|
1
|
Dufour I, Van Regemorter E, Kanaan N, Buemi A, Darius T, Mourad M, Goffin E, Jadoul M, Devresse A, Gillion V. Bridging the Gap Between CKD Management Paradigms in Transplant and Nontransplant Settings: Published Evidence, Challenges, and Perspectives. Transplantation 2025; 109:622-637. [PMID: 39198967 DOI: 10.1097/tp.0000000000005186] [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: 09/01/2024]
Abstract
Kidney transplantation (KT) is the best treatment for patients with kidney failure, associated with improved survival and quality of life compared with maintenance dialysis. However, despite constant improvements in the assessment and management of the alloimmune response, KT patients frequently demonstrate a reduced estimated glomerular filtration rate. Therefore, the usual complications of chronic kidney disease (CKD), such as anemia, hypertension, metabolic acidosis, hyperkalemia, or persistent secondary hyperparathyroidism, are highly prevalent after KT. However, their underlying mechanisms are different in the transplant setting (compared with the nontransplanted CKD population), and management recommendations are based on relatively poor-quality data. In recent years, new therapies have emerged, significantly improving kidney and cardiovascular outcomes of non-KT patients with CKD. Whether those new drugs could improve the outcomes of KT patients has largely been under investigated so far. In this review, we will address the challenges of the management of a KT patient with a reduced estimated glomerular filtration rate, cover the published evidence, and highlight the critical knowledge gaps.
Collapse
Affiliation(s)
- Inès Dufour
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Elliott Van Regemorter
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Nada Kanaan
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Antoine Buemi
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Tom Darius
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Michel Mourad
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Eric Goffin
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Michel Jadoul
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | - Arnaud Devresse
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
- Department of Abdominal Surgery and Transplantation, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
| | - Valentine Gillion
- Department of Nephrology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
- Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| |
Collapse
|
|
2
|
Yuan Z, Melamed ML, Parajuli S, Mandelbrot D, Astor BC. Association of Posttransplant Circulating 25-Hydroxyvitamin D and Late-Onset Infections Among Kidney Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD). Transpl Infect Dis 2025; 27:e70016. [PMID: 40026269 PMCID: PMC12017301 DOI: 10.1111/tid.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 02/07/2025] [Accepted: 02/17/2025] [Indexed: 03/05/2025]
Abstract
INTRODUCTION Late-onset infection occurring more than 6 months after transplantation is a major threat to the long-term survival of kidney transplant recipients (KTRs). Accumulating evidence indicates a potential role for vitamin D in host resistance to infections. While vitamin D inadequacy is common among KTRs, the association of posttransplant circulating 25-hydroxyvitamin D [25(OH)D] and late-onset infection remains uncertain. METHODS We analyzed data from adult kidney-only transplant recipients at our center from 2005 to 2020 who had at least one valid posttransplant circulating 25(OH)D measurement from 5 to 13 months posttransplant. Survival analyses were conducted using marginal proportional rates models with late-onset infection within 1 year following the 25(OH)D measurement as the event of interest. Additional analyses used time-varying 25(OH)D measurements. RESULTS Of 2207 KTRs included, 642 recipients had a total of 1448 late-onset infection episodes. Each 5 ng/mL lower serum 25(OH)D was associated with a 5% higher risk of late-onset infection (adjusted rate ratio [aRR] = 1.05; 95% confidence interval [CI]: 1.03, 1.07; p < 0.01). Vitamin D deficiency (≤ 20 ng/mL) was associated with a 1.22-fold higher incidence of late-onset infection (aRR = 1.22; 95% CI: 1.03-1.43; p = 0.02) compared with vitamin D sufficiency (≥30 ng/mL). The association was strongest for urinary tract infection among male recipients (aRR = 2.20; 95% CI: 1.57-3.08; p < 0.01). CONCLUSION Vitamin D deficiency is significantly associated with a higher incidence of late-onset infection among KTRs, especially urinary tract infections in male recipients. Further research, including clinical trials, is needed to determine the causal relationship.
Collapse
Affiliation(s)
- Zhongyu Yuan
- Department of Population Health SciencesUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
- Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Michal L. Melamed
- Department of MedicineNew York University Grossman School of MedicineNew YorkNew YorkUSA
| | - Sandesh Parajuli
- Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Didier Mandelbrot
- Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| | - Brad C. Astor
- Department of Population Health SciencesUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
- Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWisconsinUSA
| |
Collapse
|
|
3
|
Foote DC, Zhao X, You B, Done JZ, Weller J, Stemme R, Moreno N, Morris-Wiseman LF, Mathur A. Surgical outcomes of parathyroidectomy for pre-kidney transplantation versus post-kidney transplantation patients. World J Surg 2025; 49:643-651. [PMID: 39843256 PMCID: PMC11938536 DOI: 10.1002/wjs.12468] [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: 08/18/2024] [Accepted: 12/15/2024] [Indexed: 01/24/2025]
Abstract
BACKGROUND Hyperparathyroidism (HPT) is common in end-stage kidney disease and resolves in less than half of kidney transplant (KT) recipients. The ideal timing of parathyroidectomy (PTX), before or after KT, remains unclear. We sought to understand differences in morbidity and mortality after PTX pre-KT and post-KT. METHODS We identified adult patients who underwent PTX pre-KT or post-KT between 2012 and 2021 utilizing the National Surgical Quality Improvement Program database. Demographics, clinical characteristics, morbidity, and mortality were compared. Adjusted logistic regression with propensity score weighting assessed odds of 30-day composite morbidity, major adverse cardiovascular events (MACE), readmission, and mortality. RESULTS We identified 1972 patients who underwent PTX pre-KT and 541 patients who underwent PTX post-KT. Post-KT HPT patients were older (mean age 53.9 v 48.2 and p < 0.01) and more commonly White (45.3% v 32.3% and p < 0.01) and diabetic (30.0% v 18.5% and p < 0.01). In comparison, pre-KT HPT patients were more commonly Black (53.2% v 30.1%), had American Society of Anesthesiologists (ASA) class 3-4 (98.0% v 89.6% and p < 0.01), chronic obstructive pulmonary disease (4.2% v 1.5% and p < 0.01), and congestive heart failure (4.4% v 1.1% and p < 0.01). After adjusting for confounders, patients pre-KT had 1.72-fold increased odds of morbidity (95% confidence interval [CI]: 1.13-2.61), 8.39-fold increased odds of MACE (95% CI: 1.13-62.18), and 2.07-fold increased odds of readmission (95% CI: 1.38-3.10). There was no difference in mortality or risk of infections. CONCLUSIONS Patients who underwent PTX prior to KT were at significantly increased risk for 30-day morbidity and MACE, but no different odds of mortality compared to PTX after KT. This can help inform decision-making regarding timing of PTX in patients with HPT.
Collapse
Affiliation(s)
- Darci C. Foote
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Xue Zhao
- The Johns Hopkins Surgery Center for Outcomes Research (JSCOR), Johns Hopkins University School of Medicine, Baltimore, MD
| | - Bin You
- The Johns Hopkins Surgery Center for Outcomes Research (JSCOR), Johns Hopkins University School of Medicine, Baltimore, MD
| | - Joy Z. Done
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jennine Weller
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Rachel Stemme
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Natalie Moreno
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Lilah F. Morris-Wiseman
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Aarti Mathur
- Collaborative Outcomes Research in Endocrine Surgery (CORES) Lab, Division of Endocrine Surgery, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| |
Collapse
|
|
4
|
Pollastri F, Fassio A, Ferraro PM, Andreola S, Gambaro G, Spasiano A, Caletti C, Stefani L, Gatti M, Fabbrini P, Rossini M, Galvagni I, Gatti D, Adami G, Viapiana O. Long-Term Changes in Parameters of Bone Quality in Kidney Transplant Recipients Treated with Denosumab. Calcif Tissue Int 2025; 116:42. [PMID: 39982454 PMCID: PMC11845414 DOI: 10.1007/s00223-025-01349-x] [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: 11/13/2024] [Accepted: 01/30/2025] [Indexed: 02/22/2025]
Abstract
Kidney transplant recipients (KTRs) have an elevated fracture risk. While dual-energy X-ray absorptiometry (DXA) is commonly used to assess areal bone mineral density (aBMD), it does not capture all aspects of bone quality. We investigated the long-term effects on bone DXA-derived indices of bone quality in KTRs treated with denosumab and untreated with denosumab. This is a retrospective study, including KTRs treated with denosumab and untreated age and sex-matched KTR controls. DXA-derived parameters, including trabecular bone score (TBS) and 3D-DXA parameters, were measured at the lumbar spine and femur at baseline and after four years. Hierarchical linear models were used to assess the between-group effect of treatment over time, also adjusting for site-specific aBMDs. We enrolled 23 KTRs treated with denosumab and 23 KTR denosumab-untreated KTRs. Significant between-group differences over time in favor of the denosumab group were observed for TBS (0.843, 95%CI 0.439; 1.248,p < 0.001), trabecular volumetric BMD at the total hip (Tb.vBMD TH) (13.492, 95%CI 1.707; 25.278, p = 0.003), cortical volumetric BMD at the femoral neck (Ct.vBMD FN) (28.766, 95%CI 8.373; 49.158, p = 0.008), cortical surface BMD at the total hip (c.sBMD TH) (10.507, 95%CI 4.140; 16.873,p = 0.002), cortical surface at the femoral neck (c.sBMD FN) (8.795, 95%CI 2.818; 14.771, p = 0.006), and cortical thickness at the total hip (Ct.th.TH) (0.075, 95%CI 0.020; 0.130, p = 0.010). After adjusting for BMD, the differences on TBS and Ct.vBMD FN and c.sBMD FN remained significant. Denosumab treatment in KTRs was associated with better outcomes in terms of bone quality and geometry parameters, independent of changes in aBMD.
Collapse
Affiliation(s)
- Francesco Pollastri
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy.
| | - Angelo Fassio
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| | | | | | | | | | | | - Lisa Stefani
- Nephrology Unit, University of Verona, Verona, Italy
| | - Matteo Gatti
- Department of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano-Cinisello Balsamo, Milan, Italy
| | - Paolo Fabbrini
- Department of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano-Cinisello Balsamo, Milan, Italy
| | - Maurizio Rossini
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| | - Isotta Galvagni
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| | - Davide Gatti
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| | - Giovanni Adami
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| | - Ombretta Viapiana
- Rheumatology Unit, University of Verona, Policlinico GB Rossi, 37134, Verona, Italy
| |
Collapse
|
|
5
|
Fassio A, Andreola S, Gatti D, Pollastri F, Gatti M, Fabbrini P, Gambaro G, Ferraro PM, Caletti C, Rossini M, Viapiana O, Bixio R, Adami G. Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group. Calcif Tissue Int 2024; 115:23-30. [PMID: 38730099 PMCID: PMC11153264 DOI: 10.1007/s00223-024-01218-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 04/16/2024] [Indexed: 05/12/2024]
Abstract
Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.
Collapse
Affiliation(s)
- Angelo Fassio
- Rheumatology Unit, University of Verona, Verona, Italy.
- Rheumatology Unit, Policlinico GB Rossi, 37134, Verona, Italy.
| | | | - Davide Gatti
- Rheumatology Unit, University of Verona, Verona, Italy
| | | | - Matteo Gatti
- Rheumatology Unit, University of Verona, Verona, Italy
- Department of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano-Cinisello Balsamo, Milan, Italy
| | - Paolo Fabbrini
- Department of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano-Cinisello Balsamo, Milan, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
6
|
Yuan Z, Melamed ML, Singh T, Parajuli S, Panzer S, Mandelbrot D, Astor BC. Association of Circulating 25-Hydroxyvitamin D and Recurrence of Glomerulonephritis in Kidney Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD). Transplant Direct 2024; 10:e1600. [PMID: 38550773 PMCID: PMC10977583 DOI: 10.1097/txd.0000000000001600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/24/2024] [Accepted: 01/25/2024] [Indexed: 02/13/2025] Open
Abstract
BACKGROUND Recurrence of glomerulonephritis (GN) is a significant contributor to long-term allograft failure among kidney transplant recipients (KTRs) with kidney failure because of GN. Accumulating evidence has revealed the role of vitamin D in both innate and adaptive immunity. Although vitamin D deficiency is common among KTRs, the association between 25-hydroxyvitamin D (25[OH]D) and GN recurrence in KTRs remains unclear. METHODS We analyzed data from KTRs with kidney failure caused by GN who received a transplant at our center from 2000 to 2019 and had at least 1 valid posttransplant serum 25(OH)D measurement. Survival analyses were performed using a competing risk regression model considering other causes of allograft failure, including death, as competing risk events. RESULTS A total of 67 cases of GN recurrence were identified in 947 recipients with GN followed for a median of 7.0 y after transplant. Each 1 ng/mL lower serum 25(OH)D was associated with a 4% higher hazard of recurrence (subdistribution hazard ratio [HR]: 1.04; 95% confidence interval [CI], 1.01-1.06). Vitamin D deficiency (≤20 ng/mL) was associated with a 2.99-fold (subdistribution HR: 2.99; 95% CI, 1.56-5.73) higher hazard of recurrence compared with vitamin D sufficiency (≥30 ng/mL). Results were similar after further adjusting for concurrent urine protein-creatinine ratio, serum albumin, and estimated glomerular filtration rate (eGFR). CONCLUSIONS Posttransplant vitamin D deficiency is associated with a higher hazard of GN recurrence in KTRs. Further prospective observational studies and clinical trials are needed to determine any causal role of vitamin D in the recurrence of GN after kidney transplantation. More in vitro and in vivo experiments would be helpful to understand its effects on autoimmune and inflammation processes.
