Yongchun Ge

Renal histologic changes and the outcome in patients with diabetic nephropathy

BACKGROUND The progression of diabetic nephropathy (DN) is frequently determined by clinical parameters; however, the predictive value of histologic lesions remains largely unknown. Our aim was to evaluate the relationship between histologic changes and renal outcome in patients with type 2 diabetes mellitus (T2DM). METHODS A total of 396 patients with T2DM and biopsy-proven DN who received follow-up for at least 1 year were recruited. The severity of different histologic lesions was assessed using the pathologic classification established by the Renal Pathology Society. Renal outcomes were defined by progression to end-stage renal disease and doubling of serum creatinine. The influence of histologic findings on renal outcomes was assessed using univariate and multivariate Cox regression. RESULTS A univariate Cox regression showed that the severity of glomerular and interstitial lesions had a significant impact on renal outcomes (P < 0.001). Scores of vascular lesions demonstrated no association with renal outcomes (P > 0.05). A multivariate COX analysis demonstrated that the glomerular classes and scores of interstitial fibrosis and tubular atrophy were significantly associated with renal outcomes when adjusting for baseline proteinuria, mean arterial pressure and estimated glomerular filtration rate (P < 0.05). The glomerular and interstitial lesions correlated significantly among each other. However, in several patients, the severity of interstitial lesions did not correlate with glomerular lesions. CONCLUSION These findings indicated that the severity of glomerular and interstitial lesions were significantly associated with renal outcomes in patients with DN, whereas the vascular indexes did not have any impact on renal outcomes.

The spectrum of biopsy-proven kidney diseases in elderly Chinese patients

BACKGROUND Studies on biopsy-proven renal disease in the elderly (age ≥65 years) are extremely limited in China. The aim of this study was to examine the spectrum of renal diseases and their clinical presentations in elderly patients undergoing renal biopsy. METHODS All native renal biopsies (n = 851) performed in patients aged ≥65 years from January 2003 to December 2012 were retrospectively analyzed. The results were compared with a control group of 28 574 patients aged 18-64 years undergoing renal biopsy over the same period. RESULTS These 851 patients included 549 males and 302 females. Primary glomerular diseases (53.94%) occurred more frequently than secondary glomerular diseases (36.49%). The clinical manifestations were nephrotic syndrome (NS) in 29.49% of the patients, chronic renal failure in 24.68%, proteinuria and hematuria in 13.28%, proteinuria in 10.93%, acute kidney injury (AKI) in 10.81% and AKI and NS in 8.93%. Membranous nephropathy (MN) was the most frequent diagnosis (28.79%), followed by diabetic nephropathy (DN, 9.75%), IgA nephropathy (IgAN, 9.64%) and vasculitis (6.82%). When compared with the control group, the results showed that MN (P < 0.0001), DN (P < 0.0001), vasculitis (P < 0.0001) and amyloidosis (P < 0.0001) occurred more frequently and IgAN (P < 0.0001), lupus nephritis (P < 0.0001) and minimal change disease (P < 0.0001) occurred less frequently in the elderly. CONCLUSION This study is the first and largest renal biopsy series to analyze patients aged ≥65 years in China, and the results obtained from this study may increase the knowledge of renal diseases in elderly patients.

Renal biopsy in type 2 diabetes: timing of complications and evaluating of safety in Chinese patients.

Aim:  It has been recognized that renal lesions in patients with diabetes often have other causes of renal damage concomitantly. Renal biopsy is a valuable tool to provide histological evidence. However, the safety in patients with type 2 diabetes receiving renal biopsy is not well evaluated. This study was conducted to monitor the dynamic complications and to evaluate the safety of biopsy in diabetic patients.

Ultrastructural changes in the glomerular filtration barrier and occurrence of proteinuria in Chinese patients with type 2 diabetic nephropathy.

