Increased potassium excretion in children with monosymptomatic nocturnal enuresis: could it be related to Kir 4.1- KCNJ10 gene polymorphism?

BACKGROUND AND OBJECTIVES: There are controversial results in the literature regarding urinary electrolytes, especially potassium, in enuretic children. KCNJ10 channel protein, a member of the Kir 4.1 family is expressed in renal distal tubules and has an important function in renal ion transport. We investigated whether KCNJ10 gene polymorphisms are associated with clinical and laboratory findings of a group of Turkish children with monosymptomatic primary nocturnal enuresis (MNE). METHOD: Ninety-seven MNE children and 100 healthy controls were tested for three single nucleotide polymorphisms (SNPs) in the KCNJ10 gene. The transversions in SNPs were G to A for intron 1(SNP1), G to A for exon 2 (SNP2), and T to C transition for promoter (SNP3). All SNPs were genotyped by PCR-restriction fragment length polymorphism. RESULTS: SNP3 in promoter of KCNJ10 gene showed strong association with MNE children for distribution of genotype and allele frequency, while SNP1 in intron 1 and SNP2 in exon 2 were noninformative. The distribution of TT, TC, and CC genotypes for SNP3 was 66%, 26.8% and 7.2% respectively in MNE compared with 38%, 59% and 3% respectively in controls (p < 0.0001). In enuretic children, TT genotype was higher and there was an increased potassium excretion in children with TT genotype (P < 0.05). CONCLUSION: We conclude that KCNJ10 gene promoter polymorphism may have a role on potassium excretion in Turkish MNE children. This is the first study in literature evaluating KCNJ10 gene polymorphism in this patient population. Future studies investigating the other SNPs, mutations or altered regulation of Kir4.1 in larger samples would help clarify the role (s) of KCNJ10 gene in enuresis.

Successful renal transplantation in a child with ANCA-associated microscopic polyangiitis.

Crescentic glomerulonephritis (CGN) is a clinicopathologic entity which is characterized by severe renal dysfunction of rapid onset with glomerular crescents. Type III CGN is associated with the absence of glomerular immune complex deposition (pauci-immune) and is associated with antineutrophil cytoplasmic antibody (ANCA). Microscopic polyangiitis and idiopathic pauci-immune necrotizing glomerulonephritis (NCGN) are strongly associated with ANCA directed against myeloperoxidase (anti-MPO). We describe here an unusual pediatric patient with MPO-ANCA-associated rapidly progressive glomerulonephritis (RPGN), emphasizing the management and outcome of the disease.

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children.

Hepatitis B virus (HBV)-associated glomerulonephritides have been increasingly reported, and the association between HBV and glomerulopathy is striking, especially in children. In this study, we investigated clinical and immunohistological features of HBV-associated glomerulonephritis in 14 children aged from 2.5 to 16 years (mean 10 years). The nephrotic syndrome was present in 9 (64%) and the nephritic syndrome in 8 children (57%). Five children had both nephrotic and nephritic syndrome together (35%). Renal insufficiency was determined in 4 of 14 patients (28%). Surface antigen (HBsAg) was present in all, with no history of clinically apparent hepatitis. Investigation of all renal tissue samples with light and immunofluorescence microscopy confirmed the diagnosis of membranous glomerulonephritis (MGN) in 6, membranoproliferative glomerulonephritis (MPGN) in 7, and IgA nephropathy (IgAN) in 1 child. Renal tissue samples were studied by the immunoperoxidase method for HBsAg in all cases; only in 4 children was HBsAg detected in the glomeruli. Examination of liver tissue samples was available in 4 cases, revealing chronic hepatitis in all, with additional development of cirrhosis in 1 and the presence of HBsAg in hepatocytes in all. Of the patients, 8 received corticosteroid treatment; 1 of them achieved a complete remission, while 4 had a partial remission with persistent proteinuria and hematuria. Four patients who received no treatment had a spontaneous remission within 5 months to 10 years following the onset of the renal disease. Two patients died of renal failure, while 1 died of intercurrent sepsis. The patient with IgAN received interferon-alpha 2a and lamuvidine, which resulted in a remission and a marked decrease in HBV DNA titer. The remaining 2 were lost to follow-up. Although MGN has been reported as the nephropathy most commonly associated with HBsAg antigenemia in adults, our study revealed that MPGN could occur in children as well as MGN, without any clinical or historical evidence of hepatitis. The present study provides further evidence for a causal relationship between HBV hepatitis and HBs antigenemia-related glomerulonephritides in the pediatric age group. It also indicates the prognosis (71%) of the associated nephropathies with or without treatment is quite favorable in childhood.

MEFV gene mutations in familial Mediterranean fever phenotype II patients with renal amyloidosis in childhood: a retrospective clinicopathological and molecular study.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurring attacks of fever and serositis. The definition of the mutated gene has allowed molecular diagnosis of the disease. The most important complication of FMF is the development of AA type secondary amyloidosis. In a group of patients clinically designated as phenotype II amyloidosis patients, renal amyloidosis develops without being preceded by typical attacks of the disease. In this study, the mutations of the MEFV gene were analysed in a group of patients clinically recognized as phenotype II. METHODS: DNA samples were obtained from tissue samples of the subjects. PCR-RFLP methods were used to analyse the M694V, M680I, V726A and E148Q mutations that have been previously defined by us to be the most common mutations in our Turkish cohort. RESULTS: The distribution of the four most common mutations among phenotype II patients was 38% for M694V, 8% for M680I, 4% for V726A and 4% for E148Q. CONCLUSIONS: In phenotype II amyloidosis patients, the distribution of the four common MEFV mutations was not significantly different from that found in all FMF patients with typical symptoms who do or do not develop amyloidosis. We therefore suggest that secondary genetic or environmental factors are operative in the development of secondary amyloidosis in patients with FMF.