Associations of serum amino acids related to urea cycle with risk of chronic kidney disease in Chinese with type 2 diabetes

Front Endocrinol (Lausanne). 2023 Mar 2:14:1117308. doi: 10.3389/fendo.2023.1117308. eCollection 2023.

Abstract

Objective: Serum levels of amino acids related to urea cycle are associated with risk of type 2 diabetes mellitus (T2DM). Our study aimed to explore whether serum levels of amino acids related to urea cycle, i.e., arginine, citrulline, and ornithine, are also associated with increased risk of chronic kidney disease (CKD) in T2DM.

Methods: We extracted medical records of 1032 consecutive patients with T2DM from the Electronic Administrative System of Liaoning Medical University First Affiliated Hospital (LMUFAH) system from May 2015 to August 2016. Of them, 855 patients with completed data available were used in the analysis. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Serum amino acids were measured by mass spectrometry (MS) technology. Binary logistic regression was performed to obtain odds ratios (ORs) and their 95% confidence intervals (CIs).

Results: 52.3% of the 855 T2DM patients were male, and 143 had CKD. In univariable analysis, high serum citrulline, high ratio of arginine to ornithine, and low ratio of ornithine to citrulline were associated with markedly increased risk of CKD (OR of top vs. bottom tertile: 2.87, 95%CI, 1.79-4.62 & 1.98, 95%CI,1.25-3.14 & 2.56, 95%CI, 1.61-4.07, respectively). In multivariable analysis, the ORs of citrulline and ornithine/citrulline ratio for CKD remained significant (OR of top vs. bottom tertile: 2.22, 95%CI, 1.29-3.82 & 2.24, 1.29-3.87, respectively).

Conclusions: In Chinese patients with T2DM, high citrulline and low ornithine/citrulline ratio were associated with increased risk of CKD.

Keywords: chronic kidney disease; citrulline; serum amino acids; type 2 diabetes mellitus; urea cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine
  • Citrulline / metabolism
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / epidemiology
  • East Asian People
  • Female
  • Humans
  • Male
  • Ornithine / metabolism
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / epidemiology
  • Urea

Substances

  • Citrulline
  • Arginine
  • Ornithine
  • Urea

Grants and funding

This project was supported by National Key Research and Development Program of China (2021YFA1301202), National Natural Science Foundation of China (82273676), Liaoning Province Scientific and Technological Project (2021JH2/10300039), Major Research Plan of National Natural Science Foundation of China (Grant No.92163213) and General Program of National Natural Science Foundation of China (Grant No. 81970085). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.