A 16-year-old patient with steroid-dependent nephrotic syndrome with more than 35 relapses developed severe relapsing idiopathic thrombocytopenic purpura (ITP). At the age of 2 years, nephrotic syndrome was diagnosed and successfully treated with a standard prednisone regimen. Frequent relapses occurred. Treatment with oral cyclophosphamide followed by cyclosporine was successful, but several attempts to withdraw steroids failed and the patient suffered from multiple relapses. At the age of 12 years, renal biopsy revealed focal segmental glomerulosclerosis and cyclosporine toxicity. A second course of oral cyclophosphamide was unsuccessful and tacrolimus resulted in the development of diabetes mellitus, which was reversed after discontinuation of the drug. At the age of 15 years the patient, still being steroid dependent, developed ITP. Neither steroids nor intravenous immunoglobulins induced permanent remission. Only weekly immunoglobulin infusions could temporarily restore the platelet count. To treat ITP in this desperate situation we decided to deplete B-cells with the monoclonal anti-CD20 antibody rituximab. Intravenous infusions of rituximab (375 mg/m(2)) were given once weekly for 4 consecutive weeks without adverse events. Four weeks after the first rituximab dosage, the thrombocyte count increased to normal values. There has been no subsequent relapse of either thrombocytopenia or nephrotic syndrome (on cyclosporine, without steroids) to date. We conclude that B-cell depletion with rituximab might have altered the course of steroid-dependent nephrotic syndrome in our patient.

E. coli O104:H4 caused the largest HUS outbreak in children reported in detail to date and most patients received supportive treatment only. Initial morbidity, as well as short-term outcome, due to this pathogen, is comparable to previous pediatric series of Shiga toxin-producing E. coli HUS.

Impaired intrauterine nephrogenesis-most clearly illustrated by low nephron number-is frequently associated with low birthweight and has been recognized as a powerful risk factor for renal disease; it increases the risks of low glomerular filtration rate, of more rapid progression of primary kidney disease, and of increased incidence of chronic kidney disease or end-stage renal disease. Another important consequence of impaired nephrogenesis is hypertension, which further amplifies the risk of onset and progression of kidney disease. Hypertension is associated with low nephron numbers in white individuals, but the association is not universal and is not seen in individuals of African origin. The derangement of intrauterine kidney development is an example of a more general principle that illustrates the paradigm of plasticity during development-that is, that transcription of the genetic code is modified by epigenetic factors (as has increasingly been documented). This Review outlines the concept of prenatal programming and, in particular, describes its role in kidney disease and hypertension.

Background and objectives The Wilms tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Genotype/phenotype correlations of WT1 mutations with renal function and proteinuria have been observed in world-wide cohorts with nephrotic syndrome or Wilms tumor (WT). This study analyzed mid-European patients with known constitutional heterozygous mutations in WT1, including patients without proteinuria or WT.Design, setting, participants & measurements Retrospective analysis of genotype, phenotype, and treatment of 53 patients with WT1 mutation from all pediatric nephrology centers in Germany, Austria, and Switzerland performed from 2010 to 2012.Results Median age was 12.4 (interquartile range [IQR], 6-19) years. Forty-four of 53 (83%) patients had an exon mutation (36 missense, eight truncating), and nine of 53 (17%) had an intronic lysine-threonine-serine (KTS) splice site mutation. Fifty of 53 patients (94%) had proteinuria, which occurred at an earlier age in patients with missense mutations (0.6 [IQR, 0.1-1.5] years) than in those with truncating (9.7 [IQR, 5.7-11.9]; P,0.001) and splice site (4.0 [IQR, 2.6-6.6]; P=0.004) mutations. Thirteen of 50 (26%) were treated with steroids and remained irresponsive, while three of five partially responded to cyclosporine A. Seventy-three percent of all patients required RRT, those with missense mutations significantly earlier (at 1.1 [IQR, 0.01-9.3] years) than those with truncating mutations (16.5 [IQR,.8]; P,0.001) and splice site mutations (12.3 [IQR,.2]; P=0.002). Diffuse mesangial sclerosis was restricted to patients with missense mutations, while focal segmental sclerosis occurred in all groups. WT occurred only in patients with exon mutations (n=19). Fifty of 53 (94%) patients were karyotyped: Thirty-one (62%) had XY and 19 (38%) had XX chromosomes, and 96% of male karyotypes had urogenital malformations.Conclusions Type and location of WT1 mutations have predictive value for the development of proteinuria, renal insufficiency, and WT. XY karyotype was more frequent and associated with urogenital malformations in most cases.

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