Extracapillary hypercellularity

Abstract: Pathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P<0.1 were added into successively complex models. ESRD occurred in 56% of patients, and 26% of patients died before reaching ESRD. In univariate analyses, diabetic nephropathy class was not statistically significant in predicting time to ESRD. The final multivariable model (n=106) showed a borderline association between mild mesangial expansion and decreased risk for ESRD (subdistribution HR, 0.64; 95% confidence interval, 0.40 to 1.00). Poor prognostic factors in the final model included segmental sclerosis and extracapillary hypercellularity (subdistribution HR, 2.04; 95% confidence interval, 1.36 to 3.05; and subdistribution HR, 2.21; 95% confidence interval, 1.19 to 4.11, respectively). In conclusion, we identified segmental sclerosis and extracapillary hypercellularity as novel, poor prognostic indicators of time from DKD to ESRD. Whether these indicators represent a distinct pathogenetic phenotype of DKD will require a large study with a broad spectrum of disease severity.

Abstract: The Oxford classification (OC) of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as predictors of outcome. We aimed to validate the OC and to investigate the clinical significance of extracapillary hypercellularity and IgG immunostaining. We examined the renal outcome at December 31, 2014, of 121 adult patients with biopsy proven primary IgAN between 2003 and 2013. The primary endpoint was doubling of serum creatinine or renal replacement therapy initiation. The mean observation period was 59.7 months. Thirty-one percent of the patients presented with a grade of extracapillary hypercellularity. In comparison with the group with no crescents, they had higher grade of inflammation, lower eGFR and increased proteinuria. There were no differences between the IgA and IgA&IgG immunostaining groups regarding the disease progression risk factors. Mean kidney survival time for the entire cohort was 10.6 (9.1, 12.0) years. In the Cox regression model, the independent predictors of decreased renal survival were eGFR at time of biopsy, S1 and the presence of crescents. Our study showed that extracapillary proliferation and S1 had the greatest importance in establishing the renal prognosis of patients with IgAN.

Abstract: Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Abstract: The moral of the story is that the implementation of the Bowman’s capsule rupture (BCR) in prognostic classification systems is still lacking1 BCR is a common final step of the crescent formation2 for many different glomerular diseases characterised by extracapillary hypercellularity, as in anti-glomerular basement membrane (GBM) disease,3 lupus nephritis, IgA nephropathy and glomerulonephritis in the setting of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) Although the consequences of BCR in …