Risk Stratification to Predict Renal Survival in Anti–Glomerular Basement Membrane Disease

Abstract

Anti-glomerular basement membrane (GBM) disease is a rare, aggressive vasculitis with no validated prediction tools to assist its management. We investigated a retrospective multicenter international cohort with the aim to transfer the Renal Risk Score (RRS) and to identify patients that benefit from rescue immunosuppressive therapy.Of a total 191 patients, 174 patients were included in the final analysis (57% female, median age 59 years). Using Cox and Kaplan-Meier methods, the RRS was found to be a strong and effective predictor for end stage kidney disease (ESKD) with a model concordance of C=0.760. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-, moderate-, and high-risk groups, respectively (P<0.001). The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD (P<0.001, P<0.001).Considering the 129 patients initially requiring RRT, the best predictor for renal recovery was the percentage of normal glomeruli (C=0.622; P<0.001), a split either side of 10% providing good stratification. A model with the predictors RRT and normal glomeruli (N) achieved superior discrimination (C=0.840, P<0.001). Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N≥10%), 74.0% (no RRT, N<10%), 42.3% (RRT, N≥10%) and 14.1% (RRT, N<10%), respectively.In summary, we demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Here, we propose a stratification to assist in the management of anti-GBM disease.

Evaluation of the Risk Prediction Models in Predicting Kidney Outcomes in Antiglomerular Basement Membrane Disease

“…The definition of ESKD, kidney recovery, and normal glomeruli were as follows, as described previously by Floyd et al. 15 : (i) ESKD is maintenance of RRT lasting at least 12 weeks and up to the last follow-up; (ii) kidney recovery is independence from RRT lasting at least 12 weeks during follow-up; (iii) normal glomeruli are glomeruli that did not exhibit any glomerulosclerosis, crescents, or fibrinoid necrosis. Biopsies were reviewed by an experienced nephropathologist who was blinded to the outcome.…”

“… 14 The RRS was transferred to predict kidney survival of anti-GBM disease recently by Floyd et al. 15 The authors demonstrated that combining RRT at presentation with the histological parameter of N, in the setting of the risk stratification method, might be a valuable prognostic tool for predicting ESKD in patients with anti-GBM disease. 16 Nevertheless, both models require evaluation for their predictive power regarding kidney outcomes before being widely utilized in practice.…”

Goodpasture syndrome and anti-glomerular basement membrane disease

“…Dialysis dependence at admission and creatinine levels >4.7 mg/dL remained independent significant predictors of ESKD in the multivariable analysis (127). Also another study demonstrated that renal survival may be accurately predicted using a model with need for renal replacement therapy and the proportion of normal glomeruli as predictors (128). Another indicator of poor renal outcome is complement component 3 (C3).…”

Anti-GBM disease in pregnancy

“…Antiglomerular basement membrane (Anti-GBM) disease is a rare and aggressive vasculitis characterised by the triad of rapidly progressive glomerulonephritis, pulmonary haemorrhage and the presence of circulating anti-GBM antibodies 1. Anti-GBM disease in pregnancy is an absolute rarity and the few reported cases resulted in severely preterm babies or mothers recovering from Anti-GBM disease following termination of early pregnancy 2.…”