X-Linked Recessive Nephrolithiasis with Renal Failure

Abstract

This kindred manifested an X-linked recessive nephrolithiasis with renal failure, a new form of hereditary renal disease. Most of the identifiable physiologic abnormalities occurred after the development of nephrolithiasis and renal insufficiency and may not be of pathogenetic importance.

Hypothesis

“…For example, there are a few reports of FSGS associated with Dent disease (3-5), Gitelman syndrome (6,7), Bartter syndrome (8), and inherited distal renal tubular acidosis (9). ESRD can occur between the ages of 25 and 50 yr in patients with Dent disease (16). However, data on the longterm outcomes of patients with Gitelman and Bartter syndromes is scanty but important in regard to our hypothesis.…”

“…Whether FGGS is invariably a separate entity from FSGS or is part of a continuum has yet to be fully determined. Frymoyer et al (16) described at least one patient who had Dent disease and had renal biopsy findings that showed that 25% of the glomeruli had "partial-to-global sclerosis." One helpful diagnostic point is that the electron microscopy findings in Dent disease show minimal effacement of the epithelial foot processes, in contrast to FSGS with nephrotic syndrome.…”

A Patient with Nephrotic-Range Proteinuria and Focal Global Glomerulosclerosis

“…Female carriers often show milder degrees of LMW proteinuria than male carriers but may develop hypercalciuria and nephrolithiasis depending on X-chromosome inactivation (33). In most affected male patients, proteinuria is subnephrotic but may reach nephrotic levels (31,35,36). As in the present patient, albumin contributes to less than half of the proteinuria and patients do not develop a full-blown nephrotic syndrome.…”

“…It is clinically characterized by the presence of LMW proteinuria, hypercalciuria, medullary nephrocalcinosis, nephrolithiasis, and progressive renal failure (31,32). Other proximal tubular dysfunction may include aminoaciduria, glycosuria, phosphaturia, and sodium and potassium wasting, but complete Fanconi syndrome and metabolic acidosis are typically not present (33).…”

Screening for CLCN5 mutation in renal calcium stone formers patients

“…Some advances have been made in the understanding of disorders that can exhibit nephrolithiasis as a symptom such as primary hyperoxaluria (Danpure et al 1993), cystinuria (Stoller et al 1999) and Dent's disease (Xlinked hypercalciuria and nephrolithiasis) (Schein-man et al 1993), giving some insight into the ethiopathogenesis of calcium idiopathic nephrolithiasis. Dent's disease, for example, is a rare form of renal tubular disorder and it is characterized by hypercalciuria and low molecular-weight proteinuria besides all features of idiopathic nephrolithiasis, such as calcium stone formation and occasionally nephrocalcinosis and renal failure , Frymoyer et al 1991, Wrong et al 1994, Igarashi et al 1995, Hoopes et al 1998. The discovery of a 96 MARIA ALICE P. REBELO ET AL. hypercalciuric man, apparently idiopathic, that was in fact a true case of asymptomatic Dent's disease , has excited a stone investigators group to look for CLCN5 (gene that encodes for ClC-5 chloride channel) gene mutations.…”