Clinical and Histologic Determinants of Renal Outcome in ANCA-Associated Vasculitis

Abstract

This study aimed to identify clinical and histologic prognostic indicators of renal outcome in patients with ANCA-associated vasculitis and severe renal involvement (serum creatinine >500 mol/L). One hundred patients who were enrolled in an international, randomized, clinical trial to compare plasma exchange with intravenous methylprednisolone as an additional initial treatment were analyzed prospectively. Diagnostic renal biopsies were performed upon entry into the study. Thirty-nine histologic and nine clinical parameters were determined as candidate predictors of renal outcome. The end points were renal function at the time of diagnosis (GFR 0 ) and 12 mo after diagnosis (GFR 12 ), dialysis at entry and 12 mo after diagnosis, and death. Multivariate analyses were performed. Predictive of GFR 0 were age (r ‫؍‬ ؊0.40, P ‫؍‬ 0.04), arteriosclerosis (r ‫؍‬ ؊0.53, P ‫؍‬ 0.01), segmental crescents (r ‫؍‬ 0.35, P ‫؍‬ 0.07), and eosinophilic infiltrate (r ‫؍‬ ؊0.41, P ‫؍‬ 0.04). Prognostic indicators for GFR 12 were age (r ‫؍‬ ؊0.32, P ‫؍‬ 0.01), normal glomeruli (r ‫؍‬ 0.24, P ‫؍‬ 0.04), tubular atrophy (r ‫؍‬ ؊0.28, P ‫؍‬ 0.02), intraepithelial infiltrate (r ‫؍‬ ؊0.26, P ‫؍‬ 0.03), and GFR 0 (r ‫؍‬ 0.29, P ‫؍‬ 0.01). Fibrous crescents (r ‫؍‬ 0.22, P ‫؍‬ 0.03) were predictive of dialysis at entry. Normal glomeruli (r ‫؍‬ ؊0.30, P ‫؍‬ 0.01) and treatment arm (r ‫؍‬ ؊0.28, P ‫؍‬ 0.02) were predictive of dialysis after 12 mo. No parameter predicted death. Both chronic and acute tubulointerstitial lesions predicted GFR 12 in severe ANCA-associated glomerulonephritis, whereas plasma exchange was a positive predictor of dialysis independence after 12 mo for the entire patient group. Plasma exchange remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately (r ‫؍‬ ؊0.36, P ‫؍‬ 0.01). Normal glomeruli were a positive predictor of dialysis independence and improved renal function after 12 mo, indicating that the unaffected part of the kidney is vital in determining renal outcome.

Advances in apheresis therapy for glomerular diseases

“…In this study, PE was a positive predictor of dialysis independence after 12 mo for the entire patient group. PE remained a positive predictor when patients who were dialysis dependent at presentation were analyzed separately [22]. These results supporting a beneficial role of apheresis in whole small-vessel vasculitides is still small, but dialysis-dependent patients are the group who may have a benefit by PE in the presence of severe systemic diseases or high risks for complications such as infection.…”

“…The effectiveness of PE has been reported in some patients with rapidly progressive glomerulonephritis (RPGN), in which ANCA-associated vasculitis is the most common cause. In 6 randomized controlled trials [17][18][19][20][21][22], there was no statistically significant benefit from plasma exchange in a whole group, however. The significant difference was reported in the dialysis-dependent group with RPGN and systemic involvement, in which 10 out of 11 patients treated by PE and 3 of 8 control patients recovered renal function by 4 weeks in previous studies.…”

The New Histopathologic Classification of ANCA-Associated GN and Its Association with Renal Outcomes in Childhood

“…Our study also lacked power to ascertain other factors from within the crescentic/mixed group apart from need for dialysis and degree of proteinuria, which may provide further prognostic information. Perhaps other pathologic factors, such as tubular atrophy and interstitial fibrosis or the degree of CD3+ tubulitis, may help in this regard in future studies (9,(23)(24)(25).…”

“…Preceding that, various pathologic criteria, including percentage of normal glomeruli, degree of chronic (sclerotic) lesions, and active (crescentic) lesions predicted kidney outcomes in several studies (8)(9)(10). Collating these data, the working group proposed a novel and intuitive schema classifying the renal histopathologic features into four distinct categories: focal, crescentic, mixed, and sclerotic.…”

S1 guidelines Diagnostics and treatment of ANCA-associated vasculitis

“…Nierenbiopsien liefern dagegen eine hohe diagnostische Ausbeute mit spezifischen Veränderun-gen (nekrotisierende Glomerulonephritis 85 %, Halbmondbildung 92 %) [2]. Die Ergebnisse der Nierenbiopsie haben zudem einen prognostischen Wert, da aktuell entzündliche (und therapeutische beeinflussbare) Veränderungen von bereits eingetretenen irreversiblen Schäden differenziert werden können, was Einfluss aufdie Wahl derTherapie habenkann [13,75,89,134,136,233,245]. Ebensokönnen Nierenfunktionseinschränkungen durch andere Begleiterkrankungen wie Diabetes mellitus oder arterielle Hypertonie abgegrenzt werden.…”