Differences in Initial Hemodialysis Vascular Access Use Among Glomerulonephritis Subtypes in the United States.

BACKGROUND: The type of vascular access used for hemodialysis affects patient morbidity and mortality. Whether vascular access types differ by glomerulonephritis (GN) subtype in the US hemodialysis population has not been investigated. STUDY DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: We identified all adult (aged ≥ 18 years) patients within the US Renal Data System who initiated hemodialysis therapy from July 2005 through December 2011 with a diagnosis of end-stage renal disease attributed to any of 4 primary (focal segmental glomerulosclerosis, immunoglobulin A nephropathy [reference group], membranous nephropathy, and membranoproliferative GN) or 2 secondary (lupus nephritis and vasculitis) GN subtypes. PREDICTOR: GN subtype. OUTCOMES: ORs with 95% CIs for arteriovenous fistula versus central venous catheter (CVC) use and for arteriovenous graft versus CVC use were computed using multinomial logistic regression, with adjustment for demographic, socioeconomic, comorbidity, and duration of nephrology care covariates. RESULTS: Among 29,015 patients, CVC use at initiation of hemodialysis therapy was substantially higher in patients with lupus nephritis (89.2%) or vasculitis (91.2%) compared with patients with primary GN subtypes (72.7%-79.8%). After adjustment and compared with patients with immunoglobulin A nephropathy, patients with lupus nephritis or vasculitis were as likely to have used an arteriovenous graft (ORs of 0.94 [95% CI, 0.70-1.27] and 0.80 [95% CI, 0.56-1.13], respectively) but significantly less likely to have used an arteriovenous fistula (ORs of 0.66 [95% CI, 0.57-0.76] and 0.54 [95% CI, 0.45-0.63], respectively), whereas patients with any comparator primary GN subtype were at least as likely to have used either of these 2 access types. LIMITATIONS: Potential misclassification of exposure; residual confounding by unmeasured covariates; inability to determine causes of observed associations; lacking longitudinal data for vascular access use. CONCLUSIONS: Significant differences in vascular access distributions at initiation of hemodialysis therapy are apparent among GN subtypes. The unacceptably high use of CVCs in patients with lupus nephritis and vasculitis is particularly concerning. Further studies are needed to identify any potentially modifiable factors underlying these findings.

Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN.

Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m(2) Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m(2)with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death.

Characterization of a factor H mutation that perturbs the alternative pathway of complement in a family with membranoproliferative GN.

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.