***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Background Pegloticase is approved in the US for treatment of refractory chronic gout . Since chronic kidney disease ( CKD ) is common in these patients , we conducted a post-hoc analysis of 2 replicate phase 3 trials and the subsequent open-label extension study to determine the effects of pegloticase on renal function in patients with CKD stages 3 and 4 , as well as the effects of renal dysfunction on pegloticase efficacy and safety . Findings Patients with renal insufficiency were r and omized to pegloticase 8 mg every 2 weeks ( n = 42 ) , pegloticase 8 mg every 4 weeks ( n = 41 ) , or placebo ( n = 20 ) for 6 months as defined by the study protocol s. Renal function was assessed by estimated glomerular filtration rate ( eGFR ) . All patients completing the r and omized trials could participate in an open-label extension study for a further 2.5 years . Uric acid response , the primary end point in the trials , was plasma uric acid < 6.0 mg/dl for 80 % of months 3 and 6.Mean eGFR in both pegloticase dosing cohorts remained constant over the r and omized treatment phase and long-term open-label extension study . The number of patients achieving uric acid response was similar across CKD stages ( 32 % stage 1 , 23 % stage 2 , 35 % stage 3 , and 39 % stage 4 , respectively , P = 0.3 ) . There was no difference in the  pegloticase safety profile based on CKD stage . Conclusions Pegloticase treatment does not impact eGFR  in CKD patients and response to pegloticase is independent of CKD stage . Trial registration Clinical trial identifier : Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease ( CKD ) , but it is unknown if it has similar effects among patients with CKD . Furthermore , because arterial stiffness increases left ventricular afterload , any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy ( LVH ) . We conducted a r and omized , double-blind , placebo-controlled , parallel-group study in patients with stage 3 CKD and LVH . We r and omly assigned 67 subjects to allopurinol  at 300 mg/d  or placebo for 9 months ; 53 patients completed the study . We measured left ventricular mass index ( LVMI ) with cardiac magnetic resonance imaging ( MRI ) , assessed endothelial function by flow-mediated dilation ( FMD ) of the brachial artery , and evaluated central arterial stiffness by pulse-wave analysis . Allopurinol significantly reduced LVH ( P=0.036 ) , improved endothelial function ( P=0.009 ) , and improved the central augmentation index ( P=0.015 ) . This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD . Because LVH and endothelial dysfunction associate with prognosis , these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH Introduction Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of gout in combination with a xanthine oxidase inhibitor ( XOI ) in patients who have not achieved target serum uric acid ( sUA ) levels with an XOI alone . Most people with gout have chronic kidney disease . The pharmacokinetics , pharmacodynamics , and safety of lesinurad were assessed in subjects with impaired renal function . Methods Two Phase I , multicenter , open-label , single-dose studies enrolled subjects with normal renal function ( estimated creatinine clearance [ eCrCl ] > 90 mL/min ; N=12 ) or mild ( eCrCl 60–89 mL/min ; N=8 ) , moderate ( eCrCl 30–59 mL/min ; N=16 ) , or severe ( eCrCl < 30 mL/min ; N=6 ) renal impairment . Subjects were given a single oral lesinurad dose of 200 mg ( N=24 ) or 400 mg ( N=18 ) . Blood and urine sample s were analyzed for plasma lesinurad concentrations and serum and urine uric acid concentrations . Safety was assessed by adverse events and laboratory data . Results Mild , moderate , and severe renal impairment increased lesinurad plasma area under the plasma concentration – time curve by 34 % , 54%–65 % , and 102 % , respectively . Lesinurad plasma Cmax was unaffected by renal function status . Lower renal clearance and urinary excretion of lesinurad were associated with the degree of renal impairment . The sUA-lowering effect of a single dose of lesinurad was similar between mild renal impairment and normal function , reduced in moderate impairment , and greatly diminished in severe impairment . Lesinurad increased urinary urate excretion in normal function and mild renal impairment ; the increase was less with moderate or severe renal impairment . Lesinurad was well tolerated by all subjects . Conclusion Lesinurad exposure increased with decreasing renal function ; however , the effects of lesinurad on sUA were attenuated in moderate to severe renal impairment BACKGROUND AND OBJECTIVES Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease . Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease . We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol  might improve endothelial dysfunction , BP , estimated GFR ( eGFR ) , and inflammatory markers . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month r and omized prospect i ve study . Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups .  Flow-mediated dilation ( FMD ) , eGFR , ambulatory BP monitoring , spot urine protein-creatine ratio , and highly sensitive C-reactive protein were measured at baseline and at 4 months . RESULTS Age , gender , lipid profile , eGFR , hemoglobin , glucose , and level of proteinuria were similar in hyperuricemic subjects and controls at baseline . As expected , hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients . Allopurinol treatment result ed in a decrease in serum uric acid , a decrease in systolic BP , an increase in FMD , and an increase in eGFR compared with baseline . No significant difference was observed in the control hyperuricemic and normouricemic groups . In a multiple regression analysis , FMD levels were independently related to uric acid both before ( beta = -0.55 ) and after ( beta = -0.40 ) treatment . CONCLUSIONS Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition . Pegloticase , monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase , was developed to fulfill this need . OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout . DESIGN , SETTING , AND PATIENTS Two replicate , r and omized , double-blind , placebo-controlled trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practice s in the United States , Canada , and Mexico in patients with severe gout , allopurinol intolerance or refractoriness , and serum uric acid concentration of 8.0 mg/dL or greater . A total of 225 patients participated : 109 in trial C0405 and 116 in trial C0406 . INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion ( biweekly treatment group ) , pegloticase alternating with placebo at successive infusions ( monthly treatment group ) , or placebo ( placebo group ) . MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6 . RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group ( 47 % ; 95 % CI , 31%-62 % ) , 8 of 41 patients in the monthly group ( 20 % ; 95 % CI , 9%-35 % ) , and in 0 patients treated with placebo ( 0/20 ; 95 % CI , 0%-17 % ; P < .001 and < .04 for comparisons between biweekly and monthly groups vs placebo , respectively ) . Among patients treated with pegloticase in trial C0406 , 16 of 42 in the biweekly group ( 38 % ; 95 % CI , 24%-54 % ) and 21 of 43 in the monthly group ( 49 % ; 95 % CI , 33%-65 % ) achieved the primary end point ; no placebo-treated patients reached the primary end point ( 0/23 ; 95 % CI , 0%-15 % ; P = .001 and < .001 , respectively ) . When data in the 2 trials were pooled , the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42 % ; 95 % CI , 32%-54 % ) , 29 of 84 patients in the monthly group ( 35 % ; 95 % CI , 24%-46 % ) , and 0 of 43 patients in the placebo group ( 0 % ; 95 % CI , 0%-8 % ; P < .001 for each comparison ) . Seven deaths ( 4 in patients receiving pegloticase and 3 in the placebo group ) occurred between r and omization and closure of the study data base ( February 15 , 2008 ) . CONCLUSION Among patients with chronic gout , elevated serum uric acid level , and allopurinol intolerance or refractoriness , the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months result ed in lower uric acid levels compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325195 Background : The association between hyperuricemia , gout , and impaired renal function has long been recognized . Recent data provide evidence for the causal relationship between elevated serum urate ( sUA ) and renal changes , leading to declines in glomerular filtration rates . In healthy adults , glomerular filtration rate wanes with age . Urate-lowering therapy ( ULT ) with allopurinol has been shown to stabilize or reverse this . Objective : Here we examine the long-term effects of ULT with febuxostat on estimated glomerular filtration rate ( eGFR ) . Methods : This is a post hoc analysis of the Febuxostat Open-label Clinical trial of Urate-lowering efficacy and Safety study , during which 116 hyperuricemic gout subjects received daily doses of febuxostat ( 40 , 80 , or 120 mg ) for up to 5 years . sUA concentrations and eGFR were assessed regularly . Results were stratified by mean change in sUA from baseline . Mathematical modeling was used to predict the effect of sUA reduction on eGFR . Results : Maintenance or improvement in eGFR was inversely correlated with the quantitative reduction in sUA from baseline . For every 1 mg/dL decrease in sUA , the model projected an expected improvement in eGFR of 1 mL/min from the untreated value . Conclusion : Individuals with the greatest reductions in sUA may experience reduced rates of renal deterioration or even stabilization of renal function . Further studies examining the impact of long-term ULT on renal function in hyperuricemic gout patients are needed to both confirm our results and verify if improvements in renal function are feasible in such patients Hyperuricaemia is associated with an increased risk of gout , kidney stones and cardiovascular disease . The present post hoc analysis of pooled data from four placebo‐controlled phase III studies assessed the effect of canagliflozin , a sodium‐glucose co‐transporter 2 inhibitor , on serum uric acid levels in patients with type 2 diabetes mellitus ( T2DM ) and in a subset of patients with hyperuricaemia [ defined as baseline serum uric acid ≥475 µmol/l ( ∼8 mg/dl ) ] . At week 26 , canagliflozin 100 and 300 mg were associated with a ∼13 % reduction in serum uric acid compared with placebo . In the subset of patients with 
    Output:
    
Uric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD