A higher level of serum furin indicates a higher risk of microalbuminuria: results from a longitudinal study in Chinese

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ORIGINAL ARTICLE

A higher level of serum furin indicates a higher risk of microalbuminuria: results from a longitudinal study in Chinese adults Liyun Ren1 · Yan Chen2 · Qiu Zhang3 · Mingzhi Zhang1 · Jia Yu1 · Yan He1 · Hao Peng1  Received: 26 January 2020 / Accepted: 1 June 2020 © Japanese Society of Nephrology 2020

Abstract Background  Furin, a key enzyme of natriuretic peptide system, has been suggested to play a role in microalbuminuria, but the association between furin and microalbuminuria has been scarcely studied. Methods  Leveraging a longitudinal cohort of Chinese adults who had urinary albumin measured twice 4 years apart, we examined the cross-sectional and prospective associations of baseline serum furin with microalbuminuria, adjusting for age, sex, education level, smoking, drinking, obesity, blood pressure, glucose, lipids, and antihypertensive medications. Results  The cross-sectional analysis in 2175 participants (53 ± 10 years, 38% men) found that a 10-time higher level of serum furin was significantly associated with a 64% higher risk of having microalbuminuria (OR = 1.64, P = 0.005). The longitudinal analysis found a positive association between baseline serum furin and dynamic elevation of albumin excretion during follow-up. The prospective analysis in 1357 participants free of microalbuminuria at baseline found that a 10-time higher level of serum furin at baseline was significantly associated with a 1.28-time higher risk of developing microalbuminuria 4 years later (OR = 2.28, P  250 mg/g for men and > 355 mg/g for women (N = 23) [25], 2175 participants were included in the analysis of the cross-sectional association between serum furin and microalbuminuria. After further excluding 492 participants who denied to participate in Phase II examination, 1683 participants were included in the analysis of the longitudinal association between serum furin and dynamic change of UACR during follow-up. Of them, 1357 participants free of microalbuminuria at Phase I examination were included in the analysis of the prospective association between baseline serum furin and incident microalbuminuria.

Serum furin measurements were performed in the Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases at Soochow University. The staff who performed the measurements were blind to the clinical characteristics of the study participants. We used a sandwich enzyme immunoassay (Catalog: DL-FUR-Hu; DLDEVELOP, Wuxi, China) to quantify concentrations of human furin in serums which were drawn at Phase I examination and frozen at − 80 ℃ until laboratory tests. All the samples were processed in a duplicate assay. A standard curve was constructed and from which furin concentrations of unknown samples were determined. Intraand inter-assay coefficients of variation were less than 10% and 12%, respectively.

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Measurement and definition of microalbuminuria The methods of measurement and definition of microalbuminuria used in our study have been described elsewhere [26]. Briefly, a single fir