Gout: Perez-Ruiz F

Zhang W, Doherty M, Pascual E, Bardin T, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I, Anonymous00035. · Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #16707533 No free full text.

Abstract: OBJECTIVE: To develop evidence based recommendations for the diagnosis of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert, representing 13 European countries. Ten key propositions regarding diagnosis were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Wherever possible the sensitivity, specificity, likelihood ratio (LR), and incremental cost-effectiveness ratio were calculated for diagnostic tests. Relative risk and odds ratios were estimated for risk factors and co-morbidities associated with gout. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 10 key propositions were generated though three Delphi rounds including diagnostic topics in clinical manifestations, urate crystal identification, biochemical tests, radiographs, and risk factors/co-morbidities. Urate crystal identification varies according to symptoms and observer skill but is very likely to be positive in symptomatic gout (LR = 567 (95% confidence interval (CI), 35.5 to 9053)). Classic podagra and presence of tophi have the highest clinical diagnostic value for gout (LR = 30.64 (95% CI, 20.51 to 45.77), and LR = 39.95 (21.06 to 75.79), respectively). Hyperuricaemia is a major risk factor for gout and may be a useful diagnostic marker when defined by the normal range of the local population (LR = 9.74 (7.45 to 12.72)), although some gouty patients may have normal serum uric acid concentrations at the time of investigation. Radiographs have little role in diagnosis, though in late or severe gout radiographic changes of asymmetrical swelling (LR = 4.13 (2.97 to 5.74)) and subcortical cysts without erosion (LR = 6.39 (3.00 to 13.57)) may be useful to differentiate chronic gout from other joint conditions. In addition, risk factors (sex, diuretics, purine-rich foods, alcohol, lead) and co-morbidities (cardiovascular diseases, hypertension, diabetes, obesity, and chronic renal failure) are associated with gout. SOR for each proposition varied according to both the research evidence and expert opinion. CONCLUSIONS: 10 key recommendations for diagnosis of gout were developed using a combination of research based evidence and expert consensus. The evidence for diagnostic tests, risk factors, and co-morbidities was evaluated and the strength of recommendation was provided.

Zhang W, Doherty M, Bardin T, Pascual E, Barskova V, Conaghan P, Gerster J, Jacobs J, Leeb B, Lioté F, McCarthy G, Netter P, Nuki G, Perez-Ruiz F, Pignone A, Pimentão J, Punzi L, Roddy E, Uhlig T, Zimmermann-Gòrska I, Anonymous00034. · Academic Rheumatology, University of Nottingham, Clinical Sciences Building, City Hospital, Nottingham NG5 1PB, UK. · Ann Rheum Dis. · Pubmed #16707532 No free full text.

Abstract: OBJECTIVE: To develop evidence based recommendations for the management of gout. METHODS: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions on management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat, relative risk, odds ratio, and incremental cost-effectiveness ratio were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales. RESULTS: 12 key propositions were generated after three Delphi rounds. Propositions included both non-pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT), and prophylaxis of acute attacks. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption; low animal purine diet) and treatment of associated comorbidity and risk factors were emphasised. Recommended drugs for acute attacks were oral non-steroidal anti-inflammatory drugs (NSAIDs), oral colchicine (ES = 0.87 (95% confidence interval, 0.25 to 1.50)), or joint aspiration and injection of corticosteroid. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi, or radiographic changes of gout. Allopurinol was confirmed as effective long term ULT (ES = 1.39 (0.78 to 2.01)). If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation, or a uricosuric. The uricosuric benzbromarone is more effective than allopurinol (ES = 1.50 (0.76 to 2.24)) and can be used in patients with mild to moderate renal insufficiency but may be hepatotoxic. When gout is associated with the use of diuretics, the diuretic should be stopped if possible. For prophylaxis against acute attacks, either colchicine 0.5-1 mg daily or an NSAID (with gastroprotection if indicated) are recommended. CONCLUSIONS: 12 key recommendations for management of gout were developed, using a combination of research based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

Perez-Ruiz F. · No affiliation provided · Joint Bone Spine. · Pubmed #17606397 No free full text.

This publication has no abstract.

Perez-Ruiz F, Schlesinger N. · Division of Rheumatology, Hospital de Cruces, País Vasco, Baracaldo, Spain. · Scand J Rheumatol. · Pubmed #18415763 No free full text.

This publication has no abstract.

Perez-Ruiz F, Lioté F. · Hospital de Cruces, Baracaldo, Pais Vasco, Spain. · Arthritis Rheum. · Pubmed #17907217 links to  free full text

This publication has no abstract.

