Ambient heat exposure and kidney function in patients with chronic kidney disease: a post-hoc analysis of the DAPA-CKD trial.

Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101704339 Publication Model: Print Cited Medium: Internet ISSN: 2542-5196 (Electronic) Linking ISSN: 25425196 NLM ISO Abbreviation: Lancet Planet Health Subsets: MEDLINE

Original Publication: [Amsterdam] : Elsevier B.V., [2017]-

Diabetes Mellitus, Type 2* ; Renal Insufficiency, Chronic*/complications ; Renal Insufficiency, Chronic*/drug therapy; Humans ; Middle Aged ; Glomerular Filtration Rate ; Risk Factors ; Kidney

Background: Higher temperatures are associated with higher rates of hospital admissions for nephrolithiasis and acute kidney injury. Occupational heat stress is also a risk factor for kidney dysfunction in resource-poor settings. It is unclear whether ambient heat exposure is associated with loss of kidney function in patients with established chronic kidney disease. We assessed the association between heat index and change in estimated glomerular filtration rate (eGFR) in participants from the DAPA-CKD trial in a post-hoc analysis.
Methods: DAPA-CKD was a randomised controlled trial of oral dapagliflozin 10 mg once daily or placebo that enrolled participants aged 18 years or older, with or without type 2 diabetes, with a urinary albumin-to-creatinine ratio of 200-5000 mg/g, and an eGFR of 25-75 mL/min per 1·73 m ² . In this post-hoc analysis, we explored the association between time-varying daily centre-level heat index (ERA5 dataset) and individual-level change in eGFR in trial participants using linear mixed effect models and case-time series. The DAPA-CKD trial is registered with ClinicalTrials.gov, NCT03036150.
Findings: Climate and eGFR data were available for 4017 (93·3%) of 4304 participants in 21 countries (mean age: 61·9 years; mean eGFR: 43·3 mL per 1·73 m ² ; median 28 months follow-up). Across centres, a heat index of more than 30°C occurred on a median of 0·6% of days. In adjusted linear mixed effect models, within each 120-day window, each 30 days' heat index of more than 30°C was associated with a -0·6% (95% CI -0·9% to -0·3%) change in eGFR. Similar estimates were obtained using case-time series. Additional analyses over longer time-windows showed associations consistent with haemodynamic or seasonal variability, or both, but overall estimates corresponded to an additional 3·7 mL per 1·73 m ² (95% CI 0·1 to 7·0) loss of eGFR per year in a patient with an eGFR of 45 mL per 1·73 m ² located in a very hot versus a temperate environment.
Interpretation: Higher ambient heat exposure is associated with more rapid eGFR decline in those with established chronic kidney disease. Efforts to mitigate heat exposure should be tested as part of strategies to attenuate chronic kidney disease progression.
Funding: None.
Competing Interests: Declaration of interests HJLH has received honoraria, paid to his institution (University Medical Center Groningen), for participation in steering committees from AstraZeneca, Janssen, Gilead, Bayer, Chinook, and CSL Pharma; honoraria for participation in advisory boards from Merck, Mitsubishi Tanabe, Janssen, and Mundipharma; fees for consultancy from AstraZeneca, AbbVie, Retrophin, Boehringer Ingelheim, and Novo Nordisk; and research grant support from AstraZeneca, AbbVie, Janssen, and Boehringer Ingelheim. GMC has received fees from AstraZeneca for the DAPA-CKD trial steering committee; serves on the Board of Directors for Satellite Healthcare, a non-profit dialysis provider; has received research grants from the US National Institute of Diabetes and Digestive and Kidney Diseases, US National Institute of Allergy and Infectious Diseases, US National Heart, Lung, and Blood Institute, and CSL Behring; has served on trial steering committees with Akebia, AstraZeneca, Gilead, Sanifit, and Vertex; has served as an adviser to Ardelyx, CloudCath, Durect, Miromatrix, Outset, Renibus, Reata, Sanifit, Unicycive, and Vertex; and has served on data and safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Diseases, Bayer, Mineralys, and ReCor. RC-R has received honoraria as a consultant from AstraZeneca (DAPA-CKD Steering Committee), Boehringer Ingelheim, Bayer, Chinook, and Novo Nordisk; and research support and speaker fees from AstraZeneca, GSK, and Novo Nordisk. AML is an employee and stockholder of AstraZeneca. NJ has received support from AstaZeneca to attend conferences. JJVM has received payments for his work on clinical trials paid to his employer, Glasgow University; has received payments for consulting; is on the advisory board of Alnylam, Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cardurion, Cytokinetics, DAICor, GSK, Ionis Pharmaceuticals, KBP Biosciences, Novartis, and Theracos; and has received personal lecture fees from Abbott, Alkem Metabolics, Eris Lifesciences, Hikma, Lupin, Sun Pharmaceuticals, Medscape/Heart.org, ProAdWise Communications, Radcliffe Cardiology, Servier, and the Corpus. PR has received honoraria to Steno Diabetes Center Copenhagen for lecture fees, steering group participation, and advisory board participation from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Sanofi, and Eli Lilly, and research support from AstraZeneca. RDT has received consulting fees from Boehringer Ingelheim, Reata Pharma, and Chinook Pharma; received speakers fees from Medscape; participated in advisory boards for Bayer and Viofor; and participated in data monitoring committees for Akebia and Otsuka. DN reports unrelated work funded by GSK involving studies of kidney function in sub-Saharan Africa. DCW provides ongoing consultancy services to AstraZeneca and has received honoraria for participation in advisory boards and other activities, consultancy fees, or both from Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, KSk, Janssen, Napp, Mundipharma, Medscape, Merck Sharp & Dohme, Pharmacosmos, Reata, Takeda, and Vifor Fresenius. BC has received research grant funding, paid to his employers (University College London and Royal Free London NHS Foundation Trust), from the UK Medical Research Council, the Colt Foundation, and AstraZeneca along with consultancy fees (also paid to his employer) from LifeArc. All other authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

MR/R013349/1 United Kingdom MRC_ Medical Research Council

ClinicalTrials.gov NCT03036150

Date Created: 20240405 Date Completed: 20240408 Latest Revision: 20240501

20240501

10.1016/S2542-5196(24)00026-3

38580424