Potential donor-recipient MYH9 genotype interactions in posttransplant nephrotic syndrome after pediatric kidney transplantation.

Recurrence of focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome is relatively common after kidney transplantation in young recipients whose predialysis course consists of heavy proteinuria, hypertension and subacute loss of kidney function. The gene(s) mediating this effect remain unknown. We report an unusual circumstance where kidneys recovered from a deceased African American male donor with MYH9-related occult FSGS (risk variants in seven of eight MYH9 E1 haplotype single nucleotide polymorphisms) were transplanted into an African American male child with risk variants in four MYH9 E1 risk variants and a European American female teenager with two MYH9 E1 risk variants. Fulminant nephrotic syndrome rapidly developed in the African American recipient, whereas the European American had an uneventful posttransplant course. The kidney donor lacked significant proteinuria at the time of organ procurement. This scenario suggests that donor-recipient interactions in MYH9, as well as other gene-gene and gene-environment interactions, may lead to recurrent nephrotic syndrome after renal transplantation. The impact of transplanting kidneys from donors with multiple MYH9 risk alleles into recipients with similar genetic background at high risk for recurrent kidney disease needs to be determined.

Peritonitis due to Neisseria mucosa in an adolescent receiving peritoneal dialysis.

Neisseria mucosa is part of the normal nasopharyngeal flora and rarely pathogenic in humans. Reports of serious infections associated with this pathogen are very unusual. A 17-year-old boy with end-stage renal disease due to IgA nephropathy presented with acute, spontaneous, symptomatic peritoneal dialysis-associated peritonitis without reported break in sterility or PD catheter exit site infection. beta-lactamase-negative N. mucosa was isolated from the dialysate effluent. Intraperitoneal antibiotic treatment with cephalothin/gentamicin for 5 days and subsequent ceftriaxone led to complete resolution of the infection. This case demonstrates that "non-pathogenic" Neisseria species can cause clinically severe peritonitis with high intraperitoneal neutrophil counts, elevated C-reactive protein levels in the peritoneal effluent (in the presented case, 27,600/mul and 3.6 mg/l, respectively) and impaired peritoneal membrane transport function. To our knowledge, this is the first case of N. mucosa peritonitis complicating chronic peritoneal dialysis in an adolescent patient.

Pediatric biopsy of a single native kidney.

Technological improvements have reduced the frequency of complications in children receiving a percutaneous renal biopsy. No study has systematically compared the safety of open and percutaneous kidney biopsy. Yet many nephrologists consider a single native kidney an absolute contraindication to percutaneous biopsy. We have established an international registry of single native kidney biopsies in children and we now report our early results. Eight biopsies are included. Seven patients had percutaneous biopsies and one an open biopsy. None of the patients had major complications, and adequate tissue was obtained from all. Our limited experience indicates that the presence of a single native kidney is not an absolute indication for an open approach. We encourage our colleagues to report to the international registry in order to further document the safety of percutaneous biopsy of the single native kidney in children.

Molecular cloning of KS, a novel rat gene expressed exclusively in the kidney.

BACKGROUND: We aimed to identify genes with kidney specific, developmentally regulated expression. Here we report the cDNA sequence and expression pattern of KS, a novel kidney-specific rat gene. METHODS: A partial cDNA was identified by differential display polymerase chain reaction (PCR) of a renal cell fraction enriched for proximal tubular and renin-expressing cells. Using the partial cDNA as a probe, a rat kidney cDNA library was screened. The full-length KS sequence was obtained by PCR amplification of cDNA ends. The expression pattern of KS was investigated by Northern blot. RNA was extracted from several organs of newborn and adult rats, as well as from the kidneys of rats with altered tubular function, that is, rats that had undergone unilateral nephrectomy, unilateral ureteral obstruction, neonatal losartan treatment, and the appropriate control animals. The expression of KS was also investigated in the kidneys of rats with spontaneous or renovascular hypertension. RESULTS: The KS cDNA (2426 bp) contained one open reading frame encoding a predicted 572 amino acid protein. The derived peptide sequence displayed approximately 70% similarity to the hypertension-related SA gene product and approximately 50% similarity to prokaryotic and eukaryotic acetyl-CoA synthases (EC 6. 2.1.1). KS was expressed in the kidney and not in any other organ assayed. KS RNA was not detected in fetal and newborn rat kidney but became apparent after one week of postnatal life. Gene expression was downregulated in rat models of altered tubular function. KS expression was decreased in spontaneously hypertensive rats but not in renovascular hypertension. CONCLUSION: KS, a novel rat gene, exhibits a unique tissue-specific expression exclusively in mature kidneys. The data suggest KS may encode an adenosine monophosphate binding enzyme.

Hyperimmune human IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats.

Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis.