Ju Hyung Kang

Mutational analysis of idiopathic renal hypouricemia in Korea

Idiopathic renal hypouricemia is a hereditary disease characterized by abnormally high renal uric acid clearance. Most patients are clinically silent, but acute renal failure (ARF), urolithiasis, or hematuria may develop. A defect in the SLC22A12 gene, which encodes the renal uric acid transporter, URAT1, is the known major cause of this disorder. We performed a mutational analysis of the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia in this study. Two patients presented with microscopic hematuria, one with uric acid urolithiasis, and one with exercise-induced ARF. One patient was asymptomatic. Three different mutations, W258X, R90H and R477H, were detected in four of the patients. However, no mutation was found in the fifth ARF patient. This is the first study of SLC22A12 mutations in a country other than Japan. W258X was found to be the predominant SLC22A12 mutation in Korean renal hypouricemia patients, as has been reported in Japan.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis associated with CLDN16 mutations

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), an autosomal recessive renal tubular disorder, is characterized by the impaired tubular reabsorption of magnesium and calcium in the thick ascending limb of the loop of Henle and an eventual progression to end-stage renal disease. Recent studies have reported that this disease is caused by mutations in the CLDN16 gene, which encodes the tight junction protein, paracellin-1. Paracellin-1 belongs to the claudin family and regulates the paracellular transport of magnesium and calcium. Here, we report on two Korean siblings with typical clinical features of FHHNC in association with compound heterozygous mutations, G233C and 800delG, in CLDN16. Their parents were asymptomatic heterozygous carriers of the single mutations. This is the first report of FHHNC in Korea, and the mutations reported are novel.

X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.

Abstract A retrospective genotype and phenotype analysis of X-linked congenital nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25 (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non-truncating and truncating mutations. In an analysis of male patients, the median age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary tract dilatations were evident in 62% of patients and their median glomerular filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd percentile in 22% and 33% of patients, respectively. One patient had low intelligence quotient and another developed end-stage renal disease. No statistically significant genotype-phenotype correlation was found between non-truncating and truncating mutations. One patient was female; she was analyzed separately because inactivation and mosaicism of the X chromosome may influence clinical manifestations in female patients. Current unsatisfactory long-term outcome of congenital NDI necessitates a novel therapeutic strategy.

Aliskiren Regulates Neonatal Fc Receptor and IgG Metabolism with Attenuation of Anti-GBM Glomerulonephritis in Mice

Background: Renin, in addition to its activation of the renin-angiotensin system, binds to the (pro)renin receptor (PRR) and triggers inflammatory and fibrogenic signaling in tissue. In addition, aliskiren, a direct renin inhibitor, has been shown to affect IgG metabolism by altering PRR and neonatal Fc receptors (FcRns). Methods: We investigated the effect of aliskiren on proteinuria, glomerular extracellular matrix, expressions of fibronectin, transforming growth factor β1 (TGF-β1), PRR, FcRn and renal metabolism of IgG in a mice model of anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). Results: IgG deposition and expressions of FcRn and PRR were enhanced at glomeruli and urinary IgG levels increased in anti-GBM GN. Aliskiren attenuated anti-GBM GN with reduction of proteinuria and cortical expressions of fibronectin and TGF-β1. In addition, aliskiren suppressed the renal cortical expressions of FcRn and PRR. Aliskiren also reduced the glomerular IgG depositions and the urinary IgG levels albeit with increased circulating serum IgG levels. Conclusion: These results suggest that suppression of FcRn and PRR and regulation of IgG metabolism may be related to the attenuation of anti-GBM GN by aliskiren.