No abstract

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.

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.