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Characterisation of risk factors for stones in hyperuricosuric men attending a stone clinic
Valerie Walker1, Paul Cook, Damian G Griffin
1Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton, UK, valerie.walker@uhs.nhs.uk.
Insights
Hyperuricosuria, common in kidney stone formers, is linked to renal urate reabsorption defects. This subgroup shows increased hypercalciuria and hyperoxaluria, suggesting multiple stone risk factors and potential dietary interventions.
Area of Science:
- Nephrology
- Urology
- Metabolic Medicine
Background:
- Hyperuricosuria is prevalent in kidney stone patients, but its specific role and underlying causes require further elucidation.
- Identifying distinct patient subgroups with uniform pathology is crucial for targeted therapeutic strategies.
- A primary defect in renal urate reabsorption (renal hyperuricosuria) is a potential, yet under-characterized, contributor to stone formation.
Purpose of the Study:
- To identify and characterize male stone formers with renal hyperuricosuria, defined by a primary defect in urate reabsorption.
- To investigate associated risk factors for kidney stone formation within this specific hyperuricosuric subgroup.
- To explore potential underlying causes and correctable factors contributing to hyperuricosuria and stone disease.
Main Methods:
- Retrospective cross-sectional database study of 666 male kidney stone formers.
- Estimation of filtered urate, plasma urate, and 24-hour creatinine clearance to determine net urate reabsorption.
- Selection of a renal hyperuricosuria group based on filtered urate below the median for normouricosuric patients, with normal plasma urate and high urate clearance.
Main Results:
- 153 men (23%) exhibited hyperuricosuria (urine urate >4.80 mmol/24 h).
- The identified renal hyperuricosuria group (n=30) showed significantly higher incidence of hypercalciuria (67% vs. 40%) compared to matched normouricosuric controls.
- This subgroup also presented high frequencies of hyperoxaluria (25%) and phosphaturia (40%), with elevated creatinine clearance (73%) and potential links to excessive protein intake.
Conclusions:
- Renal hyperuricosuria is associated with multiple risk factors for kidney stone formation, including hypercalciuria and hyperoxaluria.
- Excessive protein intake may be a significant, correctable factor contributing to the observed metabolic abnormalities in these patients.
- Further research into renal urate handling defects is warranted for improved diagnosis and management of kidney stone disease.
Abstract:
Hyperuricosuria is common among stone formers, but its significance is uncertain. To progress our understanding and target treatment, we need to identify and characterise patients with uniform underlying pathology. We aimed to identify hyperuricosuric patients with a primary defect in renal urate reabsorption (renal hyperuricosuria) and to look for associated risk factors for stones. We undertook a retrospective cross-sectional database study of 666 male stone formers attending the Southampton stone clinic. We estimated filtered urate from plasma urate and 24-h creatinine clearance, and the net percentage reabsorbed. 153 men had hyperuricosuria (urine urate >4.80 mmol/24 h); 513 had normouricosuria. Hyperuricosuric men filtered more urate (median 68.1 and 52.5 mmol/24 h) but the ranges overlapped. Thirty hyperuricosuric men with filtered urate below the median for normouricosuria were selected as the renal hyperuricosuria group. Their normal plasma urate and high urate clearance substantiated this classification. In comparison with 60 normouricosuric stone formers matched for filtration, they had a higher incidence of hypercalciuria (67 versus 40%), but similar, high, frequencies of hyperoxaluria (25 and 11%) and phosphaturia (40 and 27%).There were no differences in age at first stone, incidence of stone recurrence or positive family history (20 and 25%). The findings demonstrate multiple risk factors for stones in this subgroup. In comparison, the 30 hyperuricosuric men with the highest filtration had a higher incidence of hyperoxaluria (58%) but fewer (7%) had a positive family history. Creatinine clearance was raised in 73%. An excessive protein intake might be a major correctable factor underlying these abnormalities.
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