Etiology of Kidney Diseases With Proteinuria in the Gambia/West Africa.

Unlabelled: In West Africa, kidney diseases are frequently seen, but diagnostic and therapeutic options are poor due to limited access to specialized facilities. To unravel the etiology and develop clinical guidelines, we collected clinical data and results of kidney biopsies in 121 pediatric and mostly young adult patients with edema and proteinuria in The Gambia. Workup included clinical examination, urine and serum analysis, and kidney biopsy findings.

[Kidney Cysts and Cystic Nephropathies in Children - A Consensus Guideline by 10 German Medical Societies].

This consensus-based guideline was developed by all relevant German pediatric medical societies. Ultrasound is the standard imaging modality for pre- and postnatal kidney cysts and should also exclude extrarenal manifestations in the abdomen and internal genital organs. MRI has selected indications.

[Primary megaureter in the newborn period: making the case for a temporary splint-free cutaneous ureterostomy].

The term "megaureter" is used to describe a markedly dilated ureter, irrespective of its underlying anatomic abnormality. Primary megaureters categorised as type I and II according to the Pfister-Hendren classification resolve spontaneously during the first years of life, whereas severely dilated type III megaureters have no potential to resolve on conservative management. Regarding this small group of very severely dilated type III megaureters, we recommend a two-step surgical approach: in a first step, we place a temporary splint-free ureterocutaneostomy for early disobstruction.

HNF1B nephropathy has a slow-progressive phenotype in childhood-with the exception of very early onset cases: results of the German Multicenter HNF1B Childhood Registry.

Background: HNF1B gene mutations are an important cause of bilateral (cystic) dysplasia in children, complicated by chronic renal insufficiency. The clinical variability, the absence of genotype-phenotype correlations, and limited long-term data render counseling of affected families difficult.

Methods: Longitudinal data of 62 children probands with genetically proven HNF1B nephropathy was obtained in a multicenter approach.

No evidence for point mutations in the novel renal cystine transporter AGT1/SLC7A13 contributing to the etiology of cystinuria.

Background: Cystinuria is caused by the defective renal reabsorption of cystine and dibasic amino acids, and results in cystine stone formation. So far, mutations in two genes have been identified as causative. The SLC3A1/rBAT gene encodes the heavy subunit of the heterodimeric rBAT-bAT transporter, whereas the light chain is encoded by the SLC7A9/ bAT gene.

Author Correction: Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo.

Unlabelled: Changes in miRNA expression glomerular of capillaries during antibody-mediated rejection (ABMR) are poorly understood and could contribute to the deleterious inflammation and fibrosis of ABMR via suppression of target genes. A better understanding could lead to novel diagnostic tools and reveal novel therapeutic targets. We explored deregulated miRNAs in an glomeruloendothelial in vitro model of ABMR due to class I human leukocyte antigen (HLA) with and without complement activation.

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality.

Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD), usually considered to be a genetically homogeneous disease caused by mutations in PKHD1, has been associated with ciliary dysfunction. Here, we describe mutations in DZIP1L, which encodes DAZ interacting protein 1-like, in patients with ARPKD. We further validated these findings through loss-of-function studies in mice and zebrafish.

Intermediate Follow-up of Pediatric Patients With Hemolytic Uremic Syndrome During the 2011 Outbreak Caused by E. coli O104:H4.

Background.: In 2011 Escherichia coli O104:H4 caused an outbreak with >800 cases of hemolytic uremic syndrome (HUS) in Germany, including 90 children. Data on the intermediate outcome in children after HUS due to E.

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy.

Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5).

Combined liver and kidney transplantation and kidney after liver transplantation in children: Indication, postoperative outcome, and long-term results.

CLKT and sequential KALT are decided on a case-by-case basis in children for special indications such as ARPKD or PH1. We report on 21 children who underwent CLKT or KALT at our hospital between 1998 and 2013. Eleven children were diagnosed with PH1 and six with ARPKD.

