The Mayo Clinic section of pediatric and adolescent nephrology has expertise in a full range of kidney and urinary tract problems. Three specially trained pediatric nephrologists work with a pediatric nephrology nurse clinician and other healthcare personnel to diagnose and treat nephrologic problems in children. Mayo Clinic pediatric nephrologists lead multidisciplinary teams of physicians from a variety of medical specialties for the most thorough patient care. Other medical specialists who frequently consult with our pediatric nephrologists include perinatologists, pediatric urologists, pediatric radiologists, neonatologists and surgeons.
Four conditions were independently described over the last 40 years (Dent's Disease, X-linked recessive nephrolithiasis with renal failure, X-linked recessive hypophosphatemic rickets, Idiopathic low molecular weight proteinuria with hypercalciuria and nephrocalcinosis) that we now know to be caused by defects in the same genetic locus on the X chromosome. Therefore, all four are now collectively referred to as Dent’s Disease. Scientists in Great Britain precisely identified this responsible gene as ClCN5, which encodes a kidney-specific voltage gated chloride channel. Characteristics of the disease include low molecular weight proteinuria and hypercalciuria. Renal stones, nephrocalcinosis and renal failure often ensue. Because it is an X-linked disorder, only males are affected with the disease, whereas females are asymptotic carriers.
The mechanism by which a defect in a chloride channel leads to hypercalciuria and proteinuria is still poorly understood, but may be related to abnormal acidification within endocytic vesicles of proximal tubular cells. The pathways that produce nephrocalcinosis, renal scarring and kidney failure in Dent’s disease are also poorly understood, and no treatment trials are available to guide therapy. Available recommendations come from those clinicians with the most experience caring for these patients. Since the nephrocalcinosis and nephrolithiasis appear to be related to the hypercalciuria, treatment typically includes a thiazide diuretic to stimulate distal tubular calcium reabsorption and reduce calciuria. In limited series, this appears to be a reasonably effective strategy. For patients with osteomalacia and vitamin D or derivatives have been employed, apparently with success.
Because this maneuver could worsen hypercalciuria, it has been suggested that the dose be carefully titrated to the minimal amount needed to normalize the serum alkaline phosphatase. Patients that progress to end-stage renal disease appear to have no increased risk for renal osteodystrophy, and have been transplanted with success. Clearly there is much need for increased study of these patients, in order to devise optimal treatment strategies.
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