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1.
Am J Cardiol ; 125(10): 1517-1523, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32238278

RESUMO

Hypomagnesemia is commonly observed in heart transplant (HT) recipients receiving calcineurin inhibitors. Since low serum magnesium (s-Mg) has been implicated in the progression of atherosclerosis, potentially leading to worsening coronary heart disease, arrhythmias and sudden death, we investigated the association between s-Mg and HT outcomes. Between 2002 and 2017, 150 HT patients assessed for s-Mg were divided into high (≥1.7 mg/dL) and low s-Mg groups according to the median value of all s-Mg levels recorded during the first 3 months post-HT. Endpoints included survival, cardiac allograft vasculopathy (CAV), any-treated rejection (ATR) and NF-MACE. Kaplan-Meier analysis showed that at 15 years after HT, both survival (76 vs 33%, log-rank p = 0.007) and freedom from CAV (75 vs 48%, log-rank p = 0.01) were higher in the high versus low s-Mg group. There were no significant differences in freedom from NF-MACE or ATR. Multivariate analyses consistently demonstrated that low s-Mg was independently associated with a significant 2.6-fold increased risk of mortality and 4-fold increased risk of CAV (95%CI 1.06 to 6.4, p = 0.04; 95%CI 1.12 to 14.42, p = 0.01, respectively). In conclusion, low s-Mg is independently associated with increased mortality and CAV in HT patients. Larger multi-center prospective studies are needed to confirm these findings and to examine the effect of Mg supplementation.


Assuntos
Cardiopatias/mortalidade , Transplante de Coração/mortalidade , Hipercalciúria/complicações , Nefrocalcinose/complicações , Complicações Pós-Operatórias/mortalidade , Erros Inatos do Transporte Tubular Renal/complicações , Feminino , Rejeição de Enxerto/mortalidade , Cardiopatias/etiologia , Humanos , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
2.
Nefrología (Madrid) ; 39(6): 592-602, nov.-dic. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-189881

RESUMO

La hipercalciuria idiopática (HI) se define como aquella situación clínica en la que se comprueba un incremento en la eliminación urinaria de calcio, en ausencia de hipercalcemia y de otras causas conocidas de hipercalciuria. En los últimos años, su diagnóstico en la edad pediátrica ha sido más frecuente debido a que se ha conocido que puede comenzar con síntomas muy diversos, en ausencia de formación de cálculos renales. El descubrimiento de las ratas hipercalciúricas ha permitido vislumbrar el mecanismo fisiopatológico de la HI ya que muestran muchos datos en común con los humanos con HI, como niveles normales de calcemia, hiperabsorción intestinal de calcio, incremento de la resorción ósea y un defecto en la reabsorción tubular renal de calcio. En 1993, se demostró que en esos animales existe un incremento en el número de receptores de la vitamina D (VDR) del intestino, lo que favorece un aumento de la capacidad funcional de los complejos calcitriol-VDR que explica el incremento en el transporte intestinal de calcio. Lo mismo ocurre a nivel óseo produciéndose una mayor resorción. En nuestra opinión, la HI es una «anomalía metabólica» o, mejor, una característica metabólica constitutiva heredable. En este sentido, lo que los pacientes con HI heredarían es la disponibilidad de tener en sus células un mayor número de VDR que aquellas personas con calciurias normales. La HI no se puede considerar una enfermedad sensu stricto, por lo que el tratamiento farmacológico debe ser individualizado


Idiopathic hypercalciuria (IH) is defined as that clinical situation in which an increase in urinary calcium excretion is observed, in the absence of hypercalcemia and other known causes of hypercalciuria. In recent years, its diagnosis in pediatric age has been more frequent because it has been known that it can debut with very different symptoms, in the absence of kidney stone formation. The discovery of genetic hypercalciuric stone-forming rats has allowed us to glimpse the pathophysiological mechanism of IH since they show many data in common with humans with IH as normal levels of blood calcium, intestinal calcium hyperabsorption, increased bone resorption and a defect in the renal tubular calcium reabsorption. In 1993, it was shown that in these animals there is an increase in the number of vitamin D receptors (VDR) in the intestine, which favors an increase in the functional capacity of calcitriol-VDR complexes that explains the increase in intestinal transport of calcium. The same happens at the bone level producing a greater resorption. In our opinion, IH is a 'metabolic anomaly' or, better, an inheritable constitutive metabolic characteristic. In this sense, what patients with IH would inherit is the availability of having a greater number of VDRs in their cells than those with normal urinary calcium excretion. IH cannot be considered a sensu stricto disease, so pharmacological treatment must be individualized


Assuntos
Humanos , Animais , Hipercalciúria/complicações , Osso e Ossos/metabolismo , Cálcio/metabolismo , Nefrolitíase/complicações , Hipercalciúria/epidemiologia , Hipercalciúria/etiologia , Nefrolitíase/etiologia , Nefrolitíase/terapia , Densidade Óssea
3.
Rev. cuba. pediatr ; 91(3): e812, jul.-set. 2019. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1093715

