Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medullary cystic kidney disease (MCKD) belongs with nephronophthisis (NPH) to the NPH-MCKD complex, a group of inherited tubulointerstitial nephritis which share some morphological and clinical features. Juvenile NPH, the most frequent variant of the complex, is a recessive disease with onset in childhood leading to end stage renal disease (ESRD) within the 2nd decade of life. The most frequent extrarenal involvement is tapeto-retinal degeneration. MCKD is a less frequent disease with dominant inheritance; it is recognized later in life, leading to ESRD at the age of 50 years, and may be associated with hyperuricemia and gout. In an early phase, both NPH and MCKD are pauci-symptomatic, major signs being confined to polyuria. Later in the course, clinical findings are related to the progressive renal insufficiency, such as anemia, uremic symptoms and, in NPH, growth retardation. On renal ultrasound, the kidneys present an increased medullary echogenicity with diminished cortico-medullary differentiation. Renal cysts may be present, usually at corticomedullary boundary. Due to the clinico-pathological identity, the two diseases were considered to be a single disorder, and the compromise appellation of NPH-MCKD complex was suggested. This unifying conception was subsequently refuted following the identification of MCKD dominant families. The recent advances of the molecular genetics changed the traditional classification of NPH-MCKD complex. The majority of cases of juvenile NPH are due to deletion of the NPHP1 gene on chromosome 2q13. Genes for infantile and adolescent NPH have been localized to chromosome 9q22-q31 and 3q22, respectively. A new locus, NPHP4, has been recently mapped on chromosome 1p36. Two genes predisposing to dominant MCKD, MCKD1 and MCKD2, have been localized to chromosome 1q21 and to chromosome 16p12. Moreover, a gene for familial juvenile hyperuricemic nephropathy (FJHN), a phenotype very similar to MCKD, was mapped to 16p12 in a region overlapping with the MCKD2 locus. The proof of the allelism between MCKD2 and FJHN has been recently provided by the identification of four novel uromodulin (UMOD) gene mutations, segregating with the disease phenotype in three families with FJHN and one with family with MCKD2. These data provide the first direct evidence that MCKD2 and FJHN arise from mutation of the UMOD gene and are allelic disorders.
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PMID:Nephronophthisis-medullary cystic kidney disease: from bedside to bench and back again. 1765 3

Gout is one of the most common inflammatory arthritides, which is considered to be a true crystal deposition disorder caused by the formation of monosodium urate crystals in and around joints. A number of epidemiological studies from a diverse range of countries suggest that gout has increased in prevalence and incidence in recent years and that the clinical pattern of gout is becoming more complex. In particular, the greatest increase has been observed in primary gout in older men. Robust epidemiological studies have established risk factors for gout including genetic factors, excess alcohol consumption, purine-rich diet, the metabolic syndrome (obesity, hypertension, hyperlipidemia and insulin resistance), use of diuretics and chronic renal failure. Trends in alcohol use, diet, obesity and the metabolic syndrome in the general population might explain changes in the prevalence and incidence of gout in the community. Osteoarthritis, which is thought to predispose patients to monosodium urate crystal deposition in their joints, is becoming more prevalent as a consequence of increased longevity. In hospital settings, widespread diuretic use, increasing prevalence of end-stage renal failure and the success of organ transplant programmes have led to an increase in clinical complexity. Suboptimal management of gout is likely to have contributed to the rise in the prevalence of clinically overt, symptomatic, chronic gout.
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PMID:The changing epidemiology of gout. 1788 62

Familial juvenile hyperuricemic nephropathy (FJHN) and medullary cystic kidney disease type 2 (MCKD2) are autosomal dominant disorders characterized by juvenile hyperuricemia of the underexcretion type, juvenile gout and chronic renal failure in the adult. FJHN/MCKD2 constitute diseases caused by mutations of the human uromodulin (UMOD) gene that encodes uromodulin, the most abundant glycoprotein in normal human urine. The mutations affect the transport of uromodulin, resulting in the accumulation of uromodulin in the kidneys of FJHN/MCKD2 patients. The purpose of this study was to confirm the accumulation of uromodulin in the kidneys of transgenic mice harboring the mutant human UMOD gene with mouse UMOD gene promoter, and to determine the relationship between its accumulation and the effect on uromodulin transport. The mutant human UMOD mRNA and its protein were expressed in the kidneys of transgenic mice. Moreover, the staining of human uromodulin was colocalized with that of mouse uromodulin. Although the human UMOD mRNA levels increased, the protein levels did not change and the accumulation of human uromodulin was not observed. However, the mouse uromodulin consists of two forms, 103 and 117 kDa, and the 103 kDa protein was gradually increased in the kidneys of transgenic mice. Human and mouse uromodulins in the kidneys of transgenic mice were mainly detected in the Triton X-100 insoluble microsomal fraction. Therefore, the progressive accumulation of uromodulin was observed in the plasma membrane of the kidneys of transgenic mice but the accumulated uromodulin protein was not that encoded by the transgene.
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PMID:Progressive accumulation of intrinsic mouse uromodulin in the kidneys of transgenic mice harboring the mutant human uromodulin gene. 1831 Sep 1

