For over 30 years cyclophosphamide (CYC) and chlorambucil (CHL) have been used to treat children with relapsing steroid-sensitive nephrotic syndrome (SSNS). A meta-analysis on treatment protocols, efficacy, and side effects of CYC and CHL was performed from the literature. Thirty-eight studies comprising 1,504 children and 1,573 courses of cytotoxic drug therapy were systematically evaluated. Relapse-free survival rates increased with the cumulative dosage of CHL and CYC and were higher in children with frequently relapsing than steroid-dependent NS. The fatality rate of the treatment was approximately 1%. Leukopenia occurred in one-third of patients treated with either drug. Severe bacterial infections developed in 1.5% of the patients under CYC and in 6.8% under CHL. Seizures were observed in 3.6% of children treated with CHL. Malignancies were observed in 14 children after high doses of either drug. Females rarely developed permanent gonadal damage. However, no safe threshold for a cumulative amount of CYC was found in males, but there was a marked increase in the risk of oligo- or azoospermia with higher cumulative doses. From this meta-analysis we recommend CYC 2-3 mg/kg body weight for 8-12 weeks as the standard scheme. CHL has higher rates of severe side effects and should be considered a second-line drug.

The results indicate that renal transplantation in children leads to a high degree of rehabilitation in adulthood. The life of a kidney transplant, however, is limited, which points out the need for more specific immunosuppression with fewer side-effects in order to reach the goal of lifelong graft function.

Addition of basiliximab induction to a regimen of cyclosporine microemulsion, mycophenolate mofetil, and steroids resulted in a numerically lower but not significant incidence of biopsy-proven acute rejection versus placebo and excellent graft and patient survival at 1 year in pediatric renal transplant recipients. Whether this numerical difference is a true therapeutic benefit in view of the higher rate and severity of subclinical rejections in the basiliximab group in the protocol biopsy will be investigated in a long-term follow-up study.

Reported frequencies of non-compliance in children with end-stage renal disease range from 8% to 70% with a mean around 40%. Sequelae amount to momentous emotional and financial burdens, including the loss of 7% of transplanted organs. Reasons for non-compliance have too often been attributed selectively to the patients (e.g., emotional, mental, social, or communication problems). Compared with general compliance research, this selective attribution appears to be too simplistic. Selective attribution neglects the patients' experiences within the context of disease and treatment and prevents open communication about non-compliance. Research on personal reasons for non-compliance is scarce. In psychological interviews, a third of our 85 patients with end-stage renal disease (34 boys, 51 girls, mean age 12.7 years, range 7.4-19.3 years) communicated psychologically meaningful reasons for non-compliance, frequently related to interrelational and systemic treatment conditions. Patients indirectly asked for more communication about their subjective reasons for non-compliance.

C hronic kidney disease (CKD) affects more than 10% of people worldwide. 1 Renal fibrosis is the common endpoint of most CKD. 2 Therefore, preventing or

Primary hyperoxaluria type I is a metabolic disorder caused by the deficiency of the peroxisomal alanine:glyoxylate aminotransferase. The disease is inherited as an autosomal recessive trait. The clinical course is outlined based on data from 330 published cases. Diagnostic cornerstones are clinical parameters, urinary excretion of oxalate and glycolate, and the determination of enzyme activity in liver tissue. Principles of conservative treatment, e.g. volume load and pyridoxine substitution, are described as well as experience with different modes of dialysis and transplantation. Kidney transplantation is associated with a high rate of recurrence of the original disease despite excellent management resulting in many instances in early graft loss. Liver transplantation offers the possibility to correct the metabolic defect and to prevent the progression of crystal deposition in the body.

BACKGROUND. Proteinuria is considered an unfavorable clinical condition that accelerates renal and cardiovascular disease. However, it is not clear whether all forms of proteinuria are damaging. Mutations in CUBN cause Imerslund-Gräsbeck syndrome (IGS), which is characterized by intestinal malabsorption of vitamin B12 and in some cases proteinuria. CUBN encodes for cubilin, an intestinal and proximal tubular uptake receptor containing 27 CUB domains for ligand binding. METHODS. We used next-generation sequencing for renal disease genes to genotype cohorts of patients with suspected hereditary renal disease and chronic proteinuria. CUBN variants were analyzed using bioinformatics, structural modeling, and epidemiological methods. RESULTS. We identified 39 patients, in whom biallelic pathogenic variants in the CUBN gene were associated with chronic isolated proteinuria and early childhood onset. Since the proteinuria in these patients had a high proportion of albuminuria, glomerular diseases such as steroid-resistant nephrotic syndrome or Alport syndrome were often the primary clinical diagnosis, motivating renal biopsies and the use of proteinuria-lowering treatments. However, renal function was normal in all cases. By contrast, we did not found any biallelic CUBN variants in proteinuric patients with reduced renal function or focal segmental glomerulosclerosis. Unlike the more N-terminal IGS mutations, 37 of the 41 proteinuria-associated CUBN variants led to modifications or truncations after the vitamin B12-binding domain. Finally, we show that 4 C-terminal CUBN variants are associated with albuminuria and slightly increased GFR in meta-analyses of large population-based cohorts. CONCLUSION. Collectively, our data suggest an important role for the C-terminal half of cubilin in renal albumin reabsorption. Albuminuria due to reduced cubilin function could be an unexpectedly common benign condition in humans that may not require any proteinuria-lowering treatment or renal biopsy.

Oxalate elimination and oxalate dialysance via hemodialysis (HD) or peritoneal dialysis (CAPD) has not been studied in detail in pediatric patients. We studied plasma oxalate, oxalate elimination, and oxalate dialysance in 15 infants and children undergoing CAPD (9 female, 6 male, aged 9 months to 18 years) and in 10 children on HD (4 female, 6 male, aged 7-18 years). Two children in each group had primary hyperoxaluria (PH). The mean duration of dialysis prior to examination was 12 +/- 11 months in CAPD and 31 +/- 23 months in HD patients. Bicarbonate HD was performed 5 h three times a week, CAPD consisted of five daily exchanges in 5 patients and four changes in the remaining 10 children (dwell volume 40 ml/kg body weight, 2.3 g/l glucose). Although oxalate dialysance was significantly higher in HD (mean 115.6 ml/ min per 1.73 m2 in HD versus 7.14 ml/min in CAPD), mean oxalate elimination per week was not different between both renal replacement therapies (3,478 mumol/1.73 m2 surface area/week in CAPD versus 3,915 mumol/1.73 m2 per week in HD). Oxalate elimination in patients with PH was between 6,650 and 9,900 mumol/week. Plasma oxalate remained elevated in both procedures [28-84 mumol/l in CAPD (92/148 in PH) and 33-101 mumol/l in HD (70/93 in PH)]. Oxalate elimination can be increased by a more frequent hemodialysis regimen.