RESUMO
Hyperoxaluria results from either inherited disorders of glyoxylate metabolism leading to hepatic oxalate overproduction (primary hyperoxaluria), or increased intestinal oxalate absorption (secondary hyperoxaluria). Hyperoxaluria may lead to urinary supersaturation of calcium oxalate and crystal formation, causing urolithiasis and deposition of calcium oxalate crystals in the kidney parenchyma, a condition termed oxalate nephropathy. Considerable progress has been made in the understanding of pathophysiological mechanisms leading to hyperoxaluria and oxalate nephropathy, whose diagnosis is frequently delayed and prognosis too often poor. Fortunately, novel promising targeted therapeutic approaches are on the horizon in patients with primary hyperoxaluria. Patients with secondary hyperoxaluria frequently have long-standing hyperoxaluria-enabling conditions, a fact suggesting the role of triggers of acute kidney injury such as dehydration. Current standard of care in these patients includes management of the underlying cause, high fluid intake, and use of calcium supplements. Overall, prompt recognition of hyperoxaluria and associated oxalate nephropathy is crucial because optimal management may improve outcomes.
Assuntos
Injúria Renal Aguda , Hiperoxalúria Primária , Hiperoxalúria , Injúria Renal Aguda/complicações , Oxalato de Cálcio , Feminino , Humanos , Hiperoxalúria/complicações , Hiperoxalúria/terapia , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/terapia , Masculino , OxalatosRESUMO
Primary hyperoxaluria (PH) patients overproduce oxalate because of rare genetic errors in glyoxylate metabolism. Recurrent urolithiasis and/or progressive nephrocalcinosis are PH hallmarks and can lead to kidney damage, systemic oxalosis and death. Based on previous studies, we hypothesised that treatment with the oxalate-metabolizing bacterium Oxalobacter formigenes would mediate active elimination of oxalate from the plasma to the intestine of PH patients, thereby reducing urinary oxalate excretion (Uox). The efficacy and safety of O. formigenes (Oxabact™ OC3) were evaluated for 24 weeks in a randomised, placebo-controlled, double-blind study. The primary endpoint was reduction in Uox. Secondary endpoints included change in plasma oxalate (Pox) concentration, frequency of stone events, number of responders, and Uox in several subgroups. Additional post hoc analyses were conducted. Thirty-six patients were randomised; two patients withdrew from placebo treatment. Both OC3 and placebo groups demonstrated a decrease in Uox/urinary creatinine ratio, but the difference was not statistically significant. No differences were observed with respect to change in Pox concentration, stone events, responders' number or safety measures. In patients with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2, Pox increased by 3.25 µmol/L in the placebo group and decreased by -1.7 µmol/L in the OC3 group (p = 0.13). After 24 weeks, eGFR had declined to a greater degree in the placebo than in the OC3 group: -8.00 ± 2.16 versus -2.71 ± 2.50; p = 0.01. OC3 treatment did not reduce urinary oxalate over 24 weeks of treatment compared with placebo in patients with PH. The treatment was well tolerated.
Assuntos
Terapia Biológica/métodos , Oxalato de Cálcio/metabolismo , Hiperoxalúria Primária/terapia , Cálculos Renais/epidemiologia , Oxalobacter formigenes/metabolismo , Adolescente , Adulto , Terapia Biológica/efeitos adversos , Oxalato de Cálcio/sangue , Criança , Pré-Escolar , Creatinina/sangue , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperoxalúria Primária/sangue , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/metabolismo , Cálculos Renais/sangue , Cálculos Renais/etiologia , Cálculos Renais/metabolismo , Testes de Função Renal , Masculino , Placebos/administração & dosagem , Eliminação Renal , Resultado do Tratamento , Adulto JovemRESUMO
We report the case of a 78-year-old patient with late diagnosis of hyperoxaluria type III (PH3). He developed renal failure after nephrectomy for clear cell papillary renal carcinoma and complained of recurrent urolithiasis for some 30 years, whose aetiology was never identified. Biochemical laboratory investigations of urine and urolithiasis composition revealed marked hyperoxaluria but normal concentrations of urinary glyceric and glycolic acid as well as stones of idiopathic calcium-oxalate appearance. Furthermore, the dietary survey showed excessive consumption of food supplements containing massive amounts of oxalate precursors. However, the persistence of excessive hyperoxaluria after his eating habits was changed leading us to perform molecular genetic testing. We found heterozygous mutations of the recently PH3-associated HOGA1 gene when sequencing PH genes. This is the first description of late diagnosis primary PH3 in a patient with several additional pro-lithogenic factors. This case illustrates the importance of undertaking a complete biological work-up to determine the aetiology of hyperoxaluria. This may reveal underdiagnosed primary hyperoxaluria, even in older patients.
