Seasonal variations in the association between proteinuria, CKD, and kidney failure

Abstract Background and hypothesis Proteinuria exhibits seasonal fluctuations, decreasing in summer and increasing in winter. It is unknown whether the association between proteinuria and the risk of kidney failure varies by season. Methods The Osaka Consortium for Kidney Disease Research (OCKR) database contained retrospective data from 15 367 patients with estimated glomerular filtration rates of 10–60 mL/min/1.73m2, who were referred to the Department of Nephrology at five clinical centers in Japan, between 2010 and 2021. Multivariate Cox models were used to examine the associations of urinary protein-to-creatinine ratio (UPCR) in summer (UPCRsummer) and winter (UPCRwinter) with kidney failure defined as initiation of kidney replacement therapy. LASSO was used to compare the strength of the association between UPCRsummer and UPCRwinter with respect to kidney failure. We also assessed whether seasonal fluctuations in UPCR were associated with kidney failure. Results The median [interquartile range] UPCRwinter was 0.89 [0.22, 2.69] g/gCre, 46% higher than UPCRsummer (0.61 [0.16, 1.87] g/gCre). During a median follow-up of 3.0 years, 1 585 patients developed kidney failure. In time-dependent Cox models, UPCRwinter showed a higher hazard of kidney failure (1.66 per 1-standard deviation [SD] increase; 95% confidence interval [CI], 1.60–1.73) than UPCRsummer (1.45 per 1-SD increase; 95%CI, 1.41–1.48). LASSO identified that UPCRwinter was more strongly associated with kidney failure than UPCRsummer. Furthermore, higher % changes in UPCRwinter relative to UPCRsummer was associated with a higher hazard of kidney failure. Conclusions Proteinuria in winter exhibited stronger associations with kidney failure than that in summer. Seasonal fluctuations in UPCR should not be overlooked in the management of CKD to make reasonable clinical decisions.