***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Findings that early changes in proteinuria independently predict long-term glomular filtration rate ( GFR ) decline ( Delta GFR ) would highlight proteinuria as a major determinant of progression in chronic renal disease . METHODS We investigated whether percent changes ( 3 months vs. baseline ) in proteinuria ( adjusted for concomitant changes in GFR ) and residual proteinuria at 3 months , predicted Delta GFR [ over a median ( IQ range ) follow up of 31.3 ( 24.5 to 50.3 ) months ] in 273 patients with proteinuric chronic nephropathies enrolled in the Ramipril Efficacy In Nephropathy ( REIN ) study . RESULTS Short-term changes and residual proteinuria ( r = -0.23 , P = 0.0001 for both ) significantly correlated with Delta GFR and , at multivariate analyses , independently predicted Delta GFR ( beta = -0.23 , P = 0.0002 ; beta = -0.21 , P = 0.0004 , respectively ) . For comparable levels of residual proteinuria , patients with greater short-term reduction had slower Delta GFR ( -0.28 + /- 0.04 mL/min/1.73 m2/ vs. -0.53 + /- 0.07 mL/min/1.73 m2/month , P = 0.04 ) . On ramipril and conventional treatment , specular short-term changes in proteinuria ( -18.2 + /- 3.5 % vs. 24.2 + /- 6.7 % , P < 0.0001 , respectively ) were associated with significantly different Delta GFRs . However , similar changes in proteinuria result ed in a difference in Delta GFR  ( ramipril , 0.39 + /- 0.07 mL/min/1.73 m2/month ; conventional therapy , 0.74 + /- 0.11 mL/min/1.73 m2/month ; P < 0.01 ) that was sevenfold higher ( 0.35 vs. 0.05 mL/min/1.73 m2/month ) in patients with basal proteinuria > or =3 g/24 hours as compared to those with basal proteinuria 1 to 3 g/24 hours ( ramipril , 0.25 + /- 0.06 mL/min/1.73 m2/month ; conventional therapy , 0.30 + /- 0.07 mL/min/1.73 m2/month ; P = NS ) . CONCLUSION Regardless of blood pressure control and treatment r and omization , short-term changes in proteinuria and residual proteinuria reliably predict long-term disease progression . Reducing proteinuria is renoprotective , particularly in nephrotic patients . As for arterial hypertension , proteinuria should be a specific target for renoprotective treatment BACKGROUND Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction . Although folic acid reduces hyperhomocysteinemia , the effect on adverse vascular events is unknown . We hypothesized that in patients with chronic renal failure , a condition associated with both hyperhomocysteinemia and atherosclerosis , treatment with folic acid would improve endothelial function . METHODS AND RESULTS In a prospect i ve , double-blind protocol , 100 patients ( mean age 62 years , 67 men ) with predialysis chronic renal failure were r and omized to 5 mg folic acid or placebo daily for 12 weeks . Endothelial function was assessed by measuring ( 1 ) endothelium-dependent dilation of the brachial artery , ( 2 ) combined serum nitrite/nitrate concentrations , and ( 3 ) plasma von Willebr and factor concentration . Baseline characteristics of the 2 groups were similar . At the end of the study , both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [ mean ( 95 % CI ) 39.0 ( 29.8 to 51.0 ) versus 7.7 ( 6.6 to 8.9 ) microg/L and 739 ( 613 to 891 ) versus 220 ( 184 to 262 ) microg/L , respectively ; both P<0.001 ] . Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [ 15.1 ( 14.1 to 16.2 ) versus 20.1 ( 18.2 to 22.2 ) micromol/L ; P<0.001 ] , there were no significant differences in endothelium-dependent dilation , combined serum nitrite/nitrate concentrations , or plasma von Willebr and factor concentration between the 2 groups . CONCLUSIONS High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure . This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia OBJECTIVE To investigate the effect of benfotiamine on urinary albumin excretion ( UAE ) and the tubular damage marker kidney injury molecule-1 ( KIM-1 ) in patients with type 2 diabetes and nephropathy . RESEARCH DESIGN AND METHODS Patients with type 2 diabetes and UAE equivalent to 15–300 mg/24 h , despite ACE inhibitors ( ACE-Is ) or angiotensin receptor blockers ( ARBs ) , were r and omly assigned to 12 weeks of  benfotiamine  ( 900 mg/day ) ( n = 39 )  or placebo ( n = 43 ) . RESULTS Compared with placebo , benfotiamine treatment result ed in significant improvement of thiamine status ( P < 0.001 ) . Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion . CONCLUSIONS In patients with type 2 diabetes and nephropathy , high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion , despite improvement of thiamine status Population -based studies report differences in folate status indicators among Mexican American ( MA ) , African American ( AA ) and Caucasian ( CA ) women . It is unclear , however , whether these differences are due to variations in dietary folate intake . The present study was design ed to investigate the influence of ethnicity/race on folate status parameters in MA , AA , and CA women ( 18 - 45 y ; n = 14 in each group ) under conditions of strictly controlled folate intake . In addition , the adequacy of the 1998 folate U.S. recommended dietary allowance ( RDA ) , 400 micro g/d as dietary folate equivalents ( DFE ) , for non-Caucasian women was assessed . Subjects ( n = 42 ) with the methylenetetrahydrofolate reductase 677 CC genotype consumed a low-folate diet ( 135 micro g DFE/d ) for 7 wk followed