RESUMO

Introducción: La hipercalciuria idiopática es una alteración metabólica relativamente frecuente y existen escasas publicaciones de su relación con la infección del tracto urinario. Objetivos: Precisar si existe asociación entre la infección urinaria e hipercalciuria idiopática para determinar si esta alteración metabólica constituye un factor de riesgo de infección urinaria. Métodos: Estudio descriptivo longitudinal prospectivo en pacientes de edad pediátrica con diagnóstico de infección urinaria atendidos en el Hospital Pediátrico Universitario William Soler entre 1ro. enero de 2016 y 31 de diciembre de 2017. Dos semanas después de controlada la infección se recogió muestra de orina de la primera micción del día para determinación de índice calcio/creatinina y precisar la excreción de calcio en 24 horas. Si esta prueba arroja resultados positivos, entre dos y cuatro semanas posteriores, se repite la muestra y si ambas son positivas y el calcio en sangre es normal se diagnostica hipercalciuria idiopática. Resultados: Se incluyeron en el estudio 130 pacientes. En 43,8 por ciento se encontró hipercalciuria idiopática. En su primer episodio infeccioso se estudiaron 52,3 por ciento y los restantes con antecedentes de infección o recurrencia. En 86,2 por ciento la infección fue catalogada como pielonefrítica. La distribución por sexo de la hipercalciuria no mostró diferencia y el síntoma hematuria con dolor abdominal recurrente resultó sugestivo de infección asociada a hipercalciuria (p < 0,05). El germen infectante no contribuye a pensar en hipercalciuria. Conclusión: La hipercalciuria idiopática constituye un factor predisponente de infección del tracto urinario(AU)


Introduction: Idiopathic hypercalciuria is a relatively frequent metabolic alteration and there are scarce publications on its relation with the urinary tract´s infection. Objective: To specify if there is a relation between urinary infection and idiopathic hypercalciuria, in order to determine if this last one constitutes a risk factor of urinary infection. Methods: Prospective, descriptive and longitudinal study in pediatric age's patients with a diagnosis of urinary infection that were attended in William Soler University Pediatric Hospital from January 1st, 2016 to December 31st, 2017. After two weeks of the infection being controlled, a urine sample from the first micturition of the day was collected to determine calcium/creatinine index and to specify calcium excretion in 24 hours. If this test shows positive results, after two to four weeks the sample is repeated, and if both are positive and calcium level in blood is normal, so idiopathic hypercalciuria is diagnosed. Results: 130 patients were included in the study. In 43.8 percent idiopathic hypercalciuria was found. 52.3 percent were studied during the first infectious episode, and there is presented a history of infection or recurrence. In 86.2 percent of the patients, the infection was catalogued as pyelonephritis. Hypercalciuria´s gender distribution didn't show any differences, and the symptom called hematuria with recurrent abdominal pain was suggestive to an infection related to hypercalciuria (p < 0.05). The infectious germ does not induce to think in hypercalciuria. Conclusions: Idiopathic hypercalciuria constitutes a predisposing factor of urinary tract's infection(AU)


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Doenças Urológicas/complicações , Hipercalciúria/complicações , Epidemiologia Descritiva , Estudos Prospectivos , Estudos Longitudinais
4.
Rev. cuba. pediatr ; 91(2): e809, abr.-jun. 2019. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1003959

RESUMO

Introducción: La hematuria es el hallazgo clínico más frecuente entre las enfermedades genitourinarias, después de las infecciones del tracto urinario a cualquier edad. Objetivo: Identificar las características generales y etiología de la hematuria monosintomática en pacientes pediátricos. Métodos: Investigación descriptiva longitudinal y prospectiva con los pacientes atendidos con hematuria monosintomática en el Servicio de Nefrología del Hospital Pediátrico Docente William Soler entre el primero de enero de 2014 y 31 de diciembre de 2015. Resultados: Se reclutaron 45 pacientes. Predominó en escolares (40 por ciento) y adolescentes (40 por ciento), sexo masculino (55,5 por ciento). Se recogió el antecedente personal o familiar de hematuria en 44,5 por ciento y 55,5 por ciento, respectivamente. La urolitiasis familiar estuvo presente en 37,7 por ciento. El tipo de hematuria más frecuente fue la macroscópica (75,8 por ciento), no glomerular (71,2 por ciento), sin proteinuria (77,8 por ciento), y hematíes eumórficos (62,2 por ciento). La causa más frecuente fue la hipercalciuria idiopática (51,1 por ciento) y el 80 por ciento de todos los pacientes solo recibió tratamiento higieno-dietético. En 20 por ciento de los pacientes no se pudo precisar la causa etiológica. Conclusiones: La causa más frecuente de hematuria fue no glomerular (hipercalciuria idiopática) y en aquellos con hematuria cuya causa etiológica no se pudo precisar, es obligado mantener un seguimiento prolongado(AU)