Collapse
Affiliation(s)
- Zhongyu Yuan
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Michal L. Melamed
- Department of Medicine, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
| | - Tripti Singh
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sandesh Parajuli
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Sarah Panzer
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Didier Mandelbrot
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | - Brad C. Astor
- Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI
| |
Collapse
|
|
7
|
Teh JW, Mac Gearailt C, Lappin DWP. Post-Transplant Bone Disease in Kidney Transplant Recipients: Diagnosis and Management. Int J Mol Sci 2024; 25:1859. [PMID: 38339137 PMCID: PMC10856017 DOI: 10.3390/ijms25031859] [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: 01/10/2024] [Revised: 01/24/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024] Open
Abstract
Kidney transplantation is the preferred gold standard modality of treatment for kidney failure. Bone disease after kidney transplantation is highly prevalent in patients living with a kidney transplant and is associated with high rates of hip fractures. Fractures are associated with increased healthcare costs, morbidity and mortality. Post-transplant bone disease (PTBD) includes renal osteodystrophy, osteoporosis, osteonecrosis and bone fractures. PTBD is complex as it encompasses pre-existing chronic kidney disease-mineral bone disease and compounding factors after transplantation, including the use of immunosuppression and the development of de novo bone disease. After transplantation, the persistence of secondary and tertiary hyperparathyroidism, renal osteodystrophy, relative vitamin D deficiency and high levels of fibroblast growth factor-23 contribute to post-transplant bone disease. Risk assessment includes identifying both general risk factors and kidney-specific risk factors. Diagnosis is complex as the gold standard bone biopsy with double-tetracycline labelling to diagnose the PTBD subtype is not always readily available. Therefore, alternative diagnostic tools may be used to aid its diagnosis. Both non-pharmacological and pharmacological therapy can be employed to treat PTBD. In this review, we will discuss pathophysiology, risk assessment, diagnosis and management strategies to manage PTBD after kidney transplantation.
Collapse
Affiliation(s)
- Jia Wei Teh
- Department of Nephrology, Galway University Hospital, H91 YR71 Galway, Ireland
| | - Conall Mac Gearailt
- Department of Rheumatology, Galway University Hospital, H91 YR71 Galway, Ireland
| | - David W. P. Lappin
- Department of Nephrology, Galway University Hospital, H91 YR71 Galway, Ireland
- School of Medicine, University of Galway, H91 TK33 Galway, Ireland
| |
Collapse
|
|
8
|
Sun L, Wang Z, Zheng M, Hang Z, Liu J, Gao X, Gui Z, Feng D, Zhang D, Han Q, Fei S, Chen H, Tao J, Han Z, Ju X, Gu M, Tan R. Mineral and bone disorder after kidney transplantation: a single-center cohort study. Ren Fail 2023; 45:2210231. [PMID: 37183797 DOI: 10.1080/0886022x.2023.2210231] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD. METHODS A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared. RESULTS MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia. CONCLUSIONS MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.
Collapse
Affiliation(s)
- Li Sun
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zijie Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ming Zheng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhou Hang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiawen Liu
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiang Gao
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zeping Gui
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dengyuan Feng
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dongliang Zhang
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Qianguang Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shuang Fei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Tao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhijian Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobing Ju
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruoyun Tan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
9
|
Sun L, Tao J, Han Z, Chen H, Huang Z, Wang Z, Fei S, Suo C, Ju X, Tan R, Gu M. Efficacy of iguratimod on mineral and bone disorders after kidney transplantation: a preliminary study. Ren Fail 2023; 45:2256418. [PMID: 37905940 PMCID: PMC11001337 DOI: 10.1080/0886022x.2023.2256418] [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: 03/23/2023] [Accepted: 09/02/2023] [Indexed: 11/02/2023] Open
Abstract
BACKGROUND Iguratimod has been shown to promote bone formation and inhibit bone resorption in rheumatoid arthritis patients. We aimed to explore its effect on bone metabolism and vascular calcification (VC) in kidney transplant recipients (KTRs). METHODS A post hoc analysis was conducted among the subjects in our previous randomized clinical trial (NCT02839941). Forty-three KTRs completing bone metabolism 52 weeks after enrollment were selected for this analysis, among whom 27 patients received VC examinations. In the iguratimod group, iguratimod (25 mg twice daily) was added adjuvant to the traditional triple regimen. At the 52-week follow-up, the following parameters were assessed: serum calcium, phosphorus, 25-hydroxyvitamin D, intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), osteocalcin, type I collagen N-terminal peptide (NTx), type I collagen C-terminal peptide (CTx), bone mineral density (BMD) of the femoral neck and lumbar spine, coronary artery calcification (CAC) and thoracic aortic calcification (TAC). Bone metabolic and VC indices were compared between the two groups using the independent samples t test and Wilcoxon nonparametric test. RESULTS At 52 weeks after enrollment, the iguratimod group had lower osteocalcin (p = 0.010), BALP (p = 0.015), NTx (p = 0.007), CTx (p = 0.012), CAC (p = 0.080) and TAC scores (p = 0.036) than the control group. There was no significant difference in serum calcium, phosphorus, 25-hydroxyvitamin D, iPTH and BMD between the groups. Iguratimod could reduce bone turnover markers (BTMs) at both high and low iPTH levels. The adverse effect of iguratimod was mild and tolerable. CONCLUSION Iguratimod is safe, can reduce BTMs and may could attenuate VC in the first year after KT.
Collapse
Affiliation(s)
- Li Sun
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jun Tao
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhijian Han
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hao Chen
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zhengkai Huang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zijie Wang
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Shuang Fei
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Chuanjian Suo
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaobing Ju
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ruoyun Tan
- Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Gu
- Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
10
|
Thorsen IS, Bleskestad IH, Åsberg A, Jonsson G, Skadberg Ø, Heldal K, Gøransson LG. Klotho and Fibroblast Growth Factor 23 Are Independent of Vitamin D, and Unlike Vitamin D, Are Not Associated With Graft- and Patient Survival After Kidney Transplantation. Transplant Direct 2023; 9:e1522. [PMID: 37575950 PMCID: PMC10414697 DOI: 10.1097/txd.0000000000001522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 06/30/2023] [Accepted: 07/01/2023] [Indexed: 08/15/2023] Open
Abstract
Short-term survival after kidney transplantation is excellent but long-term survival remains suboptimal. The aim of the study was to explore the relationship between soluble α-Klotho (sKlotho) and intact fibroblast growth factor 23 (iFGF23) measured 8 wk and 1 y posttransplant with long-term graft- and patient survival in a cohort of kidney transplant recipients with deficient and nondeficient vitamin D (25[OH]D) levels. Methods Vitamin D, sKlotho, and iFGF23 were measured 8 wk and 1 y posttransplant in 132 recipients transplanted between November 2012 and October 2013. Results Of the 132 kidney transplant recipients, 49 had deficient vitamin D levels (<30 nmol/L) and 83 had nondeficient vitamin D levels (≥30 nmol/L) at 8 wk posttransplant. The mean age was 51 y and the median follow-up was 7.4 y. At 1 y posttransplant, vitamin D increased significantly. There were no significant differences in sKlotho or iFGF23 levels between the 2 vitamin D groups neither at 8 wk nor 1 y. sKlotho increased significantly and iFGF23 decreased significantly in the whole cohort. During the follow-up, there were 36 graft losses (27%) and 27 deaths (20%). Ninety-four percent of the transplant recipients with nondeficient vitamin D levels were alive with a well-functioning graft after 5 y using Kaplan-Meier survival estimates, compared with 84% of the patients with deficient vitamin D levels (P = 0.014). Klotho and FGF23 levels did not influence graft- and patient survival. Conclusions In this nationwide cohort of kidney transplant recipients, long-term graft- and patient survival were significantly better in patients with vitamin D ≥30 nmol/L 8 wk posttransplant compared with those with vitamin D <30 nmol/L. sKlotho levels increased and iFGF23 levels decreased from 8 wk to 1 y posttransplant. Klotho and FGF23 levels were not associated with graft- and patient survival.
Collapse
Affiliation(s)
- Inga Strand Thorsen
- Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | | | - Anders Åsberg
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway
- Norwegian Renal Registry, Oslo, Norway
| | - Grete Jonsson
- Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway
| | - Øyvind Skadberg
- Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway
| | - Kristian Heldal
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
- Institute of Health and Society, University of Oslo, Oslo, Norway
| | - Lasse Gunnar Gøransson
- Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
- Department of Clinical Medicine, University of Bergen, Bergen, Norway
| |
Collapse
|
|
11
|
Wang R, Price G, Disharoon M, Stidham G, McLeod MC, McMullin JL, Gillis A, Fazendin J, Lindeman B, Ong S, Chen H. Resolution of Secondary Hyperparathyroidism After Kidney Transplantation and the Effect on Graft Survival. Ann Surg 2023; 278:366-375. [PMID: 37325915 DOI: 10.1097/sla.0000000000005946] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
OBJECTIVE Hyperparathyroidism (HPT) is nearly universal in patients with end-stage kidney disease. Kidney transplantation (KT) reverses HPT in many patients, but most studies have only focused on following calcium and not parathyroid hormone (PTH) levels. We sought to study the prevalence of persistent HPT post-KT at our center and its effect on graft survival. METHODS Patients who underwent KT from January 2015 to August 2021 were included and characterized by post-KT HPT status at the most recent follow-up: resolved (achieving normal PTH post-KT) versus persistent HPT. Those with persistent HPT were further stratified by the occurrence of hypercalcemia (normocalcemic versus hypercalcemic HPT). Patient demographics, donor kidney quality, PTH and calcium levels, and allograft function were compared between groups. Multivariable logistic regression and Cox regression with propensity score matching were conducted. RESULTS Of 1554 patients, only 390 (25.1%) patients had resolution of renal HPT post-KT with a mean (±SD) follow-up length of 40±23 months. The median (IQR) length of HPT resolution was 5 (0-16) months. Of the remaining 1164 patients with persistent HPT post-KT, 806 (69.2%) patients had high PTH and normal calcium levels, while 358 (30.8%) patients had high calcium and high PTH levels. Patients with persistent HPT had higher parathyroid hormone (PTH) at the time of KT [403 (243-659) versus 277 (163-454) pg/mL, P <0.001] and were more likely to have received cinacalcet treatment before KT (34.9% vs. 12.3%, P <0.001). Only 6.3% of patients with persistent HPT received parathyroidectomy. Multivariable logistic regression showed race, cinacalcet use pre-KT, dialysis before KT, receiving an organ from a deceased donor, high PTH, and calcium levels at KT were associated with persistent HPT post-KT. After adjusting for patient demographics and donor kidney quality by propensity score matching, persistent HPT (HR 2.5, 95% CI 1.1-5.7, P =0.033) was associated with a higher risk of allograft failure. Sub-analysis showed that both hypercalcemic HPT (HR 2.6, 95% CI 1.1-6.5, P =0.045) and normocalcemic HPT (HR 2.5, 95% CI 1.3-5.5, P =0.021) were associated with increased risk of allograft failure when compared with patients with resolved HPT. CONCLUSION Persistent HPT is common (75%) after KT and is associated with a higher risk of allograft failure. PTH levels should be closely monitored after kidney transplantation so that patients with persistent HPT can be treated appropriately.
Collapse
Affiliation(s)
- Rongzhi Wang
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Griffin Price
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Mitchell Disharoon
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Gabe Stidham
- Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - M Chandler McLeod
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | | | - Andrea Gillis
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Jessica Fazendin
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Brenessa Lindeman
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
| | - Song Ong
- Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | - Herbert Chen
- Department of Surgery, University of Alabama at Birmingham, Birmingham, AL
- Department of Surgery, University of Alabama at Birmingham, Boshell Diabetes Building (BDB), Birmingham, AL
| |
Collapse
|
|
12
|
Koh HB, Ryu JH, Kim SS, Kim MG, Park JB, Kim CD, Kang KP, Ro H, Han SY, Huh KH, Yang J. Association between sclerostin levels and vascular outcomes in kidney transplantation patients. J Nephrol 2023; 36:2091-2109. [PMID: 37751127 DOI: 10.1007/s40620-023-01732-7] [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: 05/06/2023] [Accepted: 07/03/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND The impact of circulating sclerostin levels on vascular calcification has shown conflicting results depending on the target population and vascular anatomy. This study investigated the associations of sclerostin levels with vascular outcomes in kidney transplant patients. METHODS In a prospective observational study of the Korean Cohort Study for Outcome in Patients with Kidney Transplantation, 591 patients with serum sclerostin level data prior to transplantation were analyzed. The main predictor was the pre-transplant sclerostin level. Vascular outcomes were the abdominal aortic calcification score and brachial-ankle pulse wave velocity measured at pre-transplant screening and three and five years after kidney transplantation. RESULTS In linear regression analysis, sclerostin level positively correlated with changes in abdominal aortic calcification score between baseline and five years after kidney transplantation (coefficient of 0.73 [95% CI, 0.11-1.35] and 0.74 [95% CI, 0.06-1.42] for second and third tertiles, respectively, vs the first tertile). In a longitudinal analysis over five years, using generalized estimating equations, the coefficient of the interaction (sclerostin × time) was significant with a positive value, indicating that higher sclerostin levels were associated with faster increase in post-transplant abdominal aortic calcification score. Linear regression analysis revealed a positive association between pre-transplant sclerostin levels and changes in brachial-ankle pulse wave velocity (coefficient of 126.7 [95% CI, 35.6-217.8], third vs first tertile). Moreover, a significant interaction was identified between sclerostin levels and brachial-ankle pulse wave velocity at five years. CONCLUSIONS Elevated pre-transplant sclerostin levels are associated with the progression of post-transplant aortic calcifications and arterial stiffness.
