Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease

Objective: Chronic kidney disease (CKD) related to diabetes has become more common than glomerulonephritis in recent years. Given the inefficient and difficult identification of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD) as well as a result of emerging evidence supporting a role for tubular involvement in DKD, we aimed to investigate the utility of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in the differential diagnosis and predictive value of DKD from NDKD.

Methods: Data for 100 type 2 diabetic patients with CKD at our center from June 2016 to August 2019 were reviewed. All the patients were categorized into 2 groups by the renal biopsy results: DKD and NDKD. Urinary NGAL levels were normalized by urinary creatinine and calculated as uNGAL/creatinine ratios (uNCR). The independent factors of the occurrence of DKD and the diagnostic implications of uNCR were explored by logistic regression and receiver-operating characteristic (ROC) curve analysis. In addition, we analyzed the relationship between uNCR and proteinuria in patients with DKD by Pearson test and linear regression. Kaplan-Meier survival analysis was performed to assess the prospective association of uNCR with the renal outcome.

Results: Significantly higher levels of uNCR were observed in patients with DKD when compared to those with NDKD (28.65 ng/mg vs 27.47 ng/mg, p< .001). uNCR was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD (odds ratio [OR] = 1.020; 95%CI = [1.001-1.399], p = .042). The optimal cutoff value of uNCR for predicting DKD was 60.685 ng/mg with high specificity (90.5%) but relatively low sensitivity (55.7%). In Pearson test, uNCR was positively correlated with proteinuria, serum creatine, blood urea nitrogen, duration of diabetes, interstitial inflammation score and global sclerosis, whereas it was inversely correlated with eGFR, hemoglobin, serum albumin and 25-hydroxy vitamin D. Furthermore, in a fully adjusted model including eGFR, serum albumin and total cholesterol, the group with uNCR>60.685 ng/mg was associated with 7.595 times higher likelihood of nephrotic-range proteinuria compared to the group with uNCR≤60.685 ng/mg. In the Kaplan-Meier survival analysis, the event-free survival probability in patients with uNCR>60.685 ng/mg was significantly lower than those with uNCR≤60.685 ng/mg (p = .048).

Conclusions: uNCR might serve as a potential tool for identifying cases in which there was a high clinical suspicion of DKD and that in whom confirmatory biopsy could be considered, and the best predictive cutoff value of normalized uNCR for DKD diagnosis was 60.685 ng/mg. Type 2 diabetic patients with increased level of uNCR had higher risk to nephrotic-range proteinuria and worse renal outcome.