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Objective: Although diabetic kidney disease (DKD) has been considered as a glomerulocentric disease in the past few decades, growing evidence demonstrated that tubular damage was indispensable in its pathogenesis and progression. This study was designed to investigate the association of urinary acidification dysfunction with the progression of DKD in type 2 diabetic patients.Methods: Here the urinary acidification functions were measured from 80 participants with renal biopsy-proven DKD. The different kinds of renal tubular transportation dysfunction were analyzed, including the dysfunction of bicarbonate reabsorption, titratable acid secretion, and ammonium secretion. In addition, patients were followed up for 17 (interquartile range, 11-32) months to evaluate the effect of urinary acidification dysfunction in the progression of DKD.Results: The most common urinary acidification dysfunction was the disorder of ammonium secretion, accounting for 53.75%. The more proteinuria excretion and the lower glomerular filtration rate (GFR) were observed in the urinary titratable acid disorder group than the normal group, and the same results were obtained for ammonium secretion disorder. Urine titratable acid was positively correlated with eGFR whereas it was inversely correlated with proteinuria, serum creatinine, and BUN. Moreover, 24 h urine protein, serum creatinine, BUN and cystatin C increased from DKD stage II to stage IV, whereas the eGFR and urine titratable acid decreased in the same way. Furthermore, Kaplan-Meier analysis and Cox regression showed that the disorder of titratable acid was an independent risk factor for DKD progression.Conclusions: The dysfunction of urinary titratable acid is a potential biomarker for the severity of proteinuria, eGFR and glomerular lesions in patients with DKD. Moreover, the titratable acid disorder is an independent risk factor of the DKD progression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]