Estimated plasma osmolarity and risk of end-stage kidney disease in patients with IgA nephropathy
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ORIGINAL ARTICLE
Estimated plasma osmolarity and risk of end‑stage kidney disease in patients with IgA nephropathy Shigeru Tanaka1 · Toshiaki Nakano1 · Masanori Tokumoto2 · Kosuke Masutani3 · Akihiro Tsuchimoto1 · Hiroaki Ooboshi2 · Takanari Kitazono1 Received: 16 November 2019 / Accepted: 7 June 2020 © Japanese Society of Nephrology 2020
Abstract Background Several experimental studies have indicated that increased plasma osmolarity caused by recurrent dehydration is involved in kidney injury via a mechanism, mediated by vasopressin secretion and activation of the aldose reductase pathway. Epidemiologic evidence linking increased plasma osmolarity and the onset of end-stage kidney disease (ESKD), in patients with primary glomerulonephritis, is lacking. Methods We retrospectively examined 663 patients with IgA nephropathy (IgAN) diagnosed by kidney biopsy and evaluated the association between estimated plasma osmolarity and ESKD prevalence, using a Cox proportional hazards model. Results During follow-up (median 80.4 months; interquartile range 22.2–120.1), 73 patients developed ESKD. In a baseline survey, plasma osmolarity was correlated negatively with the mean value of the estimated glomerular filtration rate, but correlated positively with the mean value of urinary protein excretion, systolic blood pressure, and pathologic severity of extracapillary proliferation, in addition to tissue fibrosis and sclerosis. The incidence rate of ESKD increased linearly with increase in plasma osmolarity (P 50%.
Kidney outcome The primary endpoint was ESKD development, which was defined as the initiation of kidney replacement therapy (hemodialysis, peritoneal dialysis, or kidney transplantation). We followed participants by reviewing their medical records or by telephone consultation with the clinics and hospitals they visited, or with the patients themselves. Patients were censored at the date of death or loss of follow-up.
Statistical analysis The relationships between plasma osmolarity and covariates were tested by means of linear regression or logistic regression analyses. The age-adjusted incidence rates, incidence rate ratios, and 95% confidence intervals (CI) for ESKD were calculated using the person–year method and compared using Poisson regression analyses. The age-, sex-, and multivariate-adjusted hazard ratios (HRs) with 95% CIs of each risk factor for ESKD development were estimated using a Cox proportional hazards model. Survival was assessed by the Kaplan–Meier method and compared by log-rank tests. In stratified analyses, the difference in the relationship between subgroups was tested by adding a multiplicative interaction term to the relevant Cox model. Statistical analyses were undertaken using SAS v9.4 (SAS Institute, Cary, NC, USA) and STATA v14 (Stata, College Station, TX, USA). P
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