33564440 PMCID: PMC7857813 DOI: 10.1093/ckj/sfz144] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 09/13/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND The objective of CaLIPSO, a Phase 2b, randomized, double-blind, placebo-controlled clinical trial, is to test the hypothesis that myo-inositol hexaphosphate (SNF472) attenuates the progression of cardiovascular calcification in patients receiving maintenance haemodialysis. Here we report the trial design and baseline characteristics of trial participants. METHODS Adult patients on maintenance haemodialysis (≥6 months) with an Agatston coronary artery calcium score, as measured by a multidetector computed tomography scanner, of 100-3500 U were enrolled. Patients were stratified by Agatston score (100-<400, 400-1000 or >1000 U) and randomized in a 1:1:1 ratio to receive placebo, SNF472 300 mg or SNF472 600 mg administered intravenously three times weekly during each haemodialysis session. RESULTS Overall, 274 patients were randomized. The mean age of trial participants was 63.6 (standard deviation 8.9) years and 39% were women. The coronary artery, aorta and aortic valve median (25th-75th percentile) Agatston scores at baseline were 730 U (315-1435), 1728 U (625-4978) and 103 U (31-262), respectively, and the median (25th-75th percentile) calcium volume scores at baseline were 666 (310-1234), 1418 (536-4052) and 107 (38-278), respectively. Older age and diabetes mellitus were associated with higher calcium scores at baseline. CONCLUSIONS The CaLIPSO trial enrolled patients on haemodialysis with pre-existent cardiovascular calcification to test the hypothesis that SNF472 attenuates its progression in the coronary arteries, aorta and aortic valve.
Collapse
Affiliation(s)
- Antonio Bellasi
- Research, Innovation and Brand Reputation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy
| | - Paolo Raggi
- Department of Medicine, Mazankowski Alberta Heart Institute and University of Alberta, Edmonton, AB, Canada
| | - Jordi Bover
- Department of Nephrology, Fundació Puigvert and Universitat Autònoma, IIB Sant Pau, REDinREN, Barcelona, Spain
| | - David A Bushinsky
- Department of Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Glenn M Chertow
- Department of Medicine, Stanford University, Palo Alto, CA, USA
| | - Markus Ketteler
- Department of General Internal Medicine and Nephrology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
| | - Mariano Rodriguez
- Nephrology Unit, Hospital Universitario Reina Sofia, IMIBIC, REDinREN, Córdoba, Spain
| | - Smeeta Sinha
- Department of Renal Medicine, Salford Royal NHS Foundation Trust, Salford, UK
| | | | - Rekha Garg
- Research and Development, Sanifit Therapeutics, San Diego, CA, USA
| | - Alex Gold
- Research and Development, Sanifit Therapeutics, San Diego, CA, USA
| | - Joan Perelló
- Research and Development, Sanifit Therapeutics, Palma, Spain
| |
Collapse
|
|
45
|
Neven E, Corremans R, Vervaet BA, Funk F, Walpen S, Behets GJ, D’Haese PC, Verhulst A. Renoprotective effects of sucroferric oxyhydroxide in a rat model of chronic renal failure. Nephrol Dial Transplant 2020; 35:1689-1699. [PMID: 33022710 PMCID: PMC7538237 DOI: 10.1093/ndt/gfaa080] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 03/14/2020] [Indexed: 12/15/2022] Open
Abstract
Introduction Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease–mineral and bone disorder (CKD-MBD) rat model. Methods To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified. Results Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone. Conclusions PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.
Collapse
Affiliation(s)
- Ellen Neven
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Raphaëlle Corremans
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Benjamin A Vervaet
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Felix Funk
- Department of Medical Affairs, Vifor (International) Ltd, Glattbrugg, Switzerland
| | - Sebastian Walpen
- Department of Medical Affairs, Vifor (International) Ltd, Glattbrugg, Switzerland
| | - Geert J Behets
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Patrick C D’Haese
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
| | - Anja Verhulst
- Laboratory of Pathophysiology, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium
- Correspondence to: Patrick C. D’Haese; E-mail:
| |
Collapse
|
|
46
|
Mukai H, Dai L, Chen Z, Lindholm B, Ripsweden J, Brismar TB, Heimbürger O, Barany P, Qureshi AR, Söderberg M, Bäck M, Stenvinkel P. Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease. Nephrol Dial Transplant 2020; 35:1202-1211. [PMID: 30534995 DOI: 10.1093/ndt/gfy352] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 09/28/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)]. METHODS In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients. RESULTS Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density. CONCLUSIONS In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification.
