RESUMO
BACKGROUND/AIMS: Hypomagnesemia may induce hypercholesterolemia, but the contrary has not been described yet. Thus, magnesium homeostasis was evaluated in rats fed a cholesterol-enriched diet for 8 days. This study has a relevant clinical application if hypomagnesemia, due to hypercholesterolemia, is confirmed in patients with long-term hypercholesterolemia. METHODS: Both hypercholesterolemic (HC) and normocholesterolemic rats (NC) were divided into sets of experiments to measure hemodynamic parameters, physiological data, maximum capacity to dilute urine (C(H)((2))(O)), variations (Δ) in [Ca(2+)](i) and the expression of transporter proteins. RESULTS: HC developed hypomagnesemia and showed high magnesuria in the absence of hemodynamic abnormalities. However, the urinary sodium excretion and C(H)((2))(O) in HC was similar to NC. On the other hand, the responses to angiotensin II by measuring Δ [Ca(2+)](i) were higher in the thick ascending limb of Henle's loop (TAL) of HC than NC. Moreover, high expression of the cotransporter NKCC2 was found in renal outer medulla fractions of HC. Taken together, the hypothesis of impairment in TAL was excluded. Actually, the expression of the epithelial Mg(2+) channel in renal cortical membrane fractions was reduced in HC. CONCLUSION: Impairment in distal convoluted tubule induced by hypercholesterolemia explains high magnesuria and hypomagnesemia observed in HC.
Assuntos
Colesterol na Dieta/efeitos adversos , Hipercalciúria/fisiopatologia , Hipercolesterolemia/fisiopatologia , Alça do Néfron/fisiopatologia , Nefrocalcinose/fisiopatologia , Erros Inatos do Transporte Tubular Renal/fisiopatologia , Animais , Colesterol na Dieta/administração & dosagem , Hipercalciúria/etiologia , Hipercalciúria/urina , Hipercolesterolemia/etiologia , Hipercolesterolemia/urina , Túbulos Renais/fisiopatologia , Magnésio/urina , Masculino , Nefrocalcinose/etiologia , Nefrocalcinose/urina , Distribuição Aleatória , Ratos , Ratos Wistar , Erros Inatos do Transporte Tubular Renal/etiologia , Erros Inatos do Transporte Tubular Renal/urinaRESUMO
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.
Assuntos
Canais de Cloreto/genética , Cálculos Renais/genética , Mutação , Nefrocalcinose/genética , Insuficiência Renal/genética , Adulto , Sequência de Bases , Creatinina/urina , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Cálculos Renais/urina , Masculino , Dados de Sequência Molecular , Peso Molecular , Nefrocalcinose/urina , Reação em Cadeia da Polimerase , Insuficiência Renal/urina , Índice de Gravidade de Doença , Microglobulina beta-2/urinaRESUMO
OBJECTIVES: To quantify urinary citrate and calcium excretion and systemic acid-base status in patients with type 1a glycogen storage disease (GSD1a) and to investigate their relationship to renal complications. STUDY DESIGN: Fifteen patients (7 male and 8 female; age range, 3--28 years) were studied during annual evaluations of metabolic control. All were treated with intermittent doses of uncooked cornstarch. Hourly blood sampling and a 24-hour urine collection were obtained while subjects followed their usual home dietary regimen. RESULTS: All but the youngest subject had low levels of citrate excretion (mean 2.4 +/- 1.8 mg/kg/d; 129 +/- 21 mg citrate/g creatinine). Normally, urinary citrate excretion increases with age; however, in patients with GSD1a, a strong inverse exponential relationship was found between age and citrate excretion (r = -0.84, P <.0001). Urinary citrate excretion was unrelated to markers of metabolic control. Hypercalciuria occurred in 9 of 15 patients (mean urinary calcium/creatinine ratio, 0.27 +/- 0.15) and was also inversely correlated with age (r = -0.62, P =.001). CONCLUSIONS: Hypocitraturia that worsens with age occurs in metabolically compensated patients with GSD1a. The combination of low citrate excretion and hypercalciuria appears to be important in the pathogenesis of nephrocalcinosis and nephrolithiasis. Citrate supplementation may be beneficial in preventing or ameliorating nephrocalcinosis and the development of urinary calculi in GSD1a.
Assuntos
Cálcio/urina , Ácido Cítrico/urina , Doença de Depósito de Glicogênio Tipo I/urina , Cálculos Renais/etiologia , Nefrocalcinose/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Doença de Depósito de Glicogênio Tipo I/complicações , Humanos , Cálculos Renais/urina , Análise dos Mínimos Quadrados , Masculino , Nefrocalcinose/urinaRESUMO
Urinary inhibitors are suggested to play a significant role in reducing crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH). Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs) were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a control group. The mean 24-h urinary excretion of Mg was similar in all groups. However, the urine Ca/Mg ratio was significantly increased (P < 0.005) in LIT and HEM groups. A higher mean value for GAGs and citrate was found in the HEM group, but a very low level of GAGs (less than 60% of the normal value) and citrate (less than 30% of the normal value) was found in the LIT group. These data suggest that, despite a high urinary Ca excretion (3.6 +/- 0.1 mg/kg per day) in the HEM group, elevated urinary GAGs (32.0 +/- 1.0 mg/g Cr) and a normal urinary citrate (428.7 +/- 62.3 mg/24 h) excretion may prevent Ca crystallization and thus renal stones. In contrast, in the LIT group low urinary GAG (10.3 +/- 0.9 mg/g Cr) and citrate (235.2 +/- 52.3 mg/24 h) excretion may precipitate stone formation in the presence of a high urinary Ca excretion. Thus, it is reasonable to suggest that patients with hematuria and IH may not develop overt renal stone due to the presence of normal levels of renal stone inhibitors.