by repletion with 400 ( 7 MA , 7 AA , 7 CA ) or 800 micro g DFE/d ( 7 MA , 7 AA , 7 CA ) for 7 wk . AA women had lower ( P < /= 0.05 ) blood folate concentrations and excreted less ( P < /= 0.05 ) urinary folate throughout folate depletion and repletion with 400 and /or 800 micro g DFE/d compared with MA and /or CA women . MA women had lower ( P < /= 0.05 ) plasma total homocysteine ( tHcy ) throughout folate depletion and during repletion with 400 micro g DFE/d relative to the other ethnic/racial groups . Repletion with the 1998 folate U.S. RDA led to normal blood folate and plasma tHcy for all 3 ethnic/racial groups . Collectively , these data demonstrate that ethnicity/race is an important determinant of folate status under conditions of strictly controlled dietary folate intake and support the adequacy of the 1998 folate U.S. RDA for the 3 largest ethnic/racial groups in the United States BACKGROUND In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose , i.v . folinic acid combined with high-dose i.v . pyridoxine was highly effective in correcting plasma total homocysteine ( tHcy ) concentrations in haemodialysis patients . To confirm these findings , we conducted a r and omized , controlled trial aim ed at evaluating whether i.v . or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid . METHODS In a 6-month prospect i ve , r and omized , controlled trial , 60 chronic haemodialysis patients , matched for age , gender , dialysis duration , and average screening pre-treatment-fasting tHcy levels , were given either 50 mg/week of i.v . calcium folinate ( group 1 ) , 50 mg/week of oral calcium folinate ( group 2 ) , or 45 mg/week oral folic acid ( group 3 ) . All 60 patients also received 750 mg/week of i.v . vitamin B6 and 3 mg/week of oral vitamin B12 . RESULTS Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months ( 16.6+/-3.5 , 18.3+/-4 , and 19.1+/-3.1 , in groups 1 , 2 , and 3 , respectively , P = NS ) . Mean percentage reduction at 6 months was also similar in the three treatment groups ( 46 , 43 , and 42 % in groups 1 , 2 , and 3 , respectively , P = NS ) . CONCLUSIONS These findings show that the tHcy-lowering effects of high-dose i.v . folinic acid , oral folinic acid , or oral folic acid were comparable , suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism . Furthermore , they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients OBJECTIVE Hyperhomocysteinemia is an independent risk factor for atherosclerotic vascular disease in chronic hemodialysis patients . This stratified r and omized controlled trial was design ed to measure the effect of high dose oral vitamin B6 , vitamin B12 , and folic acid on homocysteine levels , and to evaluate the effect on atherosclerosis as measured by Intima-Media Thickness ( IMT ) of carotid arteries . MATERIAL AND METHOD Fifty-four chronic hemodialysis patients with hyperhomocysteinemia were r and omized to receive oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 daily ( treatment group ) or oral 5 mg folic acid alone ( control group ) for 6 months . Homocysteine level and IMT were measured in both groups . RESULTS At 6 months , homocysteine levels in the treatment group were significantly reduced from 27.94 + /- 8.54 to 22.71 + /- 3.68 mmol/l ( p = 0.009 ) and were not significantly increased from 26.81 + /- 7.10 to 30.82 + /- 8.76 mmol/l in control group ( p = 0.08 ) . Mean difference between both groups was statistically significant ( p = 0.002 ) . There was no significant difference of IMT of carotid arteries , however , a tendency that the treatment group would have less thickness was observed ( 0.69 + /- 0.29 mm and 0.62 + /- 0.16 mm , p = 0.99 ) . CONCLUSION Treatment of hyperhomocysteinemia in chronic hemodialysis patients with daily oral 15 mg folic acid , 50 mg vitamin B6 , and 1 mg vitamin B12 for 6 months decreases homocysteine levels and tends to reduce IMT of carotid arteries . A long term study for the prevention of atherosclerosis is warranted Background / Aims : Treatments of diabetic nephropathy ( DN ) delay the onset of end-stage renal disease . We report the results of safety/tolerability studies in patients with overt nephropathy and type 1/type 2 diabetes treated with pyridoxamine , a broad inhibitor of advanced glycation . Methods : The two 24-week studies were multicenter Phase 2 trials in patients under st and ard-of-care . In PYR-206 , patients were r and omized 1:1 and had baseline serum creatinine ( bSCr ) ≤2.0 mg/dl . In PYR-205/207 , r and omization was 2:1 and bSCr was ≤2.0 for PYR-205 and ≧2.0 but ≤3.5 mg/dl for PYR-207 . Treated patients ( 122 active , 90 placebo ) received 50 mg pyridoxamine 
    Output:
    
No significant difference in the risk of all-cause mortality with pyridoxamine or combination therapy was reported .
None of the vitamin B derivatives used either alone or in combination improved kidney function : increased in creatinine clearance , improved the GFR ; neither were effective in controlling blood pressure significantly compared to placebo or active control .
There is an absence of evidence to recommend the use of vitamin B therapy alone or combination for delaying progression of DKD .
Thiamine was found to be beneficial for reduction in albuminuria in a single study ; however , there was lack of any improvement in kidney function or blood pressure following the use of vitamin B preparations used alone or in combination .