Histologic predictors of renal outcome in diabetic nephropathy

Abstract

The prognostic utility of histologic features in patients with diabetic nephropathy (DN) classified according to the Renal Pathology Society (RPS) classification is controversial. Therefore, we aimed to evaluate the relationship between histologic changes and renal outcome in DN patients. We examined the renal outcome at November 30, 2017 of 74 adult patients (median age of 54.6 years, 69% male, 81% diabetes mellitus (DM) type 2, estimated GFR (eGFR) 29.6 mL/min) with biopsy proven DN between 2010 and 2015. The primary endpoint was renal replacement therapy (RRT) initiation. Half of the patients progressed to end stage renal disease (ESRD) during follow-up; they had lower eGFR, increased proteinuria, hematuria and serum cholesterol. Regarding the pathologic features, they were more frequently in class III and IV, had higher interstitial fibrosis and tubular atrophy score (IFTA), increased interstitial inflammation, more frequent arteriolar hyalinosis and higher glomerular basement membrane (GBM) thickness. The mean kidney survival time was 2.7 (95%CI 2.1, 3.3) years. In univariate time-dependent analyses, higher RPS DN class, increased IFTA, the presence of arteriolar hyalinosis and arteriosclerosis were associated with RRT initiation. In the fully adjusted model, the clinical characteristics associated with poor renal survival were longer duration of DM, lower eGFR, increased proteinuria and higher hematuria and the only pathologic lesions to remain significant were the GBM thickness and the IFTA. In conclusion, in this European cohort, the severity of glomerular lesions evaluated with the RPS DN classification had limited utility in predicting RRT initiation. However, IFTA and GBM thickness were significantly associated with renal survival.

Modified arteriosclerosis score predicts the outcomes of diabetic kidney disease

“…Yu An et al [ 36 ] studied more than 300 patients with type 2 DKD confirmed by biopsy and found that vascular lesion scores demonstrated no association with renal outcomes. However, a different study demonstrated that the presence of arteriolar hyalinosis and arteriosclerosis were associated with renal replacement therapy (RRT) initiation in univariate analyses, although there was no statistical significance in multivariable analyses [ 37 ]. The original classification of arteriosclerosis in DKD only assessed the most severe arteriosclerosis but did not assess the proportion of the arteries involved.…”

Complexities of the glomerular basement membrane

“…[H2] Diabetic kidney disease GBM thickening is an early morphological feature of diabetic kidney disease (DKD) followed by mesangial matrix expansion and glomerulosclerosis, accompanied by the development of proteinuria and a progressive decline in kidney function [152][153][154][155] . A 2019 study identified GBM thickness as a predictor of renal survival in patients with DKD 156 .…”

Risk factors and urinary biomarkers of non-albuminuric and albuminuric chronic kidney disease in patients with type 2 diabetes

“…Moreover, it was reported that interstitial fibrosis, tubular atrophy and interstitial inflammation, but not glomerular lesions, are significant predictors for renal prognosis in T2D patients with overt proteinuria[15]. In a recent study, interstitial fibrosis and tubular atrophy score, as well as glomerular basement membrane thickness, were independent predictors for renal replacement therapy initiation in T2D patients[16]. Taking into account the results of morphological investigations, the assessment of urinary markers of podocyte and interstitial involvement may provide further information on the development of different CKD phenotypes.…”