Introduction: Hematuria is the most frequent clinical finding among genitourinary diseases afterwards urinary tract infection at any age. Objective: To identify general characteristics and etiology of monosymptomatic hematuria in in pediatrics patients. Methods: Descriptive, longitudinal and prospective research of the patients by monosymptomatic hematuria attended at the Nephrology service in William Soler Teaching Pediatric Hospital from January 1, 2014 to December 31, 2015. Results: 45 patients were recruited. Schoolchildren (40 percent) were predominant and adolescents (40 percent), and males (55.5 percent). It was collected personal or familial records of hematuria in 44.5 percent and 55.5 percent, respectively. Familial urolithiasis was present in 37.7 percent. The most common type of hematuria was the macroscopic (75.8 percent), non-glomerular (71.2 percent), without proteinuria (77.8 percent) and with eumorphic hematies (62.2 percent). The most frequent etiological cause was idiopathic hypercalciuria (51.1 percent), and 80 percent of all patients only received hygiene-dietetic treatment. In the 20 percent of the patients was not possible to determine the etiological cause. Conclusions: The most frequent cause of hematuria was non-glomerular (idiopathic hypercalciuria); and in those patients with hematuria of non-precised etiological cause, it is mandatory to keep long-term follow-up(AU)


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Hipercalciúria/complicações , Hematúria/etiologia , Epidemiologia Descritiva , Estudos Prospectivos , Estudos Longitudinais
5.
J Am Soc Nephrol ; 30(7): 1163-1173, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31101664

RESUMO

BACKGROUND: The pathophysiology of genetic hypercalciuric stone-forming rats parallels that of human idiopathic hypercalciuria. In this model, all animals form calcium phosphate stones. We previously found that chlorthalidone, but not potassium citrate, decreased stone formation in these rats. METHODS: To test whether chlorthalidone and potassium citrate combined would reduce calcium phosphate stone formation more than either medication alone, four groups of rats were fed a fixed amount of a normal calcium and phosphorus diet, supplemented with potassium chloride (as control), potassium citrate, chlorthalidone (with potassium chloride to equalize potassium intake), or potassium citrate plus chlorthalidone. We measured urine every 6 weeks and assessed stone formation and bone quality at 18 weeks. RESULTS: Potassium citrate reduced urine calcium compared with controls, chlorthalidone reduced it further, and potassium citrate plus chlorthalidone reduced it even more. Chlorthalidone increased urine citrate and potassium citrate increased it even more; the combination did not increase it further. Potassium citrate, alone or with chlorthalidone, increased urine calcium phosphate supersaturation, but chlorthalidone did not. All control rats formed stones. Potassium citrate did not alter stone formation. No stones formed with chlorthalidone, and rats given potassium citrate plus chlorthalidone had some stones but fewer than controls. Rats given chlorthalidone with or without potassium citrate had higher bone mineral density and better mechanical properties than controls, whereas those given potassium citrate did not. CONCLUSIONS: In genetic hypercalciuric stone-forming rats, chlorthalidone is superior to potassium citrate alone or combined with chlorthalidone in reducing calcium phosphate stone formation and improving bone quality.


Assuntos
Densidade Óssea/efeitos dos fármacos , Fosfatos de Cálcio/metabolismo , Clortalidona/farmacologia , Hipercalciúria/tratamento farmacológico , Cálculos Renais/prevenção & controle , Citrato de Potássio/farmacologia , Animais , Clortalidona/administração & dosagem , Hipercalciúria/complicações , Masculino , Oxalatos/urina , Citrato de Potássio/administração & dosagem , Ratos
6.
Am J Physiol Renal Physiol ; 316(5): F966-F969, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30838875

RESUMO

The proximal tubule (PT) is responsible for the majority of calcium reabsorption by the kidney. Most PT calcium transport appears to be passive, although the molecular facilitators have not been well established. Emerging evidence supports a major role for PT calcium transport in idiopathic hypercalciuria and the development of kidney stones. This review will cover recent developments in our understanding of PT calcium transport and the role of the PT in kidney stone formation.


Assuntos
Cálcio/metabolismo , Hipercalciúria/complicações , Cálculos Renais/etiologia , Túbulos Renais Proximais/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Nefrocalcinose/etiologia , Reabsorção Renal , Animais , Claudinas/metabolismo , Humanos , Hipercalciúria/metabolismo , Hipercalciúria/fisiopatologia , Transporte de Íons , Cálculos Renais/metabolismo , Cálculos Renais/fisiopatologia , Túbulos Renais Proximais/fisiopatologia , Nefrocalcinose/metabolismo , Nefrocalcinose/fisiopatologia
7.
Int Braz J Urol ; 45(2): 340-346, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30735332

