***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: The kidney is one of the organs most prominently affected by aging . This can be seen by a loss of renal mass which is caused by a decrease in the number of nephrons result ing in hyperfiltration , hypertrophy and elevations in glomerular pressure . The factors influencing aging of the kidney are not fully eluci date d. Epidemiological , experimental and interventional studies result ed in inconsistent results and have not firmly established whether uric acid levels affect progression of Chronic Kidney Disease ( CKD ) . Therefore , we analyzed whether uric acid levels predict the progression of CKD in the Mild to Moderate Kidney Disease Study comprising at baseline 227 Caucasian patients aged 18 - 65 years with primary non-diabetic CKD of various degrees of renal impairment . Of them , 177 completed a prospect i ve follow-up of 7 years . Primary endpoint was progression of CKD defined as doubling of baseline serum creatinine and /or terminal renal failure . Patients who reached a progression endpoint ( n = 6 5 ) were significantly older , had higher baseline serum creatinine and protein excretion rates as well as lower Glomerular Filtration Rate ( GFR ) . Uric acid levels were only higher in patients with progression of disease when patients with uric acid-lowering drugs were excluded from the analysis . Cox regression analysis revealed that increasing uric acid levels predict disease progression only when the analysis was not adjusted for baseline kidney function parameters . As soon as we adjusted the analysis for GFR and proteinuria this association completely vanished . In summary , our prospect i ve 7 year follow-up study in patients with non-diabetic primary CKD did not support uric acid as an independent predictor for CKD progression Background : Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients .  Febuxostat , being a novel xanthine oxidase inhibitor , is apparently having a beneficial role in improving the endothelial dysfunction ; however , data among hemodialysis patients are still limited . Methods : A prospect i ve , placebo-controlled , block-r and omized , double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients . Fifty-seven eligible hemodialysis patients were r and omly assigned to either the drug group ( 40 mg thrice weekly ) or the placebo group . Serum Asymmetric dimethylarginine ( ADMA ) , Serum uric acid ( UA ) , and serum high sensitivity C-reactive protein ( hsCRP ) were measured at baseline and at the end of a 2-month study . Serum alanine aminotransferase ( ALT ) , serum aspartate aminotransferase ( AST ) , and the occurrence of pancytopenia were tested as safety parameters at baseline and at the end of study . Results : Serum UA significantly decreased from 7.5 ± 0.8 to 5.1 ± 1.2 mg/dL in the febuxostat group , while it did not change significantly in the placebo group . Treatment with febuxostat result ed in a significant decrease in the serum ADMA level from 1.027 ± 0.116 to 0.944 ± 0.104 µmol/L and the serum hsCRP level from 12.5 ± 1.65 to 12.1 ± 1.70 mg/L. Testing of serum ALT , serum AST , and pancytopenia revealed no significant difference in both groups . Conclusion : Febuxostat appears to improve hyperuricemia and endothelial dysfunction and ameliorate inflammation in hemodialysis patients with no safety concerns Introduction The purpose of this study was to compare urate-lowering ( UL ) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate ( sUA ) ≥ 8.0 mg/dL in a six-month trial . Methods Subjects ( n = 2,269 ) were r and omized to febuxostat 40 mg or 80 mg , or allopurinol 300 mg ( 200 mg in moderate renal impairment ) . Endpoints included the proportion of all subjects with sUA < 6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA < 6.0 mg/dL. Safety assessment s included blinded adjudication of each cardiovascular ( CV ) adverse event ( AE ) and death . Results Comorbidities included : renal impairment ( 65 % ) ; obesity ( 64 % ) ; hyperlipidemia ( 42 % ) ; and hypertension ( 53 % ) . In febuxostat 40 mg , febuxostat 80 mg , and allopurinol groups , primary endpoint was achieved in 45 % , 67 % , and 42 % , respectively . Febuxostat 40 mg UL was statistically non-inferior to allopurinol , but febuxostat 80 mg was superior to both ( P < 0.001 ) . Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg ( 72 % ; P < 0.001 ) compared with febuxostat 40 mg ( 50 % ) or allopurinol ( 42 % ) , but febuxostat 40 mg showed greater efficacy than allopurinol ( P = 0.021 ) . Rates of AEs did not differ across treatment groups . Adjudicated ( APTC ) CV event rates were 0.0 % for febuxostat 40 mg and 0.4 % for both febuxostat 80 mg and allopurinol . One death occurred in each febuxostat group and three in the allopurinol group . Conclusions Urate-lowering efficacy  of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol ( 300/200 mg ) , which were comparable . In subjects with mild/moderate renal impairment , both febuxostat doses were more efficacious than allopurinol and equally safe . At the doses tested , safety of febuxostat and allopurinol was comparable . Clinical Trial Registration The aim of the present study was to determine the influence of severe renal dysfunction ( estimated glomerular filtration rate < 30 ml/min/1.73 m2 , including hemodialysis ) on the pharmacokinetics and therapeutic effects of  febuxostat using a population pharmacokinetic analysis . This study recruited patients with hyperuricemia who were initially treated with allopurinol , but were switched to febuxostat  , and it consists of 2 sub- studies : a pharmacokinetic study ( 26 patients ) and retrospective efficacy evaluation study ( 51 patients ) . The demographic and clinical data of patients were collected from electronic medical records .  