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Hsieh YF, Hsu LY, Tsai PH, Tsai WC, Ko MJ, Chien KL, Wu HY. Quality indicators and clinical outcomes: the role of care quality in nondiabetic chronic kidney disease management. Ren Fail 2025; 47:2469748. [PMID: 39988805 PMCID: PMC11852228 DOI: 10.1080/0886022x.2025.2469748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 01/31/2025] [Accepted: 02/12/2025] [Indexed: 02/25/2025] Open
Abstract
Quality indicators (QIs) are essential for evaluating healthcare quality, but their validation for nondiabetic chronic kidney disease (CKD) populations is limited. We aimed to assess the association between QIs and outcomes in nondiabetic CKD patients. Using Taiwan's National Health Insurance claims data and death registries, we analyzed 27,842 nondiabetic adults with stage 3B-5 CKD from 2016 to 2019. Three QIs were assessed: renin-angiotensin system (RAS) inhibitor prescription, proteinuria testing, and nonsteroidal anti-inflammatory drug (NSAID) avoidance. Each patient received an overall QI score (range: 0-3) based on the sum of the individual QI scores. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between QI scores and outcomes, including long-term dialysis, all-cause death, hospitalization for acute kidney injury (AKI), hyperkalemia, and acidosis. The study population had a mean age of 68.7 years and a female prevalence of 41.7%. Only 33.5% of patients received the highest QI score. During a median follow-up period of 23 months, higher overall QI scores were associated with lower risks of long-term dialysis (HR 0.891, 95% CI 0.846-0.938), all-cause death (HR 0.900, 95% CI 0.864-0.939), and acidosis (HR 0.882, 95% CI 0.799-0.972). Notably, the prescription of RAS inhibitors was consistently correlated with better outcomes. These findings underscore the importance of quality indicators, particularly the continued use of RAS inhibitors, in improving outcomes for nondiabetic CKD patients. Future research should focus on refining existing QIs and expanding their validation to broader populations and healthcare settings.
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Affiliation(s)
- Yun-Fang Hsieh
- Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Le-Yin Hsu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
| | - Ping-Hsiu Tsai
- Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Wan-Chuan Tsai
- Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Center for General Education, Lee-Ming Institute of Technology, New Taipei City, Taiwan
| | - Mei-Ju Ko
- Department of Dermatology, Taipei City Hospital, Taipei City, Taiwan
- Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
- Center of General Education, University of Taipei, Taipei City, Taiwan
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Hon-Yen Wu
- Division of Nephrology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
- Department of Medical Research, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei City, Taiwan
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Barber T, Neumiller JJ, Fravel MA, Page RL, Tuttle KR. Using guideline-directed medical therapies to improve kidney and cardiovascular outcomes in patients with chronic kidney disease. Am J Health Syst Pharm 2025:zxaf045. [PMID: 40197743 DOI: 10.1093/ajhp/zxaf045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2025] Open
Abstract
PURPOSE An estimated 37 million people currently live with chronic kidney disease in the US, which places them at increased risk for kidney disease progression, cardiovascular disease, and mortality. This review discusses current standard-of-care management of patients with chronic kidney disease, identifies key gaps in care, and briefly highlights how pharmacists can address gaps in care as members of the multidisciplinary care team. SUMMARY Recent advances in guideline-directed medical therapies for patients with chronic kidney disease, including agents from the sodium-glucose cotransporter, glucagon-like peptide-1 receptor agonist, and nonsteroidal mineralocorticoid receptor antagonist classes, can dramatically improve cardiovascular-kidney-metabolic care and outcomes. Unfortunately, gaps in screening, diagnosis, and implementation of recommended therapies persist. Team-based models of care-inclusive of the person with chronic kidney disease-have the potential to significantly improve care and outcomes for people with chronic kidney disease by addressing current gaps in care. CONCLUSION As members of the multidisciplinary care team, pharmacists can play a critical role in addressing current gaps in care, including optimized use of guideline-directed medical therapies, in patients with chronic kidney disease.
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Affiliation(s)
| | - Joshua J Neumiller
- Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA
- Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA
| | - Michelle A Fravel
- Division of Applied Clinical Sciences, College of Pharmacy, University of Iowa, Iowa City, IA, USA
| | - Robert L Page
- Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
| | - Katherine R Tuttle
- Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA
- Nephrology Division, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
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Quagliariello V, Berretta M, Bisceglia I, Giacobbe I, Iovine M, Barbato M, Maurea C, Canale ML, Paccone A, Inno A, Scherillo M, Oliva S, Cadeddu Dessalvi C, Mauriello A, Fonderico C, Maratea AC, Gabrielli D, Maurea N. In the Era of Cardiovascular-Kidney-Metabolic Syndrome in Cardio-Oncology: From Pathogenesis to Prevention and Therapy. Cancers (Basel) 2025; 17:1169. [PMID: 40227756 PMCID: PMC11988012 DOI: 10.3390/cancers17071169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2025] [Revised: 03/21/2025] [Accepted: 03/27/2025] [Indexed: 04/15/2025] Open
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interplay between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders, significantly impacting cancer patients. The presence of CKM syndrome in cancer patients not only worsens their prognosis but also increases the risk of major adverse cardiovascular events (MACE), reduces quality of life (QoL), and affects overall survival (OS). Furthermore, several anticancer therapies, including anthracyclines, tyrosine kinase inhibitors, immune checkpoint inhibitors, and hormonal treatments, can exacerbate CKM syndrome by inducing cardiotoxicity, nephrotoxicity, and metabolic dysregulation. This review explores the pathophysiology of CKM syndrome in cancer patients and highlights emerging therapeutic strategies to mitigate its impact. We discuss the role of novel pharmacological interventions, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and soluble guanylate cyclase (sGC) activators, as well as dietary and lifestyle interventions. Optimizing the management of CKM syndrome in cancer patients is crucial to improving OS, enhancing QoL, and reducing MACE. By integrating cardiometabolic therapies into oncologic care, we can create a more comprehensive treatment approach that reduces the burden of cardiovascular and renal complications in this vulnerable population. Further research is needed to establish personalized strategies for CKM syndrome prevention and treatment in cancer patients.
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Affiliation(s)
- Vincenzo Quagliariello
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
| | - Irma Bisceglia
- Servizi Cardiologici Integrati, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00148 Rome, Italy
| | - Ilaria Giacobbe
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Martina Iovine
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Matteo Barbato
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Carlo Maurea
- ASL NA1, UOC Neurology and Stroke Unit, Ospedale del Mare, 23807 Naples, Italy
| | | | - Andrea Paccone
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Alessandro Inno
- Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, 37024 Negrar di Valpolicella, Italy
| | - Marino Scherillo
- Cardiologia Interventistica e UTIC, A.O. San Pio, Presidio Ospedaliero Gaetano Rummo, 82100 Benevento, Italy
| | - Stefano Oliva
- Cardio-Oncology Unit, IRCCS Istituto Tumori, “Giovanni Paolo II”, 70124 Bari, Italy
| | | | - Alfredo Mauriello
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Celeste Fonderico
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Anna Chiara Maratea
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
| | - Domenico Gabrielli
- U.O.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Azienda Ospedaliera San Camillo Forlanini, 00152 Rome, Italy
| | - Nicola Maurea
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80131 Napoli, Italy
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Fouque D, Zoccali C, Pesce F. Potassium management and heart failure: a nephrologist's perspective. Clin Kidney J 2025; 18:sfae424. [PMID: 39935737 PMCID: PMC11811525 DOI: 10.1093/ckj/sfae424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Indexed: 02/13/2025] Open
Affiliation(s)
- Denis Fouque
- Dept of nephrology, Lyon Sud hospital, Hospices Civils de Lyon, Carmen Inserm U1060 and University Claude Bernard Lyon1, Pierre Benite, France
| | - Carmine Zoccali
- Renal Research Institute, NY, USA; BIOGEM, Ariano Irpino, Italy; Associazione Ipertensione Nefrologia Trapianto Renal (IPNET), C/O Nefrologia, Grande Ospedale Metropolitano, Reggio Calabria, Italy
| | - Francesco Pesce
- Division of Renal Medicine, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy
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Brady BM, Suffoletto JA, Sankary R, Chertow GM. Chronic kidney disease in older adults: challenges and opportunities for the primary care provider. BMC PRIMARY CARE 2024; 25:388. [PMID: 39487419 PMCID: PMC11529074 DOI: 10.1186/s12875-024-02638-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Accepted: 10/23/2024] [Indexed: 11/04/2024]
Abstract
Kidney disease and its comorbidities disproportionately affect older persons. Kidney disease modifying therapy is underutilized in older adults, as guidelines lack consensus on approaching diagnosis and treatment in older adults. This review aims to highlight the challenges presented by, and opportunities for, identifying and treating CKD in older adults.
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Affiliation(s)
- Brian M Brady
- Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA.
| | - Jo-Anne Suffoletto
- Department of Medicine, Division of Primary Care and Population Health, Stanford University School of Medicine, Stanford, CA, USA
| | | | - Glenn M Chertow
- Department of Medicine, Division of Nephrology, Stanford University School of Medicine, Stanford, CA, USA
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Chimura M, Petrie MC, Schou M, Martinez FA, Henderson AD, Claggett BL, Desai AS, Kolkhof P, Viswanathan P, Lage A, Lam CS, Senni M, Shah SJ, Rohwedder K, Mueller K, Voors AA, Zannad F, Pitt B, Vaduganathan M, Jhund PS, Solomon SD, McMurray JJ. Finerenone Improves Outcomes in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction Irrespective of Age: A Prespecified Analysis of FINEARTS-HF. Circ Heart Fail 2024; 17:e012437. [PMID: 39342655 PMCID: PMC11573060 DOI: 10.1161/circheartfailure.124.012437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 09/20/2024] [Indexed: 10/01/2024]
Abstract
BACKGROUND Finerenone improves outcomes in patients with heart failure and mildly reduced or preserved ejection fraction. It is important to understand the efficacy and safety of finerenone in these patients according to age. METHODS The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone Trial to Investigate Efficacy and Safety Compared to Placebo in Patients With Heart Failure). A total of 6001 patients aged 40 to 97 years were stratified by quartile (Q1-Q4) of baseline age: Q1, 40 to 66 years (n=1581); Q2, 67 to 73 years (n=1587); Q3, 74 to 79 years (n=1421); and Q4, ≥80 years (n=1412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) heart failure events, including heart failure hospitalization or urgent heart failure event, along with secondary efficacy and safety outcomes. RESULTS The incidence of primary outcomes increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: rate ratio in Q1, 0.70 (95% CI, 0.53-0.92); Q2, 0.83 (95% CI, 0.64-1.07); Q3, 0.98 (95% CI, 0.76-1.26); and Q4, 0.85 (95% CI, 0.67-1.07); Pinteraction=0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change in Q1, 2.87 (95% CI, 1.09-4.66); Q2, 1.24 (95% CI, -0.59 to 3.07); Q3, 0.94 (-0.98 to 2.86); and Q4, 1.24 (-0.90 to 3.38); Pinteraction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age. CONCLUSIONS In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04435626 and EudraCT 2020-000306-29.