Assuntos
Diagnóstico Tardio , Hiperoxalúria Primária/diagnóstico , Mutação , Oxo-Ácido-Liases/genética , Urolitíase/diagnóstico , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Expressão Gênica , Ácidos Glicéricos/urina , Glicolatos/urina , Humanos , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/genética , Hiperoxalúria Primária/urina , Rim/metabolismo , Rim/patologia , Rim/cirurgia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Nefrectomia , Oxo-Ácido-Liases/metabolismo , Urolitíase/complicações , Urolitíase/genética , Urolitíase/urinaRESUMO
Oxalate is a highly insoluble metabolic waste excreted by the kidneys. Disturbances of oxalate metabolism are encountered in enteric hyperoxaluria (secondary to malabsorption, gastric bypass or in case of insufficient Oxalobacter colonization), in hereditary hyperoxaluria and in intoxication (ethylene glycol, vitamin C). Hyperoxaluria causes a large spectrum of diseases, from isolated hyperoxaluria to kidney stones and nephrocalcinosis formation, eventually leading to kidney failure and systemic oxalosis with life-threatening deposits in vital organs. New causes of hyperoxaluria are arising recently, in particular after gastric bypass surgery, which requires regular and preemptive monitoring. The treatment of hyperoxaluria involves reduction in oxalate intake and increase in calcium intake. Optimal urine dilution and supplementation with inhibitors of kidney stone formation (citrate) are required. Some conditions may need vitamin B6 supplementation, and the addition of probiotics might be useful in the future. Primary care physicians should identify cases of recurrent calcium oxalate stones and severe hyperoxaluria. Further management of hyperoxaluria requires specialized care.
L'oxalate est un déchet métabolique peu soluble excrété par les reins, et les hyperoxaluries peuvent être distinguées en hyperoxaluries entériques, hyperoxaluries héréditaires et les intoxications (éthylène glycol, vitamine C). L'hyperoxalurie induit un large spectre de maladies allant de l'hyperoxalurie isolée, formation de calculs rénaux, voire d'une néphrocalcinose, à l'insuffisance rénale et l'oxalose systémique avec des dépôts s'accumulant dans de nombreux organes. De nouvelles causes d'hyperoxalurie sont apparues ces dernières années, en particulier les hyperoxaluries survenant à la suite d'un bypass gastrique. Le traitement des hyperoxaluries fait intervenir, d'une part, une diminution contrôlée des apports en oxalate et une augmentation des apports en calcium et, d'autre part, une dilution des urines et l'ajout d'inhibiteurs de la lithogenèse (citrate). Dans certaines conditions particulières, une supplémentation en vitamine B6 ou l'utilisation de probiotiques peuvent être envisagées. Le praticien doit rester attentif aux cas de calculs d'oxalate de calcium récidivants ou d'hyperoxalurie sévère et les adresser pour une prise en charge spécialisée et multidisciplinaire.
Assuntos
Hiperoxalúria/diagnóstico , Hiperoxalúria/etiologia , Cálcio/administração & dosagem , Diagnóstico Diferencial , Humanos , Hiperoxalúria/classificação , Hiperoxalúria/complicações , Hiperoxalúria Primária/classificação , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/genética , Intestino Grosso/microbiologia , Cálculos Renais/prevenção & controle , Cálculos Renais/urina , Oxalatos/administração & dosagem , Oxalatos/urina , Oxalobacter formigenes/fisiologia , Fatores de RiscoRESUMO
We report a case of a 6-month-old infant who presented with failure to thrive due to end-stage renal disease as a result of primary hyperoxaluria type 1. The infant was managed with a combined daily hemodialysis and peritoneal dialysis prescription in order to manage the total body oxalate burden. Medical management included oral pyridoxine, aggressive hydration and nutritional supplementation via an enteral feeding tube. At one year of age the infant underwent a combined liver/kidney transplantation with intra- and daily post-operative hemodialysis to prevent oxalate deposition in the newly transplanted organs. The post-operative course was complicated by gross hematuria and increased hyperoxaluria, requiring an increase in hydration and thiazide diuretics. This infant received a combination of dialysis modalities which was designed to lower the potential oxalate burden prior to transplantation. This case illustrates the difficulty in medical management of an infant pre- and post-combined liver/kidney transplantation.
Assuntos
Hiperoxalúria Primária/diagnóstico , Hiperoxalúria Primária/cirurgia , Transplante de Rim , Transplante de Fígado , Hematúria , Humanos , Hiperoxalúria Primária/complicações , Lactente , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Masculino , Diálise Peritoneal , Complicações Pós-Operatórias , Diálise RenalRESUMO
A 66 year-old woman was referred in 1981 because of renal insufficiency and pronounced nephrocalcinosis. The urinary oxalate excretion was elevated. Secondary hyperoxaluria was excluded. End-stage renal disease necessitated hemodialysis from late in 1982 up to her death in 1986, at the age of 71 years. During the course of the disease, an aggressive arthropathy developed in the fingers. Classical signs of oxalosis were found: deposits of calcium oxalate crystals in bone tissue, the pancreas, myocardium, subcutaneous tissue and especially in the kidneys. This rare case documents the possible occurrence of late clinical presentation and long survival in primary oxalosis.
Assuntos
Artrite/etiologia , Calcinose/etiologia , Hiperoxalúria Primária/complicações , Hiperoxalúria/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Artrite/diagnóstico por imagem , Artrite/metabolismo , Calcinose/diagnóstico por imagem , Calcinose/metabolismo , Oxalato de Cálcio/metabolismo , Feminino , Articulações dos Dedos/diagnóstico por imagem , Articulações dos Dedos/metabolismo , Humanos , Pessoa de Meia-Idade , Radiografia , Fatores de TempoRESUMO
A 14.5-year-old boy with end-stage renal failure due to familial primary hyperoxaluria underwent cadaver donor renal transplantation. The graft function was stable for a period of 22 months, while he was on conventional immunosuppressive therapy (prednisolone and azathioprine) and additional oral pyridoxine, phosphorus, and magnesium supplementation. When ciclosporin A was introduced instead of azathioprine, the blood levels of oxalate rose, and oxalate deposition in the renal tubuli became evident. These observations suggest that ciclosporin A interferes with oxalate metabolism and, therefore, should be given with utmost caution in patients with primary hyperoxaluria.