Clinical manifestations of autosomal recessive polycystic kidney disease (ARPKD): kidney-related and non-kidney-related phenotypes.

Autosomal recessive polycystic kidney disease (ARPKD), although less frequent than the dominant form, is a common, inherited ciliopathy of childhood that is caused by mutations in the PKHD1-gene on chromosome 6. The characteristic dilatation of the renal collecting ducts starts in utero and can present at any stage from infancy to adulthood. Renal insufficiency may already begin in utero and may lead to early abortion or oligohydramnios and lung hypoplasia in the newborn.

Glomerular mRNA expression of prothrombotic and antithrombotic factors in renal transplants with thrombotic microangiopathy.

Background: Thrombotic microangiopathy (TMA) in renal transplants (rTx-TMA) is a serious complication and is usually either recurrent TMA (RecTMA) due to humoral rejection (HR-TMA) or due to calcineurin inhibitor toxicity (CNI-TMA). Although the triggers are known, our knowledge about the thrombogenic transcriptome changes in the microvessels is rudimentary.

Methods: We examined the expression of several prothrombotic and antithrombotic genes in 25 biopsies with rTx-TMA (6 RecTMA, 9 HR-TMA, and 10 CNI-TMA) and 8 controls.

Long-term side effects of treatment with mTOR inhibitors in children after renal transplantation.

Background: mTOR inhibitors (mTORI) have emerged as alternative and additive immunosuppressive agents in pediatric renal transplantation (pRTx). Their immunosuppressive, anti-proliferative, and anti-neoplastic mechanisms have been described to be effective, whereas some side effects are alarming. In particular, growth and pubertal development are of concern.

Kidney grafts from donors ≤ 5 yr of age: single kidney transplantation for pediatric recipients or en bloc transplantation for adults?

Kidneys from donors ≤5 yr of age represent a controversial issue. The purpose of this study was to compare the transplant outcomes as single and single/en bloc grafts into pediatric and adult KT recipients, respectively. All recipients of kidneys from donors ≤5 yr old transplanted at our institution from 3/2003 to 12/2010 were evaluated, and corresponding data were analyzed.

Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome.

Background And Objectives: This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.

Design, Setting, Participants, & Measurements: A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA.

An outbreak of Shiga toxin-producing Escherichia coli O104:H4 hemolytic uremic syndrome in Germany: presentation and short-term outcome in children.

Background: In May and June 2011 the largest known outbreak of hemolytic uremic syndrome (HUS) occurred in northern Germany. Because, quite unusually, a large number of adults was affected and the causative Escherichia coli strain, serotype O104:H4, showed an atypical virulence factor pattern, it was speculated that this outbreak was associated with an aggressive course and an unfavorable prognosis also in children.

Methods: Retrospective analysis of medical records of 90 children and comparison to previous outbreak and sporadic case series.

Donor and recipient ACE I/D genotype are associated with loss of renal function in children following renal transplantation.

Genetic polymorphisms of the RAS correlate with allograft function. We therefore analyzed common RAS polymorphisms in kidney donors and in children following RTx to determine the relationship between genotype and decline in GFR, blood pressure, and LVM. A total of 107 children who underwent RTx were included: 70 male, 37 female, mean age 8.

Early renal failure after domino liver transplantation using organs from donors with primary hyperoxaluria type 1.

Background: Organ shortage is responsible for high mortality rates of patients awaiting liver transplantation (LT). Domino transplantation has had reported success in patients with metabolic disorders. Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder.

Complement inhibitor eculizumab in atypical hemolytic uremic syndrome.

Background And Objectives: Atypical hemolytic uremic syndrome (aHUS) is associated with a congenital or acquired dysregulation of the complement alternative pathway that leads to continuous complement activation on host cells causing inflammation and damage. Eculizumab, a humanized mAb against complement protein C5, inhibits activation of the terminal complement pathway.

Design, Setting, Participants, & Measurements: We report an adolescent with relapsing unclassified aHUS.