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Affiliation(s)
- Misato Chimura
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.C., M.C.P., A.D.H., P.S.J., J.J.V.M.)
| | - Mark C. Petrie
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.C., M.C.P., A.D.H., P.S.J., J.J.V.M.)
| | - Morten Schou
- Department of Cardiology, Herlev-Gentofte University Hospital, Hellerup, Denmark (M. Schou)
| | | | - Alasdair D. Henderson
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.C., M.C.P., A.D.H., P.S.J., J.J.V.M.)
| | - Brian L. Claggett
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (B.L.C., A.S.D., M.V., S.D.S.)
| | - Akshay S. Desai
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (B.L.C., A.S.D., M.V., S.D.S.)
| | - Peter Kolkhof
- Bayer AG, Berlin, Germany (P.K., P.V., A.L., K.R., K.M.)
| | | | - Andrea Lage
- Bayer AG, Berlin, Germany (P.K., P.V., A.L., K.R., K.M.)
| | - Carolyn S.P. Lam
- National Heart Centre Singapore and Duke-National University of Singapore (C.S.P.L.)
| | - Michele Senni
- University of Milano-Bicocca, Papa Giovanni XXIII Hospital, Bergamo, Italy (M. Senni)
| | - Sanjiv J. Shah
- Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.)
| | | | | | | | - Faiez Zannad
- Université de Lorraine, Inserm Clinical Investigation Centre, University Hospital of Nancy, France (F.Z.)
| | - Bertram Pitt
- University of Michigan, School of Medicine, Ann Arbor (B.P.)
| | - Muthiah Vaduganathan
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (B.L.C., A.S.D., M.V., S.D.S.)
| | - Pardeep S. Jhund
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.C., M.C.P., A.D.H., P.S.J., J.J.V.M.)
| | - Scott D. Solomon
- Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (B.L.C., A.S.D., M.V., S.D.S.)
| | - John J.V. McMurray
- British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (M.C., M.C.P., A.D.H., P.S.J., J.J.V.M.)
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Samaan F, Vicente CA, Pais LAC, Kirsztajn GM, Sesso R. Key Performance Indicators of Secondary Health Care in Chronic Kidney Disease: Experience in Public and Private Services in the State of São Paulo, Brazil. Int J Nephrol 2024; 2024:5401633. [PMID: 39494215 PMCID: PMC11531362 DOI: 10.1155/2024/5401633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Revised: 08/09/2024] [Accepted: 10/10/2024] [Indexed: 11/05/2024] Open
Abstract
Introduction: The objective of this study was to evaluate quality indicators of secondary health care in chronic kidney disease (CKD). Methods: This retrospective longitudinal study was conducted in an outpatient medical nephrology clinic of the Brazilian Unified Health System (UHS) and a multidisciplinary outpatient clinic of a private health plan (PHP). The inclusion criteria were age ≥ 18 years, ≥ 3 medical appointments, and follow-up time ≥ 6 months. Results: Compared to PHP patients (n = 183), UHS patients (n = 276) were older (63.4 vs. 59.7 years, p=0.04), had more arterial hypertension (AH) (91.7% vs. 84.7%, p=0.02) and dyslipidemia (58.3 vs. 38.3%, p < 0.01), and had a lower estimated baseline glomerular filtration rate (eGFR) (29.9 [21.5-42.0] vs. 39.1 [28.6-54.8] mL/min/1.73 m2, p < 0.01). Compared to PHP patients, UHS patients had a lower percentage of diabetics with glycated hemoglobin < 7.5% (46.1% vs. 61.2%, p=0.03), fewer people with potassium < 5.5 mEq/L (90.4% vs. 95.6%, p=0.04), and fewer referrals for hemodialysis with functioning arteriovenous fistula (AVF) (9.1% vs. 54.3%, p < 0.01). The percentages of people with hypertension and blood pressure < 140 × 90 mmHg were similar between the UHS and PHP groups (59.7% vs. 66.7%; p=0.17), as was the percentage of people with parathyroid hormone control (85.6% vs. 84.8%; p=0.83), dyslipidemia and LDL-cholesterol < 100 mg/dL (38.3% vs. 49.3%; p=0.13), phosphorus < 4.5 mg/dL (78.5% vs. 72.0%; p=0.16), and 25-OH-vitamin-D > 30 ng/mL (28.4% vs. 36.5%; p=0.11). The crude reduction in eGFR was greater in the UHS group than in PHP (2.3 [-0.1; 5.9] vs. 1.1 [-1.9; 4.6] mL/min/1.73 m2; p < 0.01). In the multivariate linear mixed-effects model, UHS patients also showed faster CKD progression over time than PHS ones (group effect, p < 0.01; time effect, p < 0.01; interaction, p < 0.01). Conclusions: Quality of care for patients with CKD can be improved through both services, and multidisciplinary care may have a positive impact on the control of comorbidities, the progression of CKD, and the planning of the initiation of hemodialysis.
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Affiliation(s)
- Farid Samaan
- Planning and Evaluation Group, State Department of Health of São Paulo, São Paulo 01246-901, Brazil
- Special Programs, Hapvida-NotreDame Intermédica Group, São Paulo 03164-140, Brazil
- Research Division, Dante Pazzanese Cardiology Institute, São Paulo 04012-909, Brazil
| | | | | | | | - Ricardo Sesso
- Nephrology Division, Federal University of São Paulo, São Paulo 04023-062, Brazil
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Weir MR, Rossignol P, Pitt B, Lund LH, Coats AJ, Filippatos G, Perrin A, Waechter S, Budden J, Kosiborod M, Metra M, Boehm M, Ezekowitz JA, Bayes-Genis A, Mentz RJ, Ponikowski P, Senni M, Castro-Montes E, Nicolau JC, Parkhomenko A, Seferovic P, Cohen-Solal A, Anker SD, Butler J. Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients with Heart Failure with or without Comorbid Chronic Kidney Disease: Subgroup Analysis of DIAMOND Randomized Trial. Am J Nephrol 2024; 55:672-689. [PMID: 39159624 PMCID: PMC11651233 DOI: 10.1159/000540453] [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: 03/15/2024] [Accepted: 07/03/2024] [Indexed: 08/21/2024]
Abstract
INTRODUCTION Renin-angiotensin-aldosterone system inhibitor (RAASi; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high. METHODS The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc). RESULTS In total, 81.3, 78.9, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer versus placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer versus placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups. CONCLUSION Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.
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Affiliation(s)
- Matthew R. Weir
- Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Patrick Rossignol
- INSERM CIC-P 1433, CHRU de Nancy, INSERM U1116, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Nancy, France
- Department of Medical Specialties and Nephrology-Hemodialysis, Princess Grace Hospital, Centre d’Hémodialyse Privé de Monaco, Monaco, Monaco
| | - Bertram Pitt
- Division of Cardiology, University of Michigan, Ann Arbor, MI, USA
| | - Lars H. Lund
- Department of Medicine, Unit of Cardiology, Karolinska Institutet, Solna, Sweden
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | | | - Gerasimos Filippatos
- School of Medicine, Athens University Hospital Attikon, National and Kapodistrian University of Athens, Haidari, Greece
| | | | | | | | - Mikhail Kosiborod
- Department of Cardiovascular Disease, Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Marco Metra
- Cardiology, ASST Spedali Civili and University, Brescia, Italy
| | - Michael Boehm
- Klinik für Innere Medizin III, Saarland University, Homburg, Germany
| | | | - Antoni Bayes-Genis
- Cardiology Department, Hospital Universitari Germans Trias i Pujol, CIBERCV, Barcelona, Spain
| | - Robert J. Mentz
- Department of Medicine, Duke University School of Medicine, Durham, NC, USA
| | - Piotr Ponikowski
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
| | - Michele Senni
- Cardiovascular Department, ASST Papa Giovanni XXIII Hospital, University of Milano – Bicocca, Bergamo, Italy
| | - Eliodoro Castro-Montes
- Instituto de Corazon de Queretaro (ICQ), Faculty of Medicine Universidad Autonoma de Queretaro, Santiago de Queretaro, Mexico
| | - Jose Carlos Nicolau
- Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Petar Seferovic
- University of Belgrade – Faculty of Medicine, Serbian Academy of Sciences and Arts, Belgrade, Serbia
| | - Alain Cohen-Solal
- Université de Paris, INSERM U942, APHP, Hospital Lariboisiere, Paris, France
| | - Stefan D. Anker
- Institute of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- Department of Cardiology (CVK), German Heart Center Charité, Institute of Health Center for Regenerative Therapies (BCRT), German Center for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Javed Butler
- Division of Cardiology, University of Michigan, Ann Arbor, MI, USA
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Heerspink H, Nolan S, Carrero JJ, Arnold M, Pecoits-Filho R, García Sánchez JJ, Wittbrodt E, Cabrera C, Lam CSP, Chen H, Kanda E, Lainscak M, Pollock C, Wheeler DC. Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort. Adv Ther 2024; 41:3264-3277. [PMID: 38958839 PMCID: PMC11263227 DOI: 10.1007/s12325-024-02913-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] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 05/24/2024] [Indexed: 07/04/2024]
Abstract
INTRODUCTION This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier, NCT04034992.
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Affiliation(s)
- Hiddo Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
| | - Stephen Nolan
- Global Medical Affairs, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Matthew Arnold
- Real World Data Science, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK
| | - Roberto Pecoits-Filho
- School of Medicine, Pontifical Catholic University of Parana, Curitiba, Brazil
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | | | - Eric Wittbrodt
- Cardiovascular, Renal, Metabolism Epidemiology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA
| | - Claudia Cabrera
- Real World Science and Analytics, BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden
| | - Carolyn S P Lam
- Department of Cardiology, National Heart Centre, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Hungta Chen
- Medical and Payer Evidence Statistics, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA
| | | | - Mitja Lainscak
- Division of Cardiology, General Hospital Murska Sobota, Murska Sobota, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Carol Pollock
- Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia
| | - David C Wheeler
- Department of Renal Medicine, University College London, London, UK
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10
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Zhang C, Duan ZY, Nie SS, Zhang Z, Guo XR, Zhang CY, Dong J, Cai GY. Renin-angiotensin system inhibitors prescriptions in Chinese hospitalized chronic kidney disease patients. World J Clin Cases 2024; 12:3061-3075. [PMID: 38898860 PMCID: PMC11185381 DOI: 10.12998/wjcc.v12.i17.3061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 04/23/2024] [Accepted: 04/29/2024] [Indexed: 06/04/2024] Open
Abstract
BACKGROUND Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients. AIM To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China. METHODS It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription. RESULTS A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions. CONCLUSION The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
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Affiliation(s)
- Chun Zhang
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhi-Yu Duan
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Sa-Sa Nie
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Zhou Zhang
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Xin-Ru Guo
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Chao-Yang Zhang
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
| | - Jing Dong
- National Engineering Laboratory for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing 100853, China
| | - Guang-Yan Cai
- Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China
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11
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Smetana GW, Romeo GR, Rosas SE, Burns RB. How Would You Manage This Patient With Type 2 Diabetes and Chronic Kidney Disease? Grand Rounds Discussion From Beth Israel Deaconess Medical Center. Ann Intern Med 2024; 177:800-811. [PMID: 38857499 DOI: 10.7326/m24-0764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/12/2024] Open
Abstract
Nearly 15% of U.S. adults have diabetes; type 2 diabetes (T2D) accounts for more than 90% of cases. Approximately one third of all patients with diabetes will develop chronic kidney disease (CKD). All patients with T2D should be screened annually for CKD with both a urine albumin-creatinine ratio and an estimated glomerular filtration rate. Research into strategies to slow the worsening of CKD and reduce renal and cardiovascular morbidity in patients with T2D and CKD has evolved substantially. In 2022, a consensus statement from the American Diabetes Association and the Kidney Disease: Improving Global Outcomes recommended prioritizing the use of sodium-glucose cotransporter-2 inhibitors and metformin and included guidance for add-on therapy with glucagon-like peptide 1 receptors agonists for most patients whose first-line therapy failed. It also recommended nonsteroidal mineralocorticoid receptor antagonists for patients with hypertension that is not adequately controlled with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Here, an endocrinologist and a nephrologist discuss the care of patients with T2D and CKD and how they would apply the consensus statement to the care of an individual patient with T2D who is unaware that he has CKD.
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Affiliation(s)
- Gerald W Smetana
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (G.W.S., R.B.B.)
| | - Giulio R Romeo
- Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (G.R.R., S.E.R.)
| | - Sylvia E Rosas
- Joslin Diabetes Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (G.R.R., S.E.R.)
| | - Risa B Burns
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (G.W.S., R.B.B.)
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12
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Yu MK, Vart P, Jongs N, Correa-Rotter R, Rossing P, McMurray JJV, Hou FF, Douthat W, Khullar D, Langkilde AM, Wheeler DC, Heerspink HJL, Chertow GM. Effects of Dapagliflozin in Chronic Kidney Disease Across the Spectrum of Age and by Sex. J Gen Intern Med 2024; 39:921-930. [PMID: 38097862 PMCID: PMC11074069 DOI: 10.1007/s11606-023-08397-9] [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: 05/09/2023] [Accepted: 08/24/2023] [Indexed: 05/08/2024]
Abstract
BACKGROUND The sodium-glucose cotransporter type 2 inhibitor dapagliflozin reduces the risk of progressive kidney disease and cardiovascular events in patients with chronic kidney disease, with and without type 2 diabetes. Whether its effects are uniform across the spectrum of age and among men and women is unknown. OBJECTIVE We performed a pre-specified analysis in DAPA-CKD to evaluate efficacy and safety of dapagliflozin according to baseline age and sex. DESIGN Prospective randomized placebo-controlled trial. PARTICIPANTS A total of 4304 adults with chronic kidney disease (estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio 200-5000 mg/g) with and without type 2 diabetes. INTERVENTION Dapagliflozin 10 mg versus placebo once daily. MAIN MEASURES Primary endpoint was a composite of ≥ 50% sustained eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included kidney composite endpoint (same as primary composite endpoint but without cardiovascular death), cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. KEY RESULTS Median follow-up was 2.4 years. Absolute risks of cardiovascular composite endpoint and all-cause mortality were higher in older patients. Absolute risk of kidney composite endpoint was highest in patients < 50 years (10.7 and 6.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively) and lowest in patients ≥ 80 years (3.0 and 1.2 per 100 patient-years in the placebo and dapagliflozin groups, respectively). There was no evidence of heterogeneity of the effects of dapagliflozin on the primary or secondary endpoints based on age or sex. Neither age nor sex modified the effects of dapagliflozin on total or chronic eGFR slope. CONCLUSIONS Dapagliflozin reduced the risks of mortality, cardiovascular events, and CKD progression in older patients, including in septuagenarians and octogenarians who comprised 25% of participants. Ageism and/or therapeutic nihilism should not discourage the use of dapagliflozin in older women and men who are likely to experience considerable benefit. TRIAL REGISTRY clinicaltrials.gov NIH TRIAL REGISTRY NUMBER: NCT03036150.
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Affiliation(s)
- Margaret K Yu
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | - Priya Vart
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Niels Jongs
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
| | - Ricardo Correa-Rotter
- The National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico
| | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - John J V McMurray
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
| | - Fan-Fan Hou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China
| | - Walter Douthat
- Department of Nephrology, Hospital Privado Universitario de Cordoba, Cordoba, Argentina
| | - Dinesh Khullar
- Department of Nephrology and Renal Transplant Medicine, Max Super Speciality Hospital, Saket, New Delhi, India
| | | | - David C Wheeler
- Department of Renal Medicine, University College London, London, UK
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
- The George Institute for Global Health, Sydney, New South Wales, Australia
| | - Glenn M Chertow
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Epidemiology and Population Health, Stanford University School of Medicine, Stanford, CA, USA.
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
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13
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Laville SM, Gras-Champel V, Hamroun A, Moragny J, Lambert O, Metzger M, Jacquelinet C, Combe C, Fouque D, Laville M, Frimat L, Robinson BM, Bieber B, Stengel B, Alencar De Pinho N, Massy ZA, Liabeuf S. Kidney Function Decline and Serious Adverse Drug Reactions in Patients With CKD. Am J Kidney Dis 2024; 83:601-614.e1. [PMID: 37951340 DOI: 10.1053/j.ajkd.2023.09.012] [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: 01/20/2023] [Revised: 08/16/2023] [Accepted: 09/11/2023] [Indexed: 11/13/2023]
Abstract
RATIONALE & OBJECTIVE Adverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular filtration rate (eGFR) and serious ADR risk. STUDY DESIGN Prospective cohort study. SETTING & PARTICIPANTS 3,033 participants in French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD. PREDICTORS Demographic and biological data (including eGFR), medication prescriptions. OUTCOME ADRs (preventable or not) were prospectively identified from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs. ANALYTICAL APPROACH Restricted cubic splines in fully adjusted cause-specific Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype). RESULTS During a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n=170) and hemorrhage (n=170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n=467), with 32 directly or indirectly associated with death and 22 associated with a life-threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1mL/min/1.73m2 lower baseline eGFR. LIMITATIONS The results cannot be extrapolated to patients who are not being treated by a nephrologist. CONCLUSIONS ADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor. PLAIN-LANGUAGE SUMMARY Patients with chronic kidney disease (CKD) have complex clinical presentations, take multiple medications, and often receive inappropriate prescriptions. Using data from a large, prospective CKD cohort, we found a high incidence of serious adverse drug reactions (ADRs). The 2 most common serious ADRs were drug-induced acute kidney injury and bleeding. A large proportion of serious ADRs required hospital admission, and 11% led to death or were life threatening. Lower kidney function was a major risk factor for serious ADRs. Many of these serious ADRs were determined to be partly preventable through greater adherence to prescription guidelines. This report enhances our understanding of the potential toxicity of drugs taken by patients with moderate to advanced CKD. It emphasizes the importance of monitoring kidney function when prescribing drugs, particularly for high-risk medications such as antithrombotic agents.
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Affiliation(s)
- Solène M Laville
- Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens; MP3CV Laboratory, Jules Verne University of Picardie, Amiens
| | - Valérie Gras-Champel
- Pharmacovigilance Center, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens
| | - Aghilès Hamroun
- Nephrology Department, Lille Regional University Medical Center, Lille; Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif
| | - Julien Moragny
- Pharmacovigilance Center, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens
| | - Oriane Lambert
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif
| | - Marie Metzger
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif
| | - Christian Jacquelinet
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif; Biomedecine Agency, Saint Denis La Plaine
| | - Christian Combe
- Service de Néphrologie Transplantation Dialyse Aphérèse, Centre Hospitalier Universitaire de Bordeaux, Bordeaux; INSERM, U1026, Université Bordeaux Segalen, Bordeaux
| | - Denis Fouque
- Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, Pierre-Bénite; Université de Lyon, Carmen INSERM 1060, Lyon
| | | | - Luc Frimat
- Nephrology Department, CHRU de Nancy, Vandoeuvre-lès-Nancy; Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France
| | | | - Brian Bieber
- Arbor Research Collaborative for Health, Ann Arbor, Michigan
| | - Bénédicte Stengel
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif
| | - Natalia Alencar De Pinho
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif
| | - Ziad A Massy
- Centre for Research in Epidemiology and Population Health (CESP), INSERM UMRS 1018, Université Paris-Saclay, Université Versailles Saint Quentin, Villejuif; Department of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne-Billancourt/Paris
| | - Sophie Liabeuf
- Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens; MP3CV Laboratory, Jules Verne University of Picardie, Amiens.
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14
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Riccio E, D'Ercole A, Sannino A, Hamzeh S, De Marco O, Capuano I, Buonanno P, Rizzo M, Pisani A. Real-world management of chronic and postprandial hyperkalemia in CKD patients treated with patiromer: a single-center retrospective study. J Nephrol 2024; 37:1077-1084. [PMID: 38319545 DOI: 10.1007/s40620-024-01897-9] [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: 10/20/2023] [Accepted: 01/07/2024] [Indexed: 02/07/2024]
Abstract
INTRODUCTION Hyperkalemia, one of the most important electrolyte abnormalities of chronic kidney disease (CKD), often limits the use of renin-angiotensin-aldosterone system inhibitors and can increase in the postprandial period. In this study we report a real-world experience with the new non-adsorbed potassium binder patiromer in stage 3b-4 CKD patients. Moreover, we performed a cross-sectional analysis to evaluate, for the first time, the efficacy of patiromer in the control of postprandial potassium concentrations. METHODS We retrospectively collected data of 40 patients at the time of patiromer initiation (T0), and after 2 (T2), 6 (T6) and 12 (T12) months of treatment. For cross sectional analysis, a blood sample was collected 2 h after the main meal for the evaluation of postprandial potassium concentrations. RESULTS Eighty-two point five percent of patients (33/40) reached normal potassium concentrations at T2. Serum potassium significantly decreased at T2 compared to T0 (5.13 ± 0.48 vs 5.77 ± 0.41 mmol/L, respectively; p < 0.001) and the reduction remained significant during the follow-up (5.06 ± 0.36 at T6 and 5.77 ± 0.41 at T12; p < 0.001 vs T0). Renin-angiotensin-aldosterone system inhibitors were continued by 93% of patients (27/29). Adverse events were reported in 27.5% of patients and were all mild-to-moderate. Postprandial potassium concentrations did not significantly change compared to fasting state potassium measured at T12 (4.53 ± 0.33 vs 5.06 ± 0.36 mmol/L; p = 0.15). CONCLUSIONS In a real-world setting of advanced CKD patients, patiromer is a useful treatment for hyperkalemia, since it significantly reduces serum potassium levels over the long term and is able to maintain potassium concentrations in the normal range even in the post-prandial period.
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Affiliation(s)
- Eleonora Riccio
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy.
| | - Anna D'Ercole
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Anna Sannino
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Sarah Hamzeh
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Oriana De Marco
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Ivana Capuano
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Pasquale Buonanno
- Department of Neurosciences, Reproductive and Odontostomatological Sciences, University of Naples Federico II, Naples, Italy
| | - Manuela Rizzo
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
| | - Antonio Pisani
- Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy
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15
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Stevens PE, Ahmed SB, Carrero JJ, Foster B, Francis A, Hall RK, Herrington WG, Hill G, Inker LA, Kazancıoğlu R, Lamb E, Lin P, Madero M, McIntyre N, Morrow K, Roberts G, Sabanayagam D, Schaeffner E, Shlipak M, Shroff R, Tangri N, Thanachayanont T, Ulasi I, Wong G, Yang CW, Zhang L, Levin A. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2024; 105:S117-S314. [PMID: 38490803 DOI: 10.1016/j.kint.2023.10.018] [Citation(s) in RCA: 515] [Impact Index Per Article: 515.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 10/31/2023] [Indexed: 03/17/2024]
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16
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Pina PMR, Arcon LC, Zatz R, Moysés RMA, Elias RM. Older patients are less prone to fast decline of renal function: a propensity-matched study. Int Urol Nephrol 2023; 55:3245-3252. [PMID: 37160835 DOI: 10.1007/s11255-023-03610-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 04/24/2023] [Indexed: 05/11/2023]
Abstract
PURPOSE Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. METHODS We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. RESULTS Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. CONCLUSION Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.
