Determinants of renal and patient outcomes in a Spanish cohort of patients with ANCA-associated vasculitis and renal involvement

Abstract

The classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remains controversial. The main objective of this study was to define the respective values of ANCA serotype-based classification, clinicopathological classification, and histopathological classification in predicting patient and renal outcomes in a Spanish cohort of patients with ANCA with specificity for myeloperoxidase, MPO-ANCA, versus ANCA with specificity for proteinase 3, PR3-ANCA. Two hundred and forty-five patients with ANCA-AAV and biopsy-proven renal involvement diagnosed between 2000 and 2104 were recruited in 12 nephrology services. Clinical and histologic data, renal outcomes, and mortality were analyzed. We applied the Chapel Hill Consensus Conference definition with categories for granulomatosis with the polyangiitis (GPA) and microscopic polyangiitis (MPA), the classification based on ANCA specificity, and the histopathological classification proposed in 2010. Eighty-two percent were MPO-ANCA positive and 18.0% PR3-ANCA positive. Altogether, 82.9% had MPA and 17.1% GPA. The median follow-up was 43.2 months (0.1-169.3). Neither ANCA-based serological nor clinical classification was predictive of renal outcomes or patient survival on bivariate or multivariate Cox regression analysis. Histopathological classification was found to predict development of end-stage renal disease (p = 0.005) in Kaplan-Meier analysis. ANCA specificity was more predictive of relapse than clinicopathological classification in multivariate analysis (HR 2.086; 95% CI 1.046-4.158; p = 0.037). In our Spanish cohort, a majority of patients had an MPO-ANCA-AAV. A classification based on ANCA specificity has a higher predictive value for relapse occurrence and could be used for decision-making with respect to induction treatment and maintenance therapies.

Serum uromodulin is associated with the severity of clinicopathological findings in ANCA-associated glomerulonephritis

“…The focal class, containing ≥50% of normal glomeruli, has the best renal survival, while the sclerotic class, containing ≥50% of global sclerotic glomeruli, has the worst renal survival among the categories. These results have been reproduced in other clinical studies [19, 21]. In this study, the renal survival of the focal class was 100% during our observation period, which was the best survival rate.…”

“…In 2010, a renal histopathological classification of AAG in European patients was proposed, and the four general categories (focal, crescentic, mixed, and sclerotic) significantly correspond to renal survival [18]. This histological classification has been validated for various ethnic groups and countries, and its usefulness has been established [19–21]. Concerning renal prognosis, the focal class has good prognosis, while the sclerotic class has poor prognosis, findings that have been repeatedly reproduced [19–21].…”

“…This histological classification has been validated for various ethnic groups and countries, and its usefulness has been established [19–21]. Concerning renal prognosis, the focal class has good prognosis, while the sclerotic class has poor prognosis, findings that have been repeatedly reproduced [19–21]. Although renal biopsies have an essential role in the diagnosis and treatment of various kidney diseases, this invasive procedure is sometimes associated with bleeding, which can be lethal, especially among elderly patients.…”

Efficacy of Rituximab and Plasma Exchange in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis with Severe Kidney Disease

“…48,49 In our cohort, patients presented with a mean eGFR value of 16.3 ml/min per 1.73 m 2 , similar to the values reported in other smaller cohorts. 9,10 The presence of MPO-ANCA (versus PR3-ANCA) has previously been reported as a determinant of renal outcome, 5,50,51 but multivariable modeling did not identify it as a risk factor for the development of severe renal disease in our cohort. Moreover, we showed that the presence of classic cardiovascular risk factors and increased age appear to aggravate the susceptibility of the kidney for severe renal disease in ANCA-associated GN.…”

Relapse rate and renal prognosis in ANCA-associated vasculitis according to long-term ANCA patterns

“…We have also found that patients with anti‐MPO vasculitis and a recurrent ANCA pattern were more prone to worsening renal function. It is generally accepted that patients with anti‐MPO antibodies have a worse renal prognosis and a higher risk of progression to ESRD than patients with anti‐PR3 antibodies [24,27–33], although not all studies have confirmed this association [34–36]. Patients with anti‐MPO antibodies usually have more glomerulosclerosis and interstitial fibrosis on renal biopsies than patients with anti‐PR3 antibodies [30,32,34,36].…”