Sherman MR, Saifer MG, Perez-Ruiz F. · Mountain View Pharmaceuticals, Inc., 3475-S Edison Way, Menlo Park, CA 94025, USA. · Adv Drug Deliv Rev. · Pubmed #17826865 No free full text.

Abstract: Hyperuricemia results from an imbalance between the rates of production and excretion of uric acid. Longstanding hyperuricemia can lead to gout, which is characterized by the deposition of monosodium urate monohydrate crystals in the joints and periarticular structures. Because such deposits are resolved very slowly by lowering plasma urate with available drugs or other measures, the symptoms of gout may become chronic. Persistent hyperuricemia may also increase the risk of renal and cardiovascular diseases. Unlike most mammals, humans lack the enzyme uricase (urate oxidase) that catalyzes the oxidation of uric acid to a more soluble product. This review describes the development of a poly(ethylene glycol) (PEG) conjugate of recombinant porcine-like uricase with which a substantial and persistent reduction of plasma urate concentrations has been demonstrated in a Phase 2 clinical trial. Two ongoing Phase 3 clinical trials include systematic assessments of gout symptoms, tophus resolution and quality of life, in addition to the primary endpoint of reduced plasma urate concentration.

Perez-Ruiz F, Naredo E. · Department of Rheumatology, Hospital de Cruces, Vizcaya, Spain. · Curr Opin Rheumatol. · Pubmed #17278927 No free full text.

Abstract: PURPOSE OF REVIEW: Imaging modalities for gout have been mostly restrained to radiographs. Ultrasonography, computed tomography and magnetic resonance imaging are emerging techniques that could be used for diagnosis, evaluation, and monitoring acute and chronic gout. RECENT FINDINGS: Diagnosis of gout is based on urate crystal observation with microscopy. Recently, crystal deposition in the hyaline cartilage has been described to be different in gout from that of calcium pyrophosphate, but validation of the findings is pending. Severity of gout with simple radiographs may not disclose periarticular or intra-articular urate deposition. Ultrasonography, computed tomography and magnetic resonance imaging may improve the evaluation of tophi not apparent in clinical examination or simple radiographs. Monitoring urate deposition may be accomplished with imaging techniques. This would be of outstanding interest for clinical trials, but also for evaluating clinical response to urate-lowering therapy. Although preliminary results evaluating for validity and reliability have been very recently reported for magnetic resonance imaging, computed tomography and ultrasonography, sensitivity to change studies are still pending. Also, monitoring of chronic inflammation with imaging techniques, such as power-Doppler, deserve further studies. SUMMARY: Evidence exists regarding the usefulness of imaging techniques for diagnosis, evaluation of severity, and monitoring of gout, but further investigation is needed.

Schumacher HR, Edwards LN, Perez-Ruiz F, Becker M, Chen LX, Furst DE, Joseph-Ridge N, Schlesinger N, Horowitz Z, Saag K, Boice JA, Yamanaka H, Anonymous00376. · University of Florida, Gainesville, Florida, USA. · J Rheumatol. · Pubmed #16331785 No free full text.

Abstract: Gout provides some unique challenges in classification and measurement of outcomes. Our aim was to evaluate criteria for classification and to develop and validate optimal instruments to measure outcomes for acute and chronic gout. A planning committee and interested attendees met to propose classification criteria and domains for outcomes. Seven of the current American Rheumatism Association preliminary criteria for classification were proposed as the best current criteria for acute gouty arthritis, pending further studies. The presence of gout is best established by crystal identification, although this technique has limitations. Five domains for acute gout outcomes and 9 for chronic gout were identified along with proposed instruments for testing and validation. The unique problems of gout evaluation can and will be addressed.

Perez-Ruiz F, Calabozo M, Pijoan JI, Herrero-Beites AM, Ruibal A. · Hospital de Cruces, Pais Vasco, Spain. · Arthritis Rheum. · Pubmed #12209479 links to  free full text

Abstract: OBJECTIVE: The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial. This observational, prospective study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout. METHOD: Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol, benzbromarone, or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues. The tophi targeted for evaluation during followup were the largest in diameter found during physical examination. RESULTS: Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone. The velocity of tophi reduction was linearly related to the mean serum urate level during therapy. The lower the serum urate levels, the faster the velocity of tophi reduction. CONCLUSION: Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout. Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy. Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy.

Perez-Ruiz F, Calabozo M, Herrero-Beites AM, García-Erauskin G, Pijoan JI. · Rheumatology Section, Hospital de Cruces, Barakaldo, Spain. · Nephron. · Pubmed #11096285 No free full text.

Abstract: AIM: To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms. METHODS: Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period. RESULTS: 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function. CONCLUSIONS: Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.

Perez-Ruiz F, Dalbeth N, Urresola A, de Miguel E, Schlesinger N. · Rheumatology Division, Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Arthritis Res Ther. · Pubmed #19591633 links to  free full text

Abstract: Imaging is a helpful tool for clinicians to evaluate diseases that induce chronic joint inflammation. Chronic gout is associated with changes in joint structures that may be evaluated with diverse imaging techniques. Plain radiographs show typical changes only in advanced chronic gout. Computed tomography may best evaluate bone changes, whereas magnetic resonance imaging is suitable to evaluate soft tissues, synovial membrane thickness, and inflammatory changes. Ultrasonography is a tool that may be used in the clinical setting, allowing evaluation of cartilage, soft tissues, urate crystal deposition, and synovial membrane inflammation. Also ultrasound-guided puncture may be useful for obtaining samples for crystal observation. Any of these techniques deserve some consideration for feasibility and implementation both in clinical practice and as outcome measures for clinical trials. In clinical practice they may be considered mainly for evaluating the presence and extent of crystal deposition, and structural changes that may impair function or functional outcomes, and also to monitor the response to urate-lowering therapy.

Terkeltaub R, Zelman D, Scavulli J, Perez-Ruiz F, Lioté F. · Veterans Affairs Medical Center, University of California San Diego, 111K, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. · Joint Bone Spine. · Pubmed #19559637 No free full text.

This publication has no abstract.

Schlesinger N, Dalbeth N, Perez-Ruiz F. · Division of Rheumatology Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903-0019, USA. · Expert Opin Pharmacother. · Pubmed #19463070 No free full text.

Abstract: There has been an increase in the incidence and prevalence of gout in the past several decades. A distinction needs to be made between the treatment of gout as an acute inflammatory disease and the lowering of the serum urate (SU) levels into a normal range. Treating acute gout attacks alone is not sufficient to prevent the disease from progressing. When treating gout one needs to treat acute attacks, and lower excess stores of uric acid to achieve dissolution of monosodium urate crystals through a long-term reduction of SU concentrations far beyond the threshold for saturation of urate and provide prophylaxis to prevent acute flares. The options available for the treatment of acute gout are NSAIDs, colchicine, corticosteroids, adrenocorticotropic hormone (ACTH) and intra-articular corticosteroids. The most important determinant of therapeutic success is not which anti-inflammatory agent is chosen, but rather how soon therapy is initiated and that the dose be appropriate. Prophylaxis should be considered an adjunct, rather than an alternative, to long-term urate-lowering therapy. For purposes of maintaining patient adherence to urate-lowering therapy, there is interest in improving prophylaxis of such treatment-induced attacks. The optimal agent, dose and duration for gout prophylaxis are unknown and require further investigation. The importance of long-term management of gout is the reduction and maintenance of SU in a goal range, usually defined as less than 6.0 mg/dL. Allopurinol and benzbromarone remain the cornerstone drugs for reducing SU levels lower than the saturation threshold to dissolve urate deposits effectively. Febuxostat and pegloticase help to optimize control of SU levels, especially in those patients with the most severe gout. Other agents, such as fenofibrate and losartan may be helpful as adjuvant drugs. Treatment for gout has advanced little in the last 40 years, until recently. The recent development of new therapeutic options promises to provide much needed alternatives for the many patients with gout who are intolerant of or refractory to available therapies. It is important to note that inappropriate use of medications as opposed to an apparent refractoriness to available therapies is not uncommon.

Perez-Ruiz F, Calabozo M, Fernandez-Lopez MJ, Herrero-Beites A, Ruiz-Lucea E, Garcia-Erauskin G, Duruelo J, Alonso-Ruiz A. · Rheumatology Section, Hospital de Cruces (FP-R, MC, MJF-L, ER-L, JD, AA-R); Rehabilitation Division, Hospital de Gorliz (AH-B); Nephrology Division, Hospital de Cruces (GG-E), Pais Vasco, Spain. · J Clin Rheumatol. · Pubmed #19078356 No free full text.

Abstract: 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/1.73m. 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 mumol/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.

Perez-Ruiz F, Martin I, Canteli B. · Seccion de Reumatologia and Servicio de Radiologia, Hospital de Cruces, Baracaldo, Spain. · J Rheumatol. · Pubmed #17659752 No free full text.

