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Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14±3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3-5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0±1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy.

The clinical spectrum of renal dysplasia includes the non-functioning multicystic dysplastic kidney (MCDK). We report our experience of the outcome of unilateral MCDK and its contralateral kidney in 101 children with the diagnosis of MCDK from 1985 to 2009. Data collected included urine protein/creatinine ratio, estimated GFR (eGFR), blood pressure, surgical intervention, renal length and abnormalities of the contralateral kidney, and the involution rate. There was a predominance of left-sided MCDK. Diagnosis was made prenatally in 86.7%. Contralateral abnormalities included vesicoureteral reflux (16.8%), UPJ obstruction (4.1%), and megaureter (2.4%). Complete involution of MCDK occurred within 5 years in 60%. Compensatory hypertrophy of the contralateral kidney to >97% occurred in 74.1%. Nephrectomy was performed in 19.8%. There was an increased risk of chronic kidney disease (CKD) stage ≥ 2, and hypertension in those with contralateral abnormalities (p<0.0001; p<0.001 respectively). In those without contralateral abnormalities, hyperfiltration with mean eGFR of 149 ± 13 ml/min/1.73 m(2) was seen in 32% and proteinuria in 9.8%. There was a significantly inverse relationship between proteinuria and eGFR (p<0.0001). In conclusion, children with contralateral abnormalities are at risk for developing decreased kidney function, whereas a substantial number of patients with no obvious contralateral abnormalities have markers of renal injury. Therefore, systematic follow-up of all patients is recommended.

FGF-23 levels are strongly associated with increased LVMI and with prevalent LVH in pediatric hemodialysis patients. Our cross-sectional findings provide observational evidence supporting the hypothesis linking FGF-23 to cardiac hypertrophy in patients with chronic kidney disease.

Preterm birth is associated with decreased nephron mass and obesity that may impact on kidney disease progression in later life. Our objectives were to examine the relative risks of obesity and preterm birth on the progression of kidney disease in children. In a retrospective cohort study, 80 (44 obese and 36 non-obese) patients with proteinuric kidney disease were studied for disease progression and glomerular histomorphometry. Of the obese, 22 had been born at term (Obese-T) and 22 had been preterm (Obese-PT). Seventeen non-obese children with focal glomerular sclerosis, born at term (NO-FSGS), and 19 non-obese preterm (NO-PT) children, served as controls. Insulin resistance as measured by the homeostatic model assessment (HOMA-IR) was elevated in all obese children. Obese-PT patients had increased risk of renal demise during childhood when compared with Obese-T children [hazard ratio 2.4; 95% Confidence interval (95% CI) 1.1 to 7.1; P = 0.04]. In obese children, although proteinuria often exceeded nephrotic range, average levels of serum albumin remained normal. Preterm patients were more likely to have reduced renal mass (odds ratio 4.7; P = 0.006), but obesity was not a factor. Renal histomorphometry showed glomerulomegaly in obese patients, regardless of birth weight. Obesity and preterm birth appear to impose additive risks for progression of kidney disease in childhood.

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SummaryBackground and objectives Childhood-onset lupus nephritis (LN) carries a worse renal prognosis compared with adults. Controlled treatment trials in children are lacking. We compared renal and patient survival in a cohort of pediatric patients followed over 3 decades.

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