RESUMO
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a rare autosomal recessive renal disease caused by mutations in genes for the tight junction transmembrane proteins Claudin-16 (CLDN16) and Claudin-19 (CLDN19). We present the first case report of a Mexican family with three affected sisters carrying a p.Gly20Asp mutation in CLDN19 whose heterozygous mother showed evident hypercalciuria and normal low magnesemia without any other clinical, laboratory, and radiological symptoms of renal disease making of her an unsuitable donor. The affected sisters showed variable phenotypic expression including age of first symptoms, renal urinary tract infections, nephrolithiasis, nephrocalcinosis, and eye symptoms consisting in retinochoroiditis, strabismus, macular scars, bilateral anisocoria, and severe myopia and astigmatism. End stage renal disease due to renal failure needed kidney transplantation in the three of them. Interesting findings were a heterozygous mother with asymptomatic hypercalciuria warning on the need of carefully explore clinical, laboratory, kidney ultrasonograpy, and mutation status in first degree asymptomatic relatives to avoid inappropriate kidney donors; an evident variable phenotypic expression among patients; the identification of a mutation almost confined to Spanish cases and a 3.5 Mb block of genomic homozygosis strongly suggesting a common remote parental ancestor for the gene mutation reported.
Assuntos
Claudinas/genética , Hipercalciúria , Falência Renal Crônica , Nefrocalcinose , Erros Inatos do Transporte Tubular Renal , Adulto , Feminino , Triagem de Portadores Genéticos , Humanos , Hipercalciúria/complicações , Hipercalciúria/diagnóstico , Hipercalciúria/etnologia , Hipercalciúria/genética , Hipercalciúria/fisiopatologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim , México , Pessoa de Meia-Idade , Mutação , Nefrocalcinose/complicações , Nefrocalcinose/diagnóstico , Nefrocalcinose/etnologia , Nefrocalcinose/genética , Nefrocalcinose/fisiopatologia , Linhagem , Erros Inatos do Transporte Tubular Renal/complicações , Erros Inatos do Transporte Tubular Renal/diagnóstico , Erros Inatos do Transporte Tubular Renal/etnologia , Erros Inatos do Transporte Tubular Renal/genética , Erros Inatos do Transporte Tubular Renal/fisiopatologiaRESUMO
PURPOSE: To investigate nephrocalcinosis due to hyperoxaluria induced by two different inducing agents in rats. METHODS: Forty Sprague-Dawley male rats were randomly distributed into four groups: Group1 (Clinical control, n = 10); Group 2 (0.5% Ethylene Glycol + Vitamin D3, n = 10); Group 3 (1.25% Ethylene Glycol, n = 10); and Group 4 (5%Hydroxy L-proline, n = 10). Five animals from each group were euthanized after one week of follow-up (M1 Moment) and the remaining, after four weeks (M2 Moment). All animals underwent 24h urine dosages of calcium, oxalate, uric acid, citrate and serum creatinine. Histology and histomorphometric analyses were performed using Image J program in the hematoxylin-eosin stains. Calcium deposits in the renal parenchyma were quantified by PIXE technique (Proton Induced X-Ray Emission). RESULTS: 24h urinary parameters did not show any significant variations after 28 days of experiment except by hyperoxaluria that was significantly higher in Group 3. Histomorphometric analyses showed a significantly higher nephrocalcinosis in Group 2 (p<0.01). The calcium deposits in the renal parenchyma were 10 and 100 times higher in Group 2 in comparison to other groups in the M1 and M2 moments, respectively. CONCLUSION: The Group 2 (vitamin D3+Ethylene Glycol 0.5%) was the best model to induce nephrocalcinosis in rats after 28 days.(AU)
Assuntos
Animais , Ratos , Litíase/metabolismo , Nefrocalcinose/fisiopatologia , Ratos/anatomia & histologia , Oxalatos/químicaRESUMO
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
El objetivo de este estudio es conocer la incidencia de nefrocalcinosis en recién nacidos de pretérmino y determinar la utilidad de la relación calciuria/creatininuria como predictor diagnóstico. Un total de 124 recién nacidos con edad gestacional igual o menor a 32 semanas fueron agrupados en dos categorías. Un grupo de estudio de 53 pacientes con factores de riesgo conocidos para el desarrollo de nefrocalcinosis (oxigenoterapia, uso de furosemida y nutrición parenteral prolongadas) y un grupo control de 71 pacientes sin factores de riesgo. Ambos fueron estudiados por índice calciuria/creatininuria (muestras aisladas de orina los días 15, 21 y 30 de vida). Se definió hipercalciuria como un valor igual o mayor a 0,5 de índice calciuria/creatininuria presente al menos en dos muestras aisladas de orina. Se realizó estudio ecográfico entre los dos y tres meses de vida. El 15,3 por ciento de los pacintes presentó nefrocalcinosis. El grupo con factores de riesgo presenta 35,8 por ciento de nefrocalcinosis y los valores de calciuria/creatininuria fueron 0,87, 0,96 y 1,04. En el grupo control de valores de calciuria/creatininuria fueron 0,37, 0,30 y 0,29 no presentando casos de nefrocalcinosis. La diferencia entre ambos grupos es estadísticamente significativa (p<0,01). La presencia de hipercalciuria se relaciona con el diagnóstico de nefrocalcinosis, presentando valor predictivo positivo de 38 por ciento y valor predictivo negativo de 100 por ciento. La incidencia de nefrocalcinosis es comparable con series clínicas publicadas. Parece adecuado el estudio de pacientes con factores de riesgo por medio de calciuria/creatininuria realizando seguimiento ecográfico de pacientes con hipercalciuria
Assuntos
Humanos , Recém-Nascido , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/epidemiologia , Nefrocalcinose/epidemiologia , Cálcio/urina , Cálculos Urinários/diagnóstico , Creatinina/urina , Incidência , Nefrocalcinose/complicações , Nefrocalcinose/diagnóstico , Nefrocalcinose/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
We report a new X-linked recessive nephrolithiasis kindred. X-linked recessive nephrolithiasis is a recently described disease characterized by recurrent nephrolithiasis, nephrocalcinosis, and progressive renal failure, associated with mutations in a renal chloride channel gene, chloride channel number 5. Screening individuals at risk with renal ultrasonography and measurement of urinary excretion of low molecular weight proteins and calcium will exclude boys without X-linked recessive nephrolithiasis kindred and identify boys likely to have the disease.
Assuntos
Ligação Genética , Cálculos Renais/genética , Nefrocalcinose/genética , Cromossomo X , Cálcio/urina , Pré-Escolar , Canais de Cloreto/genética , Genes Recessivos , Humanos , Rim/química , Cálculos Renais/diagnóstico , Cálculos Renais/fisiopatologia , Masculino , Mutação , Nefrocalcinose/diagnóstico , Nefrocalcinose/fisiopatologia , Linhagem , Valores de ReferênciaRESUMO
Brazilian squirrel monkey kidneys removed before and after administration of parathormone were studied by microdissection, polarizing microscopy, alizarin red and von Kossa's stains, and microchemical analysis. Intralumenal crystalline-matrix masses were observed in both groups but were increased in frequency after parathormone administration. Specific staining showed the presence of calcium and phosphorus, and specific chemical tests suggested the presence of uric acid or urate salts. Refractile alizarin red positive droplets were observed in the tubular cells of the pars convoluta in parathormone-treated animals. Urinary stone formation in these animals is unique in that the location and types of stones produced are similar to that seen in man. The squirrel monkey is a good experimental model to study renal stone disease and further studies of its etiology, structure, composition, and means of control should be performed.