Association between exercise frequency with renal and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk

Abstract

Background: Guidelines recommend physical activity to reduce cardiovascular (CV) events. The association between physical activity and progression of chronic kidney disease (CKD) with and without diabetes is unknown. We assessed the association of self-reported physical activity with renal and CV outcomes in high-risk patients aged ≥ 55 years over a median follow-up of 56 months in post-hoc analysis of a previously randomized trial program.

Methods: Analyses were done with Cox regression analysis, mixed models for repeated measures, ANOVA and χ2-test. 31,312 patients, among them 19,664 with and 11,648 without diabetes were analyzed.

Results: Physical activity was inversely associated with renal outcomes (doubling of creatinine, end-stage kidney disease (ESRD)) and CV outcomes (CV death, myocardial infarction, stroke, heart failure hospitalization). Moderate activity (at least 2 times/week to every day) was associated with lower risk of renal outcomes and lower incidence of new albuminuria (p < 0.0001 for both) compared to lower exercise levels. Similar results were observed for those with and without diabetes without interaction for renal outcomes (p = 0.097-0.27). Physical activity was associated with reduced eGFR decline with a moderate association between activity and diabetes status (p = 0.05).

Conclusions: Moderate physical activity was associated with improved kidney outcomes with a threshold at two sessions per week. The association of physical activity with renal outcomes did not meaningfully differ with or without diabetes but absolute benefit of activity was even greater in people with diabetes. Thus, risks were similar between those with diabetes undertaking high physical activity and those without diabetes but low physical activity.

Clinical trial registration: https://ichgcp.net/clinical-trials-registry/NCT00153101" title="See in ClinicalTrials.gov">NCT00153101.

Trial registration: ClinicalTrials.gov NCT00153101 NCT00015310.

Keywords: Cardiovascular outcomes; Physical activity; Renal outcomes; Secondary prevention.

Conflict of interest statement

M.B. reports personal fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Servier, Medtronic, Vifor, Novartis and Abbott outside the submitted work; F.M. reports grants and personal fees from Medtronic and Recor, outside the submitted work; R.S. reports grants and personal fees from Boehringer Ingelheim, during the conduct of the study. S.Y. reports other from Boehringer Ingelheim, during the conduct of the study. M.W. reports personal fees from Medtronic, Boston Scientific, ReCor, Omron, Ablative Solutions and Menarini, outside the submitted work. B.W. reports personal fees from Servier, Novartis, Pfizer and Boehringer Ingelheim, outside the submitted work. J.M. reports personal fees from NovoNordisk, during the conduct of the study; personal fees from AstraZeneca, Amgen, Braun, ACI, Fresenius, Gambro, Lanthio, ZS Pharma, Sanifit, Medice and Relypsa; grants and personal fees from NovoNordisk, Roche, Sandoz, Celgene, Abbvie; grants from Europe Union and McMaster University Canada outside the submitted work. U.L. reports fees from Boehringer Ingelheim outside the submitted work. G.M. reports personal fees from Boehringer Ingelheim, Ferrer, Medtronic, Menarini, Merck Serono, Novartis, Recordati and Servier, outside the submitted work. ML reports grants and personal fees from Boehringer Ingelheim, MSD and Novo Nordisk, personal fees from Amgen, Sanofi, Astra Zeneca, Bayer and Lilly H.S., K.T., E.L. J.R., N.M., K.S., I.E. have nothing to disclose.

© 2021. The Author(s).

Figures

Fig. 1

Study flow of patients included in the analysis and treatment allocation in the ONTARGET/TRANSCEND trials

Fig. 2

Decline of estimated glomerular filtration rate (eGFR) in all patients (A), all patients categorized by physical activity (B), patients with diabetes or no diabetes (C) and diabetes or no diabetes categorized by physical activity (D)

Fig. 3

Cumulative incidence for doubling of serum creatinine or end-stage renal disease (ESRD) (A), end-stage renal disease (ESRD) (B), new microalbuminuria (C) and new macroalbuminuria (D) according to physical activity level

Fig. 4

Cumulative incidence for doubling of serum creatinine or end-stage renal disease (ESRD) (A), end-stage renal disease (ESRD) (B), new microalbuminuria (C) and new macroalbuminuria (D) in patients with or without diabetes according to physical activity level