RESUMO

PURPOSE: Hypercalciuria is one of the risk factors for calcium kidney stone formation (the most common type of urinary stones). Although vitamin D deficiency is prevalent among urolithiasis patients, the effect of vitamin D supplementation on urine calcium in these patients is still unclear. MATERIALS AND METHODS: In this retrospective study, medical and laboratory tests records of 26 patients with recurrent calcium kidney stones and vitamin D deficiency treated with 50000IU vitamin D per week for 8-12 weeks were analyzed. The changes in 24-hour urine calcium (24-h Ca), serum 25-hydroxyvitamin D (25 (OH) D), serum parathormone (PTH), other 24-hour urine metabolites and calculated relative supersaturations of calcium oxalate (CaOxSS), calcium phosphate (CaPSS) and uric acid (UASS) were assessed. Moreover, correlations between changes in 24-h Ca and other aforementioned variables were assessed. RESULTS: Serum 25 (OH) D and 24-h Ca increased after vitamin D supplementation, while serum PTH decreased (p < 0.001, for all analyses). The levels of 24-hour urine sodium and urea increased significantly (p = 0.005 and p = 0.031, respectively). The levels of CaOxSS and CaPSS increased, but the changes were not significant (p = 0.177, and p = 0.218, respectively). There were no correlations between the changes in 24-h Ca and serum 25 (OH) D or PTH. CONCLUSIONS: The result of current study suggests that although urine Ca increased in vitamin D supplemented patients, this increase was not associated with the increase in serum vitamin D and may be due to other factors such as dietary factors. Further randomized clinical trials considering other factors associated with urine Ca are warranted.


Assuntos
Cálcio/urina , Urolitíase/urina , Deficiência de Vitamina D , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Idoso , Suplementos Nutricionais , Feminino , Humanos , Hipercalciúria/complicações , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/etiologia
8.
Urolithiasis ; 47(6): 511-519, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30798342

RESUMO

Loss-of-function mutations of SLC34A3 represent an established cause of a distinct renal phosphate wasting disorder termed hereditary hypophosphatemic rickets with hypercalciuria (HHRH). SLC34A3 encodes the renal phosphate transporter NaPi2c expressed at the apical brush border of proximal renal tubules. Substitution of p.Ser192Leu is one of the most frequent genetic changes among HHRH patients in Europe, but has never been systematically evaluated, clinically or on a cellular level. Identification of a 32-year-old female with a homozgyous c.575C>T, p.Ser192Leu substitution enabled a more comprehensive assessment of the impact of this missense variant. Clinically, the patient showed renal phosphate wasting and nephrocalcinosis without any bone abnormalities. Heterozygous carriers of deleterious SLC34A3 variants were previously described to harbor an increased risk of kidney stone formation and renal calcification. We hence examined the frequency of p.Ser192Leu variants in our adult kidney stone cohort and compared the results to clinical findings of previously published cases of both mono- and biallelic p.Ser192Leu changes. On a cellular level, p.Ser192Leu-mutated transporters localize to the plasma membrane in different cellular systems, but lead to significantly reduced transport activity of inorganic phosphate upon overexpression in Xenopus oocytes. Despite the reduced function in ectopic cellular systems, the clinical consequences of p.Ser192Leu may appear relatively mild, at least in our index patient, and can potentially be missed in clinical practice.


Assuntos
Raquitismo Hipofosfatêmico Familiar/genética , Hipercalciúria/genética , Mutação de Sentido Incorreto , Nefrocalcinose/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/genética , Adulto , Raquitismo Hipofosfatêmico Familiar/complicações , Feminino , Humanos , Hipercalciúria/complicações , Nefrocalcinose/complicações
9.
Res Vet Sci ; 123: 129-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30641472

RESUMO

People with calcium oxalate (CaOx) urolithiasis and idiopathic hypercalciuria (IH) often have evidence of increased bone resorption, but bone turnover has not previously been investigated in dogs with these conditions. The aim of this study was to determine whether a marker of bone resorption, ß-crosslaps, differs between dogs with CaOx urolithiasis and IH compared to controls. This retrospective, cross-sectional study used a canine specific ELISA to measure ß-crosslaps concentrations in stored frozen serum samples from 20 dogs with CaOx urolithiasis and IH and 20 breed-, sex-, and age-matched stone-free controls (18 Miniature Schnauzers, 14 Bichons Frise, and 8 Shih Tzus). Dogs with CaOx urolithiasis and IH had lower ß-crosslaps concentrations relative to controls (P = .0043), and ß-crosslaps had a moderate negative correlation with urinary calcium-to-creatinine ratios (r = -0.44, P = .0044). Miniature Schnauzers had lower ß-crosslaps concentrations than the other two breeds (P = .0035). The ELISA had acceptable intra-assay precision, but concentrations decreased when samples were repeatedly assayed over time. Assay recovery rates were also below acceptance criteria. In conclusion, Miniature Schnauzers, Bichons Frise, and Shih Tzus with CaOx urolithiasis and IH have evidence of decreased bone resorption compared to stone-free controls. This suggests that other causes of IH, such as intestinal hyperabsorption of calcium, underlie risk for CaOx urolithiasis in these breeds. Results should be confirmed in larger populations and with other ß-crosslaps assays and additional biomarkers of bone turnover. The stability of canine serum ß-crosslaps after freeze-thaw cycles and storage at various temperatures requires investigation.


