Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure

Abstract

Background and objectives: In ANCA-associated GN, severe renal dysfunction portends a poor prognosis for renal recovery and patient survival. This study evaluated the prognostic factors affecting renal and patient outcomes in patients presenting with severe kidney failure to guide immunosuppressive therapy.

Design, setting, participants, & measurements: This study retrospectively evaluated clinical and histopathologic characteristics of 155 patients who underwent biopsy between October 1985 and February 2011 (median eGFR at presentation, 7.1 ml/min per 1.73 m(2); 87% required hemodialysis), all treated with immunosuppressive medications. Three outcomes of interest were measured: patient survival, renal survival, and treatment response (defined as dialysis-free survival without active vasculitis by 4 months after biopsy). Competing risk, Cox, and logistic regression analyses were conducted for each outcome measure.

Results: Within 4 months after biopsy, treatment response was attained in 51% of patients, 35% remained on dialysis, and 14% died. In a competing risk analysis, estimated cumulative incidence rates of ESRD and disease-related mortality were 26% and 17% at 1 year and 32% and 28% at 5 years, respectively. Cyclophosphamide therapy and treatment response by 4 months were independently associated with patient and renal survival, adjusting for the percentage of normal glomeruli, histopathologic chronicity index score, and baseline clinical characteristics. Only 5% of patients still dialysis dependent at 4 months subsequently recovered renal function. Low chronicity index score (odds ratio [OR], 1.16; 95% confidence interval [95% CI], 1.04 to 1.30, per unit decrease) and baseline eGFR>10 ml/min per 1.73 m(2) (OR, 2.77; 95% CI, 1.09 to 7.01) were significantly associated with treatment response by 4 months. Among cyclophosphamide-treated patients, the likelihood of treatment response was >14% even with highest chronicity index score and eGFR<10 ml/min per 1.73 m(2).

Conclusions: Although low baseline renal function and severe renal scarring are associated with lower treatment response rate, no "futility" threshold could be identified. Conversely, continued immunosuppressive therapy beyond 4 months is unlikely to benefit patients who remain dialysis dependent.

Keywords: ANCA; glomerulonephritis; vasculitis.

Figure 1.

Clinical outcomes: the treatment response beyond 4 months after biopsy is uncommon. Treatment response was defined as dialysis independence, with eGFR>20 ml/min per 1.73 m², and without clinical sign of active vasculitis. Six of 16 were positive with anti–glomerular basement membrane antibody, and 6 had combined immune complex–mediated GN; the remaining 4 patients had membranoproliferative GN, cryoglobulin-associated necrotizing crescentic GN, fibrillary GN, and Takayasu vasculitis, respectively. ANCA-GN, ANCA-associated GN; GDCN, Glomerular Disease Collaborative Network; Tx, treatment.

Figure 2.

Cause of death according to time periods after diagnosis. Horizontal axis labels show time periods after biopsy. Other causes of dialysis represent death in dialysis-independent patients without signs of active vasculitis. CV event, cardiovascular events defined as acute coronary syndromes, strokes, or sudden cardiac deaths.

Figure 3.

Probability of cumulative incidence of ESRD, disease-related death, or death from other cause for the entire cohort. The bold line shows the cumulative incidence of ESRD, after adjusting for competing risk, mortality from disease-related causes, and others. Patients who required dialysis at presentation and never recovered renal function were considered to be at ESRD after 3 months. Mortality from other causes represents those unrelated to ANCA disease and/or ESRD.

Figure 4.

Among cyclophosphamide-treated patients, the likelihood of treatment response was >14% (lowest confidence limit) even with highest chronicity index score and eGFR<10 ml/min per 1.73 m². Chronicity index score (0–16 points) is sum of semiquantitative measurements on four items: glomerular sclerosis, crescent sclerosis, interstitial fibrosis, and tubular atrophy. Each point and error bars represents estimated mean probability and its 95% confidence intervals. eGFR, ml/min per 1.73 m².