RESUMEN
Excessive phosphorus intake adversely affects bone and mineral metabolism. Estrogen is one of the factors affecting fibroblast growth factor 23 (FGF23), a phosphorus-regulating hormone. However, the interaction between excess phosphorus and estrogen status has not been fully elucidated. This study investigated the involvement of estrogen in the effects of high phosphorus intake on bone metabolism and ectopic calcification in ovariectomized (OVX) rats. The interaction between high phosphorus diet and OVX was not observed in bone mineral density and aortic calcium. In contrast, high phosphorus intake markedly increased renal calcium concentration in sham rats, whereas the effect was attenuated in OVX rats, which was reversed by a selective estrogen-receptor modulator treatment. A strong positive correlation between renal calcium and serum FGF23 was observed. In addition, fibroblast growth factor receptor 1 (FGFR1: a predominant receptor of FGF23) inhibitor treatment partially decreased renal calcium concentrations in rats with high phosphorus intake. In conclusion, the effect of high phosphorus intake on bone metabolism and aortic calcification did not depend on the estrogen status; in contrast, high phosphorus intake synergistically induced nephrocalcinosis in the presence of estrogenic action on the bone. Furthermore, FGF23 was involved in the nephrocalcinosis induced by high phosphorus intake partially through FGFR1 signaling.
Asunto(s)
Estrógenos/metabolismo , Factores de Crecimiento de Fibroblastos/sangre , Nefrocalcinosis/metabolismo , Fósforo/efectos adversos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Animales , Aorta/metabolismo , Densidad Ósea/efectos de los fármacos , Calcio/metabolismo , Modelos Animales de Enfermedad , Femenino , Factores de Crecimiento de Fibroblastos/efectos de los fármacos , Nefrocalcinosis/sangre , Nefrocalcinosis/inducido químicamente , Ovariectomía/efectos adversos , Pirimidinas/farmacología , Clorhidrato de Raloxifeno/farmacología , RatasRESUMEN
OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.
Asunto(s)
Estatura/efectos de los fármacos , Hipoparatiroidismo/tratamiento farmacológico , Hormona Paratiroidea/uso terapéutico , Adolescente , Calcinosis , Calcio/sangre , Calcio/orina , Niño , Creatinina/orina , Análisis Mutacional de ADN , Femenino , Homeostasis , Terapia de Reemplazo de Hormonas , Humanos , Pruebas de Función Renal , Modelos Lineales , Masculino , Nefrocalcinosis/metabolismo , Hormona Paratiroidea/administración & dosificación , Fósforo/sangre , Fósforo/orina , Poliendocrinopatías Autoinmunes/genética , Receptores Sensibles al Calcio/genética , Resultado del Tratamiento , Vitamina D/sangreRESUMEN
Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.
Asunto(s)
Modelos Animales de Enfermedad , Enfermedades Transmitidas por los Alimentos/etiología , Hiperoxaluria/etiología , Nefrocalcinosis/etiología , Ácido Oxálico/envenenamiento , Hojas de la Planta/efectos adversos , Spinacia oleracea/efectos adversos , Administración Oral , Animales , Biomarcadores/sangre , Biomarcadores/metabolismo , Biomarcadores/orina , Cristalización , Glicol de Etileno/toxicidad , Enfermedades Transmitidas por los Alimentos/metabolismo , Enfermedades Transmitidas por los Alimentos/patología , Enfermedades Transmitidas por los Alimentos/fisiopatología , Regulación de la Expresión Génica/efectos de los fármacos , Hiperoxaluria/metabolismo , Hiperoxaluria/patología , Hiperoxaluria/fisiopatología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Nefrocalcinosis/metabolismo , Nefrocalcinosis/patología , Nefrocalcinosis/fisiopatología , Ácido Oxálico/administración & dosificación , Ácido Oxálico/química , Ácido Oxálico/metabolismo , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Hojas de la Planta/química , Ratas Wistar , Insuficiencia Renal/etiología , Spinacia oleracea/químicaRESUMEN
Mutations in the renal sodium-dependent phosphate cotransporters NPT2a and NPT2c have been reported in patients with renal stone disease and nephrocalcinosis. Oral phosphate supplementation is currently thought to reduce risk by reversing the hypercalciuria, but the exact mechanism remains unclear and the relative contribution of modifiers of mineralization such as osteopontin (Opn) to the formation of renal mineral deposits in renal phosphate wasting disorders has not been studied. We observed a marked decrease of renal gene expression and urinary excretion of Opn in Npt2a-/- mice, a mouse model of these disorders, at baseline. Following supplementation with phosphate Opn gene expression was restored to wild-type levels in Npt2a-/- mice; however, urine excretion of the protein remained low. To further investigate the role of Opn, we used a double-knockout strategy, which provides evidence that loss of Opn worsens the nephrocalcinosis and nephrolithiasis observed in these mice on a high-phosphate diet. These studies suggest that impaired Opn gene expression and urinary excretion in Npt2a-/- mice may be an additional risk factor for nephrolithiasis, and normalizing urine Opn levels may improve the therapy of phosphaturic disorders.