Collapse
Affiliation(s)
- Hee Byung Koh
- Department of Internal Medicine, Catholic Kwandong University International Saint Mary's Hospital, Incheon, Republic of Korea
| | - Jung Hwa Ryu
- Department of Internal Medicine, Ewha Womans University Seoul Hospital, Seoul, Republic of Korea
| | - Seung-Seob Kim
- Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myung-Gyu Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jae Berm Park
- Department of Surgery, Seoul Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Chan Duk Kim
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Kyung Pyo Kang
- Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Han Ro
- Department of Internal Medicine, Gil Hospital, Gachon University, Incheon, Republic of Korea
| | - Seung-Yeup Han
- Department of Internal Medicine, Dongsan Medical Center, Keimyung University, Daegu, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
| |
Collapse
|
|
13
|
Ватазин АВ, Паршина ЕВ, Кантария РО, Степанов ВА, Зулькарнаев АБ. [Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data]. PROBLEMY ENDOKRINOLOGII 2023; 69:47-57. [PMID: 37448271 PMCID: PMC10204791 DOI: 10.14341/probl13167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 12/03/2022] [Accepted: 12/04/2022] [Indexed: 07/15/2023]
Abstract
BACKGROUND There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia. AIM to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy. METHOD This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured. RESULTS Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p<0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018). CONCLUSION The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.
Collapse
Affiliation(s)
- А. В. Ватазин
- Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского
| | | | - Р. О. Кантария
- Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского
| | - В. А. Степанов
- Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского
| | - А. Б. Зулькарнаев
- Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского
| |
Collapse
|
|
14
|
Alpay N, Yıldız A. Effects of Cinacalcet on Post-transplantation Hypercalcemia and Hyperparathyroidism in Adult Kidney Transplant Patients: A Single-Center Experience. Cureus 2023; 15:e36248. [PMID: 37069889 PMCID: PMC10105616 DOI: 10.7759/cureus.36248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/15/2023] [Indexed: 03/18/2023] Open
Abstract
OBJECTIVE Secondary hyperparathyroidism may manifest as hypercalcemia in the post-transplant period. The classical treatment method is parathyroidectomy and the alternative is oral cinacalcet, a calcimimetic agent therapy. We retrospectively investigated the effect of cinacalcet therapy on kidney and patient survival in these patients. MATERIALS AND METHODS In our single-center, retrospective, observational study, files of 934 patients who underwent renal transplantation in our unit between 2008 and 2022 were reviewed. A total of 23 patients were started on cinacalcet for the treatment of hypercalcemia (calcium > 10.3 mg/dl) and parathyroid hormone (PTH) elevation (>65 pg/ml). Patients with calcium < 10.3 mg/dl and PTH > 700 pg/ml at any time in the follow-up after renal transplantation were included in the study. In addition, the demographic data of the patients, baseline creatine, calcium, phosphorus, and PTH levels at the time of hypercalcemia, parathyroid ultrasonography, parathyroid scintigraphy, creatinine, calcium, phosphorus, and PTH levels in the last controls, and survival status were evaluated. RESULTS The mean age of 23 patients included in the study was 52.7 ± 11 years (minimum: 32; maximum: 66). Of the patients, 16 (69.6%) were male, and 15 (65.2%) were transplanted from a living donor. Parathyroid scintigraphic revealed adenoma in three (13%) patients, hyperplasia in five patients (21.7%), and no involvement in 15 patients (65.2%). Cinacalcet treatment was initiated at a median of 33 months (interquartile range (IQR) = 13-96) after the kidney transplant operation. There was no graft loss in the patients during the follow-up period. Twenty-two patients (95.7%) were alive, and one patient died. The calcium level of the patients decreased from 11.3 ± 0.64 mg/dl to 9.98 ± 0.78 mg/dl (p = 0.001) after cinacalcet treatment. Phosphorus values increased from 2.7 ± 0.65 mg/dl to 3.10 ± 0.65 mg/dl (p = 0.004). On the other hand, there was no significant difference in PTH levels between the initial and final controls (285 (IQR = 150-573) vs. 260 pg/ml (IQR = 175-411), p = 0.650). Also, creatinine levels were similar (1.2 ± 0.38 vs. 1.24 ± 0.48 mg/dl, p = 0.43). Despite cinacalcet treatment, calcium levels did not decrease in eight patients. Complications such as renal dysfunction and pathological fracture did not develop in these patients. CONCLUSIONS It seems that cinacalcet treatment is a suitable option for patients with hypercalcemia and/or hyperparathyroidism with low drug interactions and good biochemical control after renal transplantation.
Collapse
|
|
15
|
Donate-Correa J, Matos-Perdomo E, González-Luis A, Martín-Olivera A, Ortiz A, Mora-Fernández C, Navarro-González JF. The Value of Klotho in Kidney Transplantation. Transplantation 2023; 107:616-627. [PMID: 36253904 DOI: 10.1097/tp.0000000000004331] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Kidney transplant recipients have better survival rates and improved quality of life than long-term dialysis patients. However, delayed graft function, immunosuppressive therapy nephrotoxicity, and rejection episodes may compromise graft and patient survival. The KL gene is highly expressed in kidney tubular cells and encodes the antiaging and kidney-protective protein Klotho, which has membrane-anchored and soluble forms and regulates mineral metabolism. Klotho expression decreases during acute kidney injury or chronic kidney disease, and human chronic kidney disease shares features of accelerated aging with murine Klotho deficiency. In this work, we review clinical studies on the relationship between Klotho and kidney transplantation. Specifically, we address the dynamics of serum and kidney Klotho levels in donors and kidney transplant recipients, the role of Klotho as a marker of current graft function and graft outcomes, and the potential impact of Klotho on kidney protection in the transplantation context. A better understanding of the potential biomarker and therapeutic utility of Klotho in kidney transplant recipients may provide new insights into the control of graft function and new therapeutic strategies to preserve allograft function.
Collapse
Affiliation(s)
- Javier Donate-Correa
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Instituto de Tecnologías Biomédicas, University of La Laguna, Santa Cruz de Tenerife, Spain
| | - Emiliano Matos-Perdomo
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
| | - Ainhoa González-Luis
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas, University of La Laguna, Santa Cruz de Tenerife, Spain
- Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
| | - Alberto Martín-Olivera
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- Instituto de Tecnologías Biomédicas, University of La Laguna, Santa Cruz de Tenerife, Spain
- Doctoral and Graduate School, University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
| | - Alberto Ortiz
- Instituto de Investigación Sanitaria Fundación Jiménez-Díaz-Universidad Autónoma de Madrid, Madrid, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Carmen Mora-Fernández
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
- GEENDIAB (Grupo Español para el estudio de la Nefropatía Diabética), Sociedad Española de Nefrología, Santander, Spain
- Instituto de Tecnologías Biomédicas, University of La Laguna, Santa Cruz de Tenerife, Spain
- RICORS2040 (Red de Investigación Renal-RD21/0005/0013), Instituto de Salud Carlos III, Madrid, Spain
| |
Collapse
|
|
16
|
Bone Disease in Chronic Kidney Disease and Kidney Transplant. Nutrients 2022; 15:nu15010167. [PMID: 36615824 PMCID: PMC9824497 DOI: 10.3390/nu15010167] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/19/2022] [Accepted: 12/19/2022] [Indexed: 12/31/2022] Open
Abstract
Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) comprises alterations in calcium, phosphorus, parathyroid hormone (PTH), Vitamin D, and fibroblast growth factor-23 (FGF-23) metabolism, abnormalities in bone turnover, mineralization, volume, linear growth or strength, and vascular calcification leading to an increase in bone fractures and vascular disease, which ultimately result in high morbidity and mortality. The bone component of CKD-MBD, referred to as renal osteodystrophy, starts early during the course of CKD as a result of the effects of progressive reduction in kidney function which modify the tight interaction between mineral, hormonal, and other biochemical mediators of cell function that ultimately lead to bone disease. In addition, other factors, such as osteoporosis not apparently dependent on the typical pathophysiologic abnormalities resulting from altered kidney function, may accompany the different varieties of renal osteodystrophy leading to an increment in the risk of bone fracture. After kidney transplantation, these bone alterations and others directly associated or not with changes in kidney function may persist, progress or transform into a different entity due to new pathogenetic mechanisms. With time, these alterations may improve or worsen depending to a large extent on the restoration of kidney function and correction of the metabolic abnormalities developed during the course of CKD. In this paper, we review the bone lesions that occur during both CKD progression and after kidney transplant and analyze the factors involved in their pathogenesis as a means to raise awareness of their complexity and interrelationship.
Collapse
|
|
17
|
Systematic Review of the Treatment of Persistent Hyperparathyroidism Following Kidney Transplantation. Biomedicines 2022; 11:biomedicines11010025. [PMID: 36672533 PMCID: PMC9855347 DOI: 10.3390/biomedicines11010025] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/15/2022] [Accepted: 12/19/2022] [Indexed: 12/25/2022] Open
Abstract
Chronic kidney disease-mineral and bone disorder is one of the complications associated with chronic kidney disease. About 10-50% of patients following kidney transplantation have persistent hyperparathyroidism. Hypercalcaemic hyperparathyroidism has a negative impact on the kidney transplant outcome; therefore, it requires treatment. The data regarding the treatment of persistent hyperparathyroidism provided in scientific publications are divergent and contradictory. Therefore, the aim of our systematic review was to evaluate the efficacy of persistent hyperparathyroidism treatment in patients following kidney transplantation. The Cochrane, PubMed, and Scopus databases were browsed independently by two authors. The search strategy included controlled vocabulary and keywords. The effectiveness of calcitriol, paricalcitol, cinacalcet, and parathyroidectomy was compared and analysed. The mean calcium and parathormone (PTH) concentrations per patient in the group of paricalcitol increased by 1.27% and decreased by 35.14% (n = 248); in the group of cinacalcet decreased by 12.09% and 32.16% (n = 368); and in the group of parathyroidectomy decreased by 19.06% and 86.49% (n = 15) at the end of the study compared to the baseline (n = 244, n = 342 and n = 15), respectively. Paricalcitol, cinacalcet, and parathyroidectomy decreased the intact PTH level. Cinacalcet and parathyroidectomy lowered calcium levels in renal transplant patients with hypercalcaemia. Conversely, paricalcitol increased the serum calcium concentration. Cinacalcet seems to be a good candidate in the treatment of post-transplant hyperparathyroidism.
Collapse
|
|
18
|
Cianciolo G, Tondolo F, Barbuto S, Angelini A, Ferrara F, Iacovella F, Raimondi C, La Manna G, Serra C, De Molo C, Cavicchi O, Piccin O, D'Alessio P, De Pasquale L, Felisati G, Ciceri P, Galassi A, Cozzolino M. A roadmap to parathyroidectomy for kidney transplant candidates. Clin Kidney J 2022; 15:1459-1474. [PMID: 35892022 PMCID: PMC9308095 DOI: 10.1093/ckj/sfac050] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Indexed: 11/25/2022] Open
Abstract
Chronic kidney disease mineral and bone disorder may persist after successful kidney transplantation. Persistent hyperparathyroidism has been identified in up to 80% of patients throughout the first year after kidney transplantation. International guidelines lack strict recommendations about the management of persistent hyperparathyroidism. However, it is associated with adverse graft and patient outcomes, including higher fracture risk and an increased risk of all-cause mortality and allograft loss. Secondary hyperparathyroidism may be treated medically (vitamin D, phosphate binders and calcimimetics) or surgically (parathyroidectomy). Guideline recommendations suggest medical therapy first but do not clarify optimal parathyroid hormone targets or indications and timing of parathyroidectomy. There are no clear guidelines or long-term studies about the impact of hyperparathyroidism therapy. Parathyroidectomy is more effective than medical treatment, although it is associated with increased short-term risks. Ideally parathyroidectomy should be performed before kidney transplantation to prevent persistent hyperparathyroidism and improve graft outcomes. We now propose a roadmap for the management of secondary hyperparathyroidism in patients eligible for kidney transplantation that includes the indications and timing (pre- or post-kidney transplantation) of parathyroidectomy, the evaluation of parathyroid gland size and the integration of parathyroid gland size in the decision-making process by a multidisciplinary team of nephrologists, radiologists and surgeons.
