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Hypocomplementemia is associated with more severe renal disease and worse renal outcomes in patients with ANCA-associated vasculitis: a retrospective cohort study.

ABSTRACT: BACKGROUND:The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV. METHODS:This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared. RESULTS:In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p = 0.006), were more often hemodialysis dependent (64% vs. 19%, p = 0.009) and progressed more often to ESRD (55% vs. 11%, p = 0.01) compared to normo-complementemic patients (n = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62, p = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567; p = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p = 0.033), low serum C3 levels (42% vs. 18%, p < 0.001) and serious infections during follow-up (57% vs. 18%, p = 0.047) compared to those with negative (n = 11) IF staining. CONCLUSION:Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

SUBMITTER: Chalkia A

PROVIDER: S-EPMC7472496 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMore effective and safer treatments are needed for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.MethodsWe conducted a randomized trial with a 2-by-2 factorial design to evaluate the use of plasma exchange and two regimens of oral glucocorticoids in patients with severe ANCA-associated vasculitis (defined by an estimated glomerular filtration rate of <50 ml per minute per 1.73 m2 of body-surface area or diffuse pulmonary hemorrhage). Patients were randomly assigned to undergo plasma exchange (seven plasma exchanges within 14 days after randomization) or no plasma exchange (control group). Patients were also randomly assigned to follow either a standard-dose regimen or a reduced-dose regimen of oral glucocorticoids. Patients were followed for up to 7 years for the primary composite outcome of death from any cause or end-stage kidney disease (ESKD).ResultsDeath from any cause or ESKD occurred in 100 of 352 patients (28.4%) in the plasma-exchange group and in 109 of 352 patients (31.0%) in the control group (hazard ratio, 0.86; 95% confidence interval [CI], 0.65 to 1.13; P = 0.27). The results were similar in subgroup analyses and in analyses of secondary outcomes. We also assessed the noninferiority of a reduced-dose regimen of glucocorticoids to a standard-dose regimen, using a noninferiority margin of 11 percentage points. Death from any cause or ESKD occurred in 92 of 330 patients (27.9%) in the reduced-dose group and in 83 of 325 patients (25.5%) in the standard-dose group (absolute risk difference, 2.3 percentage points; 90% CI, -3.4 to 8.0), which met the criterion for noninferiority. Serious infections at 1 year were less common in the reduced-dose group than in the standard-dose group (incidence rate ratio, 0.69; 95% CI, 0.52 to 0.93), but other secondary outcomes were similar in the two groups.ConclusionsAmong patients with severe ANCA-associated vasculitis, the use of plasma exchange did not reduce the incidence of death or ESKD. A reduced-dose regimen of glucocorticoids was noninferior to a standard-dose regimen with respect to death or ESKD. (Funded by the U.K. National Institute for Health Research and others; PEXIVAS Current Controlled Trials number, ISRCTN07757494; ClinicalTrials.gov number, NCT00987389.).

Project description:AbstractTreatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m2 vs 35 ± 26 mL/min/1.73 m2, P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m2 vs +6.0 ± 1.1 mL/min/1.73 m2, P = .33). The 2.5-3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2-6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1-4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.

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Hypocomplementemia is associated with more severe renal disease and worse renal outcomes in patients with ANCA-associated vasculitis: a retrospective cohort study.

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