Clinical Trial: Genetic Study of Nephrolithiasis in Gouty Diathesis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Observational

Official Title: Genetic Study of Nephrolithiasis in Gouty Diathesis

Brief Summary: Gouty diathesis describes uric acid or calcium oxalate nephrolithiasis and low urinary pH (<5.5). A hereditary component has been outlined for several forms of nephrolithiasis (such as hypercalciuria, hyperoxaluria, cystinuria, renal tubular acidosis), leading to the hypothesis of a genetic predisposition to nephrolithiasis. At the Unit of Nephrology, Ospedali Riuniti di Bergamo, more than 100 patients affected by gouty diathesis are followed. Fifty percent of them has a familiarity for kidney stones formation. The aim of our study is to identify the genetic factors that predispose to the development of nephrolithiasis in patients with gouty diathesis.

Detailed Summary:

INTRODUCTION Nephrolithiasis is a common disorder with a reported incidence of 12% in industrialized countries. The peak incidence is in ages 20s to 40s. Men are affected two to three times more often than women. Gouty diathesis describes uric acid or calcium oxalate nephrolithiasis and low urinary pH (<5.5) in the absence of excessive gastrointestinal alkali loses or dietary animal protein excess. Hyperuricemia, hypertriglyceridemia, and a history of gouty arthritis may be present. Subjects with gout are singularly predisposed to stone formation. Persistent acidity of the urine is a common manifestation of primary gout, that may be accompanied by uric acid nephrolithiasis. In the presence of an increase in the concentration of uric acid in the urine, the formation of uric acid stones is further facilitated.

In the primary forms of nephrolithiasis the most important predisposing factors for kidney stones are: hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, hypomagnesuria, high urinary sulfate, low urine volume, high urinary sodium, cystinuria, infection, persistently high or low urinary pH. A hereditary component has been outlined for several of these abnormalities, leading to the hypothesis of a genetic predisposition to nephrolithiasis. Pirastu and co-workers took advantage from a small, isolated population from Sardinia, characterized by a high prevalence of Uric Acid Nephrolithiasis (UAN). The disease shows familial clustering, although the transmission of UAN does not follow a simple mendelian inheritance pattern, suggesting that hereditary factors could play an important role in susceptibility to UAN. They found an association of UAN to a new gene, called ZNF365, and in particular to its variant Ala62Thr, making it a strong candidate predisposing factor.

At the Unit of Nephrology, Ospedali Riuniti
Sponsor: Mario Negri Institute for Pharmacological Research

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Mario Negri Institute for Pharmacological Research

Dates:
Date Received: September 7, 2005
Date Started: May 2005
Date Completion:
Last Updated: April 8, 2015
Last Verified: October 2009