Collapse
Affiliation(s)
- Giuseppe Cianciolo
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesco Tondolo
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Simona Barbuto
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Andrea Angelini
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesca Ferrara
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Francesca Iacovella
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Concettina Raimondi
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Gaetano La Manna
- Nephrology, Dialysis and Renal Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Alma Mater Studiorum University of Bologna, Italy
| | - Carla Serra
- Interventional, Diagnostic and Therapeutic Ultrasound Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi Hospital, Bologna, Italy
| | - Chiara De Molo
- Interventional, Diagnostic and Therapeutic Ultrasound Unit, Department of Medical and Surgical Sciences, IRCCS Azienda Ospedaliero-Universitaria Sant’Orsola Malpighi Hospital, Bologna, Italy
| | - Ottavio Cavicchi
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Ottavio Piccin
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Pasquale D'Alessio
- Department of Otolaryngology Head and Neck Surgery, IRCSS Azienda Ospedaliero Universitaria di Bologna, Policlinico Sant'Orsola, Bologna, Italy
| | - Loredana De Pasquale
- Department of Otolaryngology, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Giovanni Felisati
- Department of Otolaryngology, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Paola Ciceri
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Andrea Galassi
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| | - Mario Cozzolino
- Renal Division, ASST Santi Paolo e Carlo, Department of Health Sciences, University of Milan, Milan, Italy
| |
Collapse
|
|
19
|
Itoh M, Okajima M, Kittaka Y, Yachie A, Wada T, Saikawa Y. Tertiary hyperparathyroidism in patients with pseudohypoparathyroidism type 1a. Bone Rep 2022; 16:101569. [PMID: 35497370 PMCID: PMC9043659 DOI: 10.1016/j.bonr.2022.101569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 12/02/2022] Open
Abstract
Pseudohypoparathyroidism type 1a (PHP1a) is a genetic disorder caused by heterozygous loss-of-function mutations on the maternal allele of the GNAS gene. Patients with PHP1a predominantly exhibit parathyroid hormone (PTH) resistance and physical features of Albright's hereditary osteodystrophy. We report two unrelated cases with PHP1a who developed tertiary hyperparathyroidism (HPT). Molecular analyses of the GNAS gene identified a previously known heterozygous 4-bp deletion (c. 565_568delGACT) in exon 7 in case 1 and a novel heterozygous missense mutation (p.Lys233Glu) in exon 9 in case 2. Both patients developed tertiary HPT associated with hyperfunctioning parathyroid glands during long-term treatment of hypocalcemia. Case 1 had severe osteoporosis and underwent parathyroidectomy. Case 2 was asymptomatic with no evidence of bone diseases associated with tertiary HPT. PHP1a patients are at risk of developing tertiary HPT and should be treated with sufficient doses of calcium and vitamin D to achieve serum PTH levels within the mid - normal to double the upper limit of the normal range, regardless of serum calcium levels.
Pseudohypoparathyroidism type 1a induces tertiary hyperparathyroidism. Tertiary hyperparathyroidism can be complicated by hungry bone syndrome. Serum PTH levels should be within doubled the upper limit of normal.
Collapse
|
|
20
|
Frey S, Goronflot T, Blanchard C, Kerleau C, Gourraud PA, Wargny M, Caillard C, Hourmant M, Figueres L, Mirallié É. Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study. Langenbecks Arch Surg 2022; 407:2489-2498. [PMID: 35596781 DOI: 10.1007/s00423-022-02555-z] [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: 04/25/2021] [Accepted: 05/11/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.
Collapse
Affiliation(s)
- Samuel Frey
- Chirurgie Cancérologique, Digestive Et Endocrinienne, Institut Des Maladies de L'Appareil Digestif, Place Alexis Ricordeau, CHU Nantes, Hôtel Dieu, 44093, Nantes, CEDEX 1, France.,Université de Nantes, quai de Tourville, 44000, Nantes, France.,L'institut du Thorax, Unité Inserm UMR 1087 / CNRS UMR 6291, IRS 8 Quai Moncousu, 44000, Nantes, France
| | - Thomas Goronflot
- CHU de Nantes, INSERM, CIC 1413, Pôle Hospitalo-Universitaire 11, Santé Publique, Santé au Travail, Pharmacie, Stérilisation, Clinique des données, Nantes, France
| | - Claire Blanchard
- Chirurgie Cancérologique, Digestive Et Endocrinienne, Institut Des Maladies de L'Appareil Digestif, Place Alexis Ricordeau, CHU Nantes, Hôtel Dieu, 44093, Nantes, CEDEX 1, France.,Université de Nantes, quai de Tourville, 44000, Nantes, France.,L'institut du Thorax, Unité Inserm UMR 1087 / CNRS UMR 6291, IRS 8 Quai Moncousu, 44000, Nantes, France
| | - Clarisse Kerleau
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 30, boulevard Jean-Monnet, 44093, Nantes cedex, France
| | - Pierre-Antoine Gourraud
- Université de Nantes, quai de Tourville, 44000, Nantes, France.,CHU de Nantes, INSERM, CIC 1413, Pôle Hospitalo-Universitaire 11, Santé Publique, Santé au Travail, Pharmacie, Stérilisation, Clinique des données, Nantes, France
| | - Matthieu Wargny
- CHU de Nantes, INSERM, CIC 1413, Pôle Hospitalo-Universitaire 11, Santé Publique, Santé au Travail, Pharmacie, Stérilisation, Clinique des données, Nantes, France
| | - Cécile Caillard
- Chirurgie Cancérologique, Digestive Et Endocrinienne, Institut Des Maladies de L'Appareil Digestif, Place Alexis Ricordeau, CHU Nantes, Hôtel Dieu, 44093, Nantes, CEDEX 1, France
| | - Maryvonne Hourmant
- Université de Nantes, quai de Tourville, 44000, Nantes, France.,Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 30, boulevard Jean-Monnet, 44093, Nantes cedex, France.,Service de Néphrologie-Immunologie Clinique, CHU de Nantes, 30, boulevard Jean-Monnet, 44093, Nantes cedex, France
| | - Lucile Figueres
- Université de Nantes, quai de Tourville, 44000, Nantes, France.,Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, 30, boulevard Jean-Monnet, 44093, Nantes cedex, France.,Service de Néphrologie-Immunologie Clinique, CHU de Nantes, 30, boulevard Jean-Monnet, 44093, Nantes cedex, France
| | - Éric Mirallié
- Chirurgie Cancérologique, Digestive Et Endocrinienne, Institut Des Maladies de L'Appareil Digestif, Place Alexis Ricordeau, CHU Nantes, Hôtel Dieu, 44093, Nantes, CEDEX 1, France. .,Université de Nantes, quai de Tourville, 44000, Nantes, France.
| | | |
Collapse
|
|
21
|
Ferreira AC, Mendes M, Silva C, Cotovio P, Aires I, Navarro D, Caeiro F, Ramos R, Salvador R, Correia B, Cabral G, Nolasco F, Ferreira A. Improvement of Mineral and Bone Disorders After Renal Transplantation. Transplantation 2022; 106:e251-e261. [PMID: 35266925 PMCID: PMC9038238 DOI: 10.1097/tp.0000000000004099] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Revised: 01/07/2022] [Accepted: 01/19/2022] [Indexed: 11/25/2022]
Abstract
BACKGROUND Posttransplant mineral and bone diseases are causes of fractures, and their association with cardiovascular events is being studied. METHODS We analyzed the evolution of biochemical, histological, and imaging parameters pre- and 1 y post-renal transplantation in 69 patients and correlated mineral and bone findings with coronary calcifications. At inclusion and after 12 mo, clinical data and echocardiographic findings were recorded, and laboratory evaluations, radiography of the pelvis and hands, and bone biopsy were performed. Noncontrast cardiac computed tomography was performed during the second evaluation. RESULTS Serum levels of fibroblast growth factor 23 and sclerostin decreased in all patients, parathyroid hormone levels decreased in 89.8% of patients, bone alkaline phosphatase levels decreased in 68.1% of patients, and alpha-Klotho levels increased in 65.2% of patients. More than half of the patients presented with renal osteodystrophy at both biopsies, but histological findings improved: a significant transition from high to normal or low turnover and no significant differences in volume, mineralization defect, or cortical porosity at the 2 evaluations. Alpha-Klotho, sclerostin, and bone alkaline phosphatase shifts affect bone changes. Neither echocardiographic findings nor vascular calcification scores differed between the 2 points. Both the pretransplant period (dialysis vintage, sclerostin, and low bone volume at baseline) and the maintenance of abnormalities in the posttransplant period (high turnover posttransplant) were the most reliable predictors of the severity of the coronary calcification percentile. CONCLUSIONS Renal transplantation improved bone and mineral abnormalities. The pretransplant period determines the severity of calcification.
Collapse
Affiliation(s)
- Ana Carina Ferreira
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
- Nova Medical School, Lisbon, Portugal
| | - Marco Mendes
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Cecília Silva
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Patrícia Cotovio
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Inês Aires
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
- Nova Medical School, Lisbon, Portugal
| | - David Navarro
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Fernando Caeiro
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Rúben Ramos
- Cardiology Department, Hospital de Santa Marta, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
| | - Rute Salvador
- CEDOC, Tissue Repair and Inflammation Lab, Lisbon, Portugal
| | - Bruna Correia
- CEDOC, Tissue Repair and Inflammation Lab, Lisbon, Portugal
| | | | - Fernando Nolasco
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
- Nova Medical School, Lisbon, Portugal
| | - Aníbal Ferreira
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal
- Nova Medical School, Lisbon, Portugal
| |
Collapse
|
|
22
|
Lemoine S, Figueres L, Bacchetta J, Frey S, Dubourg L. Calcium homeostasis pathologies in hyperparathyroidism: nephrologic and endocrinologic points of view. ANNALES D'ENDOCRINOLOGIE 2022; 83:237-243. [DOI: 10.1016/j.ando.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
|
23
|
Jang Y, Park S, Lee H, Kim YH, Lee JP, Park SK, Jung IM, Ha J, Lim CS, Kim YS, Kwon H, Kim YC. Prognostic Value of Pre- and Post-Serum Alkaline Phosphatase Among Renal Transplant Recipients. Transplant Proc 2022; 54:678-684. [DOI: 10.1016/j.transproceed.2022.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 02/01/2022] [Indexed: 12/01/2022]
|
|
24
|
Keronen SM, Martola LAL, Finne P, Burton IS, Tong XF, Kröger HP, Honkanen EO. Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation. Calcif Tissue Int 2022; 110:324-333. [PMID: 34668028 PMCID: PMC8860959 DOI: 10.1007/s00223-021-00917-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 09/20/2021] [Indexed: 12/04/2022]
Abstract
Bone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18-70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.
Collapse
Affiliation(s)
- Satu M Keronen
- Abdominal Center, Department of Nephrology, University of Helsinki and Helsinki University Hospital, (Haartmaninkatu 4), P.O. Box 372, 00029, HUS, Finland.
| | - Leena A L Martola
- Abdominal Center, Department of Nephrology, University of Helsinki and Helsinki University Hospital, (Haartmaninkatu 4), P.O. Box 372, 00029, HUS, Finland
| | - Patrik Finne
- Abdominal Center, Department of Nephrology, University of Helsinki and Helsinki University Hospital, (Haartmaninkatu 4), P.O. Box 372, 00029, HUS, Finland
| | - Inari S Burton
- Kuopio Musculoskeletal Research Unit (KMRU), University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland
| | - Xiaoyu F Tong
- Kuopio Musculoskeletal Research Unit (KMRU), University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland
| | - Heikki P Kröger
- Kuopio Musculoskeletal Research Unit (KMRU), University of Eastern Finland, P.O.Box 1627, 70211, Kuopio, Finland
- Department of Orthopedics, Traumatology, and Hand Surgery, Kuopio University Hospital, P.O.Box 100, 70029, KYS, Finland
| | - Eero O Honkanen
- Abdominal Center, Department of Nephrology, University of Helsinki and Helsinki University Hospital, (Haartmaninkatu 4), P.O. Box 372, 00029, HUS, Finland
| |
Collapse
|
|
25
|
Magalhães J, Quelhas-Santos J, Pereira L, Neto R, Castro-Ferreira I, Martins S, Frazão JM, Carvalho C. Could Bone Biomarkers Predict Bone Turnover after Kidney Transplantation?—A Proof-of-Concept Study. J Clin Med 2022; 11:jcm11020457. [PMID: 35054152 PMCID: PMC8780588 DOI: 10.3390/jcm11020457] [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] [Received: 12/03/2021] [Revised: 01/10/2022] [Accepted: 01/13/2022] [Indexed: 12/17/2022] Open
Abstract
Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease–associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). Methods: To better understand the role of biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteo-protegerin (OPG). Results: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone resorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL.
Collapse
Affiliation(s)
- Juliana Magalhães
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal;
| | | | - Luciano Pereira
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Nephrology Department, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Ricardo Neto
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Nephrology Department, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Inês Castro-Ferreira
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Nephrology Department, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Sandra Martins
- Centro Hospitalar de São João and EPI Unit, Clinical Pathology Department, Institute of Public Health, University of Porto, 4200-319 Porto, Portugal;
| | - João Miguel Frazão
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Nephrology Department, Faculty of Medicine, University of Porto, 4200-250 Porto, Portugal
| | - Catarina Carvalho
- Nephrology and Infectious Diseases Research Group, Institute for Innovation and Health Research (I3S), Institute of Biomedical Engineering (INEB), University of Porto, 4200-135 Porto, Portugal; (J.M.); (L.P.); (R.N.); (I.C.-F.); (J.M.F.)