Assuntos
Reabsorção Óssea/veterinária , Oxalato de Cálcio , Doenças do Cão/etiologia , Hipercalciúria/veterinária , Nefrolitíase/veterinária , Animais , Reabsorção Óssea/complicações , Reabsorção Óssea/patologia , Estudos Transversais , Doenças do Cão/patologia , Cães , Feminino , Humanos , Hipercalciúria/complicações , Hipercalciúria/patologia , Masculino , Nefrolitíase/complicações , Nefrolitíase/patologia , Estudos Retrospectivos
10.
Adv Exp Med Biol ; 1133: 75-81, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30632117

RESUMO

The incidence of urolithiasis in infants is unknown. The aim of this study was to investigate clinical characteristics, nutrition, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), alkaline phosphate, and parathyroid hormone in infants with urolithiasis. There were 32 infants (23 boys and 9 girls) of the mean age of 6.4 ± 3.7 months (range 2-12 months), with diagnosis of urolithiasis enrolled into the study. Boys were younger than girls (5.3 vs. 9.1 months, respectively; p < 0.05). The infants were receiving prophylactic vitamin D3. Twenty-one of them were fed with milk formula, 9 were breastfed, and 2 were on a mixed diet. The major clinical symptoms consisted of irritability in 19 (59%) and urinary tract infection in 6 (19%) infants. Hypercalcemia and hyperphosphatemia were detected in the serum in 30 (94%) and 19 (60%) infants, respectively. The serum calcium level was higher in boys than girls (10.8 vs. 9.8 mg/dL, respectively; p < 0.05). Four (12.5%) infants had increased activity of alkaline phosphatase. The serum level of 25(OH)D was high in 3 (9%), low in 2 (6%), and normal in 27 (85%) infants. Parathyroid hormone was low in eight (25%) infants. Hypercalciuria and hyperphosphaturia were found in 11 (34%) boys and 8 (25%) girls. Family history of urolithiasis was positive in eight (25%) infants. We conclude that urolithiasis occurs in infancy more often in boys fed with milk formula and in those who received vitamin D supplementation. Hypercalcemia, hyperphosphatemia, and hypercalciuria are the most common changes present in clinical metabolic tests.


Assuntos
Cálcio/sangue , Urolitíase/diagnóstico , Vitamina D/sangue , Fosfatase Alcalina/sangue , Animais , Feminino , Homeostase , Humanos , Hipercalcemia/complicações , Hipercalciúria/complicações , Hiperfosfatemia/complicações , Lactente , Fórmulas Infantis , Masculino , Leite , Hormônio Paratireóideo/sangue , Vitaminas
11.
Pediatr Clin North Am ; 66(1): 15-30, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30454740

RESUMO

The causes of macroscopic and microscopic hematuria overlap; both are often caused by urinary tract infections or urethral/bladder irritation. Coexistent hypertension and proteinuria should prompt investigation for glomerular disease. The most common glomerulonephritis in children is postinfectious glomerulonephritis. In most patients, and especially with isolated microscopic hematuria, the diagnostic workup reveals no clear underlying cause. In those cases whereby a diagnosis is made, the most common causes of persistent microscopic hematuria are thin basement membrane nephropathy, immunoglobulin A nephropathy, or idiopathic hypercalciuria. Treatment and long-term prognosis varies with the underlying disease.


Assuntos
Hematúria/diagnóstico , Hematúria/etiologia , Criança , Diagnóstico Diferencial , Glomerulonefrite por IGA/complicações , Humanos , Hipercalciúria/complicações , Hipertensão/complicações , Nefropatias/complicações , Proteinúria/complicações , Infecções Urinárias/complicações
13.
An. sist. sanit. Navar ; 41(3): 393-396, sept.-dic. 2018. ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-179088

RESUMO

El síndrome de Michaelis-Manz es una tubulopatia de herencia autosómica recesiva asociada a mutaciones en las proteínas claudina 16 y 19 que se encuentran en el túbulo contorneado distal y asa de Henle en el riñón. La claudina 19 también se encuentra en el epitelio pigmentario de la retina. Clínicamente, el cuadro provoca hipomagnesemia, hipercalciuria y nefrocalcinosis que puede dar lugar a insuficiencia renal. Oftalmológicamente presentan colobomas maculares, estafilomas por miopía magna y nistagmo. Presentamos el caso de un varón de 18 años afectado de hipomagnesemia familiar con hipercalciuria y nefrocalcinosis, o síndrome de Michaelis-Manz, asociado a un coloboma macular con una agudeza visual estable


Michaelis-Manz syndrome is an autosomal recessive hereditary tubulopathy associated with mutations in the tight-junction proteins claudin-16 and claudin-19, which are present in the distal convoluted tubule and the loop of Henle in the kidney. Claudin-19 is also expressed in the retinal pigmentary epithelium. The clinical picture causes hypomagnesemia, hypercalciuria and nephrocalcinosis that can lead to renal failure, which is the condition that marks the prognosis of the disease. Ophthalmologically patients can present macular coloboma, myopic staphyloma and nystagmus. We present the case report of an 18-year-old man suffering from hereditary hypomagnesemia, hypercalciuria and nephrocalcinosis, or Michaelis-Manz syndrome, with macular coloboma and stable visual acuities


