Living Kidney Donation in a Type 1 Dent's Disease Patient from His Mother.

INTRODUCTION: Dent's disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease. Females are obligate carriers of the mutated gene, and some show a mild Dent's disease phenotype. There may be reason for concern when considering a female obligate carrier (i.e., the mother) for kidney donation because of the risk of kidney function deterioration. CASE PRESENTATION: We describe the first successful kidney transplantation involving a patient with type 1 Dent's disease and ESRD given a kidney by an obligate carrier of the gene mutation, his mother. CONCLUSIONS: After careful assessment of the female obligate carriers, intrafamilial kidney donation in Dent's disease type 1 is feasible. No deteriorating renal function in the donor was observed.

Update on Dent Disease.

Dent disease is an X-linked form of chronic kidney disease characterized by hypercalciuria, low molecular weight proteinuria, nephrocalcinosis, and proximal tubular dysfunction. Clinical presentation is highly variable. Male patients may present with early-onset rickets, recurrent nephrolithiasis, or insidiously with asymptomatic proteinuria or chronic kidney disease. Mutations in both the CLCN5 and OCRL1 genes have been associated with the Dent phenotype and are now classified as Dent-1 and Dent-2, respectively. This article describes the clinical presentation, laboratory evaluation, genetics, pathophysiology, management, and future therapies of Dent disease.

Early Recognition and Management of Rare Kidney Stone Disorders.

Kidney stones, especially those that present in childhood/adolescence, may be due to rare inherited disorders such as cystinuria. Early recognition and prompt treatment can help reduce or even prevent the serious long-term complications of these rare stone disorders.

Dent's disease complicated by an acute Budd-Chiari syndrome.

We present the case of a young boy with Dent's disease, identified as having a mutation in the kidney-specific chloride-proton antitransporter CLCN5 during investigation for nephrotic-range proteinuria. He went on to develop growth hormone deficiency and was treated with recombinant growth hormone. He later presented acutely with hepatorenal failure and thrombotic occlusion of the middle and right hepatic veins consistent with a diagnosis of Budd-Chiari syndrome, which required a prolonged period of intensive care. The diagnosis of Dent's disease should be considered early in boys with nephrotic-range proteinuria in the absence of clinical oedema and hypoalbuminaemia to allow for the timely introduction of strategies, such as a high-citrate diet, to preserve renal function. The measurement of urinary ß-2 microglobulin has been shown by this case to be a more reliable and specific marker of tubular dysfunction than the urinary retinol-binding protein.

Hereditary causes of kidney stones and chronic kidney disease.

Adenine phosphoribosyltransferase (APRT) deficiency, cystinuria, Dent disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and primary hyperoxaluria (PH) are rare but important causes of severe kidney stone disease and/or chronic kidney disease in children. Recurrent kidney stone disease and nephrocalcinosis, particularly in pre-pubertal children, should alert the physician to the possibility of an inborn error of metabolism as the underlying cause. Unfortunately, the lack of recognition and knowledge of the five disorders has frequently resulted in an unacceptable delay in diagnosis and treatment, sometimes with grave consequences. A high index of suspicion coupled with early diagnosis may reduce or even prevent the serious long-term complications of these diseases. In this paper, we review the epidemiology, clinical features, diagnosis, treatment, and outcome of patients with APRT deficiency, cystinuria, Dent disease, FHHNC, and PH, with an emphasis on childhood manifestations.

[Dent's syndrome. Nephrology follow-up of four patients of the same family]. / Le syndrome de Dent. Suivi néphrologique de quatre cas de la même famille.

Dent's syndrome is a rare inherited tubulopathy. Factors influencing renal function in this disease are not well known. The aim of our study is to investigate the evolution of the Dent's syndrome in renal plan. The study was retrospective and conducted in 2006, concerning four brothers. The genetic defect was a mutation S244L missense in exon 6 of gene CLCN5. Various parameters were studied. Patients were 8.5 to 21-years-old at the beginning of the follow-up. Two of them had chronic renal insufficiency (CRI) which evolved, at least 7 years of moderate to terminal stage. Tubular signs were made of hypokalemia, hypercalciuria, hypophosphatemia and proteinuria mostly ß2 microglobulin. Improvement of these abnormalities was obtained with symptomatic treatment which has not always been well tolerated. A case of beginner nephrocalcinosis was observed. There was size and weight delay at the beginning of patient monitoring. Dent's syndrome may be complicated by CRI. It seems to appear in the second decade of life and hypercalciuria would contribute to it. Our CRI patients had significant bone disease. The hypercalciuria and proteinuria are factors over which we try to act. Clinical trials are needed to evaluate the efficacy of treatment on the reduction of CRI or its progression by reducing these factors in patients with Dent's syndrome.

Dent's disease.

Dent's disease is a renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. These features are generally found in males only, and may be present in early childhood, whereas female carriers may show a milder phenotype. Prevalence is unknown; the disorder has been reported in around 250 families to date. Complications such as rickets or osteomalacia may occur. The disease is caused by mutations in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes that are located on chromosome Xp11.22 and Xq25, respectively. CLCN5 encodes the electrogenic Cl⁻/H(+) exchanger ClC-5, which belongs to the CLC family of Cl⁻ channels/transporters. OCRL1 encodes a phosphatidylinositol bisphosphate (PIP2) 5-phosphatase and mutations are also associated with Lowe Syndrome. The phenotype of Dent's disease is explained by the predominant expression of ClC-5 in the proximal tubule segments of the kidney. No genotype-phenotype correlation has been described thus far, and there is considerable intra-familial variability in disease severity. A few patients with Dent's disease do not harbour mutations in CLCN5 and OCRL1, pointing to the involvement of other genes. Diagnosis is based on the presence of all three of the following criteria: low-molecular-weight proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, kidney stones, hematuria, hypophosphatemia or renal insufficiency. Molecular genetic testing confirms the diagnosis. The differential diagnosis includes other causes of generalized dysfunction of the proximal tubules (renal Fanconi syndrome), hereditary, acquired, or caused by exogenous substances. Antenatal diagnosis and pre-implantation genetic testing is not advised. The care of patients with Dent's disease is supportive, focusing on the treatment of hypercalciuria and the prevention of nephrolithiasis. The vital prognosis is good in the majority of patients. Progression to end-stage renal failure occurs between the 3rd and 5th decades of life in 30-80% of affected males.