Abstract: OBJECTIVE: To validate the usefulness of measuring tophi with ultrasonography (US) as an outcome measure for chronic tophaceous gout. METHODS: Patients with crystal-proven gout were included. To evaluate validity, intraarticular and articular deep tophi were evaluated with both magnetic resonance imaging (MRI) and US. Tophi were punctured with US guidance to evaluate face validity. Interobserver and intraobserver measurement studies were done to evaluate reliability, and to estimate the smallest detectable difference. Sensitivity to change was evaluated with a 12-month followup observational study of urate-lowering therapy. RESULTS: US detected at least one tophus in all joints where MRI found nodules considered to be tophi. There was a good correlation, but just fair agreement between measurements with US and MRI. Puncture of nodules suspected of being tophi recovered urate crystals in 83% of the procedures. Intraobserver intraclass correlation was > 0.90 for diameters and volume, while it was 0.71 to 0.83 in the interobserver study. US was found to be sensitive to change, and there was an inverse correlation between serum urate concentrations and change from baseline measurement of tophi. CONCLUSION: US measurement of tophi fulfilled the OMERACT filter for an outcome measure, although it should be tested further in randomized clinical trials.

Schumacher HR, Taylor W, Joseph-Ridge N, Perez-Ruiz F, Chen LX, Schlesinger N, Khanna D, Furst DE, Becker MA, Dalbeth N, Edwards NL. · Division of Rheumatology, University of Pennsylvania School of Medicine, and Veterans Affairs Medical Center, Philadelphia, Pennsylvania 19104, USA. · J Rheumatol. · Pubmed #17552064 No free full text.

Abstract: Methods to measure outcomes in gout still require consensus and validation. This Special Interest Group was assembled to identify domains of interest and is now evaluating a series of outcomes for features of acute gouty arthritis and chronic gout. To accomplish this, working groups have been formed and domains identified. Delphi methodology has been used to address gouty flares as an outcome of greatest interest. Studies addressing other outcome measures were reported at the OMERACT 8 meeting and validation has begun on some outcomes. There has been progress on developing a definition of a flare, and validating reproducibility of some chronic gout outcome measures in some domains, such as tophus size and patient perceptions. Use of these outcomes as well as a health-related quality of life measure are being studied in clinical trials. Pain on a Likert scale appears to be a valid outcome in acute gout. Final validation of these outcomes has not yet been achieved. In summary, the unique problems of evaluating outcomes in gout are finally being addressed. While no measures are available for use yet, an agenda has been developed.

Perez-Ruiz F, Nolla JM. · Rheumatology Section, Hospital de Cruces, Baracaldo, Spain. · J Clin Rheumatol. · Pubmed #17041461 No free full text.

Abstract: Reduction of serum urate and phosphate levels has been observed in patients receiving leflunomide therapy, but the mechanism for such changes has not been evaluated. Thirty-eight patients with rheumatoid arthritis who began leflunomide were studied. Serum urate, creatinine, and phosphate, and 24-hour uric acid, creatinine, and phosphate were measured before, during, and in some instances after leflunomide treatment. Clearances of urate and creatinine, fractional excretion of urate, and tubular reabsorption of phosphate were calculated. Undissociated urinary uric acid was estimated with a nomogram. Twelve patients gave consent to withdraw leflunomide treatment of a 2-week period and underwent a third study. Decreases in serum urate and phosphate levels were observed, with parallel increases in clearances of urate and in fractional excretion of urate, and a reduction in tubular reabsorption of phosphate. Clearances of creatinine and undissociated urinary uric acid remained unchanged. Two weeks after withdrawing the drug, a partial return toward baseline values was observed, but residual changes were apparent. No case of clinical gout was observed. Leflunomide enhances urate and phosphate loss, an effect that partially persisted after 2-week withdrawal. The long-term effect of mild phosphate wasting warrants further investigation. The urate-lowering effect of leflunomide may be useful in monitoring compliance in leflunomide therapy.

Perez-Ruiz F, Atxotegi J, Hernando I, Calabozo M, Nolla JM. · Sección de Reumatologia, Hospital de Cruces, Pais Vasco, Spain. · Arthritis Rheum. · Pubmed #17013833 links to  free full text

Abstract: OBJECTIVE: Withdrawal of urate-lowering therapy (ULT) is associated with recurrence of acute gouty arthritis and tophi, but no data are available about factors associated with recurrence of gouty symptoms. Therefore, life-long therapy prescription is usually advised, but the prospect of life-long therapy may contribute to very low compliance rates. Our objective was to ascertain the outcome of ULT withdrawal after long-term, documented control of serum urate levels. METHODS: We conducted a prospective, long-term, followup study of patients treated with ULT during a 5-year period. Both diagnosis and recurrence of gout were determined based on monosodium urate crystal identification in synovial fluid or material aspirated from tophi. RESULTS: Low average serum urate levels while receiving ULT and during the followup period after ULT withdrawal were statistically associated with the longest period in which patients were free of gouty symptoms, suggesting that depletion and formation of the body's urate pool is dependent on both time and serum urate levels. Patients whose average serum urate levels were <5.05 mg/dl while receiving ULT and <8.75 mg/dl after ULT withdrawal had the longest (>4 years) time to recurrence. CONCLUSION: Proper and long-term reduction of serum urate level is associated with long-term periods in which patients are free of gouty symptoms, probably due to the reduction of the urate pool. These results suggest that 5-year intermittent, instead of life-long, ULT could be offered to patients with good serum urate control during ULT.