The overall incidence of nephrolithiasis-related acute and chronic renal failure is poorly known and surely underestimated. However, obstructive nephropathy represents a potentially curable form of kidney disease that often requires for managing an instrumentation of urinary tract. Rasburicase is an enzyme that transforms uric acid to allantoin, a compound more water soluble that will be excreted by the kidney more easily. Rasburicase has been proven to be an effective therapy for prevention of tumour lysis syndrome. But it also represents an interesting new option in managing hyperuricemia in patients with severe tophaceous gout. We administered rasburicase intravenously (0.20 mg/kg/day, for 2 days) in 2 adults with acute obstructive nephropathy from renal calculi, which was receiving temporary haemodialysis. Rasburicase produced a sharp polyuria 12-18 hours after its administration accompanied with a fast reduction of serum creatinine levels, that returned to normal range without further dialysis. If we suppose that rasburicase can pass through glomerular filter by its relatively low molecular weight, it could dissolve tubular uric acid crystals in acute renal failure associated to tumour lysis syndrome, providing the restoration of renal function. But we also could postulate that rasburicase can act in urinary tract, fragmentating renal calculi, promoting relief of obstructive uropathy and the resolution of renal failure. We suggest rasburicase should be tried in this new indication to prove its potential efficacy.
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PMID:[Efficacy of rasburicase therapy in obstructive renal failure secondary to urolithiasis: a novel therapeutic option]. 1833 40

Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal-dominant disease characterized by hyperuricemia of underexcretion type, gout, and chronic renal failure. Recent discovery of uromodulin mutations as a cause of FJHN and MCKD2 led a new concept, i.e. uromodulin-associated kidney disease (UAKD). The genotype-phenotype correlation and genetic heterogeneity of FJHN are reviewed.
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PMID:[Familial juvenile hyperuricemic nephropathy (FJHN)]. 1840 15

Previous studies have shown that gout is associated with an increased risk for cardiovascular mortality in the general population, but this has not been well studied in patients with ESRD. In this study, the incidence of gout and its association with mortality was evaluated in 259,209 patients in the United States Renal Data System. Overall, the incidence of gout in the first year of dialysis was 5% and in the first 5 yr was 15.4%. Independent risk factors for gout in adjusted analyses included black race, older age, female gender, hypertension, ischemic heart disease, congestive heart failure, and alcohol use. Factors associated with a lower risk for gout included a history of diabetes, smoking, and peripheral vascular disease. Time-dependent Cox regression analysis suggested that an episode of gout was independently associated with a 1.5-fold increase in mortality risk (adjusted hazard ratio 1.49; 95% confidence interval 1.43 to 1.55). The mechanisms underlying this association require further study.
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PMID:Association of incident gout and mortality in dialysis patients. 1850 65

Introduction. Therapeutic doses of colchicine in patients with renal compromise and cyclosporine therapy may result in increased plasma concentrations of colchicine and colchicine toxicity. Case Report. A 60-year-old heart transplant patient with chronic renal failure and cyclosporine-induced immunosuppression was started on colchicine for suspected gout. Four days later, he developed multi-organ failure with rhabdomyolysis, liver damage, polyneuropathy, and cardiotoxicity. Colchicine intoxication was suspected and plasma levels were 7 ng/mL 36 hours after the sixth dose. Neutropenia with an absolute neutrophil count of 700 cells/mm3 was observed five days after colchicine discontinuation. Drug discontinuation, supportive care, antibiotic therapy for a concurrent infection, and G-CSF administration resulted in recovery and he was discharged from the hospital 3 weeks later. Discussion. Cyclosporine co-administration increases colchicine toxicity by a dual mechanism: cyclosporine inhibits P-glycoprotein resulting in increased intracellular colchicine concentrations and decreased hepatic and renal excretion of the drug and cyclosporine interacts with CYP3A4 to decreases the hepatic elimination of colchicine. On the other hand, colchicine may increase cyclosporine neurotoxicity by an addictive mechanism. Conclusions. Shortterm administration of therapeutic colchicine doses may cause life-threatening side effects in cyclosporine-treated patients with renal failure.
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PMID:Colchicine-induced toxicity in a heart transplant patient with chronic renal failure. 1860 82

Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure. At present, there is no study available comparing the efficacy of the most widely used agent, allopurinol, and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency. We describe an open, randomized, actively controlled, comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2). Patients were randomized to take benzbromarone (100-200 mg/day) or allopurinol (100-300 mg/day). Outcome variables were the following: reduction of serum urate (Sur), Sur & tl; 6 mg/dL (357 micromol/L), reduction of gouty bouts and reduction of tophi. During 9-24 months of follow-up 36 patients were studied.The reduction of Sur was higher with benzbromarone, and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol. Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur. Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day, which showed efficacy similar in those who were initially randomized to benzbromarone. A reduction of gouty bouts and size of tophi was observed after proper control of Sur. Allopurinol is effective in controlling hyperuricemia, but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals.Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration; patients benefited include those who previously had no improvement by taking allopurinol.
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PMID:Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study. 1907 56

Spontaneous ruptures of the extensor mechanism of the knee are very rare. They tend to increase considerably in patients with metabolic diseases such as chronic renal failure, hyperparathyroidism, diabetes, gout, and systemic lupus erythematosus. The reported case regards a 48-year-old man with chronic, spontaneous and simultaneous quadriceps, and contra-lateral patellar tendon rupture. The patient suffered from chronic renal failure and for the past year from tertiary hyperparathyroidism. Ruptured tendons were repaired and both knee were evaluated monthly for the next 12 months. Good functional recovery was achieved on both knees without relapse. This case emphasizes the importance of long-term high parathyroid hormone level in the etiology of tendons ruptures.
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PMID:Simultaneous chronic rupture of quadriceps tendon and contra-lateral patellar tendon in a patient affected by tertiary hyperparatiroidism. 1938 13

A 56-year-old woman presented with a 6 month history of bullae and whitish plaques of the fingers. She had chronic renal failure, but no joint pains or evidence of arthritis. An aspirate of fluid from a bulla revealed uric acid crystals and serum uric acid was elevated at 16.2 mg/dL. A diagnosis of tophaceous gout was made.
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PMID:Whitish bullae on the fingers: what is the diagnosis? Tophaceous gout. 1972 83


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