Asunto(s)
Raquitismo Hipofosfatémico Familiar/metabolismo , Hipercalciuria/metabolismo , Riñón/metabolismo , Nefrocalcinosis/metabolismo , Osteopontina/metabolismo , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa/genética , Animales , Femenino , Factores de Crecimiento de Fibroblastos/genética , Hipofosfatemia/genética , Masculino , Ratones Noqueados , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIa/metabolismo , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIc/genéticaRESUMEN
BACKGROUND AND AIMS: It has been suggested that magnesium deficiency is associated with the triggering of acute phase response, which may contribute to type 2 diabetes and cardiovascular disease risk. We undertook this study to determine whether oral magnesium supplementation modifies serum levels of high-sensitivity C-reactive protein (hsCRP) in apparently healthy subjects with prediabetes and hypomagnesemia. METHODS: A total of 62 men and non-pregnant women aged 18-65 year, with new diagnosis of prediabetes (glucose 5.6 <7.0 mmol/L and/or post-load glucose ≥7.7 <11.1 mmol/L) and hypomagnesemia (serum magnesium levels <0.74 mmol/L) were enrolled in a clinical double-blind placebo-controlled trial and randomly allocated to receive either magnesium chloride (30 mL of MgCl2 5% solution) or NaHCO3 0.1% solution, once daily for 3 months. RESULTS: At basal conditions, anthropometric and biochemical variables were similarly distributed in both groups. At the end of follow-up, participants who received magnesium chloride showed higher serum magnesium levels (0.86 ± 0.08 vs. 0.69 ± 0.16 mmol/L, p = 0.002) and lower hsCRP levels (4.8 ± 15.2 vs. 17.1 ± 21.0 nmol/L, p = 0.01) compared with participants in the control group. CONCLUSIONS: Oral magnesium supplementation decreases hsCRP levels in apparently healthy subjects with prediabetes and hypomagnesemia.
Asunto(s)
Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipercalciuria/tratamiento farmacológico , Cloruro de Magnesio/administración & dosificación , Nefrocalcinosis/tratamiento farmacológico , Estado Prediabético/tratamiento farmacológico , Defectos Congénitos del Transporte Tubular Renal/tratamiento farmacológico , Administración Oral , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Hipercalciuria/complicaciones , Hipercalciuria/metabolismo , Cloruro de Magnesio/sangre , Masculino , Persona de Mediana Edad , Nefrocalcinosis/complicaciones , Nefrocalcinosis/metabolismo , Estado Prediabético/complicaciones , Estado Prediabético/metabolismo , Defectos Congénitos del Transporte Tubular Renal/complicaciones , Defectos Congénitos del Transporte Tubular Renal/metabolismo , Adulto JovenRESUMEN
BACKGROUND: Nephrocalcinosis (NC) is an important clinical problem seen in critically ill preterm neonates treated with loop diuretics. No reliable animal models are available to study the pathogenesis of NC in preterm infants. The purpose of this study was to develop a reproducible and clinically relevant animal model of NC for these patients and to explore the impact of extracellular fluid (ECF) volume contraction induced by sodium and chloride depletion in this process. METHODS: Three-week-old weanling Sprague-Dawley rats were fed diets deficient in either chloride or sodium or both. A subgroup of rats from each dietary group was injected daily with furosemide (40 mg/kg i.p.). RESULTS: Rats fed a control diet, with or without furosemide, or a chloride-depleted diet alone, did not develop NC. By contrast, 50% of the rats injected with furosemide and fed the chloride-depleted diet developed NC. Moreover, 94% of the rats fed the combined sodium- and chloride-depleted diet developed NC, independently of furosemide use. NC was associated with the development of severe ECF volume contraction; hypochloremic, hypokalemic, metabolic alkalosis; increased phosphaturia; and growth retardation. CONCLUSION: Severe ECF volume contraction induced by chronic sodium and chloride depletion appears to play an important role in the pathogenesis of NC.