Collapse
Affiliation(s)
- Hideyuki Mukai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Zhimin Chen
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Magnus Söderberg
- Department of Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden
| | - Magnus Bäck
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| |
Collapse
|
|
47
|
Castañeda TR, Méndez M, Davison I, Elvert R, Schwahn U, Boldina G, Rocher C, Scherer P, Singh K, Bangari DS, Falkenhahn M, Kannt A, Konkar A, Larsen PJ, Arbeeny C, Dhal PK, Hübschle T. The Novel Phosphate and Bile Acid Sequestrant Polymer SAR442357 Delays Disease Progression in a Rat Model of Diabetic Nephropathy. J Pharmacol Exp Ther 2020; 376:190-203. [PMID: 33203659 DOI: 10.1124/jpet.120.000285] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 11/10/2020] [Indexed: 12/11/2022] Open
Abstract
As a gut-restricted, nonabsorbed therapy, polymeric bile acid sequestrants (BAS) play an important role in managing hyperlipidemia and hyperglycemia. Similarly, nonabsorbable sequestrants of dietary phosphate have been used for the management of hyperphosphatemia in end-stage renal disease. To evaluate the potential utility of such polymer sequestrants to treat type 2 diabetes (T2D) and its associated renal and cardiovascular complications, we synthesized a novel polymeric sequestrant, SAR442357, possessing optimized bile acid (BA) and phosphate sequestration characteristics. Long-term treatment of T2D obese cZucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) with SAR442357 resulted in enhanced sequestration of BAs and phosphate in the gut, improved glycemic control, lowering of serum cholesterol, and attenuation of diabetic kidney disease (DKD) progression. In comparison, colesevelam, a BAS with poor phosphate binding properties, did not prevent DKD progression, whereas losartan, an angiotensin II receptor blocker that is widely used to treat DKD, showed no effect on hyperglycemia. Analysis of hepatic gene expression levels of the animals treated with SAR442357 revealed upregulation of genes responsible for the biosynthesis of cholesterol and BAs, providing clear evidence of target engagement and mode of action of the new sequestrant. Additional hepatic gene expression pathway changes were indicative of an interruption of the enterohepatic BA cycle. Histopathological analysis of ZSF1 rat kidneys treated with SAR442357 further supported its nephroprotective properties. Collectively, these findings reveal the pharmacological benefit of simultaneous sequestration of BAs and phosphate in treating T2D and its associated comorbidities and cardiovascular complications. SIGNIFICANCE STATEMENT: A new nonabsorbed polymeric sequestrant with optimum phosphate and bile salt sequestration properties was developed as a treatment option for DKD. The new polymeric sequestrant offered combined pharmacological benefits including glucose regulation, lipid lowering, and attenuation of DKD progression in a single therapeutic agent.
Collapse
Affiliation(s)
- Tamara R Castañeda
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - María Méndez
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Ian Davison
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Ralf Elvert
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Uwe Schwahn
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Galina Boldina
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Corinne Rocher
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Petra Scherer
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Kuldeep Singh
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Dinesh S Bangari
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Mechthilde Falkenhahn
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Aimo Kannt
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Anish Konkar
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Philip J Larsen
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Cynthia Arbeeny
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Pradeep K Dhal
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| | - Thomas Hübschle
- R&D Diabetes (T.R.C., R.E., A.Ka., A.Ko., P.J.L., C.A., T.H.), Integrated Drug Discovery (M.M.), Biomarkers and Clinical Bioanalysis (U.S.), Translational In Vivo Models, Global Discovery Pathology (P.S.), and Global Research Project Management (M.F.), Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt, Germany; C&BD Haverhill Operations, Sanofi GB Genzyme Limited, Haverhill, Suffolk, United Kingdom (I.D.); R&D Translational Sciences France, Bioinformatics, Sanofi, Chilly-Mazarin Cedex, France (C.R.); Translational In Vivo Models, Global Discovery Pathology, Framingham, Massachusetts (K.S., D.S.B.); and Pharmaceutical Development Platform, Sanofi Global R&D, Waltham, Massachusetts (P.K.D.)
