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)

Forty-three patients suffering from hypertension of different origin (chronic renal failure, gout, or idiopathic) were treated with propranolol (121 +/- 12 mg q.d.) plus hydrochlorothiazide (50 mg q.d.) for 75 +/- 9 days. Blood pressure did not return to normal limits in 15 patients, who were continued on the same protocol plus 10 to 50 mg oxdralazine q.d. After an average of 68 +/- 35 days blood pressure fell from 180/110 mm Hg to 145/90 mm Hg without orthostatism, significant side effects, or changes in GFR. This combination seems particularly successful since propranolol will prevent the undesired rise in cardiac output due to oxdralazine as well as the activation of the renin-angiotensin axis due to diuretics. Thus, the antihypertensive properties of each agent will be enhanced by a reduction in side effects by the associated drug, resulting in optimal blood pressure control.
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PMID:Oxdralazine, a new peripheral vasodilator, combined with propranolol and hydrochlorothiazide: a rational approach to antihypertensive treatment. 53 72

This paper reports investigations in a young woman with renal disease and six other seemingly healthy young members of a new kindred (four male:two female) with familial juvenile gouty nephropathy (McKusick 16200). The family had previously been known to have a "familial" renal disease, but came to attention through an isolated episode of gout in the propositus when renal function was already impaired. A reduced GFR was found in three of the other six subjects. Hyperuricemia associated with a grossly reduced fractional uric acid clearance (Cur/Ccr x 100) was present in the propositus and five kindred members, three of whom were children. The finding of this abnormality in two subjects with normal GFR suggests that this apparent hallmark of the disease precedes the onset of renal damage. The results confirm the dominant nature of the disorder, and highlight the need to investigate all kindred members of patients with juvenile gout and renal failure. Early recognition is important, since allopurinol therapy in doses adjusted to the reduced renal function may ameliorate the progression of the renal lesion.
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PMID:Familial juvenile gouty nephropathy with renal urate hypoexcretion preceding renal disease. 187 40

Chronic interstitial nephropathy with disproportionate hyperuricemia (serum uric acid 10.5-14.8 mg/dl [625-880 mumol/l] at a GFR of 40 ml/min/1.73 m2) was observed in 2 girls and their mother who suffered from gout since the age of 20 years. Urinary excretion of uric acid was normal. Renal biopsies in the 3 patients showed focal tubulointerstitial nephropathy. Absolute values of GFR remained stable in the 2 pediatric patients over a period of 10 years, whereas the older patient required dialysis at the age of 34 years. We speculate that this family suffers from a primary interstitial nephropathy which is accompanied by a subtle defect in tubular excretion of urate. A few similar observations have been reported in literature which suggests that dominantly inherited interstitial nephropathy with hyperuricemia and gout represents a distinct entity.
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PMID:Familial nephropathy with hyperuricemia and gout. 685 96

Six members of kindred with only one surviving male in three generations, a history of an unusual combination of precocious gout in a girl of nine and rapidly progressive renal disease in young women, have been investigated. Sensitive indicators of the familial defect were the early development of hyperuricemia, an inability to concentrate the urine, and a patchy non-specific interstitial nephritis at biopsy. All these features were disproportionately severe for the young age and sex of affected subjects, and the relatively moderate reduction of GFR in some. Identification of these characteristics enabled the recognition of an early stage of the disease in one young family member whose renal function had previously been normal. The histopathology of the renal lesion in this normotensive teenage girl was similar to that frequently attributed to ageing or hypertension in the archetypal middle-aged gouty male, indicating that neither age nor vascular lesions are necessarily implicated in the latter. Allopurinol has halted further progression of the renal lesion in this young girl over two years. It is thus possible that early diagnosis may benefit the subsequent clinical course and may be important since the number of such families in our experience suggests that precocious familial gout with renal failure is more prevalent than currently recognized.
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PMID:Familial gout and renal failure in young women. 742 92

Hypertension and hypertension-associated ESRD are epidemic in society. The mechanisms responsible for renal progression in mild to moderate hypertension and those groups most at risk need to be identified. Historic, epidemiologic, clinical, and experimental studies on the pathogenesis of hypertension and hypertension-associated renal disease are reviewed and an overview/hypothesis for the mechanisms involved in renal progression is presented. There is increasing evidence that hypertension may exist in one of two forms/stages. The first stage, most commonly observed in early or borderline hypertension, is characterized by salt-resistance, normal or only slightly decreased GFR, relatively normal or mild renal arteriolosclerosis, and normal renal autoregulation. This group is at minimal risk for renal progression. The second stage, characterized by salt-sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines a group at highest risk for the development of microalbuminuria, albuminuria, and progressive renal disease. This second stage is more likely to be observed in blacks, in subjects with gout or hyperuricemia, with low level lead intoxication, or with severe obesity/metabolic syndrome. The two major mechanistic pathways for causing impaired autoregulation at mild to moderate elevations in BP appear to be hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression.
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PMID:Essential hypertension, progressive renal disease, and uric acid: a pathogenetic link? 1584 66

Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited disorder. Complete deficiency of HPRT activity is phenotypically expressed as the devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18-year follow-up of a 5-year old boy with partial HPRT deficiency and report a novel mutation in his HPRT gene. He presented with overproduction of uric acid and passage of uric acid renal stones, and without gout or neurological and behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary alkalization, and a low-purine diet was started. No subsequent nephrolithiasis has occurred. After 18-year of this therapy his physical and neuropsychological status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of initial renal impairment in our patient is uric and/or xanthine crystalluria. A missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the patient's HPRT gene was identified and the mother was the carrier of the mutation. As far as we are aware, the identified mutation has not previously been reported. We named the mutant HPRT Maribor.
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PMID:Eighteen-year follow-up of a patient with partial hypoxanthine phosphoribosyltransferase deficiency and a new mutation. 1596 71