AIM Diabetic nephropathy (DN) is one of the most important causes of end stage renal disease in the world. Its hallmark is proteinuria. Therefore, we set out to clarify the structural changes that occur in the glomerular filtration barrier in Chinese patients with true type 2 diabetic nephropathy, and to examine the relationship between these structural changes and proteinuria. METHODS 42 Chinese patients with true T2DN were divided into three groups according to urinary protein excretion. Glomerular volume, endothelial cell density, endothelial cell number, glomerular basement membrane (GBM) width, podocyte density, podocyte number and foot process width were evaluated using light and electron microscopic morphometry. RESULT Glomerular volume and endothelial cell number were increased in diabetic patients, but there was no difference between patients with respect to the degree of proteinuria. As proteinuria progressed, endothelial cell density remained unchanged, while the glomerular basement membrane (GBM) and podocyte foot process width increased, podocyte density and number decreased. CONCLUSIONS Podocyte and GBM change more obviously during the development of proteinuria. Besides, proteinuria was inversely related to podocyte density, and directly related to GBM and glomerular volume.

PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with membranous nephropathy

BackgroundThe association between psoriasis and membranous nephropathy (MN) remains largely unclear. We examined the prevalence of serum PLA2R antibody and characterized the expression of PLA2R and THSD7A in glomeruli in patients with MN and psoriasis.MethodsA total of 24 patients with MN without evidence of a secondary cause except psoriasis were enrolled. The clinical and pathological features were retrospectively analyzed. Serum anti-PLA2R antibody was measured using IFA Mosaic. Renal tissue samples stored in the laboratory bio-bank were used for PLA2R staining under immunofluorescence microscopy and THSD7A immunohistochemical analysis.ResultsTwenty-four patients (21 male and 3 female) with a mean age of 43.6 ± 15.7 years old were enrolled. Serum anti-PLA2R antibody was positive in 7 patients, which was significantly lower than the positivity observed in idiopathic MN (29.2% vs. 81.7%, P < 0.001). Glomerular PLA2R staining was positive in 7 patients with positive serum anti-PLA2R antibody. THSD7A staining was negative in all 24 patients. During the follow-up visits, 13 patients with negative serum PLA2R antibody achieved CR. In contrast, CR was only achieved in 1 patient with positive serum PLA2R antibody, PR was achieved in 2 patients.ConclusionsThe prevalence of serum anti-PLA2R antibody and glomerular expression of PLA2R was significantly lower in patients with psoriasis and MN than in those with idiopathic MN, and THSD7A staining was negative, suggesting that MN is associated with psoriasis in the majority of patients. However, idiopathic MN might also accompany psoriasis in a minority of psoriatic patients with positive serum anti-PLA2R antibody.

Comparing the GFR estimation equations using both creatinine and cystatin c to predict the long-term renal outcome in type 2 diabetic nephropathy patients

AIMS This study aimed to determine whether eGFRcre-cys and its slope could improve the prediction of the long-term renal outcome in patients with type 2 diabetic nephropathy (DN). METHODS The cross-sectional and longitudinal analyses included 501 type 2DN patients from 2003 to 2009. GFR was estimated using either eGFRcre-cys or the serum creatinine-based equation (eGFRcre) or the cystatin C-based equation (eGFRcys), and was classified into 3 categories (≥90, 60-90, ≤60ml/min per 1.73m2). The proportion of patients was evaluated in each creatinine-calculated eGFR category for which the category was reclassified based on either cystatin C or the combined measurement. Long-term changes in eGFRcre-cys, eGFRcys and eGFRcre were estimated using linear mixed effect models. The receiver operating characteristic (ROC) curves was applied to study the sensitivity and specificity of different eGFR slopes for predicting the renal endpoint. RESULTS In the cross-sectional analyses, eGFRcre was overestimated compared to eGFRcre-cys [median bias -8.5 (95% CI: -25.01, 1.21)]. The reclassification of eGFRcre to a higher value was associated with an increased risk of ESRD [OR: 4.01 (95% CI: 2.36 to 6.82)]. In the longitudinal analyses for predicting end-stage renal disease (ERSD), the ROC curves for eGFRcre-cys (AUC=0.86±0.03) over 24months were increased compared with the ROC curves for eGFRcre and eGFRcys (p<0.05). CONCLUSIONS The study suggests that the eGFRcre-cys equation may be more precise and sensitive for predicting the renal outcome in T2DN patients. Tracking renal decline using eGFRcre-cys may be used as a surrogate for determining the renal endpoint in a clinical setting.