Female or black patients, or those with severe kidney disease, may be resistant to initial treatment more often than other patients with ANCA-associated small-vessel vasculitis. Increased risk for relapse appears to be related to the presence of lung or upper airway disease and anti-PR3 antibody seropositivity.

Objectives Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis is a complex disease, with much debate about the utility of systems for classification and diagnosis. We compared three currently used classification systems in predicting disease prognosis. Methods Three classification systems were applied to 502 patients with biopsy proven ANCA vasculitis: the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA, Wegener’s granulomatosis), microscopic polyangiitis (MPA) and the Kidney Limited Disease (KLD); European Medicines Agency (EMA) system with categories for GPA and MPA, and classification based on ANCA specificity (PR3 versus MPO). Outcomes included treatment resistance, relapse, end stage kidney disease (ESKD) and death. Proportional hazards models were compared between systems using an information-theoretic approach to rank models by predictive fit. Hazard Ratios (HR) with 95% confidence intervals (CI) and p-values are reported. Results ANCA specificity was predictive of relapse, with PR3-ANCA patients almost twice as likely as those with MPO-ANCA to relapse (HR=1.89, 95% CI=1.33–2.69, p=0.0004), and ANCA specificity had the best predictive model fit (Model Rank=1) compared to CHCC and EMA. CHCC and EMA systems did not predict relapse. By ANCA specificity, categories of GPA, MPA and KLD did not distinguish differences in probability of relapse-free survival. None of the systems predicted treatment resistance, ESKD or death. Conclusion ANCA specificity independently predicts relapse among patients with ANCA vasculitis with renal disease. Classification and diagnostic systems that incorporate ANCA specificity, such as PR3-ANCA-MPA and MPO-ANCA-MPA, provide a more useful tool for predicting relapse than the clinic pathologic category alone.

The Nephrotic Syndrome Study Network (NEPTUNE) is a North American multi-center collaborative consortium established to develop a translational research infrastructure for Nephrotic Syndrome. This includes a longitudinal observational cohort study, a pilot and ancillary studies program, a training program, and a patient contact registry. NEPTUNE will enroll 450 adults and children with minimal change disease, focal segmental glomerulosclerosis and membranous nephropathy for detailed clinical, histopathologic, and molecular phenotyping at the time of clinically-indicated renal biopsy. Initial visits will include an extensive clinical history, physical examination, collection of urine, blood and renal tissue samples, and assessments of quality of life and patient-reported outcomes. Follow-up history, physical measures, urine and blood samples, and questionnaires will be obtained every 4 months in the first year and bi-annually, thereafter. Molecular profiles and gene expression data will be linked to phenotypic, genetic, and digitalized histologic data for comprehensive analyses using systems biology approaches. Analytical strategies were designed to transform descriptive information to mechanistic disease classification for Nephrotic Syndrome and to identify clinical, histological, and genomic disease predictors. Thus, understanding the complexity of the disease pathogenesis will guide further investigation for targeted therapeutic strategies.

Histologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) may have prognostic value. A recent working classification system has distinguished five FSGS variants. We evaluated a cohort of adult patients with biopsy-proven FSGS diagnosed between March 1982 and July 2001 to determine if subtypes were associated with renal outcome. Renal biopsies were reviewed by two pathologists. Demographic and clinical data were obtained from charts. Outcomes were partial and complete remission of the nephrotic syndrome, and renal failure. The frequency of FSGS variants was: 3% cellular (N=6), 11% collapsing (N=22), 17% tip lesion (N=34), 26% perihilar (N=52), and 42% not otherwise specified (NOS) (N=83). Collapsing FSGS affected younger and more often black patients. Black race was uncommon in tip variant. Collapsing and tip variants had higher proteinuria and lower serum albumin than perihilar and NOS variants. Better renal function and less severe tubulointerstitial injury were observed in patients with tip variant. These patients were more likely to receive steroids and more often achieved complete remission (50%). After a median follow-up of 1.8 years, 23% of patients were on dialysis and 28% had renal failure. Collapsing FSGS had worse 1-year (74%) and 3-year (33%) renal survival compared to other variants (overall cohort renal survival at 1 and 3 years: 86 and 67%). Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes.

Intravenous cyclophosphamide is widely used to treat severe lupus nephritis. Yet interpretation of the literature is limited by the small number of patients evaluated with varied renal histology. We analyzed the renal outcome of cyclophosphamide therapy for diffuse proliferative lupus glomerulonephritis in a cohort of 89 patients from the Glomerular Disease Collaborative Network. Statistical analysis included Wilcoxon rank sum tests or continuity-adjusted chi-square for comparisons between groups. Kaplan-Meier survival function estimates were calculated for renal survival curves. Cox's proportional hazards models were employed for multivariate evaluation. The renal survival rate declined yearly from 89%, to 86%, 81%, 75%, and 71% at year 5. Renal survival was significantly worse in blacks compared with white patients. Among white patients 95% retained renal function at year 5 whereas black patients showed a progressive yearly decline from 85% at year 1, to 79%, 72%, 62%, and 58% at year 5. Racial differences in renal outcome were independent of age, duration of lupus, history of hypertension, hypertension control during therapy, and activity or chronicity indices on renal biopsy. The factors that predispose black patients to more aggressive and treatment-resistant lupus nephritis are not apparent.