Screening for CLCN5 mutation in renal calcium stone formers patients.

UNLABELLED: Thirty-five patients (23 males and 12 females), age 35 +/- 13 years old, presenting either idiopathic calcium nephrolithiasis, nephrocalcinosis or mild renal failure with idiopathic calcium nephrolithiasis were selected for the analysis of low molecular weight proteinuria and the possible mutations occurrence in the chloride channel gene CLCN5. The urinary ratio of beta2-microglobulin and creatinine (beta2M/Cr) was very high in a transplanted woman with nephrocalcinosis (> 3.23 mg/mmol) and slightly high in five patients (> 0.052 or < 1.0 mg/mmol) with multiple urological manipulations. Other studied patients showed beta2M/Cr ratio at normal range (0.003-0.052 mg/mmol) without gender difference (p > 0.05). Mutation analysis of CLCN5 gene was performed in 26 patients of 35 selected (11 with idiopathic hypercalciuria; 6 men with normal calciuria; 3 with mild renal insufficiency and 6 with nephrocalcinosis) and was normal in all subjects even in those with abnormal molecular weight proteinuria. CONCLUSION: CLCN5 gene mutation is not a common cause of kidney stone disease or nephrocalcinosis in a group of Brazilian patients studied.

Screening for CLCN5 mutation in renal calcium stone formers patients

Trinta e cinco pacientes (23 homens e 12 mulheres) com idade de 35 ±13 anos apresentando nefrolitíase idiopática cálcica, nefrocalcinose ou insuficiência renal leve com nefrolitíase idiopática cálcica foram selecionados para análise de proteinúria de baixo peso molecular e a ocorrência de possíveis mutações no gene CLCN5. A razão entre a b2-microglobulina urinária e a creatinina urinária (b2M/Cr) foi muito elevada em uma mulher transplantada com nefrocalcinose ( > 3.23 mg/mmol) e levemente elevada em cinco pacientes ( > 0.052 ou < 1.0 mg/mmol) com manipulação urológica múltipla. Outros pacientes estudados mostraram uma razão b2M/Cr nos limites normais (0.003-0.052 mg/mmol) sem diferença entre os sexos (p > 0.05). A análise da mutação do gene do gene CLCN5 foi realizada em 26 pacientes dos 35 selecionados (11 com hipercalciúria idiopática; 6 homens com calciúria normal; 3 com leve insuficiência renal e 6 com nefrocalcinose) e não apresentou alteração em nenhum dos casos, mesmo naqueles com proteinúria de baixo peso molecular anormal. Conclusão: A mutação do gene do CLCN5 não é uma causa comum de calculose renal ou nefrocalcinose no grupo de pacientes brasileiros estudados.

Modulation of renal CNG-A3 sodium channel in rats subjected to low- and high-sodium diets.

In this work, we studied the mRNA distribution of CNG-A3, an amiloride-sensitive sodium channel that belongs to the cyclic nucleotide-gated (CNG) family of channels, along the rat nephron. The possible involvement of aldosterone in this process was also studied. We also evaluated its expression in rats subjected to diets with different concentrations of sodium or to alterations in aldosterone plasma levels. Total RNA isolated from whole kidney and/or dissected nephron segments of Wistar rats subjected to low- and high-sodium diets, furosemide treatment, adrenalectomy, and adrenalectomy with replacement by aldosterone were analyzed by the use of Western blot, ribonuclease protection assay (RPA) and/or reverse transcription followed by semi-quantitative polymerase chain reaction (RT-PCR). CNG-A3 sodium channel mRNA and protein expression, in whole kidneys of rats subjected to high-Na+ diet, were lower than those in animals given a low-salt diet. Renal CNG-A3 mRNA expression was also decreased in adrenalectomized rats, and was normalized by aldosterone replacement. Moreover, a CNG-A3 mRNA expression study in different nephron segments revealed that aldosterone modulation is present in the cortical thick ascending loop (cTAL) and cortical collecting duct (CCD). This result suggests that CNG-A3 is responsive to the same hormone signaling as the amiloride sensitive sodium channel ENaC and suggests the CNG-A3 may have a physiological role in sodium reabsorption.