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Clinical predictors and long-term impact of acute kidney injury on progression of diabetic kidney disease in Chinese patients with Type 2 diabetes

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posted on 18.01.2022, 13:11 authored by Guozhi Jiang, Andrea O. Luk, Claudia H.T. Tam, Risa Ozaki, Cadmon K.P. Lim, Elaine Y.K. Chow, Eric S. Lau, Alice P.S. Kong, Baoqi Fan, Hong Kong Diabetes Register TRS Study Group, Ka Fai Lee, Shing Chung Siu, Grace Hui, Chiu Chi Tsang, Kam Piu Lau, Jenny Y. Leung, Man-wo Tsang, Grace Kam, Ip Tim Lau, June K. Li, Vincent T. Yeung, Emmy Lau, Stanley Lo, Samuel Fung, Yuk Lun Cheng, Chun Chung Chow, Hong Kong Diabetes Biobank Study Group, Nelson LS Tang, Yu Huang, Hui-yao Lan, Richard A Oram, Cheuk Chun Szeto, Wing Yee So, Juliana C.N. Chan, Ronald C.W. Ma
We aim to assess the long-term impact of AKI on progression of diabetic kidney disease and all-cause mortality, and investigate determinants of AKI in Chinese patients with type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register were followed for 12 years (mean[SD] age 57±13.2 years; 46.9% men; duration of diabetes 5 years). AKI was defined based on the KDIGO criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 SNPs known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD and ESRD. Validation was sought in an independent cohort including 6,007 patients (mean age 61.2±10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (HR [95% CI]: 14.3[12.69-16.11]), ESRD (12.1[10.74-13.62]) and all-cause death (7.99[7.31-8.74]), compared with those without AKI. Incidence rate for ESRD among patients with 0, 1, 2, ³ 3 episodes of AKI were 7.1, 24.4, 32.4, 37.3 per 1000 person-years. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts, but not ESRD. Elevated SUA may increase the risk of diabetic kidney disease through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a non-modifiable risk factor may facilitate the identification of high-risk individuals to prevent AKI and its long-term impact in T2D.

Funding

This work was supported by the NSFC-NHMRC Joint Research Scheme (Ref. 81561128017, 721 81561128017), Research Grants Council Theme-based Research Scheme (T12-402/13N), Croucher Foundation Senior Medical Research Fellowship, the Focused Innovation Scheme, Vice-Chancellor One-off Discretionary Fund, the Postdoctoral Fellowship Scheme of the Chinese University of Hong Kong, the Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Fund, and a grant from the Research Grants Council of the Hong Kong Special Administrative Region (CU R4012-18).

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