Plasma febuxostat  concentrations were obtained at each hospital visit . Population pharmacokinetic modeling was performed with NONMEM version 7.2 . A total of 128 plasma  febuxostat concentrations from 26 patients were used in the population pharmacokinetic analysis . The data were best described by a 1-compartment model with first order absorption . Covariate analysis revealed that renal function did not influence the pharmacokinetics of febuxostat , whereas actual body weight significantly influenced apparent clearance and apparent volume of distribution . The retrospective efficacy analysis showed the favorable therapeutic response of febuxostat switched from allopurinol in patients with moderate to severe renal impairment . No serious adverse event associated with febuxostat was observed irrespective of renal function . The population pharmacokinetic analysis and therapeutic analysis of febuxostat revealed that severe renal dysfunction had no influence on the pharmacokinetic parameters of febuxostat .  These results suggest that febuxostat is tolerated well by patients with severe renal impairment Background Hyperuricemia is associated with the onset of chronic kidney disease ( CKD ) and renal disease progression . Febuxostat , a novel , non-purine , selective xanthine oxidase inhibitor , has been reported to have a stronger effect on hyperuricemia than conventional therapy with allopurinol . However , few data are available regarding the clinical effect of febuxostat in patients with CKD . Methods A prospect i ve , r and omized , open-label , parallel-group trial was conducted in hyperuricemic patients with stage 3 CKD . Patients were r and omly assigned to treatment with febuxostat  ( n = 21 ) or to continue conventional therapy  ( n = 19 ) . Treatment was continued for 12 weeks . The efficacy of febuxostat was determined by monitoring serum uric acid ( UA ) levels , blood pressures , renal function , and urinary protein levels . In addition , urinary liver-type fatty acid-binding protein ( L-FABP ) , urinary albumin , urinary beta 2 microglobulin ( β2MG ) , and serum high sensitivity C-reactive protein were measured before and 12 weeks after febuxostat was added to the treatment . Results Febuxostat result ed in a significantly greater reduction in serum UA ( −2.2 mg/dL ) than conventional therapy ( −0.3 mg/dL , P < 0.001 ) . Serum creatinine and estimated glomerular filtration rate changed little during the study period in each group . However , treatment with febuxostat for 12 weeks reduced the urinary levels of L-FABP , albumin , and β2MG , whereas the levels of these markers did not change in the control group . Conclusion Febuxostat  reduced serum UA levels more effectively than conventional therapy and might have a renoprotective effect in hyperuricemic patients with CKD . Further studies should clarify whether febuxostat prevents the progression of renal disease and improves the prognosis of CKD BACKGROUND Hyperuricemia is associated strongly with the development of hypertension , renal disease , and progression . Allopurinol decreases serum uric acid levels by inhibiting the enzyme xanthine oxidase . We hypothesized that administrating allopurinol to decrease serum uric acid levels to the normal range in hyperuricemic patients with chronic kidney disease may be of benefit in decreasing blood pressure and slowing the rate of renal disease progression in these patients . METHODS We conducted a prospect i ve , r and omized , controlled trial of 54 hyperuricemic patients with chronic kidney disease . Patients were r and omly assigned to treatment with allopurinol , 100 to 300 mg/d , or to continue the usual therapy for 12 months .  Clinical , hematologic , and biochemical parameters were measured at baseline and 3 , 6 , and 12 months of treatment . We define our study end points as : ( 1 ) stable kidney function with less than 40 % increase in serum creatinine level , ( 2 ) impaired renal function with creatinine level increase greater than 40 % of baseline value , ( 3 ) initiation of dialysis therapy , and ( 4 ) death . RESULTS One patient in the treatment group dropped out because of skin allergy to allopurinol . Serum uric acid levels were significantly decreased in subjects treated with allopurinol , from 9.75 + /- 1.18 mg/dL ( 0.58 + /- 0.07 mmol/L ) to 5.88 + /- 1.01 mg/dL ( 0.35 + /- 0.06 mmol/L ; P < 0.001 ) . There were no significant differences in systolic or diastolic blood pressure at the end of the study comparing the 2 groups . There was a trend toward a lower serum creatinine level in the treatment group compared with controls after 12 months of therapy , although it did not reach statistical significance ( P = 0.08 ) . Overall , 4 of 25 patients ( 16 % ) in the allopurinol group reached the combined end points of significant deterioration in renal function and dialysis dependence compared with 12 of 26 patients ( 46.1 % ) in the control group ( P = 0.015 ) . CONCLUSION Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate chronic kidney disease . Its use is safe and helps preserve kidney function during 12 months of therapy compared with controls . Results of this study need to be confirmed with an additional prospect i ve trial involving a larger cohort of patients to determine the long-term efficacy of allopurinol therapy and in specific chronic kidney disease sub population Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease , but it is unclear whether uric acid is an independent risk factor . In this study , data from 21,475 healthy volunteers who were followed prospect ively for a median of 7 yr were analyzed to examine the association between  uric acid level  and incident kidney disease ( estimated GFR [ eGFR ] < 60 ml/min per 1.73 m(2 ) ) . After adjustment for baseline eGFR , a slightly elevated uric acid level ( 7.0 to 8.9 mg/dl ) was associated with a nearly doubled risk for incident kidney disease ( odds ratio 1.74 ; 95 % confidence interval 1.45 to 2.09 ) , and an elevated uric acid ( > or = 9.0 mg/dl ) was associated with a tripled risk ( odds ratio 3.12 ; 95 % confidence interval  
    Output:
    
The meta- analysis showed that other than its urate-lowering effect , febuxostat presented a reno-protective effect in CKD patients .