- Correspondence: ; Tel.: +351-226-074900; Fax: +351-226-094567
| |
Collapse
|
|
26
|
Sutton W, Chen X, Patel P, Karzai S, Prescott JD, Segev DL, McAdams-DeMarco M, Mathur A. Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients. Surgery 2022; 171:69-76. [PMID: 34266650 PMCID: PMC8688275 DOI: 10.1016/j.surg.2021.03.067] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/22/2021] [Accepted: 03/29/2021] [Indexed: 01/03/2023]
Abstract
BACKGROUND Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.
Collapse
Affiliation(s)
- Whitney Sutton
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Xiaomeng Chen
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Palak Patel
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Shkala Karzai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Jason D. Prescott
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Dorry L. Segev
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Mara McAdams-DeMarco
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD,Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Aarti Mathur
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
| |
Collapse
|
|
27
|
Neves CL, Marques IDB, Custódio MR. Mineral and bone disorder after kidney transplantation (KTx). J Bras Nefrol 2021; 43:674-679. [PMID: 34910805 PMCID: PMC8823922 DOI: 10.1590/2175-8239-jbn-2021-s113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 06/03/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
- Carolina Lara Neves
- Universidade Federal da Bahia, Hospital das Clínicas, Salvador, BA, Brazil.,Hospital Ana Nery, Salvador, BA, Brazil
| | | | | |
Collapse
|
|
28
|
Ralston MR, Stevenson KS, Mark PB, Geddes CC. Clinical factors associated with severe hypophosphataemia after kidney transplant. BMC Nephrol 2021; 22:407. [PMID: 34886802 PMCID: PMC8656060 DOI: 10.1186/s12882-021-02624-3] [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: 05/08/2021] [Accepted: 11/24/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The mechanism by which hypophosphataemia develops following kidney transplantation remains debated, and limited research is available regarding risk factors. This study aimed to assess the association between recipient and donor variables, and the severity of post-transplantation hypophosphataemia. METHODS We performed a single-centre retrospective observational study. We assessed the association between demographic, clinical and biochemical variables and the development of hypophosphataemia. We used linear regression analysis to assess association between these variables and phosphate nadir. RESULTS 87.6% of patients developed hypophosphataemia. Patients developing hypophosphataemia were younger, had a shorter time on renal replacement therapy, were less likely to have had a parathyroidectomy or to experience delayed graft function, were more likely to have received a living donor transplant, from a younger donor. They had higher pre-transplantation calcium levels, and lower alkaline phosphatase levels. Receipt of a living donor transplant, lower donor age, not having had a parathyroidectomy, receiving a transplant during the era of tacrolimus-based immunosuppression, not having delayed graft function, higher pre-transplantation calcium, and higher pre-transplantation phosphate were associated with lower phosphate nadir by multiple linear regression. CONCLUSIONS This analysis demonstrates an association between variables relating to better graft function and hypophosphataemia. The links with biochemical measures of mineral-bone disease remain less clear.
Collapse
Affiliation(s)
- Maximilian R Ralston
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.
| | - Karen S Stevenson
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK
| | - Patrick B Mark
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK.,Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Colin C Geddes
- Glasgow Renal & Transplant Unit, Queen Elizabeth University Hospital, 1345 Govan Road, Glasgow, G51 4TF, UK
| |
Collapse
|
|
29
|
Abreu ALCS, Soeiro EMD, Bedram LG, de Andrade MC, Lopes R. Brazilian guidelines for chronic kidney disease-mineral and bone metabolism disorders in children and adolescents. J Bras Nefrol 2021; 43:680-692. [PMID: 34910806 PMCID: PMC8823923 DOI: 10.1590/2175-8239-jbn-2021-s114] [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: 06/29/2021] [Accepted: 07/09/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
| | - Emília Maria Dantas Soeiro
- Universidade Federal de Pernambuco, Recife, PE, Brazil
- Instituto de Medicina Integral Professor Fernando Figueira - IMIP,
Recife, PE, Brazil
| | | | | | - Renata Lopes
- Universidade Federal de São Paulo, São Paulo, SP, Brazil
| |
Collapse
|
|
30
|
Outcomes of Subtotal Parathyroidectomy Versus Total Parathyroidectomy With Autotransplantation for Tertiary Hyperparathyroidism: Multi-institutional Study. Ann Surg 2021; 274:674-679. [PMID: 34506323 DOI: 10.1097/sla.0000000000005059] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Due to the paucity of data and controversy regarding the preferred surgical approach for managing tertiary HPT, we sought to investigate the outcomes of different surgical approaches in managing this challenging disease. METHODS We performed a multi-center retrospective study to include patients with tertiary HPT who underwent STPX or total parathyroidectomy with autotransplantation (TPX-A). RESULTS One hundred five patients had kidney transplant, and 43 were on dialysis. In the kidney transplant group, 61 patients underwent STPX, and 44 for TPX-A. Patients' demographics were not significantly different (48.61 ± 9.31 vs 47.95 ± 12.73 years, P = 0.759. The postoperative follow-up showed that the TPX-A cohort had a higher rate of hypoparathyroidism (N = 20, 45.45%) versus (N = 14, 22.95%) with the STPX cohort (P = 0.013). The cure among the TPX-A cohorts (84.09%) over the STPX cohort (73.77%) (P = 0.153). The long-term follow-up showed that the rate of developing temporary (N = 16, 41.03%) or permanent (N = 8, 20.51%) hypoparathyroidism was significantly higher among patients who underwent TPX-A over the patients who underwent STPX (N = 7, 17.95%), and (N = 4, 10.26%), respectively (P = 0.012). There was no statistical difference between the persistence (N = 3, 7.69%) or the recurrence (N = 2, 5.13%) of the HPT in the TPX-A cohort and the STPX cohort (N = 2, 5.13%). (N = 4, 10.26%), respectively, P = 0.644. CONCLUSIONS To our knowledge, this is the largest multi-center study that compared different approaches for managing tertiary HPT. Showing that STPX is the better modality in patients diagnosed with tertiary HPT and had kidney transplants avoiding the risk of hypoparathyroidism.
Collapse
|
|
31
|
Rivelli GG, Lima MLD, Mazzali M. Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy. ACTA ACUST UNITED AC 2021; 42:315-322. [PMID: 32720971 PMCID: PMC7657049 DOI: 10.1590/2175-8239-jbn-2019-0207] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 05/04/2020] [Indexed: 01/14/2023]
Abstract
Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.
Collapse
Affiliation(s)
- Gabriel Giollo Rivelli
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Clínica Médica, Campinas, SP, Brasil.,Universidade Estadual de Campinas, Laboratório de Investigação em Transplante, Campinas, SP, Brasil
| | - Marcelo Lopes de Lima
- Universidade Estadual de Campinas, Laboratório de Investigação em Transplante, Campinas, SP, Brasil.,Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Cirurgia, Campinas, SP, Brasil
| | - Marilda Mazzali
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Clínica Médica, Campinas, SP, Brasil.,Universidade Estadual de Campinas, Laboratório de Investigação em Transplante, Campinas, SP, Brasil
| |
Collapse
|
|
32
|
Ferreira AC, Mendes M, Silva C, Cotovio P, Aires I, Navarro D, Caeiro F, Salvador R, Correia B, Cabral G, Nolasco F, Ferreira A. Bone densitometry versus bone histomorphometry in renal transplanted patients: a cross-sectional study. Transpl Int 2021; 34:1065-1073. [PMID: 33909300 DOI: 10.1111/tri.13888] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/23/2021] [Accepted: 04/14/2021] [Indexed: 11/28/2022]
Abstract
Bone loss leads to increase risk of fractures in renal transplantation. The aim of this study was to analyse the relationship between bone densitometry (DXA) findings, bone histomorphometry and bone-related molecules 1-year after renal transplantation. We performed a cross-sectional study of de novo renal transplanted patients that agreed to perform a bone biopsy and a DXA examination 1 year after transplantation. All patients underwent a laboratory evaluation, bone biopsy, DXA examination and cardiac CT 1 year after transplantation. 67 patients were included, 16 had a normal examination, and 18 patients were classified as having osteoporosis by DXA. Correlations between bone mineral density and T-scores of total femur and femoral neck were the ones that best correlated with bone volume assessed by a bone biopsy. The sensitivity of DXA for osteoporosis diagnosis was 47.0%, and the specificity was 81.2%. The positive predictive value was 50.0%, and the negative predictive value (NPV) was 80.0%. DXA parameters also correlated with klotho and sclerostin serum levels. In this population, a normal examination excluded the presence of osteoporosis, helping in identifying patients that would not benefit from therapy. Overall, densitometry in total femur and femoral neck correlated well with bone volume measured by bone biopsy.
Collapse
Affiliation(s)
- Ana Carina Ferreira
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal.,Nova Medical School, Lisbon, Portugal
| | - Marco Mendes
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal
| | - Cecília Silva
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal
| | - Patrícia Cotovio
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal
| | - Inês Aires
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal.,Nova Medical School, Lisbon, Portugal
| | - David Navarro
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal
| | - Fernando Caeiro
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal
| | - Rute Salvador
- Tissue Repair and Inflammation Lab, CEDOC, Lisbon, Portugal
| | - Bruna Correia
- Tissue Repair and Inflammation Lab, CEDOC, Lisbon, Portugal
| | | | - Fernando Nolasco
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal.,Nova Medical School, Lisbon, Portugal
| | - Aníbal Ferreira
- Nephrology Department, Hospital Curry Cabral, CHULC, Lisbon, Portugal.,Nova Medical School, Lisbon, Portugal
| |
Collapse
|
|
33
|
Torregrosa JV, Ferreira AC, Cucchiari D, Ferreira A. Bone Mineral Disease After Kidney Transplantation. Calcif Tissue Int 2021; 108:551-560. [PMID: 33765230 DOI: 10.1007/s00223-021-00837-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 03/09/2021] [Indexed: 12/18/2022]
Abstract
Chronic kidney disease-mineral bone disorder (CKD-MBD) after kidney transplantation is a mix of pre-existing disorders and new alterations. The final consequences are reflected fundamentally as abnormal mineral metabolism (hypercalcemia, hypophosphatemia) and bone alterations [high or low bone turnover disease (as fibrous osteitis or adynamic bone disease), an eventual compromise of bone mineralization, decrease bone mineral density and bone fractures]. The major cause of post-transplantation hypercalcemia is the persistence of severe secondary hyperparathyroidism, and treatment options include calcimimetics or parathyroidectomy. On turn, hypophosphatemia is caused by both the persistence of high blood levels of PTH and/or high blood levels of FGF23, with its correction being very difficult to achieve. The most frequent bone morphology alteration is low bone turnover disease, while high-turnover osteopathy decreases in frequency after transplantation. Although the pathogenic mechanisms of these abnormalities have not been fully clarified, the available evidence suggests that there are a number of factors that play a very important role, such as immunosuppressive treatment, persistently high levels of PTH, vitamin D deficiency and hypophosphatemia. Fracture risk is four-fold higher in transplanted patients compared to general population. The most relevant risk factors for fracture in the kidney transplant population are diabetes mellitus, female sex, advanced age (especially > 65 years), dialysis vintage, high PTH levels and low phosphate levels, osteoporosis, pre-transplant stress fracture and high doses or prolonged steroids therapy. Treatment alternatives for CKD-MBD after transplantation include minimization of corticosteroids, use of calcium and vitamin D supplements, antiresorptives (bisphosphonates or Denosumab) and osteoformers (synthetic parathyroid hormone). As both mineral metabolism and bone disorders lead to increased morbidity and mortality, the presence of these changes after transplantation has to be prevented (if possible), minimized, diagnosed, and treated as soon as possible.
Collapse
Affiliation(s)
- Josep-Vicent Torregrosa
- Nephrology & Renal Transplant Department - Hospital Clínic, Barcelona, Spain.
- Universidad de Barcelona, Barcelona, Spain.
| | - Ana Carina Ferreira
- Nephrology Department, Centro Hospitalare, Universitário de Lisboa Central, Lisbon, Portugal
- Nova Medical School, Nova University, Lisbon, Portugal
| | - David Cucchiari
- Nephrology & Renal Transplant Department - Hospital Clínic, Barcelona, Spain
| | - Aníbal Ferreira
- Nephrology Department, Centro Hospitalare, Universitário de Lisboa Central, Lisbon, Portugal
- Nova Medical School, Nova University, Lisbon, Portugal
| |
Collapse
|
|
34
|
Frey S, Goronflot T, Kerleau C, Gourraud PA, Caillard C, Hourmant M, Mirallié É, Figueres L. Parathyroidectomy or cinacalcet: Do we still not know the best option for graft function in kidney-transplanted patients? A meta-analysis. Surgery 2021; 170:727-735. [PMID: 33810851 DOI: 10.1016/j.surg.2021.02.048] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 01/15/2021] [Accepted: 02/17/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Tertiary hyperparathyroidism occurs in 25% to 50% of kidney-transplanted patients. Indication of parathyroidectomy is now discussed, since the calcimimetic agent, cinacalcet, is an alternate option. The effects of either of these treatments on graft function remain controversial, studied only in small cohorts showing either decrease or absence of modification. We performed a meta-analysis to evaluate the evolution of graft function after surgical or medical treatment. METHODS Studies assessing graft function in tertiary hyperparathyroidism after parathyroidectomy or cinacalcet introduction were enrolled into quantitative analysis using Pubmed, Embase, and Cochrane databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. Among 68 screened studies, 18 had no missing data and were included for statistical analyses. We performed random effect meta-analysis to determine changes in serum creatinine and estimated glomerular filtration rate. RESULTS Seven studies assessing the evolution of graft function 6 and/or 12 months after parathyroidectomy and 13 after administration of cinacalcet were included. Meta-analysis found no significant variations after parathyroidectomy in serum creatinine (6 studies, 314 patients) and estimated glomerular filtration rate (2 studies, 105 patients). No significant variation was found after administration of cinacalcet in serum creatinine (10 studies, 404 patients) and estimated glomerular filtration rate (6 studies, 149 patients). A significant heterogeneity between the studies (P < .01, Cochran's Q) was found. CONCLUSION Meta-analysis shows that parathyroidectomy and cinacalcet do not significantly impair graft function in patients with tertiary hyperparathyroidism. However, the significant heterogeneity between selected studies, partially explained by the lack of consensual definition of tertiary hyperparathyroidism, limits the conclusions of all previously published series.