Assuntos
Humanos , Masculino , Adolescente , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/tratamento farmacológico , Coloboma/diagnóstico por imagem , Acuidade Visual , Deficiência de Magnésio/complicações , Hipercalciúria/complicações , Nefrocalcinose/complicações , Coloboma/terapia , Retina/diagnóstico por imagem , Retina/patologia , Tomografia de Coerência Óptica/métodos , Diagnóstico Diferencial
14.
Int Urol Nephrol ; 50(11): 1949-1954, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30209738

RESUMO

PURPOSE: To study (1) the differences in the relative abundance of urinary proteins between children with kidney stones (RS) and hypercalciuria, hypocitraturia, normal metabolic work-up, and healthy controls (HC); (2) the association of these proteins with various diseases. METHODS: Quantitative proteomic comparison of pooled urine from RS (N = 30, 24 females, mean age 12.95 ± 4.03 years) versus age- and gender-matched HC, using mass spectrometry. Relative protein abundance was estimated using spectral counting. Proteins of interest were selected using the following criteria: (1) ≥ 5 spectral counts; (2) ≥ twofold difference in spectral counts; and (3) ≤ 0.05 p value for the Fisher's Exact Test. RESULTS: Of the 1813 proteins identified, 229 met the above criteria, with 162 proteins up-regulated in the RS group and 67 up-regulated in HC. The largest group of proteins (30 out of 229) was found to be associated with cardiovascular disease (CVD). Of those, 16 were involved in coagulation, fibrinolysis, and adhesion, 10 in inflammation, 5 in lipid transport and metabolism, and 4 in oxidative stress. All except two were exclusively found in children with hypercalciuria and hypocitraturia, and were not seen in children with normal metabolic work-up. CONCLUSION: Using a proteomic approach, we found a significant association between hypercalciuric and hypocitraturic nephrolithiasis and CVD in children. The shared risk factors among both diseases are endothelial dysfunction and atherosclerosis caused by abnormal coagulation, adhesion, disturbance of lipid transport and metabolism, oxidative stress and inflammation. Further understanding of the pathophysiological link between nephrolithiasis and CVD is necessary for developing new therapeutic targets.


Assuntos
Ácido Cítrico/urina , Hipercalciúria/urina , Cálculos Renais/urina , Proteinúria/urina , Proteômica , Adolescente , Coagulação Sanguínea , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fibrinólise , Humanos , Hipercalciúria/complicações , Inflamação/urina , Cálculos Renais/complicações , Metabolismo dos Lipídeos , Masculino , Regulação para Cima
15.
Pediatr Nephrol ; 33(12): 2321-2328, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30043116

RESUMO

BACKGROUND: A limited number of studies have evaluated biochemical bone metabolism markers in children with idiopathic hypercalciuria, which in adults has been linked with osteopenia. Our aim was to investigate in children with idiopathic hypercalciuria biochemical markers of bone formation and resorption and the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kB ligand (sRANKL) system which is involved in the osteoclastogenesis process. METHODS: A prospective study was conducted on 50 children with idiopathic hypercalciuria and 50 healthy age-, sex-, and Tanner stage-matched control subjects. Following the diagnosis, patients were requested to follow a 3-month dietary recommendation for idiopathic hypercalciuria. In patients, at diagnosis and at 3 months of follow-up, and in controls, bone-related hormones and serum/urine biochemical parameters were studied. The bone formation markers (total ALP and osteocalcin) and the bone resorption markers (ß-Crosslaps) and the OPG and sRANKL levels were determined. RESULTS: No differences were found in the bone formation markers or OPG and sRANKL between the children with idiopathic hypercalciuria and controls. The ß-Crosslaps and the ß-Crosslaps/osteocalcin ratio were higher in the patients at diagnosis than in controls (p = 0.019 and p = 0.029, respectively), with a trend to decrease after the 3-month dietary intervention. The initially increased 24-h urinary Ca in the patients decreased after the 3-month dietary intervention (p = 0.002). CONCLUSIONS: Children with idiopathic hypercalciuria had biochemical markers compatible with normal bone formation but increased bone resorption. After a 3-month dietary intervention, the trend observed towards decrease in the serum ß-Crosslaps may reflect a beneficial response.


Assuntos
Doenças Ósseas Metabólicas/diagnóstico , Reabsorção Óssea/diagnóstico , Osso e Ossos/metabolismo , Hipercalciúria/complicações , Osteogênese , Biomarcadores/sangue , Biomarcadores/metabolismo , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/prevenção & controle , Reabsorção Óssea/sangue , Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipercalciúria/sangue , Hipercalciúria/dietoterapia , Hipercalciúria/metabolismo , Estudos Longitudinais , Masculino , Osteocalcina/sangue , Osteocalcina/metabolismo , Osteoprotegerina/sangue , Osteoprotegerina/metabolismo , Estudos Prospectivos , Ligante RANK/sangue , Ligante RANK/metabolismo , Resultado do Tratamento
16.
BMC Nephrol ; 19(1): 181, 2018 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-30005619