Asunto(s)
Cloruros/metabolismo , Riñón/metabolismo , Nefrocalcinosis/etiología , Cloruro de Sodio Dietético/metabolismo , Sodio/deficiencia , Equilibrio Hidroelectrolítico , Animales , Presión Sanguínea , Calcio/orina , Modelos Animales de Enfermedad , Furosemida , Riñón/fisiopatología , Masculino , Nefrocalcinosis/inducido químicamente , Nefrocalcinosis/metabolismo , Nefrocalcinosis/fisiopatología , Fósforo/orina , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Aumento de PesoRESUMEN
We report a case of a 59-year old Japanese woman with short bowel syndrome, whose hypokalemia and hypocalcemia were successfully treated with magnesium (Mg) supplementation. Two years previously, she underwent Mile's operation for advanced rectal cancer, which could have been the cause of subsequent extensive resection of the small intestine by strangulation. After serial resection, she gradually developed chronic diarrhea and anorexia. Three weeks before admission, she developed general fatigue and tetany, and was hospitalized at another hospital. On admission, her serum K and Ca were 2.5 mEq/L and 4.3 mg/dL, respectively, hence regular fluid therapy containing potassium (K) and calcium (Ca) was provided following admission. However, her hypokalemia and hypocalcemia persisted, and she also displayed renal dysfunction and thereafter was transferred to our department for further evaluation and treatment. Since the laboratory tests revealed severe hypomagnesemia (0.4 mg/dL), we started intravenous Mg supplementation together with fluid therapy containing K and Ca. After the combination therapy, her clinical symptoms and electrolyte disorders were remarkably improved within a week. As Mg is essential for PTH secretion in response to hypocalcemia and to inhibit the K channel activity that controls urinary K excretion, hypomagnesemia can cause hypocalcemia and hypokalemia, which is refractory to repletion therapy unless Mg is administered. Therefore, for patients who present with signs of Mg deficiency, early and accurate diagnosis of Mg deficiency should be made and corrected.
Asunto(s)
Hipercalciuria/etiología , Hipocalcemia/complicaciones , Hipopotasemia/complicaciones , Nefrocalcinosis/etiología , Defectos Congénitos del Transporte Tubular Renal/etiología , Síndrome del Intestino Corto/complicaciones , Femenino , Humanos , Hipercalciuria/metabolismo , Hipercalciuria/terapia , Hipocalcemia/diagnóstico , Hipocalcemia/terapia , Hipopotasemia/diagnóstico , Persona de Mediana Edad , Nefrocalcinosis/metabolismo , Nefrocalcinosis/terapia , Potasio/sangre , Defectos Congénitos del Transporte Tubular Renal/metabolismo , Defectos Congénitos del Transporte Tubular Renal/terapia , Síndrome del Intestino Corto/diagnóstico , Síndrome del Intestino Corto/metabolismo , Síndrome del Intestino Corto/terapia , Desequilibrio Hidroelectrolítico/fisiopatologíaRESUMEN
BACKGROUND: Here we report the serum carnitine ester profile during and after 1g iv/day L-carnitine supplementation in haemodialysis patients. MATERIALS AND METHODS: Seven patients were studied over 29 weeks. After a control day, 12 weeks of replacement therapy was introduced followed by 17 weeks of washout period. The serum acylcarnitine concentrations were determined by isotope dilution ESI MS/MS technique. RESULTS: At baseline significantly decreased free carnitine (48%, p < 0.01) and a 1.5-16-fold elevation of 16 out of 27 acylcarnitines were detected in HD patients compared with the controls. On the last day of L-carnitine supplementation a 1.6-4.8-fold increase was observed in the acylcarnitine levels compared with day 0; the increase-profile was achieved in four different patterns. The increase rate was rapid and early saturable for C5, C5OH, C6DC, C8:1, C10DC and C18:2 esters, slower for C2, C4, C6, C18 and C18:1 esters, it was slowest and reached a late plateau for C3, C8DC, C14:2, C16 and C16:1, and finally almost gradual increase was seen for 11 acylcarnitines. Three months after the cessation of carnitine treatment marked concentration drops were found for almost all acylcarnitines (by 11-74 % of week 12, p < 0.05); the values further decreased over the five remaining weeks of the observation period. CONCLUSION: Carnitine administration affected the levels of circulating esters in different dynamics and kinetics suggesting a regulated, non-random adaptive reallocation of nutrients. A considerable washout was achieved 3 months after discontinuation of the supplementation; however, the profile still was suggestive for presence of rest of accumulated supplement.
