C3 Glomerulopathy and Related Disorders in Children: Etiology-Phenotype Correlation and Outcomes.

BACKGROUND AND OBJECTIVES: Membranoproliferative GN and C3 glomerulopathy are rare and overlapping disorders associated with dysregulation of the alternative complement pathway. Specific etiologic data for pediatric membranoproliferative GN/C3 glomerulopathy are lacking, and outcome data are based on retrospective studies without etiologic data. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 80 prevalent pediatric patients with membranoproliferative GN/C3 glomerulopathy underwent detailed phenotyping and long-term follow-up within the National Registry of Rare Kidney Diseases (RaDaR). Risk factors for kidney survival were determined using a Cox proportional hazards model. Kidney and transplant graft survival was determined using the Kaplan-Meier method. RESULTS: Central histology review determined 39 patients with C3 glomerulopathy, 31 with immune-complex membranoproliferative GN, and ten with immune-complex GN. Patients were aged 2-15 (median, 9; interquartile range, 7-11) years. Median complement C3 and C4 levels were 0.31 g/L and 0.14 g/L, respectively; acquired (anticomplement autoantibodies) or genetic alternative pathway abnormalities were detected in 46% and 9% of patients, respectively, across all groups, including those with immune-complex GN. Median follow-up was 5.18 (interquartile range, 2.13-8.08) years. Eleven patients (14%) progressed to kidney failure, with nine transplants performed in eight patients, two of which failed due to recurrent disease. Presence of >50% crescents on the initial biopsy specimen was the sole variable associated with kidney failure in multivariable analysis (hazard ratio, 6.2; 95% confidence interval, 1.05 to 36.6; P<0.05). Three distinct C3 glomerulopathy prognostic groups were identified according to presenting eGFR and >50% crescents on the initial biopsy specimen. CONCLUSIONS: Crescentic disease was a key risk factor associated with kidney failure in a national cohort of pediatric patients with membranoproliferative GN/C3 glomerulopathy and immune-complex GN. Presenting eGFR and crescentic disease help define prognostic groups in pediatric C3 glomerulopathy. Acquired abnormalities of the alternative pathway were commonly identified but not a risk factor for kidney failure.

Low serum mannose-binding lectin level is not associated with disease severity in non-cystic fibrosis bronchiectasis.

Deficiency of mannose-binding lectin (MBL), a serum protein involved in killing and promoting phagocytosis of pathogens, is associated with respiratory infection and disease progression in a number of acute and chronic lung diseases, including cystic fibrosis (CF)- associated bronchiectasis. No such association has been studied in non-CF bronchiectasis (nCF-Br). One hundred and thirty-three adult patients with nCF-Br were studied. Serum MBL levels were measured and deficiency defined using two cut-off levels, i.e. MBL ≤100 ng/ml and ≤600 ng/ml. Parameters of severity included lung function impairment, annual exacerbation and hospital admission rates, breathlessness, and Pseudomonas aeruginosa and Haemophilus influenzae infection rates. The incidence of MBL deficiency using cut-off levels of 100 ng/ml and 600 ng/ml was 10% and 26% respectively, similar to rates seen in the general population. There was no significant difference in mean FEV(1)% predicted between MBL deficient and sufficient patients at both cut-off levels (≤100 ng/ml: 63.8% vs. 64.6%, P = 0.91; ≤ 600 ng/ml: 66.5% vs. 63.9%, P = 0.56). In addition, exacerbation/hospital admission rates, symptoms of breathlessness and isolation/colonisation rates with P. aeruginosa and H. influenzae were similar in both groups at both cut-off levels. In conclusion, MBL deficiency is not associated with markers of disease severity in patients with nCF-Br.