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Affiliation(s)
- Paula M R Pina
- LIM 16, Faculdade de Medicina da Universidade de São Paulo, Serviço de Nefrologia, Rua Dr. Enéas de Carvalho Aguiar 255, 7º Andar, São Paulo, SP, CEP, 05403-000, Brazil
| | - Luis Carlos Arcon
- LIM 16, Faculdade de Medicina da Universidade de São Paulo, Serviço de Nefrologia, Rua Dr. Enéas de Carvalho Aguiar 255, 7º Andar, São Paulo, SP, CEP, 05403-000, Brazil
| | - Roberto Zatz
- LIM 16, Faculdade de Medicina da Universidade de São Paulo, Serviço de Nefrologia, Rua Dr. Enéas de Carvalho Aguiar 255, 7º Andar, São Paulo, SP, CEP, 05403-000, Brazil
| | - Rosa M A Moysés
- LIM 16, Faculdade de Medicina da Universidade de São Paulo, Serviço de Nefrologia, Rua Dr. Enéas de Carvalho Aguiar 255, 7º Andar, São Paulo, SP, CEP, 05403-000, Brazil
| | - Rosilene M Elias
- Universidade Nove de Julho (UNINOVE), Sao Paulo, Brazil.
- LIM 16, Faculdade de Medicina da Universidade de São Paulo, Serviço de Nefrologia, Rua Dr. Enéas de Carvalho Aguiar 255, 7º Andar, São Paulo, SP, CEP, 05403-000, Brazil.
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Nicholas SB, Daratha KB, Alicic RZ, Jones CR, Kornowske LM, Neumiller JJ, Fatoba ST, Kong SX, Singh R, Norris KC, Tuttle KR. Prescription of guideline-directed medical therapies in patients with diabetes and chronic kidney disease from the CURE-CKD Registry, 2019-2020. Diabetes Obes Metab 2023; 25:2970-2979. [PMID: 37395334 DOI: 10.1111/dom.15194] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 05/23/2023] [Accepted: 06/05/2023] [Indexed: 07/04/2023]
Abstract
AIM Guideline-directed medical therapy (GDMT) is designed to improve clinical outcomes. The study aim was to assess GDMT prescribing rates and prescribing-persistence predictors in patients with diabetes and chronic kidney disease (CKD) from the Center for Kidney Disease Research, Education, and Hope Registry. MATERIALS AND METHODS Data were obtained from adults ≥18 years old with diabetes and CKD between 1 January 2019 and 31 December 2020 (N = 39 158). Baseline and persistent (≥90 days) prescriptions for GDMT, including angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB), sodium-glucose cotransporter-2 (SGLT2) inhibitor and glucagon-like peptide 1 (GLP-1) receptor agonist were assessed. RESULTS The population age (mean ± SD) was 70 ± 14 years, and 49.6% (n = 19 415) were women. Baseline estimated glomerular filtration rate (2021 CKD-Epidemiology Collaboration creatinine equation) was 57.5 ± 23.0 ml/min/1.73 m2 and urine albumin/creatinine 57.5 mg/g (31.7-158.2; median, interquartile range). Baseline and ≥90-day persistent prescribing rates, respectively, were 70.7% and 40.4% for ACE inhibitor/ARB, 6.0% and 5.0% for SGLT2 inhibitors, and 6.8% and 6.3% for GLP-1 receptor agonist (all p < .001). Patients lacking primary commercial health insurance coverage were less likely to be prescribed an ACE inhibitor/ARB [odds ratio (OR) = 0.89; 95% confidence interval (CI) 0.84-0.95; p < .001], SGLT2 inhibitor (OR 0.72; 95% CI 0.64-0.81; p < .001) or GLP-1 receptor agonist (OR 0.89; 95% CI 0.80-0.98; p = .02). GDMT prescribing rates were lower at Providence than UCLA Health. CONCLUSIONS Prescribing for GDMT was suboptimal and waned quickly in patients with diabetes and CKD. Type of primary health insurance coverage and health system were associated with GDMT prescribing.
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Affiliation(s)
- Susanne B Nicholas
- Nephrology Division, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Kenn B Daratha
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
| | - Radica Z Alicic
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
- Department of Medicine, University of Washington, Seattle, Spokane, Washington, USA
| | - Cami R Jones
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
| | - Lindsey M Kornowske
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
| | - Joshua J Neumiller
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
- Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA
| | | | | | - Rakesh Singh
- Bayer US, LLC, Medical Affairs, Whippany, Whippany, USA
| | - Keith C Norris
- Nephrology Division, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Katherine R Tuttle
- Providence Medical Research Center, Providence Inland Northwest, Spokane, Washington, USA
- Department of Medicine, University of Washington, Seattle, Spokane, Washington, USA
- Kidney Research Institute, Institute of Translational Health Sciences, University of Washington, Seattle, Washington, USA
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18
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Costa D, Patella G, Provenzano M, Ielapi N, Faga T, Zicarelli M, Arturi F, Coppolino G, Bolignano D, De Sarro G, Bracale UM, De Nicola L, Chiodini P, Serra R, Andreucci M. Hyperkalemia in CKD: an overview of available therapeutic strategies. Front Med (Lausanne) 2023; 10:1178140. [PMID: 37583425 PMCID: PMC10424443 DOI: 10.3389/fmed.2023.1178140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/10/2023] [Indexed: 08/17/2023] Open
Abstract
Hyperkalemia (HK) is a life-threatening condition that often occurs in patients with chronic kidney disease (CKD). High serum potassium (sKsK) is responsible for a higher risk of end-stage renal disease, arrhythmias and mortality. This risk increases in patients that discontinue cardio-nephroprotective renin-angiotensin-aldosterone system inhibitor (RAASi) therapy after developing HK. Hence, the management of HK deserves the attention of the clinician in order to optimize the therapeutic strategies of chronic treatment of HK in the CKD patient. The adoption in clinical practice of the new hypokalaemic agents patiromer and sodium zirconium cyclosilicate (SZC) for the prevention and chronic treatment of HK could allow patients, suffering from heart failure and chronic renal failure, to continue to benefit from RAASi therapy. We have updated a narrative review of the clear variables, correct definition, epidemiology, pathogenesis, etiology and classifications for HK among non-dialysis CKD (ND CKD) patients. Furthermore, by describing the prognostic impact on mortality and on the progression of renal damage, we want to outline the strategies currently available for the control of potassium (K+) plasma levels.
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Affiliation(s)
- Davide Costa
- Department of Law, Economics and Sociology, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Gemma Patella
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Michele Provenzano
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Nicola Ielapi
- Department of Public Health and Infectious Disease, Sapienza University of Rome, Rome, Italy
| | - Teresa Faga
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Mariateresa Zicarelli
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Franco Arturi
- Unit of Internal Medicine, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Giuseppe Coppolino
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
| | - Davide Bolignano
- Renal Unit, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | | | | | - Luca De Nicola
- Renal Unit, University of Campania “LuigiVanvitelli”, Naples, Italy
| | - Paolo Chiodini
- Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Raffaele Serra
- Unit of Vascular Surgery, Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy
| | - Michele Andreucci
- Renal Unit, Department of Health Sciences, “Magna Graecia” University of Catanzaro, Catanzaro, Italy
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Giannese D, D'Alessandro C, Pellegrino N, Panichi V, Cupisti A. RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients. Nutrients 2023; 15:nu15112454. [PMID: 37299418 DOI: 10.3390/nu15112454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 05/10/2023] [Accepted: 05/19/2023] [Indexed: 06/12/2023] Open
Abstract
The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3-4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = -0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.
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Affiliation(s)
- Domenico Giannese
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Claudia D'Alessandro
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Nicola Pellegrino
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Vincenzo Panichi
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
| | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
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20
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Clinical impact of suboptimal RAASi therapy following an episode of hyperkalemia. BMC Nephrol 2023; 24:18. [PMID: 36658531 PMCID: PMC9854063 DOI: 10.1186/s12882-022-03054-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 12/28/2022] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Hyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD. METHODS This observational study utilized data from hospital records, claims, and health registers from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode. RESULTS A total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p < 0.001) and in Japan (19.7, 20.0, and 15.1%; p < 0.001). CONCLUSION HK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.
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21
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Vart P, Vaduganathan M, Jongs N, Remuzzi G, Wheeler DC, Hou FF, McCausland F, Chertow GM, Heerspink HJL. Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes. Clin J Am Soc Nephrol 2022; 17:1754-1762. [PMID: 36414316 PMCID: PMC9718016 DOI: 10.2215/cjn.08900722] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 10/19/2022] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Despite high rates of complications in patients with CKD without diabetes, the implementation of proven therapies in this group remains low. Expressing the clinical benefit of a therapy in terms of extra years free from the disease or death may facilitate implementation. We estimated lifetime survival free of kidney failure for patients with albuminuric CKD without diabetes treated with the combination therapy of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors relative to patients not treated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used trial-level estimates of the effect of treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ramipril/benazepril; n=690) and SGLT2 inhibitors (dapagliflozin; n=1398) compared with placebo to derive the effect of combination therapy versus no treatment. Using this effect, we estimated treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (n=697) and projected eventfree and overall survival for those treated and not treated with combination therapy. We also performed our calculations anticipating lower adherence and less pronounced benefits than were observed in the clinical trials. The primary outcome was a composite of doubling of serum creatinine, kidney failure, or death. RESULTS The aggregate estimated hazard ratio comparing combination therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor versus no treatment for the primary end point was 0.35 (95% confidence interval, 0.30 to 0.41). For a 50-year-old patient until the age of 75 years, the estimated survival free from the primary composite end point was 17.0 (95% confidence interval, 12.4 to 19.6) years with the combination therapy and 9.6 years (95% confidence interval, 8.4 to 10.7) with no treatment with any of these agents, corresponding to a gain in eventfree survival of 7.4 (95% confidence interval, 6.4 to 8.7) years. When assuming lower adherence and less pronounced efficacy of combination therapy, the gain in eventfree survival ranged from 5.3 years (95% confidence interval, 4.4 to 6.1) to 5.8 years (95% confidence interval, 4.8 to 6.8). CONCLUSIONS Treatment with the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor in patients with albuminuric CKD without diabetes is expected to substantially increase kidney failure-free survival. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Benazepril for Advanced Chronic Renal Insufficiency, NCT00270426, and a Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (Dapa-CKD), NCT03036150.
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Affiliation(s)
- Priya Vart
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Muthiah Vaduganathan
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Niels Jongs
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Giuseppe Remuzzi
- Mario Negri Institute for Pharmacological Research, Bergamo, Italy
| | - David C Wheeler
- Department of Renal Medicine, University of College London Medical School, London, United Kingdom
| | - Fan Fan Hou
- Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, Guangzhou, China
| | - Finnian McCausland
- Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
| | - Glenn M Chertow
- Department of Medicine (Nephrology), Stanford University, Palo Alto, California
- Department of Epidemiology and Population Health, Stanford University, Palo Alto, California
| | - Hiddo J L Heerspink
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- The George Institute for Global Health, Sydney, New South Wales, Australia
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22
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Pecoits-Filho R, McCullough K, Muenz D, Quinn CM, Budden J, Golden J, de Arellano AR, Tillmann FP, Duttlinger J, Calice-Silva V, Massy ZA, Bieber B, Robinson BM, Fliser D, Reichel H. Patiromer utilization in patients with advanced chronic kidney disease under nephrology care in Germany. Clin Kidney J 2022; 16:176-183. [PMID: 36726438 PMCID: PMC9871846 DOI: 10.1093/ckj/sfac209] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Indexed: 02/04/2023] Open
Abstract
Background Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3-5 patients starting patiromer. Methods Duration of patiromer use was estimated by Kaplan-Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin-angiotensin-aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. Results We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%-82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Conclusion Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation.