Asunto(s)
Carnitina/administración & dosificación , Suplementos Dietéticos , Glomerulonefritis/terapia , Nefrocalcinosis/terapia , Pielonefritis/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carnitina/sangre , Carnitina/farmacocinética , Estudios de Casos y Controles , Femenino , Glomerulonefritis/metabolismo , Humanos , Persona de Mediana Edad , Nefrocalcinosis/metabolismo , Estudios Prospectivos , Pielonefritis/metabolismo , Diálisis Renal , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
BACKGROUND: Parathyroidectomy is associated with renal functional losses in transplant patients; cinacalcet offers an attractive alternative. METHODS: We performed a prospective observational study in 58 patients with persisting hyperparathyroidism after renal transplantation (Ca≥2.6 mmol/L) and impaired renal transplant function (estimated glomerular filtration rate [eGFR] <50 mL/min). The patients received 30 to 90 mg cinacalcet for 12 months with the target to normalize serum Ca. We measured parathyroid hormone (PTH), serum Ca, serum phosphorus, alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, and telopeptide at 0, 1, 2, 3, 6, 9, and 12 months of cinacalcet treatment. Fractional excretion of calcium and phosphorus (n=24) were monitored at 0 and 1 month. RESULTS: At inclusion, creatinine was 181±70 µmol/L, eGFR 43±19 mL/min, PTH 371±279 pg/mL, and Ca 2.73±0.22 mmol/L. We observed nephrocalcinosis in 58% of biopsied patients at enrollment. After cinacalcet, Ca decreased significantly and normalized at nearly any measurement. Phosphorus increased significantly at months 1, 9, and 12. PTH decreased significantly, but only at months 9 and 12 and did not normalize. Bone-specific alkaline phosphatase increased significantly (>normal) by month 12. eGFR decreased and serum creatinine increased at all time points. The Δ(creatinine) % increase correlated significantly with the Δ(PTH) % decrease at month 1 and 12. Telopeptide and alkaline phosphatase correlated with PTH and telopeptide also correlated with serum creatinine. CONCLUSION: Calcium-phosphorus homeostasis in hypercalcemic renal transplant patients normalizes under cinacalcet and PTH decreases, albeit not to normal. The renal functional decline could be PTH mediated, analogous to the effects observed after parathyroidectomy.
Asunto(s)
Huesos/efectos de los fármacos , Hiperparatiroidismo/metabolismo , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Riñón/efectos de los fármacos , Naftalenos/farmacología , Anciano , Biopsia , Huesos/metabolismo , Calcio/metabolismo , Cinacalcet , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Humanos , Hiperparatiroidismo/tratamiento farmacológico , Hiperparatiroidismo/etiología , Riñón/patología , Riñón/fisiología , Fallo Renal Crónico/complicaciones , Masculino , Persona de Mediana Edad , Naftalenos/uso terapéutico , Nefrocalcinosis/metabolismo , Nefrocalcinosis/patología , Hormona Paratiroidea/metabolismo , Fósforo/metabolismo , Estudios ProspectivosRESUMEN
Female Sprague-Dawley rats provide an animal model for studying the role of nutrition in renal health due to their sensitivity to diet-induced alterations in kidney function. Nephrocalcinosis, a common renal abnormality found in rats, has been implicated in subsequent renal failure. Simple dietary manipulations, such as changing the source of dietary protein, may influence nephrocalcinosis. This study evaluates the consumption of krill protein concentrate (KPC), a novel and high-quality protein, on renal and bone health. Young female Sprague-Dawley rats (n = 10/group) were individually housed in metabolic cages and fed ad libitum diets consisting of 10% crude protein supplied as KPC or casein for 4 weeks. Diets were isocaloric, isonitrogenous, and matched for calcium (Ca) and phosphorus (P). Urinary n-acetyl glucosaminidase (NAG) was measured and kidney histology performed to assess kidney damage. Biomarkers of kidney function were determined by calorimetric assays. Ca and P balance and bone concentrations were measured using inductively coupled plasma mass spectrometry. Femoral strength was determined by three-point bend testing. Rats fed KPC had lower (P = 0.005) urinary NAG levels and minimal microtubular Ca deposition compared to rats fed casein. There was a tendency (P < 0.06) for higher glomerular filtration rates and lower proteinuria, and higher (P = 0.03) urinary output in rats fed KPC compared to casein. There were no differences in Ca and P balance or bone measurements of total bone mineral content, Ca, P or strength between rats fed KPC and casein. Based on the study results, KPC prevented early renal injury leading to nephrocalcinosis and potential bone loss.
Asunto(s)
Proteínas en la Dieta/farmacología , Riñón/metabolismo , Nefrocalcinosis/dietoterapia , Animales , Huesos/química , Huesos/metabolismo , Calcio/análisis , Calcio/metabolismo , Calcio de la Dieta/análisis , Calcio de la Dieta/metabolismo , Caseínas/análisis , Caseínas/metabolismo , Crustáceos , Euphausiacea/metabolismo , Femenino , Riñón/química , Riñón/patología , Nefrocalcinosis/metabolismo , Nefrocalcinosis/patología , Fósforo/análisis , Fósforo/metabolismo , Fósforo Dietético/análisis , Fósforo Dietético/metabolismo , Proteinuria/metabolismo , Proteinuria/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
We investigated the effects of a traditional Chinese herbal formula, Wulingsan (WLS), on renal stone prevention using an ethylene glycol-induced nephrocalcinosis rat model. Forty-one male Sprague-Dawley (SD) rats were divided into four groups. Group 1 (n=8) was the normal control; group 2 (n=11) served as the placebo group, and received a gastric gavage of starch and 0.75% ethylene glycol (EG) as a stone inducer; group 3 received EG and a low dose of WLS (375 mg/kg); and group 4 received EG and a high dose of WLS (1,125 mg/kg). Baseline and final 24 h urine samples were collected individually; biochemical data of urine and serum were also obtained at the beginning and at the end of the experiment. After 4 weeks, animals were killed and kidneys were harvested. The kidney specimens were examined by polarized light microscopy and the crystal deposits were evaluated by a semi-quantitative scoring method using computer software (ImageScoring). The results revealed that the rats of placebo group gained the least significant body weight; in contrast, the rats of WLS-fed groups could effectively reverse it. The placebo group exhibited lower levels of free calcium (p=0.059) and significantly lower serum phosphorus (p=0.015) in urine than WLS-fed rats. Histological findings of kidneys revealed tubular destruction, damage and inflammatory reactions in the EG-water rats. The crystal deposit scores dropped significantly in the WLS groups, from 1.40 to 0.46 in the low-dose group and from 1.40 to 0.45 in the high-dose group. Overall, WLS effectively inhibited the deposition of calcium oxalate (CaOx) crystal and lowered the incidence of stones in rats (p=0.035). In conclusion, WLS significantly reduced the severity of calcium oxalate crystal deposits in rat kidneys, indicating that Wulingsan may be an effective antilithic herbal formula.