RESUMO

BACKGROUND: Sixty mutations of claudin 16 coding gene have been reported in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) patients. Recent investigations revealed that a highly conserved glycine-leucine-tryptophan (115G-L-W117) motif in the first extracellular segment (ESC1) of claudin 16 might be essential for stabilization of the appropriately folded ECS1 structure and conservation of normal claudin 16 function. However, neither missense nor nonsense mutation has ever been described in this motif. Our study aimed at identifying mutations in a Chinese patient with FHHNC and exploring the association between genotype and phenotype. CASE PRESENTATION: A 33-year-old female presented with 4 years history of recurrent acute pyelonephritis without other notable past medical history. Her healthy parents, who aged 56 and 53 respectively, were second cousins, and her only sibling died from renal failure without definite cause at age 25. Renal ultrasound imaging demonstrated atrophic kidneys and bilateral nephrocalcinosis. The laboratory workup revealed impaired renal function (Stage CKD IV), hypocalcemia and mild hypomagnesemia, accompanied with marked renal loss of magnesium and hypercalciuria. During the follow-up, treatment with calcitriol and calcium but not with magnesium was difficult to achieve normal serum calcium levels, whereas her serum magnesium concentration fluctuated within normal ranges. In the end, the patient unavoidably reached ESRD at 36 years old. The clinical features and family history suggested the diagnosis of FHHNC. To make a definite diagnosis, we use whole-exome sequencing to identify the disease-causing mutations and Sanger sequencing to confirm the mutation co-segregation in the family. As a result, a novel homozygous mutation (c.346C > G, p.Leu116Val) in 115G-L-W117 motif of claudin 16 was identified. Her parents, grandmother and one of her cousins carried heterozygous p.Leu116Val, whereas 200 unrelated controls did not carry this mutation. CONCLUSIONS: We described a delayed diagnosis patient with FHHNC in the Chinese population and identified a novel missense mutation in the highly conserved 115G-L-W117 motif of claudin 16 for the first time. According to the reported data and the information deduced from 3D modeling, we speculate that this mutation probably reserve partial residual function which might be related to the slight phenotype of the patient.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Claudinas/genética , Códon sem Sentido/genética , Hipercalciúria/genética , Deficiência de Magnésio/genética , Nefrocalcinose/genética , Adulto , Claudinas/química , Diagnóstico Tardio , Feminino , Humanos , Hipercalciúria/complicações , Hipercalciúria/diagnóstico , Leucina/genética , Deficiência de Magnésio/complicações , Deficiência de Magnésio/diagnóstico , Nefrocalcinose/complicações , Nefrocalcinose/diagnóstico , Linhagem , Estrutura Secundária de Proteína
17.
J Clin Res Pediatr Endocrinol ; 10(4): 343-349, 2018 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-29809158

RESUMO

Objective: To describe clinical findings, biochemical profile and genetic analysis in an Iranian kindred with hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Methods: Clinical examination and biochemical profile results and gene analysis of 12 members of a family of a patient previously diagnosed with HHRH due to SLC34A3 mutation. Ten healthy controls were also evaluated. Results: Of the twelve family members three were homozygote and seven heterozygote for the same SLC34A3 variant found in the proband while two others were unaffected. All patients had significantly increased risk of kidney stone formation, bone deformities and short stature compared with unrelated healthy controls. The heterozygous patients displayed milder clinical symptoms compared with homozygous patients. In particular they had mild or no hypophosphatemia and they did not develop skeletal deformities. Recurrent renal stones and hypercalciuria were the main presentations of the heterozygous patients which may be confused with familial hypercalciuria. In addition, biochemical analysis showed significantly low serum sodium and elevated alkaline phosphatase levels in these patients. Conclusion: Genetic counseling and screening for SLC34A3 mutations can be helpful in adult onset phenotype with unexplained osteoporosis, bone deformities and especial recurrent renal stones. In subjects with vitamin D deficiency the results should be interpreted cautiously.


Assuntos
Raquitismo Hipofosfatêmico Familiar/genética , Deleção de Genes , Hipercalciúria/genética , Íntrons/genética , Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc/genética , Adolescente , Adulto , Criança , Pré-Escolar , Raquitismo Hipofosfatêmico Familiar/complicações , Saúde da Família , Feminino , Genótipo , Humanos , Hipercalciúria/complicações , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Linhagem
18.
An. pediatr. (2003. Ed. impr.) ; 88(4): 204-208, abr. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-172990

