Urinary biomarkers in obstructive nephropathy

Abstract

Background and objectives: Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging.

Design, setting, participants, & measurements: This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR.

Results: The median urinary protein-to-creatinine ratio was higher in children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol; range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = -0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly decreased, whereas that of TGFβ and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFβ excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio performed best, with areas under the ROC curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio were associated with low GFR in the case-patients.

Conclusions: Candidate biomarkers of obstructive nephropathy can be readily measured in whole urine and in urine exosomes. In boys with PUV, these biomarkers correlate with GFR.

Figure 1.

Excretion of biomarker proteins. (A) Whole-urine aquaporin-2 (AQP2) was decreased (P<0.01) and TGFβ was increased (P<0.05) in case-patients with posterior urethral valves (PUVs) compared with values in both normal and control groups, whereas excretion of L1 cell adhesion molecule (L1CAM) was increased in case-patients compared with excretion in the normal group (P<0.05). (B) Exosome E-cadherin (P<0.01) and N-cadherin (P<0.01) were decreased and TGFβ (P<0.05) and L1CAM (P<0.01) were increased in case-patients with PUV compared with values in both normal and control groups. Dots are individual data points, horizontal bars represent the median values, and all data are plotted on a log-transformed y-axis. AU, arbitrary unit.

Figure 2.

Relationship between CKD stage, proteinuria, and urinary biomarker proteins in case-patients with obstructive nephropathy due to posterior urethral valves. Whole-urine analysis demonstrates increasing urine TGFβ, L1 cell adhesion molecule (L1CAM), and urinary protein-to-creatinine ratio (Uprot:cr) with advancing CKD stage. *P<0.05 versus CKD stage 1 and 2; ⁺P<0.05 versus CKD stage 2. CKD stage based on GFR in ml/min per 1.73 m²: stage 1, ≥90; stage 2, 60–89; stage 3, 30–59; stage 4, 15–29.