Familial juvenile hyperuricemic nephropathy: report on a new mutation and a pregnancy

Lhotta, Karl; Gehringer, Anke; Jennings, Paul; Kronenberg, Florian; Brezinka, C; Andersone, I.; Strazdins, Vladimirs

doi:10.5414/cnp71080

Cited by 21 publications

(15 citation statements)

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“…Renal cysts are a frequent finding and renal histology shows tubular atrophy and interstitial fibrosis with mild inflammatory infiltration. Urinary uromodulin excretion decreases during childhood and reaches very low levels in adulthood [14,15] . To date, more than 50 UMOD mutations have been identified.…”

Section: Uromodulin Storage Diseasesmentioning

confidence: 99%

Uromodulin and Chronic Kidney Disease

Lhotta¹

2010

Kidney Blood Press Res

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Uromodulin (Tamm-Horsfall protein) is produced in the kidney by cells of the thick ascending limb and distal tubule. Recent genetic studies suggest a role of uromodulin in chronic kidney disease. Mutations in the UMOD gene cause uromodulin storage disease. They code for amino acid substitutions that lead to misfolding of the molecule and its retention in the endoplasmic reticulum. Single nucleotide polymorphisms in the region of the UMOD gene have been shown to be associated with chronic kidney disease and reduced glomerular filtration rate. These polymorphisms affect uromodulin concentration in the urine, and lower genetically determined urinary uromodulin concentrations seem to protect against renal disease. Chronic kidney disease is associated with higher serum levels of uromodulin. From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease.

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Section: Uromodulin Storage Diseasesmentioning

confidence: 99%

Uromodulin and Chronic Kidney Disease

Lhotta¹

2010

Kidney Blood Press Res

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“…Uromodulin (UMOD) is encoded by the UMOD gene on chromosome 16p12 and is the most abundant protein found in human urine (1). UMOD is postulated to affect urine concentration by maintaining tubular water impermeability and regulating salt transport (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…It is possible that mutations that differentially affect the rate of UMOD maturation and expression on the cellular membrane can influence the clinical course of the disease. Most UMOD mutations cluster in exons 4 and 5 and cause changes to cysteine residues, which leads to a misfolding of the UMOD molecule (1).…”

Section: Introductionmentioning

confidence: 99%

Association between Genotype and Phenotype in Uromodulin-Associated Kidney Disease

Moskowitz

Piret

Lhotta³

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Uromodulin-associated kidney disease (UAKD) is an autosomal dominant disease caused by uromodulin (UMOD) gene mutations. This study explored genotype-phenotype correlations by examining the relationship between the type of UMOD mutation and the age at onset of ESRD.Design, setting, participants & measurements Extensive bibliographic research was used to ascertain patient-level data of all patients with UAKD published up to October 2011. Data included sex; ages at onset of hyperuricemia, gout, and ESRD; and UMOD genotype. Kaplan-Meier analysis and Cox proportional hazards models fitted with shared gamma frailty terms to adjust for within-family correlations were used to model time to event.Results Thirty-one peer-reviewed publications reporting on 202 patients from 74 families with 59 different UMOD mutations were included. Median ages at onset of hyperuricemia, gout, and ESRD were 24, 40, and 56 years, respectively. Men developed gout and ESRD significantly earlier than did women (age at ESRD was 50 years for men and 60 for women; P=0.04, shared frailty model). Median ages at ESRD development were lowest with Cys77Tyr (37.5 years) and highest with Gln316Pro (65.5 years) UMOD mutations. Onset of ESRD was significantly earlier with UMOD mutations located within the epidermal growth factor domains 2 and 3 (range, 45-52 years; P,0.01 and 0.04, respectively) compared with the cysteine-rich domains (range, 60-65 years; by shared frailty model). ConclusionsThe UMOD genotype is related to the clinical phenotype of UAKD. This finding may assist in counseling of patients.

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“…The case reports yielded 7 case reports for gout [4,8,9,10,11,12,13], 1 for gouty arthritis due to pseudo-Bartter syndrome [14], and 1 for familial juvenile hyperuricemic nephropathy [15]. Of the 7 cases with gout, describing 6 patients, 4 had renal complications [4,8,9,12,16], similar to the patient is this case report.…”

Section: Literaturementioning

confidence: 55%

“…Treatment during the pregnancies was highly variable and included allopurinol in 3 [9,15], this report], colchicine with probenecid in 5 [4,8], only colchicine in 1 pregnancy [14], and prednisone in 2 [4,14]. …”

Section: Literaturementioning

confidence: 99%

Gout in Pregnancy: A Case Report and Review of the Literature

Veen

Haeri²

2015

Gynecol Obstet Invest

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While gout is a common inflammatory joint disease, its occurrence in women in their reproductive years is very rare. This is thought to be the result of the uricosuric effect of estrogen. The higher estrogen levels during pregnancy are believed to protect the mother against an acute gout flare. We report a case of a patient with gout who experienced a flare in the third trimester of her pregnancy and a review of the English literature on gout in pregnancy. In addition to this case, we identified 19 pregnancies in 8 women with a diagnosis of gout. Of those, 6 experienced an antepartum flare and 7 a postpartum flare. Our patient developed a gout flare in the third trimester of the pregnancy, which was otherwise complicated by gestational diabetes. Her flare was well controlled with pharmacotherapy (hydrocodone and allopurinol). We hypothesize that her pregnancy induced insulin resistance, which decreased the renal excretion of urate provoked this flare. Little is known about the treatment of acute gout and long-term management during pregnancy. The initiation of preventive treatment with allopurinol should be based on individualized risks and benefits, but we suggest that gestational diabetes justifies its use in the second half of pregnancy.

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Familial juvenile hyperuricemic nephropathy: report on a new mutation and a pregnancy

Cited by 21 publications

References 0 publications

Uromodulin and Chronic Kidney Disease

Uromodulin and Chronic Kidney Disease

Association between Genotype and Phenotype in Uromodulin-Associated Kidney Disease

Gout in Pregnancy: A Case Report and Review of the Literature

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