Urine metabolites are associated with glomerular lesions in type 2 diabetes

Abstract

Introduction: Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives: We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods: Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson's correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results: Participants (n = 62, mean age 45 ± 10 years) had mean ± standard deviation glomerular filtration rate of 137 ± 50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14-85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r = 0.29, P = 0.030 and r = 0.50, P < 0.001) and total filtration surface per glomerulus (partial r = 0.32, P = 0.019 and r = 0.43, P = 0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r = 0.32, P = 0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P = 0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P = 0.022).

Conclusions: Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

Keywords: Biomarkers; Kidney structure; Metabolites; Type 2 Diabetes.

Fig. 1

Partial regression residual plot of the associations between urine citric acid and morphometric variables. The residuals were computed from regressing each of these variables on age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, GFR, and treatment assignment. Pearson’s partial r and the corresponding P value are shown. Abbreviations: Sv glomerular filtration surface density, VvMes mesangial fractional volume, TFS total filtration surface per glomerulus