Renal disease is rare today in classic adult gout, and gout is rare in renal disease--especially in the young. Here we summarise studies in 158 patients from 31 kindreds diagnosed with familial juvenile hyperuricaemic nephropathy FJHN from a total of 230 kindred members studied in Great Britain. Some patients have been followed for up to 30 years, and allopurinol has ameliorated the progression of the renal disease in all 113 surviving members provided: They have been diagnosed and treated sufficiently early. Compliance with allopurinol treatment and diet has been as important as early recognition. Hypertension has been rigorously controlled. The use of oral contraceptives has been avoided, as has pregnancy in any female with a Glomelar Filtration Rate GFR <70 ml/min. The question arising is: Why is FJHN the most prevalent genetic purine disorder diagnosed in Britain? Is it a lack of awareness which needs to be improved Europe-wide?
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PMID:Familial juvenile hyperuricaemic nephropathy is not such a rare genetic metabolic purine disease in Britain. 1706 66

Coexistence of septic arthritis and gouty arthritis is rare. In particular, no reports have described the development of both gouty and septic arthritis after arthroscopic shoulder surgery. The patient was an 83-year-old man who underwent arthroscopic rotator cuff repair. He had a history of diabetes mellitus (HbA1c: 7.4%), but not of gout, and the GFR was decreased (GFR=46). During the postoperative course fever suddenly developed and joint fluid retention was found. Uric acid crystals were detected when the joint fluid was aspirated, after which when the culture results became available sepsis due to methicillin sensitive Staphylococcus aureus (MSSA) was diagnosed. On the 2(nd) day after fever onset, lavage and debridement were performed under arthroscopy, with the subsequent course uneventful with no recurrence of the infection or gouty arthritis and no joint destruction. When uric acid crystals are found in aspirated joint fluid, gouty arthritis tends to be diagnosed, but like in the present case if infection also supervenes, joint destruction and a poor general state may result if appropriate intervention is not initiated swiftly. Accordingly, even if uric acid crystals are found, the possibility of coexistence of septic arthritis and gouty arthritis should be kept in mind.
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PMID:Rare coexistence of gouty and septic arthritis after arthroscopic rotator cuff repair: a case report. 2606 11

To provide insight into pharmacological treatment of hyperuricemia we developed a semi-mechanistic, dynamical model of uric acid (UA) disposition in human. Our model represents the hyperuricemic state in terms of production of UA (rate, PUA), its renal filtration (glomerular filtration rate, GFR) and proximal tubular reabsorption (fractional excretion coefficient, FE). Model parameters were estimated using data from 9 Phase I studies of xanthine oxidase inhibitors (XOI) allopurinol and febuxostat and a novel uricosuric, the selective UA reabsorption inhibitor lesinurad, approved for use in combination with a XOI. The model was qualified for prediction of the effect of patients' GFR and FE on concentration of UA in serum (sUA) and UA excretion in urine and their response to drug treatment, using data from 2 Phase I and 4 Phase III studies of lesinurad. Percent reduction in sUA from baseline by a XOI is predicted to be independent of GFR, FE or PUA. Uricosurics are more effective in underexcreters of UA or patients with normal GFR. Co-administration of a XOI and an uricosuric agent should be considered for patients with high sUA first in the treatment algorithm of gout before uptitration of XOI. The XOI dose in combination with a uricosuric can be reduced compared to XOI alone for the same target sUA to the degree dependent on patient's GFR and FE. This exposure-response model of UA can be used to rationally select the best drug treatment option to lower elevated sUA in gout patients under differing pathophysiological situations.
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PMID:Individualized treatment strategies for hyperuricemia informed by a semi-mechanistic exposure-response model of uric acid dynamics. 2948 55

Gout is an inflammatory arthritis influenced by environmental risk factors and genetic variants. The common dysfunctional p.Q141K allele of the ABCG2 gene affects gout development. We sought after the possible association between the p.Q141K variant and gout risk factors, biochemical, and clinical determinants in hyperuricemic, gouty, and acute gouty arthritis cohorts. Further, we studied the correlation of p.Q141K allele and levels of pro-/anti-inflammatory cytokines. Coding regions of the ABCG2 gene were analyzed in 70 primary hyperuricemic, 182 gout patients, and 132 normouricemic individuals. Their genotypes were compared with demographic and clinical parameters. Plasma levels of 27 cytokines were determined using a human multiplex cytokine assay. The p.Q141K variant was observed in younger hyperuricemic/gout individuals (p = 0.0003), which was associated with earlier disease onset (p = 0.004), trend toward lower BMI (p = 0.056), and C-reactive protein (CRP, p = 0.007) but a higher glomerular filtration rate (GFR, p = 0.035). Levels of 19 cytokines were higher, mainly in patients with acute gouty arthritis (p < 0.001), irrespective of the presence of the p.Q141K variant. The p.Q141K variant influences the age of onset of primary hyperuricemia or gout and other disease-linked risk factors and symptoms. There was no association with cytokine levels in the circulation.
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PMID:Interaction of the p.Q141K Variant of the ABCG2 Gene with Clinical Data and Cytokine Levels in Primary Hyperuricemia and Gout. 3173 30


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