Asunto(s)
Oxalato de Calcio/metabolismo , Medicamentos Herbarios Chinos/uso terapéutico , Nefrocalcinosis/prevención & control , Extractos Vegetales/farmacología , Cálculos Urinarios/metabolismo , Cálculos Urinarios/prevención & control , Animales , Relación Dosis-Respuesta a Droga , Glicol de Etileno , Procesamiento de Imagen Asistido por Computador , Riñón/metabolismo , Riñón/patología , Masculino , Nefrocalcinosis/inducido químicamente , Nefrocalcinosis/metabolismo , Ratas , Ratas Sprague-Dawley , Cálculos Urinarios/inducido químicamenteRESUMEN
The aim of this study was to test the effect of L: -arginine methyl ester (L-Arg) on indices of free radical involvement in a rat model of experimental nephrocalcinosis. Twenty-eight Sprague-Dawley rats were randomized into four groups of seven. The first group (G1), the sham-control group received pure distilled drinking water. The second group (G2) received drinking water containing 0.7% ethylene glycol (EG) in distilled water for 3 weeks. The third group (G3) received drinking water containing 0.7% EG in distilled water for 3 weeks and L-Arg was administered for 3 weeks. The fourth group (G4) received drinking water containing 0.7% EG in distilled water for 3 weeks and L-NAME was administered for 3 weeks. Urine and aortic blood was collected to determine some parameters. The kidneys were also removed for histological examination. The increase in blood urea nitrogen, serum creatinine, K(+), Mg(2+ )and uric acid were mild in group 3 compared with the groups 2 and 4. The urinary concentrations of Na(+), K(+), Mg(2+) and uric acid were noticed to be similar among the groups. However, Ca(2+ )and oxalate excretion were significantly higher in groups 2, 3 and 4 than in group 1. The mean values of SOD, CAT and GSH-Px values were significantly increased in group 3 when compared to groups 2 and 4. Presence of aggregated urinary crystals was clearer in experimental groups compared to group 1. The tubular dilatation, epithelial degeneration and lymphocytic infiltration were significantly found in groups 2 and 4. Mild tissue damage was observed in L-Arg-pretreated rats. Under polarized light microscope intense crystals in the cortex and medulla were observed in the kidney of group 2 and 4 and moderate crystals were noticed in group 3. In conclusion, L-Arg supplementation may decrease free radicals and tubulary membrane injury in nephrocalcinosis due to infiltrating leukocytes and decreased antioxidant enzyme activities in rats fed with EG diet.
Asunto(s)
Arginina/análogos & derivados , Nefrocalcinosis/tratamiento farmacológico , Nefrocalcinosis/metabolismo , Animales , Arginina/farmacología , Nitrógeno de la Urea Sanguínea , Oxalato de Calcio/química , Oxalato de Calcio/orina , Catalasa/metabolismo , Creatinina/sangre , Cristalización , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Radicales Libres/metabolismo , Glutatión/metabolismo , Magnesio/sangre , Magnesio/orina , Masculino , NG-Nitroarginina Metil Éster/farmacología , Nefrocalcinosis/patología , Estrés Oxidativo , Potasio/sangre , Potasio/orina , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Sodio/orina , Superóxido Dismutasa/metabolismo , Ácido Úrico/sangre , Ácido Úrico/orinaRESUMEN
Acute renal failure (ARF) is rarely reported after bowel preparation with sodium phosphate. We report a patient with mild Crohn disease (in remission), without history of renal disease, and with normal baseline renal function, who developed ARF 14 days after bowel preparation for colonoscopy with oral sodium phosphate. A renal biopsy showed multifocal calcium phosphate deposition in the renal tubules against a background of diffuse chronic tubulointerstitial injury. Review of the literature suggested 2 distinct patterns of ARF in the context of sodium phosphate bowel cleansing. One pattern is characterized by ARF, which develops a few hours or days after sodium phosphate administration, as a component of a systemic syndrome associated with severe hyperphosphatemia and hypocalcemia. Correction of these electrolyte abnormalities was frequently associated with rapid recovery of renal function. The cause of ARF in this context was not clear because the favorable outcome negated the need for renal biopsy. In the second pattern, exemplified by the current patient, ARF was identified incidentally. These patients did not have any features of an acute syndrome immediately after sodium phosphate administration and presented much later (usually weeks) with mild, nonspecific symptoms. At the time of presentation, the serum calcium and phosphate levels were normal. The renal biopsies in each of these patients showed nephrocalcinosis as the possible cause of ARF. The renal failure improved at least partially in most of these patients, but persisted in rare cases.
