Kidney stone disease

Coe, Fredric L.; Evan, Andrew P.; Worcester, Elaine M.

doi:10.1172/jci26662

Cited by 674 publications

(595 citation statements)

References 123 publications

(75 reference statements)

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“…The association of heterozygous PHIII mutations to idiopathic calcium oxalate urolithiasis reported by Monico et al 21 presents an exciting hypothesis, in particular in conjunction with the observations from this family, although the low rate of urolithiasis observed in our parental cohort may question this conclusion. 27 Our findings are of particular relevance as mutation screening is usually halted as soon as causative mutations have been identified in a first gene. In the light of our working hypothesis that in some cases the PH phenotype may be modulated by mutations in other genes affecting glyoxylate metabolism, complete sequencing of all known causative genes should be considered, notably in those patients who lack a second causative mutation or those with an atypical presentation.…”

Section: Discussionmentioning

confidence: 85%

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

et al. 2012

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Identification of mutations in the HOGA1 gene as the cause of autosomal recessive primary hyperoxaluria (PH) type III has revitalized research in the field of PH and related stone disease. In contrast to the well-characterized entities of PH type I and type II, the pathophysiology and prevalence of type III is largely unknown. In this study, we analyzed a large cohort of subjects previously tested negative for type I/II by complete HOGA1 sequencing. Seven distinct mutations, among them four novel, were found in 15 patients. In patients of non-consanguineous European descent the previously reported c.700 þ 5G4T splice-site mutation was predominant and represents a potential founder mutation, while in consanguineous families private homozygous mutations were identified throughout the gene. Furthermore, we identified a family where a homozygous mutation in HOGA1 (p.P190L) segregated in two siblings with an additional AGXT mutation (p.D201E). The two girls exhibiting triallelic inheritance presented a more severe phenotype than their only mildly affected p.P190L homozygous father. In silico analysis of five mutations reveals that HOGA1 deficiency is causing type III, yet reduced HOGA1 expression or aberrant subcellular protein targeting is unlikely to be the responsible pathomechanism. Our results strongly suggest HOGA1 as a major cause of PH, indicate a greater genetic heterogeneity of hyperoxaluria, and point to a favorable outcome of type III in the context of PH despite incomplete or absent biochemical remission. Multiallelic inheritance could have implications for genetic testing strategies and might represent an unrecognized mechanism for phenotype variability in PH.

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Section: Discussionmentioning

confidence: 85%

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

et al. 2012

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“…Many unilateral obstructions are caused by nephrolithiasis, with calcium oxalate and calcium phosphate stones accounting for 80% of these. The lifetime incidence of nephrolithiasis is 12% in men and 6% in women [1]. Urological intervention secondary to obstruction is necessary when stones exceed 7mm in diameter.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Quinlan¹,

Pérez‐Barriocanal²,

Wright³

et al. 2008

TOUNJ

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Abstract:Following unilateral ureteric obstruction (UUO), hydronephrosis is associated with long term reductions in renal blood flow (RBF) and glomerular filtration rate (GFR), tubular resistance to arginine-vasopressin (AVP), and reduced expression of aquaporin water channels and sodium (Na + ) and urea transporters. During UUO, renal function is contingent upon adaptive changes in the contralateral kidney. In the short term this response is associated with an increased GFR and a reduced expression of Na + transporters. We aimed to assess global renal function in UUO, including a comparison between the obstructed and non-obstructed kidneys.Adult male rats were subjected to UUO of either 3 or 10 days duration. Control rats underwent sham surgery. Before release of the ureteric ligature, blood and both bladder and obstructed renal pelvis urine was sampled, then both kidneys harvested. Urinary and plasma electrolytes and osmolality, and kidney weights, were measured.We observed i) mild uraemia in the obstructed animals, ii) extreme dilution of urine from the pelvis of the obstructed kidney in the absence of noteworthy alterations in plasma ions, and iii) evidence indicative of a contralateral diuresis/natriuresis.To the best of our knowledge, this is the first study simultaneously examining such an extensive range of urinary (bladder and obstructed renal pelvis) and plasma markers of renal function in UUO. The results demonstrate that UUO is associated with a small deterioration in overall renal function and marked changes in renal electrolyte handling, leading to changes in the composition of urinary output from both the non-obstructed and obstructed kidneys.

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“…Each heterozygous change segregated from his mother and father, respectively. The second patient was described as a 38-year-old man, with recurrent (calcium phosphate) renal stones since the age of 25 and hyperkalaemia, hypercalciuria, suppressed PTH and elevation of 1,25(OH) 2 vitamin D. He also had bi-allelic mutations, a c.1226T>C, p.L409S change inherited from his mother and the c.428_430del; p.E143del mutation inherited from his father. Metabolic studies in both patients confirmed reduced enzyme function with undetectable activity of CYP24A1 15 .…”

Section: Discussionmentioning

confidence: 99%

“…The oldest known stone (from approximately 4800 BCE) was found in an Egyptian grave in 1901 1 . Today, renal stones pose a significant public health problem, with lifetime risk of forming a stone exceeding 5% in women and 12% in men 2 . The direct and indirect costs are substantial, with the annual cost in the United States estimated to be in excess of $5 billion 3 .…”

Section: Introductionmentioning

confidence: 99%

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Searching for CYP24A1 mutations in cohorts of patients with calcium nephrolithiasis

Sayers¹,

Hynes²,

Rice³

et al. 2013

OA Nephrology

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IntroductionThe genetics underlying the idiopathic hypercalciuria leading to calciumcontaining renal stones remains elusive. The discovery of rare monogenic tubulopathies, often leading to hypercalciuria, has increased our understanding of tubular physiology and patho-physiology. However, insights into idiopathic calcium stone formation have not been gained from these disorders. The aim of this study is to examine CYP24A1 mutations in cohorts of patients with calcium nephrolithiasis. Materials and MethodsWe examined two cohorts of stoneforming patients for mutations in CYP24A1, which encodes the vitamin D24-hydroxylase enzyme. The first cohort had a biochemical phenotype of suppressed parathyroid hormone and high normal serum calcium, whilst the second cohort had a hypercalciuria phenotype. We did not identify bi-allelic sequence variants in CYP24A1 in our cohorts. ResultsIn cohort 1, we identified 9 known sequence variants. In cohort 2 we identified 7 known sequence variants. Conclusion CYP24A1 mutations remain a rare cause of calcium nephrolithiasis and hypercalciuria.

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Kidney stone disease

Cited by 674 publications

References 123 publications

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Searching for CYP24A1 mutations in cohorts of patients with calcium nephrolithiasis

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