Metabolic Burden and Hyperuricemia Are Associated With CKD‐Related Outcomes in Individuals With and Without Steatotic Liver Disease
Michihiro Iwaki, Hideki Fujii, Yoshihiro Kamada, Yuichiro Suzuki, Koji Sawada, Miwa Tatsuta, Tatsuji Maeshiro, Hiroshi Tobita, Tsubasa Tsutsumi, Takemi Akahane, Chitomi Hasebe, Miwa Kawanaka, Takaomi Kessoku, Yuichiro Eguchi, Hayashi Syokita, Masato Yoneda, Atsushi Nakajima, Tomoari Kamada, Hitoshi Yoshiji, Takumi Kawaguchi, Hiroshi Sakugawa, Asahiro Morishita, Tsutomu Masaki, Takumi Ohmura, Toshio Watanabe, Yoshioki Yoda, Nobuyuki Enomoto, Masafumi Ono, Kanako Fuyama, Kazufumi Okada, Naoki Nishimoto, Yoichi M. Ito, Hirokazu Takahashi, Yoshio Sumida,ABSTRACT
Aim
Although steatotic liver disease (SLD) has been associated with chronic kidney disease (CKD), it remains unclear whether CKD‐related outcomes are driven by hepatic steatosis itself or by accompanying cardiometabolic abnormalities. We investigated the relative contribution of hepatic steatosis and cardiometabolic risk factors to CKD‐related outcomes using a large Japanese health screening cohort.
Methods
In total, 30,648 SLD and 76,182 non‐SLD participants enrolled in the MIRACLE‐J cohort across 13 centers in Japan between 2014 and 2018 were analyzed. CKD‐related outcomes were defined as reduced estimated glomerular filtration rate (eGFR< 60 mL/min/1.73 m 2 ) and proteinuria. Multivariable logistic regression and trend analyses were performed to identify factors associated with these outcomes.
Results
Compared with non‐SLD participants, those with SLD exhibited a higher burden of cardiometabolic abnormalities. Type 2 diabetes mellitus, obesity, and hyperuricemia were independently associated with proteinuria, whereas advanced age (≥ 65 years), low alcohol intake, and hyperuricemia were strongly associated with reduced eGFR. After multivariable adjustment, SLD showed an inverse association with CKD‐related outcomes. In both SLD and non‐SLD populations, the prevalence of CKD‐related outcomes increased stepwise with a higher number of cardiometabolic risk factors. Incorporation of hyperuricemia significantly improved model fit for reduced eGFR (Δ−2 log likelihood = 119.4, p < 0.001) and modestly improved model fit for proteinuria ( p = 0.002).
Conclusions
CKD‐related outcomes were more strongly associated with the burden of cardiometabolic abnormalities than with hepatic steatosis itself, and these associations were consistent in individuals with and without SLD. Hyperuricemia provided incremental value for renal risk stratification within this cardiometabolic framework, underscoring the importance of comprehensive metabolic risk assessment beyond liver fat status.