Asunto(s)
Catárticos/efectos adversos , Enema , Riñón/efectos de los fármacos , Nefrocalcinosis/inducido químicamente , Fosfatos/efectos adversos , Insuficiencia Renal/inducido químicamente , Administración Oral , Biopsia , Enfermedades del Colon/diagnóstico , Colonoscopía , Femenino , Humanos , Riñón/metabolismo , Riñón/patología , Persona de Mediana Edad , Nefrocalcinosis/metabolismo , Nefrocalcinosis/patología , Insuficiencia Renal/patologíaRESUMEN
Although a magnesium (Mg)-deficient diet is generally known to induce nephrocalcinosis, our previous study observed that despite the administration of a Mg-deficient diet, the kidney calcium (Ca) and phosphorus (P) concentrations were not increased in male rats. We speculated that this result was due to the P concentration of the experimental diet based on the AIN-93G formula used in the previous study. In the present study, male rats were fed modified AIN-93G diets containing the two different Mg concentrations [0.5 g per kg diet (normal-Mg) or Mg-free (Mg-deficient)] and three different P concentrations [3 (3-P), 5 (5-P) or 7 (7-P) g per kg diet]. By histological examination of the kidney, nephrocalcinosis was not observed in rats fed on the Mg-deficient diet containing 3-P While nephrocalcinosis appeared in rats fed on the Mg-deficient diet containing 5-P and 7-P The degree of nephrocalcinosis was severe in rats fed on the Mg-deficient diet containing 7-P compared with rats fed on the Mg-deficient diet containing 5-P These results demonstrated that the Mg-deficient diet based on AIN-93G formula dose not induce nephrocalcinosis and that the Mg-deficient diet based on AIN-93G formula with increased dietary P concentrations induces nephrocalcinosis in male rats. We suggest that the onset of nephrocalcinosis could depend on the dietary P concentration in male rats fed on a Mg-deficient diet.
Asunto(s)
Deficiencia de Magnesio/complicaciones , Nefrocalcinosis/etiología , Fósforo Dietético/administración & dosificación , Alimentación Animal , Animales , Calcio/metabolismo , Dieta/efectos adversos , Riñón/metabolismo , Magnesio/sangre , Deficiencia de Magnesio/metabolismo , Masculino , Nefrocalcinosis/metabolismo , Fósforo/metabolismo , Ratas , Ratas WistarRESUMEN
Supplementation with essential fatty acids has been shown to prevent the experimentally induced ectopic calcification of the kidneys known as nephrocalcinosis. Male Sprague-Dawley rats were fed a semi-synthetic diet supplemented with different essential fatty acids while being injected for a period of 10 days with calcium glubionate. After 3 weeks their kidneys and aorta were removed and the respective calcium content measured compared to the control, saline injected animals. Lipoic acid-EPA, fish oil (EPA rich) as well as the EPA monoester reduced the calcium concentration of both the kidneys and the aorta towards control values. Lipoic-EPA was the best absorbed of the three compounds and its combination of anti-oxidant together with EPA lowered the calcium content of both the aortas and the kidneys.