Collapse
Affiliation(s)
- Samuel Frey
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des maladies de l'Appareil Digestif, Hôtel Dieu, CHU Nantes, France; Université de Nantes, France
| | - Thomas Goronflot
- CHU de Nantes, INSERM, CIC 1413, Pôle Hospitalo-Universitaire 11: Santé Publique, Santé au Travail, Pharmacie, Stérilisation, Clinique des Données, France
| | - Clarisse Kerleau
- Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, France
| | - Pierre-Antoine Gourraud
- Université de Nantes, France; CHU de Nantes, INSERM, CIC 1413, Pôle Hospitalo-Universitaire 11: Santé Publique, Santé au Travail, Pharmacie, Stérilisation, Clinique des Données, France
| | - Cécile Caillard
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des maladies de l'Appareil Digestif, Hôtel Dieu, CHU Nantes, France
| | - Maryvonne Hourmant
- Université de Nantes, France; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, France; Service de néphrologie-immunologie clinique, CHU de Nantes, France
| | - Éric Mirallié
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des maladies de l'Appareil Digestif, Hôtel Dieu, CHU Nantes, France; Université de Nantes, France
| | - Lucile Figueres
- Université de Nantes, France; Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes, France; Service de néphrologie-immunologie clinique, CHU de Nantes, France.
| |
Collapse
|
|
35
|
Ngendahimana DK, Deo SV, Sundaram V, Lentine KL, Herzog CA, Al Dahabreh L, Srinivas TR, Chavin KD, Sarabu N. Outcomes of Surgical Mitral and Aortic Valve Replacements Among Kidney Transplant Candidates: Implications for Valve Selection. J Am Heart Assoc 2021; 10:e018971. [PMID: 33599143 PMCID: PMC8174273 DOI: 10.1161/jaha.120.018971] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Limited literature exists that evaluated outcomes of kidney transplant–eligible patients who are having dialysis and who are undergoing valve replacement. Our main objective in this study was to compare mortality, reoperation, and bleeding episodes between bioprosthetic and mechanical valve procedures among kidney transplant–eligible patients who are having dialysis. Methods and Results We studied 887 and 1925 dialysis patients from the United States Renal Data System, who underwent mitral valve replacement and aortic valve replacement (AVR) after being waitlisted for a kidney transplant (2000–2015), respectively. Time to death, time to reoperation, and time to bleeding requiring hospitalizations were compared separately for AVR and mitral valve replacement. Kaplan–Meier survival curves, Cox proportional hazards model for time to death, accelerated time to event model for time to reoperation, and counting process model for time to recurrent bleeding were used. There were no differences in mortality (hazard ratio [HR], 0.92; 95% CI, 0.77–1.09) or risk of reoperation or risk of significant bleeding events between bioprosthetic and mechanical mitral valve replacement. However, mechanical AVR was associated with a modestly significant less hazard of death (HR, 0.83; 95% CI, 0.74–0.94) compared with bioprosthetic AVR. There were no differences in time to reoperation, or time to significant bleeding events between bioprosthetic and mechanical AVR. Conclusions For kidney transplant waitlisted patients who are on dialysis and who are undergoing surgical valve replacement, bioprosthetic and mechanical valves have comparable survival, reoperation rates, and bleeding episodes requiring hospitalizations at both mitral and aortic locations. These findings emphasize that an individualized informed decision is recommended when choosing the type of valve for this special group of patients having dialysis.
Collapse
Affiliation(s)
| | - Salil V Deo
- Division of Cardiac Surgery Louis Stokes Veterans Affairs Medical Center Cleveland OH
| | - Varun Sundaram
- Division of Cardiology Department of Medicine University Hospitals Cleveland Medical Center Cleveland OH
| | - Krista L Lentine
- Center for Abdominal Transplantation Saint Louis University St. Louis MO
| | - Charles A Herzog
- Division of Cardiology Department of Internal Medicine Hennepin Healthcare and University of Minnesota Minneapolis MN
| | - Laith Al Dahabreh
- Transplant Institute University Hospitals Cleveland Medical Center Cleveland OH
| | - Titte R Srinivas
- Transplant Institute University Hospitals Cleveland Medical Center Cleveland OH
| | - Kenneth D Chavin
- Transplant Institute University Hospitals Cleveland Medical Center Cleveland OH
| | - Nagaraju Sarabu
- Transplant Institute University Hospitals Cleveland Medical Center Cleveland OH
| |
Collapse
|
|
36
|
Bokuda K, Morimoto S, Seki Y, Takano N, Ichihara A. Effect of Pretransplant Use of Calcimimetic on Parathyroid Function after Renal Transplantation. Int J Endocrinol 2021; 2021:1999777. [PMID: 34616449 PMCID: PMC8490070 DOI: 10.1155/2021/1999777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 09/16/2021] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE Persistence of hyperparathyroidism (HPT) after renal transplantation leads to undesirable outcomes such as increase in cardiovascular events, graft dysfunction, and increased mortality. Options for therapy include medical management with calcimimetic or operative management. The present study was undertaken to evaluate the natural history of HPT after renal transplantation and to determine risk factors for persistent HPT in the era of calcimimetic. DESIGN The study is a retrospective review of data from 74 consecutive patients who underwent renal transplantation at our institution from April 2011 to November 2019. METHODS The natural history of HPT after renal transplantation and associations between intact parathyroid hormone (PTH) level after transplantation and clinical variables such as age, sex, duration of pretransplant dialysis, and use of calcimimetic before transplantation were evaluated. RESULTS Intact PTH decreased after renal transplantation in most of the patients without receiving parathyroidectomy. Known risk factors of persistent HPT did not associate with intact PTH level after renal transplantation in patients who had been receiving calcimimetic before transplantation. CONCLUSION In conclusion, we have found that HPT after renal transplantation could be managed successfully by medical treatments. When predicting the prognosis of HPT after transplantation, pretransplant use of calcimimetic should be taken into consideration.
Collapse
Affiliation(s)
- Kanako Bokuda
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Satoshi Morimoto
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Yasufumi Seki
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Noriyoshi Takano
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| | - Atsuhiro Ichihara
- Department of Endocrinology and Hypertension, Tokyo Women's Medical University, Tokyo, Japan
| |
Collapse
|
|
37
|
Isakov O, Ghinea R, Beckerman P, Mor E, Riella LV, Hod T. Early persistent hyperparathyroidism post-renal transplantation as a predictor of worse graft function and mortality after transplantation. Clin Transplant 2020; 34:e14085. [PMID: 32949044 DOI: 10.1111/ctr.14085] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/19/2020] [Accepted: 08/27/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND Persistent hyperparathyroidism (pHPT) is frequently seen after transplantation contributing to post-transplant complications. METHODS We conducted a retrospective single center analysis to explore the relationship of early pHPT and long-term allograft outcome. Patients were divided into high (N = 153) and low (N = 252) PTH groups based on serum parathyroid hormone (PTH) level 3 months post-transplant (PTH ≥ 150 and < 150 pg/mL, respectively). RESULTS High PTH was found to be an independent predictor for reduced kidney allograft function up to 3 years post-transplant. eGFR decreased by 11.4 mL/min (P < .001) and the odds of having an eGFR < 60 mL/min 3 years post-transplant were sixfold higher (P < .01) in the high compared to the low PTH group. Subgroup analysis based on eGFR 1 year post-transplant, presence of slow graft function (SGF), and transplant type revealed similar results. High PTH three months post-transplant was also independently associated with an increased risk for overall mortality and for death with a functioning graft (P < .05). CONCLUSIONS pHPT three months post-renal transplantation is an independent predictor for a worse allograft function up to 3 years post-transplant and a risk factor for mortality. This relationship remains statistically significant after accounting for baseline allograft function, presence of SGF and serum mineral levels abnormalities.
Collapse
Affiliation(s)
- Ofer Isakov
- Department of Internal Medicine "T", Tel Aviv Souraski Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Ronen Ghinea
- Department of Surgery, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.,Transplant Nephrology Center, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Pazit Beckerman
- Department of Nephrology, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Eytan Mor
- Transplant Nephrology Center, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| | - Leonardo V Riella
- Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Tammy Hod
- Transplant Nephrology Center, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.,Department of Nephrology, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
38
|
Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients. Sci Rep 2020; 10:13766. [PMID: 32792668 PMCID: PMC7426845 DOI: 10.1038/s41598-020-70709-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 07/01/2020] [Indexed: 02/08/2023] Open
Abstract
Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19–2.14, 1.60 per mg/dL; 1.14–2.23 and 0.82 per 10 pg/mL; 0.68–0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.
Collapse
|
|
39
|
Influence of Parathyroidectomy on Kidney Graft Function in Secondary and Tertiary Hyperparathyroidism. Transplant Proc 2020; 52:3134-3143. [PMID: 32402458 DOI: 10.1016/j.transproceed.2020.03.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2019] [Revised: 02/20/2020] [Accepted: 03/12/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Timing of parathyroidectomy (PTX) remains controversial in candidates for kidney transplant with concomitant renal hyperparathyroidism (HPT). The aim of this retrospective study was to identify the influence of early vs late posttransplant PTX compared to pretransplant PTX on renal graft function and morbidity. METHODS This single-center cohort study includes 57 patients with renal HPT and kidney transplantation treated between 2007 and 2017. Ninety-six patients had surgery for renal HPT between 2007 and 2017 as a consecutive sample. Group 1 (n = 30; tertiary HPT), group 2 (n = 66; secondary HPT). Of group 1, 4 patients were excluded for PTX before and after kidney transplantation. In group 2, 20 patients were excluded since they had not undergone kidney transplantation during follow-up. Twelve patients were excluded because of short follow-up (kidney transplantation in 2018), and 3 patients were excluded because of transplant failure within 90 days. Twenty-six patients underwent posttransplant PTX (10 patients within 12 months after transplant), and 31 patients had undergone PTX prior to kidney transplantation. Graft function, serum calcium concentrations, parathyroid hormone (PTH) levels, postoperative morbidity, and 90-day mortality were recorded. RESULTS Median age was 53.1 years in group 1 and 49.1 years in group 2. Most patients were male (53.8% in group 1; 54.8% in group 2). Median preoperative PTH levels were significantly different with 331.6 pg/mL in group 1 and 667.5 pg/mL in group 2 (P = .003). Creatinine levels changed little from 1.4 mg/dL (range, 0.8-2.5) to 1.7 mg/dL (range, 0.7-7.3) in group 1, and no difference was seen between early or late PTX after transplantation. In group 2, creatinine levels were 8.5 mg/dL (range, 4.6-11.7) before PTX and 8.7 mg/dL (range, 5.1-11.9) after PTX. We saw no correlation between postoperative PTH and kidney function. Thirty-five patients with postoperative PTH < 15 pg/mL displayed a mean postoperative creatinine of 5.5 mg/dL (range, 4.3-6.8), similar to other patients. Both the 30-day and 90-day mortality rates were zero. CONCLUSIONS PTX had no negative effect on graft function, whether performed before or after (early or late) kidney transplantation. Surgical cure of renal HPT should be performed as soon as possible to prevent secondary complications and can also be safely carried out early after transplantation.