RESUMO

Introducción: Las infecciones de la vía urinaria (IVU) causadas por Escherichia coli (E. coli) son frecuentes en pacientes con hipercalciuria idiopática. Al ser tanto IVU como hipercalciuria (prelitiasis) de origen genético, planteamos si la historia familiar de urolitiasis es más frecuente en niños con IVU causada por E. coli. Secundariamente, planteamos si las cicatrices renales son más frecuentes en niños con prelitiasis. Material y métodos: Estudio ambispectivo con datos de 104 pacientes (40 masculinos y 64 femeninos) seguidos tras haber sido diagnosticados, al menos una vez, de IVU por E. coli. Se preguntó por la existencia de urolitiasis en familiares (primer y segundo grado). En 80 pacientes se determinó la eliminación urinaria de calcio y citrato. Resultados: En toda la muestra, la historia familiar de urolitiasis fue positiva en una frecuencia significativamente mayor de estos niños (n = 71; 68,3%) que en la población de control del mismo área (el 29,7% según datos previos publicados). La frecuencia de prelitiasis en niños con IVU fue del 47,5% (38/80). Se observó asociación entre prelitiasis tanto con la historia familiar de urolitiasis (p = 0,030) como con el reflujo vesicoureteral (p = 0,034). Además, los pacientes que desarrollaron cicatrices renales tenían más prelitiasis (OR 5,3; p = 0,033). Conclusiones: La frecuencia de historia familiar de urolitiasis en niños con IVU causada por E. coli es muy alta. Basándonos en nuestros resultados, sugerimos la hipótesis de que la predisposición a litiasis involucra una defensa alterada contra E. coli y, consecuentemente, una mayor posibilidad de cicatrices renales


Introduction: Urinary tract infections (UTI) caused by Escherichia coli (E. coli) are common in patients with idiopathic hypercalciuria. As both UTI and hypercalciuria (prelithiasis) have a genetic basis, we wanted to know whether the family history of urolithiasis is more common in children with UTIs caused by E. coli. Secondarily, we wondered if the renal scars are more common in children with prelithiasis. Material and methods: Ambispective study with collected data from 104 patients (40 male, 64 female) followed after having been diagnosed of UTI by E. coli at least once. These patients were asked about the existence of urolithiasis in relatives. The calcium and citrate urinary elimination was qunatified in 80 children. Results: In the total sample, family history was positive for urolithiasis in a significantly higher frequency in those children (n = 71; 68.3%) than in the control population in our area (29.7%; previously published data). Prelithiasis frequency in children with UTI was 47.5% (38/80). An association was observed between the diagnosis of prelithiasis both with family history of urolithiasis (P=.030) and the diagnosis of vesicoureteral reflux (P=.034). Children who developed renal scarring had an increased risk of prelithiasis (OR 5.3; P=.033). Conclusions: The frequency of family history of urolithiasis in children with UTI caused by E. coli is very high. Based on our results we hypothesize that the predisposition to lithiasis can involve a constitutively altered defense to E. coli and, therefore, a greater possibility for renal scars


Assuntos
Humanos , Masculino , Feminino , Criança , Nefrolitíase/diagnóstico por imagem , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia , Escherichia coli/isolamento & purificação , Anamnese/métodos , Hipercalciúria/complicações , Infecções Urinárias/diagnóstico por imagem , Colorimetria/métodos , Modelos Logísticos
19.
Cleve Clin J Med ; 85(1): 47-54, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29328898

RESUMO

Idiopathic hypercalciuria increases the risk of urinary stones and osteoporosis. The aim of this review is to delineate our current understanding of idiopathic hypercalciuria in the context of bone health, specifically its definition, causes, epidemiology, laboratory evaluation, and potential treatments.


Assuntos
Hipercalciúria/complicações , Cálculos Renais/etiologia , Osteoporose/etiologia , Cálculos Urinários/etiologia , Adulto , Densidade Óssea , Cálcio/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
20.
J Nephrol ; 31(2): 189-196, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29368300

RESUMO

Hyperuricosuric calcium urolithiasis is a condition of mixed calcium oxalate stones characterized by hyperuricosuria either in isolation or in conjunction with other risk factors for calcium oxalate stones such as hypercalciuria, hyperoxaluria, and hypocitraturia. There are three proposed physicochemical models of pathogenesis where urate in its crystalline phase via heterogeneous nucleation, in its colloidal phase via removal of crystallization inhibitors, and in solution via precipitation crystallization, can all increase propensity to calcium oxalate precipitation. Regardless of the model, the phenomenologic observation of urate increasing calcium oxalate precipitation appears solid. Another supporting factor are retrospective data analysis and prospective trials showing uric acid lowering reduces stones events in hyperuricosuric calcium stone formers. Due to the heterogeneity of pathogenesis of calcium oxalate stones in the unselected stone-formers, association cannot be demonstrated between uric acid excretion rate and risk of kidney stone the general population. In calcium oxalate stoners with isolated hyperuricosuria or hyperuricosuria in combination with other calcium stone risks where treatment of these traditional risks fails to reduce stone formation, urate acid lowering should be cautiously attempted. More refinement of pathogenic models and prospective controlled trials in phenotypically defined subgroups of subjects with calcium oxalate urolithiasis will be informative.


Assuntos
Oxalato de Cálcio/química , Ácido Úrico/química , Ácido Úrico/urina , Urolitíase/etiologia , Urolitíase/urina , Alopurinol/uso terapêutico , Fenômenos Químicos , Supressores da Gota/uso terapêutico , Humanos , Hipercalciúria/complicações , Fatores de Risco , Urolitíase/prevenção & controle
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