Asunto(s)
Aorta/patología , Calcio/metabolismo , Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Nefrocalcinosis/metabolismo , Animales , Calcio/análisis , Eicosanoides/metabolismo , Eritrocitos/química , Ácidos Grasos Esenciales/metabolismo , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6 , Ácidos Grasos Insaturados/metabolismo , Riñón/patología , Masculino , Compuestos Organometálicos/administración & dosificación , Ratas , Ratas Sprague-Dawley , Trisacáridos/administración & dosificaciónRESUMEN
There is an urgent need for drugs capable of inhibiting renal calcifications, nephrocalcinosis and stones included, in humans. Current anticalcification medication is based mainly on alkalinization of the metabolism using potassium-containing citrate alone, despite the fact that calcium stone patients suffer marginally from both magnesium and potassium deficiency. We investigated the anticalcification efficacy of oral potassium citrate versus the combined administration of this drug and magnesium citrate in the magnesium-deficient rat developing corticomedullary nephrocalcinosis and luminal microliths in the long term. Among other things we employed specific stains for calcium and oxalate, light microscopy and element analysis for renal tissue and calcifications, respectively. In addition, minerals in renal tissue, urine and plasma were determined, as well as the state of extracellular calcium homeostasis. Magnesium deficiency caused pure calcium phosphate tissue deposits, containing no magnesium, but no deposition of calcium oxalate in the tubular lumen; tissue magnesium, calcium and phosphorus were increased, and there was marked potassium wastage via urine; despite mild hypercalcemia other signs of hyperparathyroidism were not found. Alkalinization with the two kinds of medication evoked an increase in urinary pH, citrate, and potassium; however, potassium citrate alone tended to aggravate renal concretions, whereas the combination of this drug with magnesium citrate completely prevented concretions. It was concluded that: (1) magnesium deficiency-induced calcifications are oxalate-free and are not sensitive to mobilization by alkalinization with potassium citrate, which might explain the failure of the drug to prevent stone recurrence in clinical stone patients, and (2) the combination of potassium citrate and magnesium citrate, which shows enormous anticalcification efficacy, deserves high priority in clinical trials aimed at evaluating strategies for the prevention of stones.
Asunto(s)
Fosfatos de Calcio/metabolismo , Calcio/metabolismo , Deficiencia de Magnesio/metabolismo , Magnesio/metabolismo , Nefrocalcinosis/metabolismo , Fósforo/metabolismo , Potasio/metabolismo , Animales , Catárticos/uso terapéutico , Ácido Cítrico/uso terapéutico , Modelos Animales de Enfermedad , Diuréticos/uso terapéutico , Quimioterapia Combinada , Riñón/metabolismo , Riñón/ultraestructura , Deficiencia de Magnesio/complicaciones , Deficiencia de Magnesio/tratamiento farmacológico , Masculino , Nefrocalcinosis/etiología , Nefrocalcinosis/prevención & control , Compuestos Organometálicos/uso terapéutico , Citrato de Potasio/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
The development of nephrocalcinosis and the time course of changes in kidney function, especially proximal tubular function, were studied in young male rats fed a high-phosphorus diet. The animals were fed a purified diet with a phosphorus content of either 0.5% (normal phosphorus diet) or 1.5% (high-phosphorus diet). In the group fed the high-phosphorus diet, nephrocalcinosis was found in 4 of 42 rats after 1 d of feeding and in all rats of this group at 3 d. The degree of nephrocalcinosis gradually increased with time. Upon histological observation by electron microscopy, vacuoles, lysosomes and swelling of microvilli in the proximal tubules were observed in rats fed the high-phosphorus diet after 1 d of feeding. Giant lysosomes with deposition of calcium and deposition of hydroxyapatite in mitochondria were observed in the proximal tubules of rats fed the high-phosphorus diet at 3 d. Albumin concentration in the urine of these rats was significantly increased at 3 d. The activity of N-acetyl-beta-D-glucosaminidase in the urine was also significantly increased after 1 d of feeding the high-phosphorus diet, and then reached a plateau. The beta 2-microglobulin concentration in the urine of rats fed the high-phosphorus diet was significantly increased at 14 d, and increased more toward 21 d. We concluded that nephrocalcinosis and injury to the proximal tubules are rapidly induced in rats fed a high-phosphorus diet.
Asunto(s)
Dieta , Túbulos Renales Proximales/efectos de los fármacos , Nefrocalcinosis/inducido químicamente , Fósforo/administración & dosificación , Animales , Calcio/metabolismo , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/ultraestructura , Masculino , Microscopía Electrónica , Nefrocalcinosis/metabolismo , Nefrocalcinosis/fisiopatología , Tamaño de los Órganos , Orgánulos/ultraestructura , Fósforo/metabolismo , Fósforo/toxicidad , Ratas , Ratas WistarRESUMEN
1. To assess whether the mineral content of drinking water influences both risk of stone formation and bone metabolism in idiopathic calcium nephrolithiasis, 21 patients were switched from their usual home diets to a 10 mmol calcium, low-oxalate, protein-controlled diet, supplemented with 21 of three different types of mineral water. Drinking water added 1, 6 and 20 mmol of calcium and 0.5, 10 and 50 mmol of bicarbonate respectively to the controlled diet. 2. The three controlled study periods lasted 1 month each and were separated by a 20 day washout interval. Blood and urine chemistries, including intact parathyroid hormone, calcitriol and two markers of bone resorption, were performed at the end of each study period. The stone-forming risk was assessed by calculating urine saturation with calcium oxalate (beta CaOx), calcium phosphate (beta bsh) and uric acid (beta UA). 3. The addition of any mineral water produced the expected increase in urine output and was associated with similar decreases in beta CaOx and beta UA, whereas beta bsh varied marginally. These equal decreases in beta CaOx, however, resulted from peculiar changes in calcium, oxalate and citrate excretion during each study period. The increase in overall calcium intake due to different drinking water induced modest increases in calcium excretion, whereas oxalate excretion tended to decrease. The changes in oxalate excretion during any one study period compared with another were significantly related to those in calcium intake. Citrate excretion was significantly higher with the high-calcium, alkaline water. 4. Parathyroid hormone, calcitriol and markers of bone resorption increased when patients were changed from the high-calcium, alkaline to the low-calcium drinking water. 5. We suggest that overall calcium intake may be tailored by supplying calcium in drinking water. Adverse effects on bone turnover with low-calcium diets can be prevented by giving high-calcium, alkaline drinking water, and the stone-forming risk can be decreased as effectively as with low-calcium drinking water.