Collapse
|
|
40
|
Sella S, Bonfante L, Fusaro M, Neri F, Plebani M, Zaninotto M, Aghi A, Innico G, Tripepi G, Michielin A, Prandini T, Calò LA, Giannini S. Efficacy of weekly administration of cholecalciferol on parathyroid hormone in stable kidney-transplanted patients with CKD stage 1-3. Clin Chem Lab Med 2020; 59:343-351. [PMID: 32374278 DOI: 10.1515/cclm-2020-0282] [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: 03/08/2020] [Accepted: 04/10/2020] [Indexed: 11/15/2022]
Abstract
Objectives Kidney transplant (KTx) recipients frequently have deficient or insufficient levels of serum vitamin D. Few studies have investigated the effect of cholecalciferol in these patients. We evaluated the efficacy of weekly cholecalciferol administration on parathyroid hormone (PTH) levels in stable KTx patients with chronic kidney disease stage 1-3. Methods In this retrospective cohort study, 48 stable KTx recipients (37 males, 11 females, aged 52 ± 11 years and 26 months post-transplantation) were treated weekly with oral cholecalciferol (7500-8750 IU) for 12 months and compared to 44 untreated age- and gender-matched recipients. Changes in levels of PTH, 25(OH) vitamin D (25[OH]D), serum calcium, phosphate, creatinine and estimated glomerular filtration rate (eGFR) were measured at baseline, 6 and 12 months. Results At baseline, clinical characteristics were similar between treated and untreated patients. Considering the entire cohort, 87 (94.6%) were deficient in vitamin D and 64 (69.6%) had PTH ≥130 pg/mL. Serum calcium, phosphate, creatinine and eGFR did not differ between groups over the follow-up period. However, 25(OH)D levels were significantly higher at both 6 (63.5 vs. 30.3 nmol/L, p < 0.001) and 12 months (69.4 vs. 30 nmol/L, p < 0.001) in treated vs. untreated patients, corresponding with a significant reduction in PTH at both 6 (112 vs. 161 pg/mL) and 12 months (109 vs. 154 pg/mL) in treated vs. untreated patients, respectively (p < 0.001 for both). Conclusions Weekly administration of cholecalciferol can significantly and stably reduce PTH levels, without any adverse effects on serum calcium and renal function.
Collapse
Affiliation(s)
- Stefania Sella
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Luciana Bonfante
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Maria Fusaro
- National Research Council, Institute of Clinical Physiology, Pisa, Italy
| | - Flavia Neri
- Department of Surgery, Renal and Pancreas Transplant Unit, University of Padova, Padova, Italy
| | - Mario Plebani
- Department of Medicine, Laboratory Medicine Unit, University of Padova, Padova, Italy
| | - Martina Zaninotto
- Department of Medicine, Laboratory Medicine Unit, University of Padova, Padova, Italy
| | - Andrea Aghi
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Georgie Innico
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Giovanni Tripepi
- Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, CNR, Institute of Biomedicine, Reggio Calabria, Italy
| | - Alberto Michielin
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Tancredi Prandini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| | - Lorenzo A Calò
- Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy
| | - Sandro Giannini
- Department of Medicine, Clinica Medica 1, University of Padova, Padova, Italy
| |
Collapse
|
|
41
|
Safety and Efficacy of a 3-Year Therapy With Cinacalcet in Persistent Hyperparathyroidism After Renal Transplant. Transplant Proc 2020; 52:1284-1286. [PMID: 32204903 DOI: 10.1016/j.transproceed.2020.02.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 02/04/2020] [Accepted: 02/09/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Persistent post-transplant hyperparathyroidism (PPTHP) can occur in 20% to 50% of renal transplant recipients. The aim of this study was to analyze safety and efficacy of long-term cinacalcet therapy in a group of renal transplant recipients with PPTHP. METHODS A single center retrospective cohort study including renal transplant recipients, adults (>18 years old) with PPTHP and hypercalcemia. Inclusion criteria for cinacalcet therapy was increased parathormone levels (PTH > 65 pg/mL) associated with serum calcium >11.5 mg/dL any time after transplant or calcium >10.2 mg/dL within the first year after transplant. The follow-up period was 3 years. Demographic, laboratory data and adverse events were assessed. RESULTS Forty-six patients were included, mean age of 50 ± 11 years old, majority of white race (60%), male (58%), with a pretransplant length on dialysis of 67 ± 34 months. Cinacalcet therapy was started 37 ± 40 months after transplant, and normal calcium levels were achieved after 6 months of therapy. PTH levels presented a steady reduction over time, reaching levels near normal after 36 months (317 ± 242 vs 145 ± 72 pg/mL, baseline × month 36, P < .05). Renal function remained stable over time (GFR > 60 mL/min/1.73 m2) and no acute rejection episodes were observed. Most common adverse events were mild gastrointestinal symptoms. In 6 patients (12.5%) treatment was interrupted due to adverse events. Only 1 case (2%) was classified as treatment failure. CONCLUSION Cinacalcet therapy proved to be efficient for PPTHP and safe for graft and patient. Long-term treatment reduced PTH levels to near normal range.
Collapse
|
|
42
|
Bone biomarkers in de novo renal transplant recipients. Clin Chim Acta 2019; 501:179-185. [PMID: 31734147 DOI: 10.1016/j.cca.2019.10.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 10/24/2019] [Indexed: 12/30/2022]
Abstract
Successful kidney transplantation (partly) corrects the physiologic and metabolic abnormalities driving chronic kidney disease - mineral and bone disorders. At the same time, renal transplant recipients are exposed to immunosuppressive agents that may affect bone metabolism. Bone biomarkers have been suggested as surrogates of or adjuncts to bone biopsy and imaging techniques to assess bone health and to classify risk of bone loss and fractures. Bone biomarkers may be classified as circulating factors that affect bone metabolism (commonly referred to as bone metabolism markers) or that reflect bone cell number and/or activity (commonly referred to as bone turnover markers). A growing body of evidence shows that successful renal transplantation has a major impact on both bone metabolism and bone turnover. Analytical issues, including the cross-reactivity with fragments, complicate the interpretation of bone biomarkers, especially in the setting of a rapid changing kidney function, as is the case after successful renal transplantation. Overall, bone turnover seems to decline following renal transplantation, but inter-individual variability is substantial. Preliminary evidence indicates that bone biomarkers may be useful in guiding mineral and bone therapy in renal transplant recipients.
Collapse
|
|
43
|
Jo HA, Han KH, So YK, Jun H, Han SY. Effect of Cinacalcet in Kidney Transplant Patients With Hyperparathyroidism. Transplant Proc 2019; 51:1397-1401. [PMID: 31155177 DOI: 10.1016/j.transproceed.2019.01.141] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 01/28/2019] [Indexed: 11/17/2022]
Abstract
OBJECTIVE In dialysis patients, cinacalcet could be an effective alternative to parathyroidectomy for treating hyperparathyroidism. In the present study, we aimed to determine the characteristics of subjects with persistent hyperparathyroidism who require parathyroidectomy despite the use of cinacalcet. METHODS Nine kidney transplant patients (7 men, 2 women; mean age 53.2 [SD, 8.9] years) who had tertiary hyperparathyroidism were reviewed in a single center. Pre- and postcinacalcet levels of calcium, phosphorous, intact parathyroid hormone (iPTH), and renal function were analyzed to evaluate the effect of cinacalcet treatment in these patients. The baseline parameters before cinacalcet treatment were compared in patients who did and did not undergo parathyroidectomy. RESULTS Cinacalcet reduced serum calcium levels in all patients (11.48 [SD, 0.73] mg/dL to 10.20 [0.70] mg/dL; P = .008). Serum phosphorous levels significantly increased from 2.28 (SD, 0.77) mg/dL to 3.02 (SD, 0.65) mg/dL (P = .03). The iPTH levels in 7 patients decreased, while the mean level remained unchanged in total subjects. The iPTH levels increased even with cinacalcet treatment in 2 patients. In 3 patients, serum calcium levels abruptly increased after cinacalcet withdrawal. Five patients who showed persistent hypercalcemia due to hyperparathyroidism underwent parathyroidectomy. These 5 patients had significantly different characteristics compared with 4 patients who did not undergo parathyroidectomy: hypercalcemia (11.92 [SD, 0.68] mg/dL vs 10.93 [SD, 0.26] mg/dL; P = .02), hypophosphatemia (1.74 [SD, 0.36] mg/dL vs 2.95 [SD, 0.58] mg/dL; P = .03), and hyperparathyroidism (252.2 [SD, 131.4] pg/dL vs 101.5 [SD, 18.4] pg/dL; P = .02). CONCLUSION Cinacalcet reduced hypercalcemia due to hyperparathyroidism in the transplant patients. However, patients who had pre-existing higher iPTH, hypercalcemia, and hypophosphatemia needed parathyroidectomy. Therefore, cinacalcet could be considered an alternative to parathyroidectomy in selected patients.
Collapse
Affiliation(s)
- Hyung Ah Jo
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Kum Hyun Han
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Yoon Kyoung So
- Department of Otolaryngology-Head and Neck Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Heungman Jun
- Department of Surgery, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea
| | - Sang Youb Han
- Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea.
| |
Collapse
|
|
44
|
Parathyroidectomy versus cinacalcet for tertiary hyperparathyroidism; a retrospective analysis. Langenbecks Arch Surg 2019; 404:71-79. [PMID: 30729318 PMCID: PMC6394681 DOI: 10.1007/s00423-019-01755-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Accepted: 01/17/2019] [Indexed: 01/12/2023]
Abstract
Introduction Tertiary hyperparathyroidism (tHPT), i.e., persistent HPT after kidney transplantation, affects 17–50% of transplant recipients. Treatment of tHPT is mandatory since persistently elevated PTH concentrations after KTx increase the risk of renal allograft dysfunction and osteoporosis. The introduction of cinacalcet in 2004 seemed to offer a medical treatment alternative to parathyroidectomy (PTx). However, the optimal management of tHPT remains unclear. Methods A retrospective analysis was performed on patients receiving a kidney transplantation (KT) in two academic centers in the Netherlands. Thirty patients undergoing PTx within 3 years of transplantation and 64 patients treated with cinacalcet 1 year after transplantation for tHPT were included. Primary outcomes were serum calcium and PTH concentrations 1 year after KT and after PTx. Results Serum calcium normalized in both the cinacalcet and the PTx patients. PTH concentrations remained above the upper limit of normal (median 22.0 pmol/L) 1 year after KT, but returned to within the normal range in the PTx group (median 3.7 pmol/L). Side effects of cinacalcet were difficult to assess; minor complications occurred in three patients. Re-exploration due to persistent tHPT was performed in three (10%) patients. Conclusion In patients with tHPT, cinacalcet normalizes serum calcium, but does not lead to a normalization of serum PTH concentrations. In contrast, PTx leads to a normalization of both serum calcium and PTH concentrations. These findings suggest that PTx is the treatment of choice for tHPT.
Collapse
|
|
45
|
Abstract
PURPOSE OF REVIEW Despite metabolic improvements following kidney transplantation, transplant recipients still often suffer from complex mineral and bone disease after transplantation. RECENT FINDINGS The pathophysiology of post-transplant disease is unique, secondary to underlying pre-transplant mineral and bone disease, immunosuppression, and changing kidney function. Changes in modern immunosuppression regimens continue to alter the clinical picture. Modern management includes reducing cumulative steroid exposure and correcting the biochemical abnormalities in mineral metabolism. While bone mineral density screening appears to help predict fracture risk and anti-osteoporotic therapy appears to have a positive effect on bone mineral density, more data regarding specific treatment is necessary. Patients with mineral and bone disease after kidney transplantation require special care in order to properly manage and mitigate their mineral and bone disease. Recent changes in clinical management of transplant patients may also be changing the implications on patients' mineral and bone disease.
Collapse
Affiliation(s)
- Ariella M Altman
- Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Stuart M Sprague
- Division of Nephrology and Hypertension, NorthShore University HealthSystem, University of Chicago Medical School, 2650 Ridge Avenue, Evanston, IL, 60201, USA.
| |
Collapse
|
|
46
|
Nanmoku K, Shinzato T, Kubo T, Shimizu T, Yagisawa T. Prevalence and predictors of early hypercalcemia after kidney transplantation: a nested case-control study within a cohort of 100 patients. Clin Exp Nephrol 2018; 23:268-274. [PMID: 30121799 DOI: 10.1007/s10157-018-1627-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 08/05/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hypercalcemia (HC) after kidney transplantation (KTx) can deteriorate both graft and patient survival. However, HC as a clinical condition and its clinical significance after KTx remain unknown. We evaluated the prevalence and risk factors of early HC after KTx. METHODS We performed a nested case-control study using a cohort of 100 KTx patients. KTx patients were divided into the HC and normocalcemia (NC) groups based on the baseline serum-corrected calcium (cCa) levels (≥ 10.5 and < 10.5 mg/dL) within 1 year after KTx. RESULTS Overall, the median value of maximum serum cCa level within 1 year after KTx was 10.1 (9.1-13.8) mg/dL. Of the 100 KTx patients within the cohort, 31 patients (31.0%) were classified as the HC group. The maximum serum cCa level was reached significantly earlier in the HC group compared with the NC group (2 vs. 4 months, p = 0.024). In univariate analysis, the risk factors of early HC after KTx were dialysis duration ≥ 10 years, serum cCa level the day before KTx, and cinacalcet administration before KTx. Among these risk factors, serum cCa level the day before KTx and cinacalcet administration before KTx were identified as significant independent risk factors of early HC after KTx in multivariate analysis. CONCLUSIONS One-third of the KTx patients presented early HC within 1 year after KTx. Early HC after KTx resulted from persistent hyperparathyroidism. Therapeutic strategies to manage HC after KTx must be established.