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Affiliation(s)
| | | | - Daniel Muenz
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | | | | | | | | | - Frank-Peter Tillmann
- Department of Medicine I – Nephrology, Transplantation & Medical Intensive Care, University Witten/Herdecke, Medical Center Cologne-Merheim, Cologne, Germany
| | | | | | - Ziad A Massy
- Department of Nephrology, CHU Ambroise Paré, APHP, Boulogne, France,Center for Research in Epidemiology and Population Health (CESP), University Paris Saclay, University Versailles Saint-Quentin en Yvelines, National Institute of Health, Clinical Epidemiology Team, Villejuif, France,Division of Nephrology, Ambroise Paré Universitry Hospital, APHP, Paris, France
| | - Brian Bieber
- Arbor Research Collaborative for Health, Ann Arbor, MI, USA
| | | | - Danilo Fliser
- Saarland University Medical Centre, Homburg, Germany
| | - Helmut Reichel
- Nephrological Center, Villingen-Schwenningen, Baden-Württemberg, Germany
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23
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Alencar de Pinho N, Henn L, Raina R, Reichel H, Lopes AA, Combe C, Speyer E, Bieber B, Robinson BM, Stengel B, Pecoits-Filho R. Understanding International Variations in Kidney Failure Incidence and Initiation of Replacement Therapy. Kidney Int Rep 2022; 7:2364-2375. [DOI: 10.1016/j.ekir.2022.08.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/22/2022] [Indexed: 10/14/2022] Open
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Cost-Effectiveness of Treating Patients with Chronic Kidney Disease and Prior Hyperkalemia with Renin-Angiotensin-Aldosterone System Inhibitor and Patiromer: A Swiss Public Healthcare Perspective. Adv Ther 2022; 39:2717-2730. [PMID: 35416597 PMCID: PMC9122858 DOI: 10.1007/s12325-022-02123-3] [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: 01/20/2022] [Accepted: 03/10/2022] [Indexed: 11/01/2022]
Abstract
INTRODUCTION Hyperkalemia is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). Patiromer (Veltassa®) is an oral potassium binder indicated for the treatment of hyperkalemia in adults. We evaluated the impact of patiromer on the Swiss healthcare resources when used in patients with CKD and hyperkalemia who were on renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. METHODS We built a decision tree and calculated the number needed to treat (NNT) to prevent hyperkalemia, hospitalization, and death based on published aggregated data. The decision tree was populated with available data from relevant patiromer clinical trials and data were applied to create a simple model showing the expected effectiveness of adding patiromer to the treatment of patients with medium-to-severe stage CKD on RAASi compared to RAASi only. Adapting the model to the Swiss healthcare system allowed us to estimate the impact of the new treatment on healthcare expenditures from a payer as well as a Swiss public healthcare perspective. RESULTS Patiromer reduced the absolute risk for recurrent hyperkalemia by 48% within 8 weeks, resulting in an NNT of 2.1 [95% CI 1.4, 3.7]. If one assumes that 90%, 50%, or 10% of all moderate-to-severe hyperkalemic events lead to hospitalization, the NNT to prevent one hospitalization would be 2.5, 4.4, and 22.2, respectively. On the basis of the death rate of patients with mild or moderate-to-severe hyperkalemia, and the prevalence of mild or moderate-to-severe hyperkalemia in the treatment and control groups, the NNT was 78.7 [95% CI 64.0, 99.3] to prevent one death. Patiromer resulted in expected cost offsets of CHF 303 (1 CHF = 0.95 EUR as of 2022) per patient over 8 weeks in Switzerland. CONCLUSION Patiromer used for the treatment of CKD reduces hyperkalemia recurrence leading to improved patient care. This results in substantial offset costs for the Swiss healthcare system.
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25
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Guedes M, Pecoits-Filho R. Can we cure diabetic kidney disease? Present and future perspectives from a nephrologist's point of view. J Intern Med 2022; 291:165-180. [PMID: 34914852 DOI: 10.1111/joim.13424] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide, contributing to a great burden across a variety of patient-reported and clinical outcomes. New interventions for DKD management have been established in recent years, unleashing a novel paradigm, in which kidney-dedicated trials yield informative and robust data to guide optimal clinical management. After unprecedented results from groundbreaking randomized controlled trials were released, a new scenario of evidence-based recommendations has evolved for the management of diabetic patients with CKD. The current guidelines place great emphasis on multidimensional and interdisciplinary approaches, but the challenges of implementation are just starting and will be pivotal to optimize clinical results and to understand the new threshold for residual risk in DKD. We thereby provide an updated review on recent advances in DKD management based on new guideline recommendations, summarizing recent evidence while projecting the landscape for innovative ongoing initiatives in the field. Specifically, we review current insights on the natural history, epidemiology, pathogenesis, and therapeutics of DKD, mapping the new scientific information into the recently released Kidney Disease - Improving Global Outcomes Guidelines translating results from major novel randomized controlled trials to the clinical practice. Additionally, we approach the landscape of new therapeutics in the field, summarizing ongoing phase IIb and III trials focused on DKD. Finally, reflecting on the past and looking into the future, we highlight unmet needs in the current DKD management based on real-world evidence and offer a nephrologist's perspective into the challenge of fostering continuous improvement on clinical and patient-reported outcomes for individuals living with DKD.
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Affiliation(s)
- Murilo Guedes
- School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Parana, Brazil
| | - Roberto Pecoits-Filho
- School of Medicine, Pontificia Universidade Catolica do Parana, Curitiba, Parana, Brazil.,DOPPS Program Area, Arbor Research Collaborative for Health, Ann Arbor, Michigan, USA
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26
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Agiro A, Duling I, Eudicone J, Davis J, Brahmbhatt YG, Cooper K. The prevalence of predialysis hyperkalemia and associated characteristics among hemodialysis patients: The RE-UTILIZE study. Hemodial Int 2022; 26:397-407. [PMID: 35037388 PMCID: PMC9543597 DOI: 10.1111/hdi.13006] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 11/30/2022]
Abstract
Introduction Hyperkalemia (HK), defined as serum potassium (K+) >5.0 mEq/L, is an independent predictor of mortality in patients on maintenance hemodialysis (HD). This study investigated the annual prevalence of HK and examined patient characteristics potentially associated with a higher annual HK prevalence. Methods This retrospective observational cohort study used Dialysis Outcomes and Practice Patterns Study (DOPPS) survey data from US patients undergoing in‐center HD thrice weekly from 2018 to 2019. The primary endpoint was the proportion of patients with any predialysis HK (K+ >5.0 mEq/L) within 1 year from the index date (date of DOPPS enrollment), using the first hyperkalemic K+ value. Secondary endpoints were the proportion of patients with moderate‐to‐severe (K+ >5.5 mEq/L) or severe (K+ >6.0 mEq/L) HK. Findings Overall, 9347 patients on HD were included in this analysis (58% male and 49% aged >66 years). Any predialysis HK (K+ >5.0 mEq/L) occurred in 74% of patients within 1 year of the index date, 52% within 3 months, and 38% within 1 month. The annual prevalence of moderate‐to‐severe and severe HK was 43% and 17%, respectively. Recurrent HK (at least two K+ >5.0 mEq/L within 1 year) occurred in 60% of patients, and 2.8% of patients were prescribed an oral K+ binder. Multivariable logistic regression analysis showed younger age, female sex, Hispanic ethnicity, and renin–angiotensin–aldosterone system inhibitor use were significantly associated with a higher annual prevalence of any predialysis HK, while Black race, obesity, recent initiation of HD, and dialysate K+ bath concentration ≥3 mEq/L were associated with a lower prevalence of HK. Discussion The annual prevalence of predialysis HK and recurrence were high among US patients on HD, whereas oral K+ binder use was low. Further studies are needed to understand the impact of dialysate K+ bath concentrations on predialysis HK among patients on HD.
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27
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Hecking M, Tu C, Zee J, Bieber B, Hödlmoser S, Reichel H, Sesso R, Port FK, Robinson BM, Carrero JJ, Tong A, Combe C, Stengel B, Pecoits-Filho R. Sex-Specific Differences in Mortality and Incident Dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study. Kidney Int Rep 2021; 7:410-423. [PMID: 35257054 PMCID: PMC8897674 DOI: 10.1016/j.ekir.2021.11.018] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/18/2021] [Accepted: 11/15/2021] [Indexed: 11/20/2022] Open
Abstract
Introduction More men than women start kidney replacement therapy (KRT) although the prevalence of chronic kidney disease (CKD) is higher in women than men. We therefore aimed at analyzing sex-specific differences in clinical outcomes among 8237 individuals with CKD in stages 3 to 5 from Brazil, France, Germany, and the United States participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps). Methods Fine and Gray models, evaluating the effect of sex on time to events, were adjusted for age, Black race (model A); plus diabetes, cardiovascular disease, albuminuria (model B); plus estimated glomerular filtration rate (eGFR) slope during the first 12 months after enrollment and first eGFR after enrollment (model C). Results There were more men than women at baseline (58% vs. 42%), men were younger than women, and men had higher eGFR (28.9 ± 11.5 vs. 27.0 ± 10.8 ml/min per 1.73 m2). Over a median follow-up of 2.7 and 2.5 years for men and women, respectively, the crude dialysis initiation and pre-emptive transplantation rates were higher in men whereas that of pre-KRT death was more similar. The adjusted subdistribution hazard ratios (SHRs) between men versus women for dialysis were 1.51 (1.27–1.80) (model A), 1.32 (1.10–1.59) (model B), and 1.50 (1.25–1.80) (model C); for pre-KRT death, were 1.25 (1.02–1.54) (model A), 1.14 (0.92–1.40) (model B), and 1.15 (0.93–1.42) (model C); for transplantation, were 1.31 (0.73–2.36) (model A), 1.44 (0.76–2.74) (model B), and 1.53 (0.79–2.94) (model C). Conclusion Men had a higher probability of commencing dialysis before death, unexplained by CKD progression alone. Although the causal mechanisms are uncertain, this finding helps interpret the preponderance of men in the dialysis population.
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Villain C, Metzger M, Liabeuf S, Hamroun A, Laville S, Mansencal N, Combe C, Fouque D, Frimat L, Jacquelinet C, Laville M, Ayav C, Briançon S, Pecoits-Filho R, Hannedouche T, Stengel B, Massy ZA. Effectiveness and Tolerance of Renin-Angiotensin System Inhibitors With Aging in Chronic Kidney Disease. J Am Med Dir Assoc 2021; 23:998-1004.e7. [PMID: 34856172 DOI: 10.1016/j.jamda.2021.10.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 10/22/2021] [Accepted: 10/23/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Renin-angiotensin system inhibitors (RASi) are recommended for slowing chronic kidney disease (CKD) progression to kidney failure. Their effectiveness and tolerance as patients age remain uncertain because older patients have often been excluded from clinical trials. DESIGN CKD-REIN cohort study. SETTING AND PARTICIPANTS We studied 2762 patients with CKD stages 3 and 4 and a clinical indication for RASi enrolled between 2013 and 2016 in 40 nephrology clinics nationally representative in France. METHODS The primary outcome was the occurrence of kidney failure or death. The secondary outcomes were the occurrence of cardiovascular events and hospitalizations with acute kidney injury (AKI) or hyperkalemia. A propensity score analysis was performed. We used Cox models to estimate hazard ratios (HRs) for each outcome associated with RASi prescription and tested interactions with age. RESULTS Patients' mean age was 67 years, including 841 (30%) aged 75 years and older; 2178 (79%) were prescribed RASi's. During a median follow-up of 4.6 years, 33% of patients reached kidney failure or died. RASi prescription was associated with a lower risk of kidney failure or death (HR 0.79, 95% CI 0.66, 0.95), an association not modified by age (P for interaction = .72). It was not significantly associated with cardiovascular events. During the first 3 years of follow-up, 14% of patients were hospitalized with AKI or hyperkalemia, but risk was not higher among those prescribed RASi's (HR 0.75, 95% CI 0.55-1.02) and age did not modify its effect (P for interaction = .28). CONCLUSIONS AND IMPLICATIONS This study shows that aging does not appear to modify either RASi's beneficial effects on major CKD outcomes or their potential adverse effects.
