The role of tubulointerstitial markers in differential diagnosis and prognosis in patients with type 2 diabetes and biopsy proven diabetic kidney disease.

Objective: To evaluate the potential application of tubularinterstitial biomarkers in the differential diagnosis of diabetic kidney disease (DKD) from non-diabetic kidney disease (NDKD), as well as investigate key clinical and pathological parameters to help improve the stratification of patients according to end-stage renal disease risk.

Methods: 132 type 2 diabetic patients with chronic kidney disease were enrolled. Patients were categorized into 2 groups according to the renal biopsy results: DKD (n = 61) and NDKD (n = 71).The independent factors of the occurrence of DKD and the diagnostic implications of tubular biomarkers were explored by logistic regression and receiver-operating characteristic curve analysis. Furthermore, predictors were analyzed by least absolute shrinkage and selection operator regression, and constructed a new model for predicting the unfavorable renal outcomes through Cox proportional hazard regression analysis.

Results: Serum neutrophil gelatinase-associated lipocalin (sNGAL) (OR = 1.007; 95%CI = [1.003, 1.012], p = 0.001) was identified as an independent risk factor for the occurrence of DKD in diabetic patients with CKD. Tubular biomarkers including sNGAL, N-acetyl-β-D-glucosaminidase and β2 microglobulin (β2-MG) could complement albuminuria for DKD detection (AUC = 0.926, specificity = 90.14%, sensitivity = 80.33%).Moreover, among of the 47 variables, 4 predictors such as sNGAL, interstitial fibrosis and tubular atrophy (IFTA)score, β2-MG and estimated glomerular filtration rate were selected to construct a new model for predicting the unfavorable renal outcomes through regression analysis. sNGAL (HR = 1.004; 95%CI = [1.001, 1.007], p = 0.013), IFTA score of 2 (HR = 4.283; 95%CI = [1.086, 16.881], p = 0.038), and IFTA score of 3 (HR = 6.855; 95%CI = [1.766, 26.610], p = 0.005) were considered to be independent risk factors for unfavorable renal outcomes.

Conclusions: Tubulointerstitial injury in DKD is independently associated with renal function decline and routinely detected tubular biomarkers are able to enhance the level of non-invasive diagnosis of DKD beyond traditional factors.