{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T16:08:41Z","timestamp":1792080521175,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>To investigate the association between cardiovascular autonomic neuropathy (CAN) assessed by the coefficient of variation of the R\u2010R interval and the reduction in the estimated glomerular filtration rate (eGFR) in patients with type\u20092 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>This retrospective observational cohort study enrolled type\u20092 diabetes patients who had their coefficient of variation of the R\u2010R interval measured on an electrocardiogram from January 2005 to December 2018. CAN was defined using the reference coefficient of variation of the R\u2010R interval value based on age and sex. The primary outcome was set as a 40% eGFR decline from baseline. Regression analyses using the Cox proportional hazards model were carried out to evaluate the association.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 831 patients, 118 (14.2%) were diagnosed with CAN. In the analysis of the primary outcome, the median follow\u2010up period was 5.3\u2009years, and 25 (21.2%) patients with CAN and 78 (10.9%) patients without CAN developed a 40% eGFR decline. In the univariate regression analysis, CAN was significantly associated with a 40% eGFR decline (hazard ratio 2.42, 95% confidence interval 1.54\u20133.80). In the multivariate analysis, CAN remained almost significant after adjusting for the prognostic risk factors for CAN and the decline in the renal function, and an interaction with proteinuria was found. In analyses for the interaction effect between CAN and proteinuria, the presence of CAN synergistically increased the risk of an eGFR decline in patients with macroproteinuria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>CAN strongly increased the risk of a 40% eGFR decline from baseline, especially in type\u20092 diabetes patients with macroproteinuria.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13625","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T18:59:42Z","timestamp":1625597982000},"page":"102-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Decline in renal function associated with cardiovascular autonomic neuropathy positively coordinated with proteinuria in patients with type\u20092 diabetes"],"prefix":"10.1111","volume":"13","author":[{"given":"Taichi","family":"Muramatsu","sequence":"first","affiliation":[{"name":"Department of 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