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Affiliation(s)
- Cédric Villain
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Gériatrie, CHU de Caen, Normandie Université UNICAEN, Caen, France.
| | - Marie Metzger
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Sophie Liabeuf
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Pharmacologie Clinique, Département de Recherche Clinique, CHU d'Amiens, Université de Picardie Jules Verne, INSERM U-1088, Amiens, France
| | - Aghilès Hamroun
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Solene Laville
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Nicolas Mansencal
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Cardiologie, CHU Ambroise Paré, APHP, Boulogne-Billancourt, Université de Versailles-Saint Quentin (UVSQ), France
| | - Christian Combe
- Service de Néphrologie Transplantation Dialyse Aphérèses, CHU de Bordeaux, Bordeaux, France; INSERM Unité 1026, Université de Bordeaux, Bordeaux, France
| | - Denis Fouque
- Université de Lyon, Service de Néphrologie, CarMeN INSERM 1060, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Luc Frimat
- Service de Néphrologie, Université de Lorraine, APEMAC, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | - Christian Jacquelinet
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Agence de Biomédecine, La Plaine Saint-Denis, France
| | - Maurice Laville
- Université de Lyon, Service de Néphrologie, CarMeN INSERM 1060, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
| | - Carole Ayav
- CIC 1433 Epidémiologie Clinique, INSERM, CHRU, Université de Lorraine, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | - Serge Briançon
- CIC 1433 Epidémiologie Clinique, INSERM, CHRU, Université de Lorraine, CHRU de Nancy-Hôpitaux de Brabois, Nancy, France
| | | | - Thierry Hannedouche
- Service de Néphrologie-Hémodialyse, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine de Strasbourg, Strasbourg, France
| | - Bénédicte Stengel
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France
| | - Ziad A Massy
- Université Paris-Saclay, UVSQ, Inserm, Clinical Epidemiology Team, CESP (Centre de recherche en Epidémiologie et Santé des Populations), Villejuif, France; Service de Néphrologie-Dialyse, CHU Ambroise Paré, APHP, Boulogne-Billancourt, France
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Rossignol P, Agarwal R. Should renin-angiotensin-aldosterone system inhibition enablement be a therapeutic target in CKD patients? Nephrol Dial Transplant 2021; 36:1771-1772. [PMID: 33677569 DOI: 10.1093/ndt/gfab061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Patrick Rossignol
- Université de Lorraine, INSERM, Centre d'Investigations Cliniques-Plurithématique 14-33, and INSERM U1116, CHRU de Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Rajiv Agarwal
- Department of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN, USA
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Chu L, Fuller M, Jervis K, Ciaccia A, Abitbol A. Prevalence of Chronic Kidney Disease in Type 2 Diabetes: The Canadian REgistry of Chronic Kidney Disease in Diabetes Outcomes (CREDO) Study. Clin Ther 2021; 43:1558-1573. [PMID: 34426012 DOI: 10.1016/j.clinthera.2021.07.015] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 07/08/2021] [Accepted: 07/15/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an elevated risk of end-stage kidney disease, cardiovascular disease (CVD), and death. As the breadth of treatment options for CKD in patients with T2D (CKD in T2D) continues to expand, an analysis of the current use of therapies and cardiovascular and kidney outcomes is necessary. The objectives of the study were to assess the prevalence of CKD in T2D among a contemporary cohort of patients, to describe patient characteristics and treatment patterns, and to examine health care practitioner rationale for initiating therapies. METHODS The study was a retrospective, observational study (module A) with a prospective component (module B). For module A, sociodemographic data, medical history, prescription information, and laboratory investigations for patients seen by an endocrinologist in 2019 were retrieved from the LMC Diabetes Registry. Module B included a subset of patients for health care practitioner surveys to understand rationale for administering angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs), steroidal mineralocorticoid receptor antagonists (MRAs), sodium-glucose cotransporter 2 inhibitors (SGLT2is), and glucagon-like peptide 1 receptor agonists (GLP-1RAs). Descriptive analyses were conducted. FINDINGS The study included 14,873 patients (59% male). Mean patient age was 67 years, mean body mass index was 31 kg/m2, and mean glycosylated hemoglobin was 7.6%. Mean diabetes duration was 16 years. The prevalence of CKD in patients with T2D was 47.9%. Common comorbidities were hypertension (76%), dyslipidemia (71%), and obesity (51%). CVD was reported in 22%. The proportion of kidney medications and emerging therapies varied, with 76% of patients using an ACEi or ARB, 48% using an SGLT2i, 30% using a GLP-1RA, and 3% using a steroidal MRA. In module B, physicians identified that ACEis/ARBs, SGLT2is, GLP-1RAs, or steroidal MRAs were administered to primarily treat CKD in 33%, 12%, 0%, and 4% of the patients (n = 500), respectively. IMPLICATIONS These findings improved our understanding of the current landscape and treatment patterns of CKD inT2D and highlighted the importance of considering treatments that will provide a comprehensive strategy for cardiovascular and kidney risk protection. Despite the high prevalence of CKD and comorbidities reported in a large, Canadian T2D specialist population, ACEis/ARBs, SGLT2is, and GLP-1RAs were underused, especially considering recent clinical trial reports. The relative use of steroidal MRAs was expectedly low. With an immense burden of CKD progression and among patients with T2D, the use of treatments that provide a comprehensive strategy for kidney protection will transform the landscape of CKD in T2D. ClinicalTrials.gov identifier: NCT04445181.
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Affiliation(s)
- Lisa Chu
- LMC Diabetes & Endocrinology, Toronto, Ontario, Canada
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Heart Failure and Chronic Kidney Disease Patients: First It Is Necessary to Act. J Am Coll Cardiol 2021; 78:344-347. [PMID: 34294270 DOI: 10.1016/j.jacc.2021.05.027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 05/13/2021] [Accepted: 05/14/2021] [Indexed: 11/23/2022]
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Loutradis C, Price A, Ferro CJ, Sarafidis P. Renin-angiotensin system blockade in patients with chronic kidney disease: benefits, problems in everyday clinical use, and open questions for advanced renal dysfunction. J Hum Hypertens 2021; 35:499-509. [PMID: 33654237 DOI: 10.1038/s41371-021-00504-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/23/2021] [Accepted: 02/03/2021] [Indexed: 01/13/2023]
Abstract
Management of hypertension and albuminuria are considered among the primary goals of treatment to slow the progression of chronic kidney disease (CKD). Renin-angiotensin system (RAS) blockers, i.e., angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are the main drugs to achieve these goals. Seminal studies have showed that RAS blockers present significant renoprotective effects in CKD patients with very high albuminuria. In post hoc analyses of such trials, these renoprotective effects appeared more robust in patients with more advanced CKD. However, randomized trials specifically addressing whether RAS blockers should be initiated or maintained in patients with advanced CKD are scarce and do not include subjects with normoalbuminuria, thus, many clinicians are unconvinced for the beneficial effects of RAS blockade in these patients. Further, the fear of hyperkalemia or acute renal decline is another factor due to which RAS blockers are usually underprescribed and are easily discontinued in patients with more advanced CKD; i.e., those in Stages 4 and 5. This review summarizes evidence from the literature regarding the use of RAS blockers in patients with advanced CKD.
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Affiliation(s)
- Charalampos Loutradis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | - Anna Price
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Charles J Ferro
- Department of Renal Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Pantelis Sarafidis
- Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review. Adv Ther 2021; 38:180-200. [PMID: 33231861 PMCID: PMC7854398 DOI: 10.1007/s12325-020-01568-8] [Citation(s) in RCA: 89] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Accepted: 11/10/2020] [Indexed: 12/19/2022]
Abstract
Introduction The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories. Methods MEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality. Results The review included ten observational studies with 3033 to 46,949 participants, conducted in the USA, China, France, Italy and Spain. The most frequently reported outcome was the prevalence of CKD (GFR categories G3–5), ranging from 2% to 17%. Most participants were normoalbuminuric, with 0.4–3.2% macroalbuminuric, and most fell within the KDIGO 2012 low-risk or moderate-risk groups, with 0.9–5.6% in the high-risk and 0.3–4.8% in the very high-risk groups. Although scarce, data on the prevalence of comorbidities in CKD according to the KDIGO classification suggest that they increase with albuminuria severity. Conclusions Patients with CKD frequently have complications, but only a small proportion have severely increased albuminuria or fall within the KDIGO high-risk or very high-risk groups. These groups, however, are associated with the highest burden of disease, as comorbidities are more prevalent with increasing albuminuria severity. New studies framed by the KDIGO 2012 classification are needed to address key gaps in the understanding of CKD burden and outcomes. Electronic supplementary material The online version of this article (10.1007/s12325-020-01568-8) contains supplementary material, which is available to authorized users.
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D'Alessandro C, Cumetti A, Pardini E, Mannucci C, Serio P, Morganti R, Cupisti A. Prevalence and correlates of hyperkalemia in a renal nutrition clinic. Intern Emerg Med 2021; 16:125-132. [PMID: 32382848 DOI: 10.1007/s11739-020-02353-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 04/21/2020] [Indexed: 12/18/2022]
Abstract
Hyperkalemia (HK) is a frequent complication of chronic kidney disease (CKD). Vegetable-based renal diets are considered at risk due to the high potassium (K) content. The aim of this study was to describe the prevalence and correlates of chronic hyperkalemia (HK) in CKD patients on nutritional care, and in particular, the risk of HK in patients on plant-based versus animal-based low-protein diets. We recruited adult patients affected by CKD not on dialysis, afferent to our renal nutrition clinic from November 2014 to May 2019. We evaluated a total of 870 accesses in 219 patients (172 m, 47 f, age 67 ± 13 years). HK was defined as mild when K serum level was 5.1-5.9 mEq/l, moderate when K serum level was 6.0-6.9 mEq/l, and severe HK when K serum level was ≥ 7 mEq/l. Biochemical, anthropometric data and medications were recorded. The prevalence of HK in all the renal nutrition visits was 26.1%; all but six cases were mild HK, whereas no severe HK was observed. The prevalence of HK was associated with decreased eGFR, up to 36.5% for eGFR < 20 ml/min. Medications were similar in hyperkalemic and normokalemic patients, RAASi being present in up to 85% of patients. In a follow-up of 40 ± 14 months, no association was found between HK and mortality, whereas HK, at the start of follow-up, showed a trend to increased ESRD risk. Serum potassium levels and prevalence of HK were not different between patients on animal-based low-protein diet and plant-based low-protein diet. In conclusion, chronic HK is quite prevalent in a renal nutrition clinic, especially when eGFR falls down below 60 ml/min, thereby reaching the highest prevalence in CKD stage 4. Hyperkalemia is mostly mild, being moderate to severe HK quite infrequent. Hyperkalemia was not associated with higher risk of mortality, whereas a trend, although not statistically significant, was observed for lower ESRD-free survival. Plant-based low-protein diet is not associated with significant higher prevalence of HK with respect to animal-based LPD at the same residual kidney function.
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Affiliation(s)
- Claudia D'Alessandro
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Andrea Cumetti
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Erica Pardini
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Claudia Mannucci
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | - Piera Serio
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy
| | | | - Adamasco Cupisti
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy.