Collapse
Affiliation(s)
- Koji Nanmoku
- Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan.
| | - Takahiro Shinzato
- Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Taro Kubo
- Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Toshihiro Shimizu
- Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Takashi Yagisawa
- Surgical Branch, Institute of Kidney Diseases, Jichi Medical University Hospital, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| |
Collapse
|
|
47
|
Spence RAJ, Patterson TJ, Currie P, Convie L, Tong L, Brown T, Spence RAJ. Renal failure parathyroidectomy - Is pre-operative imaging worthwhile? Surgeon 2018; 17:201-206. [PMID: 30097345 DOI: 10.1016/j.surge.2018.07.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 07/07/2018] [Accepted: 07/10/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Tertiary hyperparathyroidism is a significant issue in renal failure patients and some require surgery to control their serum calcium. A number of imaging techniques are used to localise the position of the parathyroid glands prior to surgery. Currently, a combination of ultrasound and isotope preoperative localisation imaging is accepted as useful in parathyroid surgery for primary disease. However, the use of pre-operative imaging in parathyroid surgery in renal failure patients is uncertain. The role of pre-operative imaging of the parathyroid glands in patients with renal failure hyperparathyroidism was assessed with imaging outcomes compared to operative and pathological findings in two cohorts of patients undergoing parathyroid surgery - primary and tertiary. METHODS All data were collected prospectively over a 10-year period (2003-2013) from the practice of a single surgeon. Patients were grouped into either primary hyperparathyroidism (49 patients) or tertiary hyperparathyroidism (41 patients). The majority, 63 of 90 (70%) patients, underwent both ultrasound (US) and isotope (MIBI) pre-operative imaging. Pre-operative imaging was correlated with operative and pathological findings. FINDINGS Comparison of the results of the two groups using ordinal regression analysis confirmed these imaging techniques are significantly more accurate in primary than tertiary parathyroid surgery (p = 0.022). CONCLUSIONS While accepted practice of pre-operative combined USS and MIBI imaging is essential in unilateral imaged-focused neck exploration for primary disease, these imaging techniques have a more limited use pre-operatively in renal failure parathyroidectomy.
Collapse
Affiliation(s)
- Robert A J Spence
- General Surgical Unit, Belfast City Hospital, 51 Lisburn Road, Belfast, BT9 7AB, Northern Ireland, United Kingdom.
| | - Timothy J Patterson
- Queen's University Belfast, University Road, Belfast, BT9 1NN, Northern Ireland, United Kingdom
| | - Peter Currie
- Queen's University Belfast, University Road, Belfast, BT9 1NN, Northern Ireland, United Kingdom
| | - Liam Convie
- General Surgical Unit, Belfast City Hospital, 51 Lisburn Road, Belfast, BT9 7AB, Northern Ireland, United Kingdom
| | - Lioe Tong
- Pathology, Belfast City Hospital, 51 Lisburn Road, Belfast, BT9 7AB, Northern Ireland, United Kingdom
| | - Tim Brown
- Renal Transplant Unit, Belfast City Hospital, 51 Lisburn Road, Belfast, BT9 7AB, Northern Ireland, United Kingdom
| | - Roy A J Spence
- General Surgical Unit, Belfast City Hospital, 51 Lisburn Road, Belfast, BT9 7AB, Northern Ireland, United Kingdom
| |
Collapse
|
|
48
|
Walder A, Müller M, Dahdal S, Sidler D, Devetzis V, Leichtle AB, Fiedler MG, Popp AW, Lippuner K, Vogt B, Uehlinger D, Huynh-Do U, Arampatzis S. The effect of a previous created distal arteriovenous-fistula on radial bone DXA measurements in prevalent renal transplant recipients. PLoS One 2018; 13:e0200708. [PMID: 30048464 PMCID: PMC6061984 DOI: 10.1371/journal.pone.0200708] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Accepted: 07/02/2018] [Indexed: 11/18/2022] Open
Abstract
Background Accelerated bone loss occurs rapidly following renal transplantation due to intensive immunosuppression and persistent hyperparathyroidism. In renal transplant recipients (RTRs) due to the hyperparathyroidism the non-dominant forearm is often utilized as a peripheral measurement site for dual-energy x-ray absorptiometry (DXA) measurements. The forearm is also the site of previous created distal arteriovenous fistulas (AVF). Although AVF remain patent long after successful transplantation, there are no data available concerning their impact on radial bone DXA measurements. Methods In this cross-sectional study we performed DXA in 40 RTRs with preexisting distal AVF (RTRs-AVF) to assess areal bone mineral density (aBMD) differences between both forearms (three areas) and compared our findings to patients with chronic kidney disease (CKD, n = 40), pre-emptive RTRs (RTRs-pre, n = 15) and healthy volunteers (n = 20). In addition, we assessed relevant demographic, biochemical and clinical aspects. Results We found a marked radial asymmetry between the forearms in RTRs with preexisting AVF. The radial aBMD at the distal AVF forearm was lower compared to the contralateral forearm, resulting in significant differences for all three areas analyzed: the Rad-1/3: median (interquartile range) in g/cm2, Rad-1/3: 0.760 (0.641–0.804) vs. 0.742 (0.642, 0.794), p = 0.016; ultradistal radius, Rad-UD: 0.433 (0.392–0.507) vs. 0.420 (0.356, 0.475), p = 0.004; and total radius, Rad-total: 0.603 (0.518, 0.655) vs. 0.599 (0.504, 0.642), p = 0.001). No such asymmetries were observed in any other groups. Lower aBMD in AVF forearm subregions resulted in misclassification of osteoporosis. Conclusions In renal transplant recipients, a previously created distal fistula may exert a negative impact on the radial bone leading to significant site-to-site aBMD differences, which can result in diagnostic misclassifications.
Collapse
Affiliation(s)
- Anna Walder
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Martin Müller
- Department of Emergency Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Suzan Dahdal
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Vasilios Devetzis
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Alexander B. Leichtle
- Center of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Martin G. Fiedler
- Center of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Albrecht W. Popp
- Department of Osteoporosis, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Kurt Lippuner
- Department of Osteoporosis, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Bruno Vogt
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Dominik Uehlinger
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Uyen Huynh-Do
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Spyridon Arampatzis
- Department of Nephrology and Hypertension, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
- * E-mail:
| |
Collapse
|
|
49
|
Ureña-Torres PA, Vervloet M, Mazzaferro S, Oury F, Brandenburg V, Bover J, Cavalier E, Cohen-Solal M, Covic A, Drüeke TB, Hindié E, Evenepoel P, Frazão J, Goldsmith D, Kazama JJ, Cozzolino M, Massy ZA. Novel insights into parathyroid hormone: report of The Parathyroid Day in Chronic Kidney Disease. Clin Kidney J 2018; 12:269-280. [PMID: 30976408 PMCID: PMC6452197 DOI: 10.1093/ckj/sfy061] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Indexed: 12/14/2022] Open
Abstract
Chronic kidney disease (CKD) is often associated with a mineral and bone disorder globally described as CKD-Mineral and Bone Disease (MBD), including renal osteodystrophy, the latter ranging from high bone turnover, as in case of secondary hyperparathyroidism (SHPT), to low bone turnover. The present article summarizes the important subjects that were covered during ‘The Parathyroid Day in Chronic Kidney Disease’ CME course organized in Paris in September 2017. It includes the latest insights on parathyroid gland growth, parathyroid hormone (PTH) synthesis, secretion and regulation by the calcium-sensing receptor, vitamin D receptor and fibroblast growth factor 23 (FGF23)–Klotho axis, as well as on parathyroid glands imaging. The skeletal action of PTH in early CKD stages to the steadily increasing activation of the often downregulated PTH receptor type 1 has been critically reviewed, emphasizing that therapeutic strategies to decrease PTH levels at these stages might not be recommended. The effects of PTH on the central nervous system, in particular cognitive functions, and on the cardiovascular system are revised, and the reliability and exchangeability of second- and third-generation PTH immunoassays discussed. The article also reviews the different circulating biomarkers used for the diagnosis and monitoring of CKD-MBD, including PTH and alkaline phosphatases isoforms. Moreover, it presents an update on the control of SHPT by vitamin D compounds, old and new calcimimetics, and parathyroidectomy. Finally, it covers the latest insights on the persistence and de novo occurrence of SHPT in renal transplant recipients.
Collapse
Affiliation(s)
- Pablo A Ureña-Torres
- Ramsay-Générale de Santé, Clinique du Landy, Department of Nephrology and Dialysis and Department of Renal Physiology, Necker Hospital, University of Paris Descartes, Paris, France
| | - Marc Vervloet
- Department of Nephrology and Amsterdam Cardiovascular Sciences (ACS), VU University Medical Center, Amsterdam, The Netherlands
| | - Sandro Mazzaferro
- Department of Cardiovascular Respiratory Nephrologic Anaesthetic and Geriatric Sciences, Sapienza University of Rome, Rome, Italy
| | - Franck Oury
- INEM, Centre de Mdecine Moléculaire Faculté de Médecine Paris Descartes, Sorbonne, Paris Cité Bâtiment Leriche, France
| | - Vincent Brandenburg
- Department of Cardiology, University Hospital RWTH Aachen, Pauwelsstraße, Aachen, Germany
| | - Jordi Bover
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, RedinRen, C. Cartagena, Catalonia, 340-350 Barcelona, Spain
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - Martine Cohen-Solal
- INSERM U1132 & USPC Paris-Diderot, Department of Rheumatology, Hôpital Lariboisière, Paris, France
| | - Adrian Covic
- Department of Nephrology, University of Medicine and Pharmacy "Gr. T. Popa", Iasi, Romania
| | - Tilman B Drüeke
- Inserm Unit 1018, CESP, Team 5, Paul Brousse Hospital, Villejuif/Paris, France
| | - Elif Hindié
- Nuclear Medicine, University of Bordeaux, Haut-Lévêque Hospital, Pessac, France
| | - Pieter Evenepoel
- Department of Medicine, Division of Nephrology, University Hospital Leuven, Leuven, Belgium.,Dienst nefrologie, Universitair Ziekenhuis Gasthuisberg, Herestraat, Leuven, Belgium
| | - João Frazão
- Institute of Investigation and Innovation in Health, University of Porto, Porto, Portugal.,INEB-National Institute of Biomedical Engineer, University of Porto, Porto, Portugal.,Department of Nephrology, São João Hospital Center, Porto, Portugal.,School of Medicine of University of Porto, Porto, Portugal
| | | | - Junichiro James Kazama
- Department of Nephrology and Hypertension, Fukushima Medical University, 1 Hikarigaoka, Fukushima 960-1247, Japan
| | - Mario Cozzolino
- Renal Division, San Paolo Hospital, Department of Health Sciences, University of Milan, Milan, Italy
| | - Ziad A Massy
- Division of Nephrology, Ambroise Paré University Medical Center, APHP, University of Paris Ouest (UVSQ), Boulogne Billancourt/Paris, France
| | | |
Collapse
|
|
50
|
Evenepoel P, D'Haese P, Bacchetta J, Cannata-Andia J, Ferreira A, Haarhaus M, Mazzaferro S, Lafage Proust MH, Salam S, Spasovski G, Cozzolino M. Bone biopsy practice patterns across Europe: the European renal osteodystrophy initiative-a position paper. Nephrol Dial Transplant 2018; 32:1608-1613. [PMID: 28339949 DOI: 10.1093/ndt/gfw468] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2016] [Accepted: 12/20/2016] [Indexed: 02/04/2023] Open
Abstract
Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease (CKD). Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD but do have important inherent limitations. By informing on bone turnover and mineralization, a bone biopsy may help to guide prevention and treatment of ROD and its consequences. According to a recent survey conducted among European nephrologists, bone biopsies are performed rather exceptionally, both for clinical and research purposes. Obviously, clinical research in the field of ROD is threatened by vanishing clinical and pathological expertise, small patient cohorts and scientific isolation. In March 2016, the European Renal Osteodystrophy (EU-ROD) initiative was created under the umbrella of the ERA-EDTA CKD-mineral and bone disorder (MBD) Working Group to revitalize bone biopsy as a clinically useful tool in the diagnostic workup of CKD-MBD and to foster research on the epidemiology, implications and reversibility of ROD. As such, the EU-ROD initiative aims to increase the understanding of ROD and ultimately to improve outcomes in CKD patients.
Collapse
Affiliation(s)
- Pieter Evenepoel
- Department of Immunology and Microbiology, Laboratory of Nephrology, KU Leuven - University of Leuven and Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium
| | - Patrick D'Haese
- Department of Biomedical Sciences, Laboratory of Pathophysiology, Antwerp University, Wilrijk, Belgium
| | - Justine Bacchetta
- Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant, Bron, France
| | - Jorge Cannata-Andia
- Hospital Universitario Central de Asturias, Oviedo University REDinREN IIS Carlos III, Bone and Mineral Research Unit, Oviedo, Spain
| | - Anibal Ferreira
- Nova Medical School - Faculdade de Ciências Médicas da Universidade Nova de Lisboa e Centro Hospitalar Lisboa Central - Hospital de Curry Cabral, Lisboa, Portugal
| | - Mathias Haarhaus
- Department of Clinical Science, Intervention and Technology, Division of Renal Medicine, Karolinska Institutet and Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden
| | - Sandro Mazzaferro
- Department of Cardiovascular, Respiratory, Nephrologic and Geriatric Sciences, Sapienza University, Rome, Italy
| | | | - Syazrah Salam
- Sheffield Kidney Institute and Academic Unit of Bone Metabolism, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Goce Spasovski
- Department of Nephrology, Medical Faculty, University of Skopje, Macedonia
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, San Paolo Hospital, University of Milan, Milan, Italy
| | | |
Collapse
|