Hereditary Nephropathy Associated With Hyperuricemia and Gout

Puig, Juan; Miranda, Maria Eugenia; Mateos, F; Picazo, M.L.; Jiménez, Manuel L.; Calvin, Teresa S.; Gil, Amparo

doi:10.1001/archinte.1993.00410030063009

Cited by 55 publications

(22 citation statements)

References 44 publications

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“…Renal excretion of uric acid is commonly involved in the development of gout, hyperuricemia, and nephropathy [1, 2]. The kidney filters freely circulating uric acid, accounting for ~70% of total uric acid excretion from the body [3].…”

Section: Introductionmentioning

confidence: 99%

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

et al. 2017

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BackgroundReduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study.MethodsWe performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members.ResultsAll renal urate excretion measures were significantly heritable (p <2 × 10−6) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10−7. We observed a strong association (p < 8 × 10−8) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10−6, MAFs: 0.28–0.31).ConclusionFor the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0366-3) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

et al. 2017

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“…Duncan and Dixon [1]first reported a family with above condition in 1960, and Moro et al [2]called it ‘familial juvenile gouty nephropathy’ (FJGN). The pathogenesis of the renal disease is still unknown; however, the histological findings in kidney show nonspecific tubulointerstitial nephropathy with insignificant deposition of urate [3, 4, 5]. Correction of hyperuricemia with allopurinol is reported to ameliorate the progression of renal damage [6, 7].…”

Section: Introductionmentioning

confidence: 99%

Familial Juvenile Gouty Nephropathy: Exclusion of 16p12 from the Candidate Locus

Ohno

Ichida²,

Okabe³

et al. 2002

Nephron

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Background/Aims: Familial juvenile gouty nephropathy (FJGN, MIM 162000) is an autosomal-dominant renal disease characterized by underexcretion-type hyperuricemia, gouty arthritis, and progressive renal disease at younger ages. We analyzed the localization of the responsible gene for FJGN concerning the chromosomal region of 16p12 using parametric linkage analysis in our FJGN. Methods: The affected members of this family were accompanied with polyuria due to nephrogenic diabetes insipidus and without hypertension. Fifteen samples were collected from 9 affected and 6 nonaffected members of the family. By using microsatellite markers mainly focused on the short arm of chromosome 16, two point and multipoint linkage analyses were carried out. Results: All of the 2-point logarithm of odds (LOD) scores were typically negative and all of the multipoint LOD scores were less than –3.0 in our FJGN family. Conclusion: The results suggested that the localization of the responsible gene to 16p12 can be excluded in our FJGN family. This finding means that the responsible gene for FJGN is not common.

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“…Assuming that urate secretion in these patients is unimpaired, the only explanation for low urate excretion is increased postsecretory reabsorption. This is unlikely to be a consequence of disturbed renal hemodynamics, as has been suggested [7]. Impaired renal perfusion or hypovolemia stimulate renal urate reabsorption, but usually do not cause gout or renal damage.…”

Section: Discussionmentioning

confidence: 96%

“…It has been reported that treatment with allopurinol, an inhibitor of xanthine oxidase, slows progression of chronic renal failure [8]. Others, however, did not find a protective effect of allopurinol [7]. In general, FJGN patients seem to progress rather rapidly towards end-stage renal failure despite treatment.…”

Section: Discussionmentioning

confidence: 99%

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Apoptosis of Tubular Epithelial Cells in Familial Juvenile Gouty Nephropathy

Lhotta

Gruber²,

Sgonc³

et al. 1998

Nephron

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Two patients, a 47-year-old woman suffering from chronic renal failure, hyper- uricemia and gout, and her 26-year-old son with hyperuricemia and chronic renal failure, are described. The father and two siblings of the woman had died of chronic renal failure. Both patients had a markedly reduced fractional excretion of urate, which was significantly increased by both benzbromarone and probenecid. A renal biopsy of the son revealed an unspecific chronic tubulointerstitial nephropathy. By light microscopy, many proximal tubular epithelial cells showed signs of apoptosis, which was confirmed with the specific TUNEL assay. We propose a hypothesis based on a gain-of-function mutation of the luminal anion exchanger of the proximal tubulus to explain reduced uric acid excretion, dominant inheritance and apoptosis of tubular epithelial cells in this rare disease. Treatment with a combination of allopurinol to reduce the renal urate load and benzbromarone to block the tubular anion exchanger and normalize fractional uric acid excretion is suggested.

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Hereditary Nephropathy Associated With Hyperuricemia and Gout

Cited by 55 publications

References 44 publications

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study

Familial Juvenile Gouty Nephropathy: Exclusion of 16p12 from the Candidate Locus

Apoptosis of Tubular Epithelial Cells in Familial Juvenile Gouty Nephropathy

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