The effect of rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease.

BACKGROUND: Rituximab is a B cell depleting anti-CD20 monoclonal antibody. CD20 is not expressed on mature plasma cells and accordingly rituximab does not have immediate effects on immunoglobulin levels. However, after rituximab some patients develop hypogammaglobulinaemia. METHODS: We performed a single centre retrospective review of 177 patients with multisystem autoimmune disease receiving rituximab between 2002 and 2010. The incidence, severity and complications of hypogammaglobulinaemia were investigated. RESULTS: Median rituximab dose was 6 g (1-20.2) and total follow-up was 8012 patient-months. At first rituximab, the proportion of patients with IgG <6 g/L was 13% and remained stable at 17% at 24 months and 14% at 60 months. Following rituximab, 61/177 patients (34%) had IgG <6 g/L for at least three consecutive months, of whom 7/177 (4%) had IgG <3 g/L. Low immunoglobulin levels were associated with higher glucocorticoid doses during follow up and there was a trend for median IgG levels to fall after ≥ 6 g rituximab. 45/115 (39%) with IgG ≥ 6 g/L versus 26/62 (42%) with IgG <6 g/L experienced severe infections (p=0.750). 6/177 patients (3%) received intravenous immunoglobulin replacement therapy, all with IgG <5 g/L and recurrent infection. CONCLUSIONS: In multi-system autoimmune disease, prior cyclophosphamide exposure and glucocorticoid therapy but not cumulative rituximab dose was associated with an increased incidence of hypogammaglobulinaemia. Severe infections were common but were not associated with immunoglobulin levels. Repeat dose rituximab therapy appears safe with judicious monitoring

An Unusual Cardiac Manifestation in Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease is a common hereditary disorder characterized by renal and extrarenal, cystic and noncystic manifestations. Connective tissue defects, including cerebral aneurysm, meningeal diverticula, abdominal wall hernias, intestinal diverticula, and cardiac valvular abnormalities, are widely known manifestations. Instead intracardiac aneurysms have never been reported in adults with autosomal dominant polycystic kidney disease. We describe a 65-year-old patient with end-stage renal disease due to autosomal dominant polycystic kidney disease and an atrial septum aneurysm associated with platypnoea-orthodeoxia syndrome

Plasma Exchange for Renal Vasculitis and Idiopathic Rapidly Progressive Glomerulonephritis: A Meta-analysis

BACKGROUND: Plasma exchange may be effective adjunctive treatment for renal vasculitis. We performed a systematic review and meta-analysis of randomized control trials of plasma exchange for renal vasculitis. STUDY DESIGN: Systematic review and meta-analysis of manuscripts identified from electronic databases, bibliographies, and studies identified by experts. Data was abstracted in parallel by two reviewers. SETTING & POPULATION: Adults with idiopathic renal vasculitis or rapidly progressive glomerulonephritis SELECTION CRITERIA FOR STUDIES: Randomized controlled trials that compared standard care with standard care plus adjuvant plasma exchange in adult patients with either renal vasculitis or idiopathic rapidly progressive glomerulonephritis. INTERVENTION: Adjuvant plasma exchange OUTCOME: Composite of end-stage renal disease or death. RESULTS: We identified 9 trials including 387 patients. In a fixed-effects model the pooled relative risk of end-stage renal disease or death was 0.80 for patients treated with adjunctive plasma exchange compared to standard care alone (95% confidence interval 0.65 to 0.99; p=0.04). No significant heterogeneity was detected (p=0.5; I(2)=0%). The effect of plasma exchange did not differ significantly across the range of baseline serum creatinine values (p=0.7) or number of plasma exchange treatments (p=0.8). The relative risk for end-stage renal disease was 0.64 (95% confidence interval 0.47 to 0.88; p=0.006) while the relative risk for death alone was 1.01 (95% confidence interval 0.71 to 1.4; p=0.9). LIMITATIONS: Although the primary result was statistically significant, there is insufficient statistical information to reliable determine if plasma exchange reduces the composite of end-stage renal disease or death. CONCLUSIONS: Plasma exchange may reduce the composite endpoint of end-stage renal disease or death in renal vasculitis. Further trials are required given the limited data available