Asunto(s)
Bicarbonatos/administración & dosificación , Huesos/metabolismo , Calcio/administración & dosificación , Ingestión de Líquidos , Nefrocalcinosis/terapia , Agua/química , Adulto , Calcitriol/sangre , Calcio/orina , Oxalato de Calcio/orina , Fosfatos de Calcio/orina , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Hidroxiprolina/orina , Masculino , Persona de Mediana Edad , Nefrocalcinosis/dietoterapia , Nefrocalcinosis/metabolismo , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Péptidos/orina , Ácido Úrico/orinaRESUMEN
The effects of calcium gluconate on the utilization of magnesium and nephrocalcinosis in male Wistar rats made magnesium-deficient by adding excess dietary phosphorus (1.195 g of phosphorus/100 g of diet) and calcium (1.04 g of calcium/100 g of diet) were compared with the effects of calcium carbonate. The effects of dietary magnesium concentration on the magnesium status and nephrocalcinosis were also examined. Adding excess dietary phosphorus and calcium decreased the apparent magnesium absorption ratios and the concentrations of magnesium in the serum and femur and increased the deposition of calcium in the kidney, and the low magnesium condition (0.024 g of magnesium/100 g of diet) aggravated the deposition of calcium and the low magnesium status. The apparent magnesium absorption ratios and femur magnesium concentration in the rats fed a calcium gluconate diet (an equimolar mixture of calcium gluconate and calcium carbonate was used as a source of calcium) were significantly higher than in the rats fed a calcium carbonate diet (only calcium carbonate was used as a source of calcium), irrespective of dietary magnesium concentration. Dietary calcium gluconate lessened the accumulation of calcium in the kidney and increased the serum magnesium concentration compared with dietary calcium carbonate, when the rats were fed the normal magnesium diet (0.049 g of magnesium/100 g of diet) but not the low magnesium diet. We speculate that the increased utilization of magnesium by feeding the calcium gluconate diet to a limited extent prevented the low magnesium status and the severity of nephrocalcinosis caused by adding excess dietary phosphorus and calcium.
Asunto(s)
Gluconato de Calcio/farmacología , Calcio/administración & dosificación , Dieta , Magnesio/metabolismo , Nefrocalcinosis/metabolismo , Fósforo/administración & dosificación , Absorción , Animales , Huesos/metabolismo , Calcio/metabolismo , Carbonato de Calcio/farmacología , Ingestión de Alimentos , Fémur , Riñón/metabolismo , Masculino , Fósforo/metabolismo , Ratas , Ratas Wistar , Aumento de PesoRESUMEN
The effect of altering the dietary Ca:P ratio during critical points of growth (based on reproductive and skeletal age) on kidney calcification in female rats was investigated. Groups of weanling animals were fed one of three nutritionally complete but calcium-altered diets (0.25, 0.5 or 1.0 g Ca/100 g diet) from 4 to 12 wk of age (Phase 1). Phosphorus concentration remained constant at 0.4 g/100 g diet resulting in Ca:P molar ratios of 0.48, 0.96 and 1.92, respectively. During Phase 2, the same animals within each diet group were then rerandomized into one of the above diets and fed for an additional 25 wk. Each group contained five rats. The data from the nine treatment groups were analyzed statistically using a two-way ANOVA (Phase 1 dietary Ca level by Phase 2 dietary Ca level). The level of dietary Ca during Phase 1 only exerted a significant influence on kidney Ca accumulation. Rats fed the two lower dietary Ca levels, and hence lower dietary Ca:P molar ratios, during Phase 1 had two- to threefold greater kidney Ca concentration and kidney ash Ca concentration than rats fed the diet with the highest dietary Ca level (1.92 Ca:P molar ratio) during Phase 1, regardless of the Ca intake during Phase 2. In contrast, the dietary Ca:P molar ratio during Phase 2 had little effect either positively or negatively on the kidney Ca concentration that had been established during Phase 1. The results indicate that dietary-induced nephrocalcinosis in female rats is irreversible and is induced primarily before the completion of adolescence (approximately 12 wk of age) in Sprague-Dawley female rats.