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Abstract
Background and Aims
Kidney biopsy is the gold standard for establishing the diagnosis of ANCA-associated glomerulonephritis (GN). Previous studies have validated the prognostic significance of histopathological classification for the development of end stage renal disease (ESRD). We sought to evaluate the prognostic value of the EUVAS histopathological classification in terms of renal and overall survival (OS) in a single center retrospective cohort study.
Method
Forty-six consecutive patients (mean age 69, range; 29-84 years) with biopsy-proven ANCA-associated GN diagnosed at our hospital between January 2003 and January 2019 were included in the study. All biopsies had ≥10 glomeruli and were reviewed by two independent pathologists blinded to clinical data. Renal morphology was classified as sclerotic (if ≥50% globally sclerotic glomeruli), focal (if ≥50% normal glomeruli), crescentic (if ≥50% crescents with cellular component) and mixed. Probabilities of renal and overall survival were estimated using Kaplan-Meier method. Cumulative incidence function for ESRD was estimated using death as competing risk.
Results
Three biopsies were classified as focal (6%), twenty-nine as crescentic (63%), ten as mixed (22%) and four as sclerotic (9%). With a median follow-up of 39 months the 3-year probability of renal survival was 100% for the focal class, 66,37% for the crescentic class, 64% for the mixed class and 50% for the sclerotic class (p>0.05). Other parameters associated with increased probability of ESRD were interstitial fibrosis (IF) and eGFR at time of diagnosis. IF of ≥40% at diagnosis was associated with high incidence of ESRD, while IF of 20-40% and <20% had significantly lower incidence of ESRD (100% vs 34.2% vs 17.6%, p=0.014). Half (50%) of the patients with eGFR<15ml/min at diagnosis developed ESRD at 36 months compared to only 8% of the patients with eGFR≥15ml/min (p=0.024) at diagnosis. Median overall survival for the entire cohort reached 128 months (95% CI; 35-221). Twelve patients died at median time of 19,5 months (range; 3-129) after diagnosis. Three patients died before developing ESRD and nine patients developed ESRD prior to death. Leading cause of death was sepsis (8/12). Other causes included sudden death (n=2), malignancy (n=1) and intestinal obstruction (n=1). In terms of histopathological classification, OS at 3 years was 100% (95% CI; N/A) for the focal class, 73.5% (95% CI; 57-94.8) for the crescentic class, 100% (95% CI; N/A) for the mixed class and 37,5% (95% CI; 83,9-100) for the sclerotic class (p>0.05).
Conclusion
Our results suggest that the focal class has the best and the sclerotic the worst outcome, while both crescentic and mixed subtype are of intermediate risk. Although our results did not reach statistical significance, due to primarily the small number of patients included, the incidence of ESRD and the probability of renal survival in each histopathological subtype in our cohort are comparable to those reported by larger studies. Thus, the EUVAS histological classification of ANCA-associated glomerulonephritis appears to be a useful predictor of renal outcome at the time of diagnosis. As previously reported, no significant prognostic difference was observed between the crescentic and mixed subtype. Thus, this classification system should be optimized by inclusion of other histological characteristics, such as the specific percentage of normal glomeruli, tubular atrophy and interstitial fibrosis. These characteristics may prove useful in highlighting significant differences between mixed and crescentic classes.