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Adherence to the Kidney Disease: Improving Global Outcomes CKD Guideline in Nephrology Practice Across Countries. Kidney Int Rep 2020; 6:437-448. [PMID: 33615069 PMCID: PMC7879121 DOI: 10.1016/j.ekir.2020.11.039] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 11/11/2020] [Accepted: 11/30/2020] [Indexed: 01/13/2023] Open
Abstract
Introduction The uptake of the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 chronic kidney disease (CKD) Guideline is not fully described in real-world nephrology practice across the world. Methods We used baseline data from the CKD Outcomes and Practice Patterns Study (2013-2017), a 4-country cohort of patients with estimated glomerular filtration rate <60 ml/min per 1.73 m2 recruited from national samples of nephrology clinics, to describe adherence to measures for monitoring and delaying CKD progression. Data were collected as in clinical practice, except laboratory measures per protocol in France. Results The mean age ranged from 65 years in Brazil to 72 years in Germany. Albuminuria (mostly proteinuria) was measured routinely in 36% to 43% of patients in Brazil, Germany, and the United States. Blood pressure control (≤140/90 mm Hg) ranged from 49% in France to 76% in Brazil; <40% of patients had blood pressure ≤130/80 mm Hg everywhere but Brazil (52%). More than 40% of nephrologists in Brazil reported a systolic blood pressure target ≤130 mm Hg for nondiabetic patients without proteinuria, but only 19% to 24% elsewhere. Prescription of renin-angiotensin aldosterone system inhibitors ranged from 52% in the United States to 81% in Germany. Dietary advice was more frequent for salt than protein intake; dietitian visits were uncommon. In nondiabetic patients, achievement of all 3 targets including blood pressure ≤130/80 mm Hg, renin-angiotensin aldosterone system inhibition, and dietary advice, ranged from 10% in the United States to 32% in Brazil; in treated diabetic patients, this ranged from 6% to 11% after including hemoglobin A1c target. Conclusion Adherence to recommendations to slow CKD progression is low in typical practice settings, and substantial variation among countries for some indicates opportunities for improvement.
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van Rijn MH, Alencar de Pinho N, Wetzels JF, van den Brand JA, Stengel B. Worldwide Disparity in the Relation Between CKD Prevalence and Kidney Failure Risk. Kidney Int Rep 2020; 5:2284-2291. [PMID: 33305122 PMCID: PMC7710841 DOI: 10.1016/j.ekir.2020.09.040] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 08/21/2020] [Accepted: 09/22/2020] [Indexed: 12/24/2022] Open
Abstract
Introduction The incidence of kidney replacement therapy (KRT) for kidney failure varies internationally much more than chronic kidney disease (CKD) prevalence. This ecologic study investigated the relation of CKD prevalence to KRT and mortality risks by world region. Methods We used data from Global Burden of Disease and KRT registries worldwide with linear models to estimate the percentages of variance in KRT incidence and all-cause mortality explained by age-adjusted prevalence of CKD stages 3 to 5, overall and by gender, in 61 countries classified in 3 regions: high income (n = 28), Eastern and Central Europe (n = 15), and other (n = 18). Results The incidence of KRT ranged from 89 to 378 per million population in high-income regions, 32 to 222 per million population in Central and Eastern Europe, and 22 to 493 per million population in the other region; age-adjusted CKD prevalence ranged from 5.5% to 10.4%, 7.6% to 13.7%, and 7.4% to 13.1%, respectively. The relation between these indicators was positive in high-income countries, negative in Central and Eastern Europe, and null in the other region. Age-adjusted CKD prevalence explained 40% of the variance in KRT incidence (P < 0.001) in high-income countries. The explained variance of age-adjusted mortality was close to 0 in high-income countries and positive at 19% (P = 0.10) in Central and Eastern Europe and at 11% (P = 0.17) in the other region. Results were consistent by gender. Conclusion This study raises awareness on the significant part of the gaps in KRT incidence across countries not explained by the number of individuals with CKD, even in high-income countries where access to KRT is not limited.
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Affiliation(s)
- Marieke H.C. van Rijn
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
- Université Paris-Saclay, Université de Versailles-Saint-Quentin-en-Yvelines, University Paris Sud, INSERM, Clinical Epidemiology Team, Centre for Research in Epidemiology and Population Health, Villejuif, France
| | - Natalia Alencar de Pinho
- Université Paris-Saclay, Université de Versailles-Saint-Quentin-en-Yvelines, University Paris Sud, INSERM, Clinical Epidemiology Team, Centre for Research in Epidemiology and Population Health, Villejuif, France
- Correspondence: Natalia Alencar de Pinho, Clinical Epidemiology Team, Centre for Research in Epidemiology and Population Health, INSERM U1018, 16, avenue Paul Vaillant Couturier, 94807 Villejuif, France.
| | - Jack F. Wetzels
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jan A.J.G. van den Brand
- Department of Nephrology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Benedicte Stengel
- Université Paris-Saclay, Université de Versailles-Saint-Quentin-en-Yvelines, University Paris Sud, INSERM, Clinical Epidemiology Team, Centre for Research in Epidemiology and Population Health, Villejuif, France
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Fu EL, Clase CM, Evans M, Lindholm B, Rotmans JI, Dekker FW, van Diepen M, Carrero JJ. Comparative Effectiveness of Renin-Angiotensin System Inhibitors and Calcium Channel Blockers in Individuals With Advanced CKD: A Nationwide Observational Cohort Study. Am J Kidney Dis 2020; 77:719-729.e1. [PMID: 33246024 DOI: 10.1053/j.ajkd.2020.10.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 10/15/2020] [Indexed: 01/09/2023]
Abstract
RATIONALE & OBJECTIVE It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy. STUDY DESIGN Observational study in the Swedish Renal Registry, 2007 to 2017. SETTINGS & PARTICIPANTS 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates<30mL/min/1.73m2 (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60mL/min/1.73m2) were evaluated. EXPOSURES RAS inhibitor versus CCB therapy initiation. OUTCOME Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke). ANALYTICAL APPROACH HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates. RESULTS Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs. LIMITATIONS Potential confounding by indication. CONCLUSIONS Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.
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Affiliation(s)
- Edouard L Fu
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
| | - Catherine M Clase
- Department of Medicine and Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada
| | - Marie Evans
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Bengt Lindholm
- Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
| | - Joris I Rotmans
- Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Friedo W Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Merel van Diepen
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden
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Senninger L, Abensur Vuillaume L, Frimat L, Girerd N, Lamiral Z, Rossignol P, Boivin JM. Dyskalemia: a management problem for students. Fundam Clin Pharmacol 2020; 35:473-484. [PMID: 33098726 DOI: 10.1111/fcp.12621] [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: 06/11/2020] [Revised: 09/17/2020] [Accepted: 10/13/2020] [Indexed: 11/28/2022]
Abstract
BACKGROUND Although dyskalemia is common, its management can be problematic for students and general practitioners, especially when it occurs in patients with heart and renal failure. The basic academic knowledge of general medicine students, who have often not yet encountered clinical situations of dyskalemia, remains unclear in this regard. OBJECTIVES The purpose of this study was to evaluate the knowledge and reflexive practices of general medicine students in regard to dyskalemia. METHODS A cross-sectional survey, based on a self-questionnaire, of all of the students enrolled in general medicine studies at the Faculty of Medicine at the University of Nancy (France) at the end of their degree. The students were asked questions pertaining to specific clinical situations. The answers were compared to the information provided in the medical curriculum as well as to the relevant European guidelines. RESULTS We collected 290 of the questionnaires (participation rate: 81.2%). The hyper- and hypokalemia thresholds considered pathological (3.5-5.0 mmol/L) were known by 78% and 67% of the students, respectively. The perception of danger in case of severe hypokalemia was underestimated by 62.7% of them. In most cases, the proposed management of hyperkalemia in heart and renal failure did not comply with the relevant guidelines. The students tended to favor permanent discontinuation of the administration of converting enzyme inhibitors (ACE) and/or mineralocorticoid receptor antagonists (MRA) without considering the need for their reintroduction (51.6%). Sodium polystyrene sulfate was frequently seen as an appropriate first-line treatment for hyperkalemia (45%). CONCLUSIONS The knowledge and competence of general medicine students appear to be lacking for hyperkalemia in heart and renal failure, and they are long way from full compliance with the relevant European guidelines. Exposure to complex clinical situations as part of the medical curriculum, therefore, seems essential to improve the way dyskalemia is managed in France.
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Affiliation(s)
| | - Laure Abensur Vuillaume
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France.,Emergency Departement, Regional Hospital Metz, Thionville, France
| | - Luc Frimat
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France
| | - Nicolas Girerd
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France
| | - Zohra Lamiral
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France
| | - Patrick Rossignol
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France
| | - Jean-Marc Boivin
- Inserm, Centre d'Investigations Cliniques- Plurithématique 14-33, and Inserm U1116, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Université de Lorraine, Vandoeuvre, France
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39
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Laville SM, Gras-Champel V, Moragny J, Metzger M, Jacquelinet C, Combe C, Fouque D, Laville M, Frimat L, Robinson BM, Stengel B, Massy ZA, Liabeuf S. Adverse Drug Reactions in Patients with CKD. Clin J Am Soc Nephrol 2020; 15:1090-1102. [PMID: 32611662 PMCID: PMC7409761 DOI: 10.2215/cjn.01030120] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 05/13/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVES Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR<60 ml/min per 1.73 m2, with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology. RESULTS Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m2, and 45% had eGFR<30 ml/min per 1.73 m2. Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR<30 versus ≥30 ml/min per 1.73 m2 (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4). CONCLUSIONS Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.
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Affiliation(s)
- Solène M Laville
- Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France
| | | | - Julien Moragny
- Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France
| | - Marie Metzger
- Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France
| | - Christian Jacquelinet
- Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France.,Renal Epidemiology and Information Network Registry, Biomedicine Agency, Saint Denis, France
| | - Christian Combe
- Department of Nephrology Transplantation Dialysis, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.,Inserm Unit 1026, University of Bordeaux Segalen, Bordeaux, France
| | - Denis Fouque
- Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, Pierre-Bénite, France
| | - Maurice Laville
- Nephrology Department, Centre Hospitalier Lyon Sud, Université de Lyon, Carmen, Pierre-Bénite, France
| | - Luc Frimat
- Nephrology Department, Centre Hospitalier Régional Universitaire de Nancy, Vandoeuvre-lès-Nancy, France.,Lorraine University, APEMAC, Vandoeuvre-lès-Nancy, France
| | | | - Bénédicte Stengel
- Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France
| | - Ziad A Massy
- Paris-Saclay University, Versailles Saint-Quentin-en-Yvelines University, National Institute of Health and Medical Research, Center for research in Epidemiology and Population Health (CESP), Clinical Epidemiology Team, Villejuif, France.,Division of Nephrology, Ambroise Paré University Hospital, Assistance publique - Hôpitaux de Paris, Boulogne-Billancourt/Paris, France
| | - Sophie Liabeuf
- Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.,MP3CV Laboratory, EA7517, University of Picardie Jules Verne, Amiens, France
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Abensur Vuillaume L, Rossignol P, Lamiral Z, Girerd N, Boivin JM. Hyperkalaemia and hypokalaemia outpatient management: a survey of 500 French general practitioners. ESC Heart Fail 2020; 7:2042-2050. [PMID: 32602236 PMCID: PMC7524073 DOI: 10.1002/ehf2.12834] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 05/15/2020] [Accepted: 05/27/2020] [Indexed: 12/15/2022] Open
Abstract
AIMS How general practitioners (GPs) manage dyskalaemia is currently unknown. This study aimed at describing GP practices regarding hypokalaemia or hyperkalaemia diagnosis and management in their outpatients. METHODS AND RESULTS A telephone survey was conducted among French GPs with a 20-item questionnaire (16 closed-ended questions and 12 open-ended questions) regarding their usual management of hypokalaemia or hyperkalaemia patients, both broadly and more specifically in patients with heart failure and/or chronic kidney disease and/or in patients treated with angiotensin-converting enzyme/angiotensin receptor blockers or mineralocorticoid receptor antagonists. We aimed to interview 500 GPs spread geographically throughout France. This descriptive survey results are presented as mean ± standard deviation (if normally distributed or as median and inter-quartile range if the distribution was skewed). Categorical variables are expressed as frequencies and proportions (%). A total of 500 GPs participated in the study. Dyskalaemia thresholds (for diagnosis and intervention) and management patterns were highly heterogeneous. The mean ± SD (range) potassium level leading to 'intervene' was 5.32 ± 0.34 mmol/L (4.5-6.5) for hyperkalaemia and 3.23 ± 0.34 mmol/L (2.0-6.5) for hypokalaemia. Potassium levels leading to refer the patient to the emergency department (ED) were 6.14 ± 0.55 (4.5-10) and 2.69 ± 0.42 mmol/L (1-4), respectively. Potassium binders (51-65%) or potassium supplements (67-74%) were frequently used to manage hyperkalaemia or hypokalaemia. GPs uncommonly referred their dyskalaemic patients to cardiologists or nephrologists (or to the emergency department, if the latter was deemed necessary owing to the severity of the dyskalaemia). We identified an association between the close vicinity of GP office from an ED and 'referring a heart failure patient' (19.2% with ED vs. 8.6% without ED) and referring a heart failure and chronic kidney disease patient on mineralocorticoid receptor antagonist (16.7% with ED vs. 9.3% without ED). Although the majority (67%) of GPs had an electrocardiogram on hand, it was rarely used (14%) in dyskalaemic patients. Subgroup analyses considering gender, age of the participating GPs, and high-income/low-income regions did not identify specific patterns regarding the multidimensional aspect of dyskalaemia management. CONCLUSIONS Owing to the considerable heterogeneity of French GP practices toward dyskalaemia diagnosis and management approaches, there is a likely need to standardize (potentially enabled by therapeutic algorithms) practices.
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Affiliation(s)
- Laure Abensur Vuillaume
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France.,Emergency Department, Centre Hospitalier Régional Metz-Thionville, Metz, France
| | - Patrick Rossignol
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Zohra Lamiral
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Nicolas Girerd
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
| | - Jean-Marc Boivin
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithématique 1433, and Inserm 1116 DCAC, CHRU, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France
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41
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Jitraknatee J, Ruengorn C, Nochaiwong S. Prevalence and Risk Factors of Chronic Kidney Disease among Type 2 Diabetes Patients: A Cross-Sectional Study in Primary Care Practice. Sci Rep 2020; 10:6205. [PMID: 32277150 PMCID: PMC7148316 DOI: 10.1038/s41598-020-63443-4] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Accepted: 03/31/2020] [Indexed: 12/11/2022] Open
Abstract
This cross-sectional study aimed to investigate the prevalence and risk factors of chronic kidney disease (CKD) among 1,096 primary care type 2 diabetes (T2DM) patients in northern Thailand between October 2016 and September 2017. CKD was defined as estimated glomerular rate filtration values of <60 mL/min/1.73 m2. Prevalence with confidence intervals across CKD advanced stages 3–5 were estimated. Factors associated with CKD were evaluated by multivariate logistic regression. The overall prevalence of CKD was 24.4% (21.9–27.0), with severities of 11.4% (9.7–13.4), 6.8% (5.5–8.5), 4.6% (3.5–6.0), and 1.6% (1.0–2.5) for stages 3 A, 3B, 4, and 5, respectively. Regarding age and glycaemic control, individuals older than 75 years and those with a haemoglobin A1c ≥ 8% had the highest prevalence of 61.3% (51.7–70.1) and 38.6% (34.3–43.2), respectively. The multivariable logistic regression model explained 87.3% of the probability of CKD. The six independent significant risk factors of CKD were older age, retinopathy, albuminuria, haemoglobin A1c ≥ 7%, anaemia, and uric acid>7.5 mg/dL. A relatively high prevalence of CKD, especially in older patients and those with diabetic complications-related to poor glycaemic control, was encountered in this primary care practice. Early identification may help to target optimise care and prevention programs for CKD among T2DM patients.
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Affiliation(s)
| | - Chidchanok Ruengorn
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.,Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Surapon Nochaiwong
- Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand. .,Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, 50200, Thailand.
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42
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Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 2020; 97:42-61. [DOI: 10.1016/j.kint.2019.09.018] [Citation(s) in RCA: 141] [Impact Index Per Article: 28.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 09/13/2019] [Accepted: 09/30/2019] [Indexed: 12/19/2022]
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Vidal-Petiot E, Greenlaw N, Kalra PR, Garcia-Moll X, Tardif JC, Ford I, Zamorano J, Ferrari R, Tendera M, Fox KM, Steg PG. Chronic Kidney Disease Has a Graded Association with Death and Cardiovascular Outcomes in Stable Coronary Artery Disease: An Analysis of 21,911 Patients from the CLARIFY Registry. J Clin Med 2019; 9:E4. [PMID: 31861379 PMCID: PMC7019870 DOI: 10.3390/jcm9010004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Revised: 12/11/2019] [Accepted: 12/13/2019] [Indexed: 12/01/2022] Open
Abstract
: Chronic kidney disease (CKD) is associated with an increased cardiovascular risk in a broad spectrum of populations. However, the risk associated with a reduced estimated glomerular filtration rate (eGFR) in patients with stable coronary artery disease receiving standard care in the modern era, independently of baseline cardiovascular disease, risk factors, and comorbidities, remains unclear. We analyzed data from 21,911 patients with stable coronary artery disease, enrolled in 45 countries between November 2009 and July 2010 in the CLARIFY registry. Patients with abnormal renal function were older, with more comorbidities, and received slightly lower-although overall high-rates of evidence-based secondary prevention therapies than patients with normal renal function. The event rate of patients with CKD stage 3b or more (eGFR <45 mL/min/1.73 m2) was much higher than that associated with any comorbid condition. In a multivariable adjusted Cox proportional hazards model, lower eGFR was independently associated with a graded increased risk of cardiovascular mortality, with adjusted HRs (95% CI) of 0.98 (0.81-1.18), 1.31 (1.05-1.63), 1.77 (1.38-2.27), and 3.12 (2.25-4.33) for eGFR 60-89, 45-59, 30-44, and <30 mL/min/1.73 m2, compared with eGFR ≥90 mL/min/1.73 m2. A strong graded independent relationship exists between the degree of CKD and cardiovascular mortality in this large cohort of patients with chronic coronary artery disease, despite high rates of secondary prevention therapies. Among clinical risk factors and comorbid conditions, CKD stage 3b or more is associated with the highest cardiovascular mortality.
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Affiliation(s)
- Emmanuelle Vidal-Petiot
- Université de Paris, Paris, France;
- Physiology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, 75018 Paris, France
- Institut nationale de la santé et de la recherché médicale (INSERM) U1149, Centre de Recherche sur l’Inflammation, 75018 Paris, France
| | - Nicola Greenlaw
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK; (N.G.); (I.F.)
| | - Paul R. Kalra
- Portsmouth Hospitals NHS Trust, Portsmouth PO6 3LY, UK;
| | | | - Jean-Claude Tardif
- Montreal Heart Institute, Université de Montreal, Montreal, QC H1T1C8, Canada;
| | - Ian Ford
- Robertson Centre for Biostatistics, University of Glasgow, Glasgow G12 8QQ, UK; (N.G.); (I.F.)
| | - Jose Zamorano
- University Hospital Ramon y Cajal, 28040 Madrid, Spain;
| | - Roberto Ferrari
- Centro Cardiologico Universitario di Ferrara, University of Ferrara, 44124 Cona, FE, Italy;
- Maria Cecilia Hospital, GVM Care & Research, 48033 Cotignola, RA, Italy
| | - Michal Tendera
- Department of Cardiology and Structural Heart Disease, School of Medicine in Katowice, Medical University of Silesia, 40-055 Katowice, Poland;
| | - Kim M. Fox
- National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London SW3 6NP, UK;
| | - Philippe Gabriel Steg
- Université de Paris, Paris, France;
- National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London SW3 6NP, UK;
- Cardiology Department, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, French Alliance for Cardiovascular Trials, INSERM U1148, 75018 Paris, France
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Pecoits‐Filho R, Fliser D, Tu C, Zee J, Bieber B, Wong MMY, Port F, Combe C, Lopes AA, Reichel H, Narita I, Stengel B, Robinson BM, Massy Z. Prescription of renin-angiotensin-aldosterone system inhibitors (RAASi) and its determinants in patients with advanced CKD under nephrologist care. J Clin Hypertens (Greenwich) 2019; 21:991-1001. [PMID: 31169352 PMCID: PMC6771881 DOI: 10.1111/jch.13563] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/24/2019] [Accepted: 05/05/2019] [Indexed: 01/09/2023]
Abstract
Renin-angiotensin-aldosterone system inhibitors (RAASi) are recommended for chronic kidney disease (CKD) patients. In this study, we describe RAASi prescription patterns in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps) in Brazil, Germany, France, and the United States (US). 5870 patients (mean age 66-72 years; congestive heart failure [CHF] in 11%-19%; diabetes in 43%-54%; serum potassium ≥5 in 20%-35%) were included. RAASi prescription was more common in Germany (80%) and France (77%) than Brazil (66%) and the United States (52%), where the prevalence of prescription decreases particularly in patients with CKD stage 5. In the multivariable regression model, RAASi prescription was least common in the United States and more common in patients who were younger, had diabetes, hypertension, or less advanced CKD. In conclusion, RAASi prescription patterns vary by country, and by demographic and clinical characteristics. RAASi appear to be underused, even among patients with strong class-specific recommendations. Although the reasons for this variation could not be fully identified in this cross-sectional observation, our data indicate that the risk of hyperkalemia may contribute to the underuse of this class of agents in moderate to advanced CKD.
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Affiliation(s)
- Roberto Pecoits‐Filho
- School of MedicinePontificia Universidade Catolica do ParanaCuritibaBrazil
- Arbor Research Collaborative for HealthAnn ArborMichigan
| | - Danilo Fliser
- Department of Internal Medicine IVSaarland University Medical CenterHomburgGermany
| | - Charlotte Tu
- Arbor Research Collaborative for HealthAnn ArborMichigan
| | - Jarcy Zee
- Arbor Research Collaborative for HealthAnn ArborMichigan
| | - Brian Bieber
- Arbor Research Collaborative for HealthAnn ArborMichigan
| | - Michelle M. Y. Wong
- Arbor Research Collaborative for HealthAnn ArborMichigan
- Department of MedicineUniversity of British ColumbiaVancouverCanada
| | - Friedrich Port
- Arbor Research Collaborative for HealthAnn ArborMichigan
- Department of Internal Medicine, Michigan Medicine, and Department of Epidemiology, School of Public HealthUniversity of MichiganAnn ArborMichigan
| | - Christian Combe
- Service de Néphrologie Transplantation DialyseCentre Hospitalier Universitaire de BordeauxBordeauxFrance
| | - Antonio A. Lopes
- Faculdade de Medicina da Bahia School of MedicineUniversidade Federal da BahiaBrazil
| | | | - Ichiei Narita
- Division of Clinical Nephrology and RheumatologyNiigata University Graduate School of Medical and Dental ScienceNiigataJapan
| | - Benedicte Stengel
- CESP, Center for Research in Epidemiology and Population HealthUniversity Paris‐Saclay, University Paris‐Sud, UVSQVillejuifFrance
| | | | - Ziad Massy
- CESP, Center for Research in Epidemiology and Population HealthUniversity Paris‐Saclay, University Paris‐Sud, UVSQVillejuifFrance
- Division of NephrologyAmbroise Paré University Hospital, APHPBoulogneBillancourt/ParisFrance
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