| |
Collapse
|
|
48
|
Kim SM, Jung JY. Nutritional management in patients with chronic kidney disease. Korean J Intern Med 2020; 35:1279-1290. [PMID: 32872726 PMCID: PMC7652660 DOI: 10.3904/kjim.2020.408] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 09/09/2020] [Indexed: 12/11/2022] Open
Abstract
The global prevalence of chronic kidney disease (CKD) is increasing with the aging of populations worldwide. As kidney function declines, the accumulation of metabolic waste products and excessive electrolytes can significantly impair the health of patients with CKD. As nutritional management of patients with CKD is thought to control uremic symptoms and provide beneficial effects on the progression of kidney dysfunction, the diet of patients with CKD should be an important consideration in their care. Many guidelines recommend limiting protein intake in these patients, as high-protein diets aggravate kidney dysfunction. Excess sodium may be associated with CKD progression and all-cause mortality and, therefore, limiting salt intake is generally recommended. Low potassium is associated with muscle weakness and hypertension, whereas high potassium is associated with cardiac arrhythmia. Therefore, recent guidelines recommend adjusting dietary potassium intake on an individual basis to maintain serum potassium levels within the normal range. Appropriate dietary calcium intake is recommended to maintain calcium balance in patients with CKD G3, G4. Given the many dietary considerations for patients with CKD, effective nutritional management is challenging. Individualized strategies are needed to ensure the best outcome for patients with CKD.
Collapse
Affiliation(s)
- Sun Moon Kim
- Division of Nephrology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
| | - Ji Yong Jung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
- Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea
| |
Collapse
|
|
49
|
Tsai JP, Hsu BG. Arterial stiffness: A brief review. Tzu Chi Med J 2020; 33:115-121. [PMID: 33912407 PMCID: PMC8059465 DOI: 10.4103/tcmj.tcmj_44_20] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 05/01/2020] [Accepted: 07/11/2020] [Indexed: 12/21/2022] Open
Abstract
Apart from the result of multiple diseases as well as aging, arterial stiffness (AS) predicts cardiovascular disease (CVD), especially in patients with chronic kidney disease (CKD). Patients with CKD have high CVD prevalence, and an extraordinarily high risk for CVD might be related to nontraditional risk factors, including AS. The mechanism of AS development could be attributed to oxidative stress, inflammation, uremic milieu (e.g., uremic toxins), vascular calcification, and cumulative effects of traditional cardiovascular risk factors on arteries such as diabetes mellitus or hypertension. There were a variety of non-invasive techniques to measure AS. One of these techniques is carotid–femoral pulse wave velocity, which is the reference measurement of AS and is related to long-term CVD outcomes. AS progression has corresponding medical treatments with modest beneficial results. This review briefly discusses the risk factors, measurements, and treatments associated with AS.
Collapse
Affiliation(s)
- Jen-Pi Tsai
- School of Medicine, Tzu Chi University, Hualien, Taiwan.,Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Bang-Gee Hsu
- School of Medicine, Tzu Chi University, Hualien, Taiwan.,Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| |
Collapse
|
|
50
|
Hamano N, Endo Y, Kawata T, Fukagawa M. Development of evocalcet for unmet needs among calcimimetic agents. Expert Rev Endocrinol Metab 2020; 15:299-310. [PMID: 32552012 DOI: 10.1080/17446651.2020.1780911] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 06/08/2020] [Indexed: 10/24/2022]
Abstract
INTRODUCTION The calcium-sensing receptor is an important treatment target for secondary hyperparathyroidism (SHPT) in patients undergoing dialysis. In addition to vitamin D receptor activator, cinacalcet has recently been widely used for SHPT management, and the significant suppression of parathyroid hormone (PTH) with better control of serum calcium and phosphorus has been reported. However, low adherence and insufficient dose escalation mainly due to frequent gastrointestinal adverse events, still remain as major issues. To overcome these unmet needs, we have developed a new oral calcimimetic agent evocalcet, which has recently been approved by the Pharmaceutical Affairs Act in Japan. AREAS COVERED PubMed was searched from inception until April 2020 with the word evocalcet to summarize the development of this new calcimimetic agent, its pharmacokinetics, and the results of clinical trials, along with an overview of the differences among calcimimetic agents. This review also includes the management of SHPT with a focus on calcimimetics. EXPERT OPINION Evocalcet evoked fewer gastrointestinal-related adverse events while suppressing PTH at a lower dose than cinacalcet. These data suggest evocalcet may contribute to better adherence and sufficient dose escalation in patients with SHPT. Whether or not evocalcet improves clinical outcomes remains to be elucidated.
Collapse
Affiliation(s)
- Naoto Hamano
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine , Isehara, Japan
| | - Yuichi Endo
- R&D Division, Kyowa Kirin Co., Ltd , Tokyo, Japan
| | | | - Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine , Isehara, Japan
| |
Collapse
|