Physical activity and renal outcome in diabetic and non-diabetic patients with chronic kidney disease stage G3b to G5 – Scientific Reports

Study design and patient sample

The REACH-J study is an ongoing 5-year prospective cohort study of non-dialysis patients with CKD stage G3b to G5 (eGFR ≤ 45 ml/min/1.73m²) being treated at 31 nephrology clinics in Japan. To minimize patient selection bias, the clinics were randomly selected from the nationwide nephrology specialist list after stratification by region and facility size, in alignment with the international Chronic Kidney Disease Outcomes and Practice Patterns (CKDopps) project. The study design of the REACH-J study and CKDopps project have been published previously^10,11,12. Briefly, anonymized data were collected annually from patients and physicians, including clinical data and a patient questionnaire. Information on patients’ medical history and complications, including diabetes, hypertension, cardiovascular diseases, and cancers, were collected from medical records. Patients aged younger than 20 years, those with a history of kidney transplantation or dialysis, and those who did not agree to participate in the study were excluded.

The study protocol was approved by the Tsukuba institutional review board (approval number: H27-199) and the review board of the Japanese Society of Nephrology (approval number: 29). The study adhered to the Declaration of Helsinki and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and was registered with the University Hospital Medical Information Network (registration number: UMIN000022145).

Physical activity levels

Patients’ baseline physical activity levels were assessed by the Rapid Assessment of Physical Activity (RAPA) questionnaire, which shows a good correlation with direct measurement of physical activity by accelerometers^13,14. The RAPA questionnaire was included in the baseline self-reported patient questionnaire. The RAPA questionnaire consists of nine binary questions (yes/no) with graphical illustrations. In this study, we defined binary levels of physical activity (active or inactive) by applying the approach used in our previous study and by Topolski et al.¹⁴. Active was defined as being often or very active according to the responses to the first seven RAPA questions, and inactive, as being never, infrequently, or sometimes active¹⁵.

Outcomes

We defined CKD progression as a 40% decline in eGFR from baseline, an eGFR of less than 10 ml/min/1.73m², or end-stage kidney disease requiring dialysis or transplantation, whichever occurred first, and mortality as fatal events from any cause during follow-up. As additional outcomes, we compared eGFR decline in patients with and without diabetes and between CKD stages in the active and inactive groups.

Statistical analyses

Patient demographics were summarized as mean and standard deviation (SD) or median and interquartile range (IQR). We evaluated incidence rates and hazard ratios (HRs) for renal outcome and death with a modified Poisson regression model and a Cox proportional hazard model, respectively. We also evaluated eGFR decline per year with a linear mixed model with subject and center as random effects. All models were adjusted for age, sex, smoking status, body mass index, eGFR, level of proteinuria, serum albumin, hemoglobin, diabetes, comorbidity score, congestive heart failure, and lung disease and evaluated by activity group, the presence or absence of diabetes, and CKD stage. Multiple imputation was used in all analyses to impute missing covariate values. Twenty complete data sets were imputed, all analyses were performed with each data set, and results were combined using Rubin’s rules.

A comorbidity score was calculated for each patient as the number of comorbidities out of the following 10: coronary heart disease, hypertension, other cardiovascular disease, cerebrovascular disease, peripheral vascular disease, recurrent cellulitis/gangrene, neurologic disease, psychiatric disorder, gastrointestinal bleeding, and cancer¹⁵. If separation problems were observed because of the small number of samples, the applicable explanatory variables were excluded from the analyses.

P values of less than 0.05 were considered significant. All analyses were performed with SAS software, version 9.4 (SAS Institute, Cary, NC). Confidence intervals (CIs) were reported as 95% CIs.

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• Source: https://www.nature.com/articles/s41598-024-77497-1