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 EN

Background.

Carnosinase-1 (CN-1) can be detected in 24 h 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 mg/g or ACR>300 mg/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 mg/g as compared to those with ACR≤300 mg/g irrespective of the baseline disease (T2DM: 554 ng/ml [IQR 212-934 ng/ml] vs.

31 ng/ml [IQR 31-63 ng/ml] (p<0.0001) and nondiabetic CKD: 197 ng/ml [IQR 112-739] vs.

31 ng/ml [IQR 31-226 ng/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 h urine and may indicate that urinary CN-1 in macroalbuminuric patients is primarily serum-derived and not locally produced.