Perez-Ruiz F, Hernando I, Villar I, Nolla JM. · Rheumatology Section, Hospital de Cruces, Vizcaya, Spain. · J Clin Rheumatol. · Pubmed #16357730 No free full text.

Abstract: BACKGROUND: Dosing of allopurinol should be corrected depending on renal function, but corrections based on either plasma creatinine (Pcr) or creatinine clearance (CrCl) have been suggested to be minimal standards of care. METHODS: Data from a cohort database of 484 gouty patients were used to calculate estimated allopurinol doses using CrCl and estimation of the clearance of creatinine using the equation of Cockroft and Gault (CrCl-CG) if, as a hypothesis, a dosage of 300 mg/d would be prescribed in any patient with Pcr <2.0 mg/dL. Also, allopurinol-related toxicity previous to rheumatologic consultation, during previous allopurinol therapy, and the relationship between both and estimated allopurinol doses were reviewed. RESULTS: The cutoff point of plasma creatinine <2 showed 13% sensitivity and 100% specificity to detect CrCl <50 mL/min. Correlation and agreement between CrCl and CrCl-CG were good, as was the correlation between corrected doses using CrCl and CrCl-CG. One third of patients with Pcr 1.0-1.5 mg/dL and 90% of those with Pcr 1.5-2.0 mg/dL would receive estimated doses over 400 mg/dL/d CrCl. Also, 10% and 34% would receive estimated doses over 600 mg/dL/d CrCl, respectively. Allopurinol-related toxicity previous to consultation (11%) was associated with estimated doses over 400 mg/dL/d CrCl and severe toxicity with estimated doses over 600 mg/dL/d CrCl. When patients were given doses corrected on CrCl, few side effects were observed during follow up (6.7%), and the only severe one was associated with corrected dose over 600 mg/d. CONCLUSIONS: Dosage adjustment of allopurinol should be based on clearance of creatinine or estimation of glomerular filtration using the Cockcroft-Gault equation. Pcr is insensitive enough to detect renal function impairment so that patients may be placed at risk for overdosing side effects. Corrected doses over 600 mg/dL/d CrCl may be associated with increased risk of severe toxicity.

Perez-Ruiz F, Gomez-Ullate P, Amenabar JJ, Zarraga S, Calabozo M, Herrero-Beites AM, Nolla JM. · Hospital de Cruces, Rheumatology Section and Nephrology Division, Baracaldo, Pais Vasco, Spain. · Nephrol Dial Transplant. · Pubmed #12584286 links to  free full text

Abstract: BACKGROUND: Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients. METHODS: We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions. RESULTS: Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups. CONCLUSIONS: Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero-Beites AM. · Hospital de Cruces, Baracaldo, Vizcaya, Spain. · Arthritis Rheum. · Pubmed #12522834 links to  free full text

Abstract: OBJECTIVE: To compare renal handling of uric acid in patients with primary gout with that of a control group. METHODS: A case-control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. RESULTS: Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.

Perez-Ruiz F, Testillano M, Gastaca MA, Herrero-Beites AM. · Rheumatology Section, Hospital de Cruces, Pais Vasco, Spain. · Transplantation. · Pubmed #11292305 No free full text.

Abstract: Hypomagnesemia has been associated with deposition of calcium pyrophosphate dihydrate crystals in articular structures, causing pseudogout, also known as calcic gout. Occasionally, pseudogout may mimic septic arthritis; this "pseudoseptic" attack may be of especial concern in the immunocompromised host, such as transplant recipient patients, who may be indeed at risk of developing septic arthritis. We report the cases of two patients in whom pseudogout developed after liver transplantation. Synovial fluid appearance and leukocyte counting in synovial fluid mimicked septic arthritis, but calcium pyrophosphate dihydrate crystals were observed. Magnesium depletion before transplantation and further tacrolimus-induced renal magnesium leakage were probably working in these patients.

Dalbeth N, Perez-Ruiz F, Edwards NL, Schlesinger N. · No affiliation provided · J Rheumatol. · Pubmed #19004057 links to  free full text

This publication has no abstract.