Serum Carnosinase-1 and Albuminuria Rather than the CNDP1 Genotype Correlate with Urinary Carnosinase-1 in Diabetic and Nondiabetic Patients with Chronic Kidney Disease

Abstract

Background Carnosinase-1 (CN-1) can be detected in 24\u2009h urine of healthy individuals and patients with type 2 diabetes (T2DM). We aimed to assess whether urinary CN-1 is also reliably measured in spot urine and investigated its association with renal function and the albumin/creatinine ratio (ACR). We also assessed associations between the CNDP1 (CTG)n genotype and CN-1 concentrations in serum and urine. Methods Patients with T2DM (n = 85) and nondiabetic patients with chronic kidney disease (CKD) (n = 26) stratified by albuminuria (ACR ≤ 300\u2009mg/g or ACR > 300\u2009mg/g) recruited from the nephrology clinic and healthy subjects (n = 24) were studied. Results Urinary CN-1 was more frequently detected and displayed higher concentrations in patients with ACR > 300\u2009mg/g as compared to those with ACR ≤ 300\u2009mg/g irrespective of the baseline disease (T2DM: 554\u2009ng/ml [IQR 212-934\u2009ng/ml] vs. 31\u2009ng/ml [IQR 31-63\u2009ng/ml] (p < 0.0001) and nondiabetic CKD: 197\u2009ng/ml [IQR 112-739] vs. 31\u2009ng/ml [IQR 31-226\u2009ng/ml] (p = 0.015)). A positive correlation between urinary CN-1 and ACR was found (r = 0.68, p < 0.0001). Multivariate linear regression analysis revealed that ACR and serum CN-1 concentrations but not eGFR or the CNDP1 genotype are independent predictors of urinary CN-1, explaining 47% of variation of urinary CN-1 concentrations (R2 = 0.47, p < 0.0001). Conclusion These results confirm and extend previous findings on urinary CN-1 concentrations, suggesting that assessment of CN-1 in spot urine is as reliable as in 24\u2009h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.