***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 : The Norfolk Quality of Life Question naire-Diabetic Neuropathy ( Norfolk QOL-DN ) is a vali date d comprehensive question naire design ed to capture the entire spectrum of DN related to large fiber , small fiber , and autonomic neuropathy not captured in existing instruments . We aim ed to determine if the Norfolk QOL-DN could be used to capture changes in QOL that correlate with nerve fiber-specific objective measures in a placebo-controlled trial of two agents that affect different nerve fibers . Methods : Sixty patients with DN were allocated to treatment on ruboxistaurin ( RBX ) ( n = 18 ) , topiramate ( TPX ) ( n = 18 ) , or placebo ( n = 18 ) . QOL-DN was administered and objective measures of nerve function were performed at entry and end of the study period . Results : Total QOL scores improved significantly in the active treatment groups ( RBX −9.56 ± 4.13 ; TPX −12.22 ± 2.76 ) but not in placebo ( −5.56 ± 3.49 ) . There were differences in nerve function improvement between treatments . Neurological symptom scores ( NSS ) improved with TPX from 5.5 ( 2.3 ) to 4.3 ( 0.65 ) ( p = .007 ) , sensory scores improved with TPX from 15.5 ( 1.79 ) to 8.3 ( 1.19 ) ( p < .001 ) , motor scores did not change , and sensory and motor impairment scores improved with TPX from 18.8 ( 2.15 ) to 12.1 ( 1.71 ) ( p = .003 ) . Total neuropathy scores ( TNS ) improved with TPX from 24.35 ( 2.61 ) to 16.35 ( 2.02 ) ( p = .001 ) . Neuropathy total symptom score−6 ( NTSS−6 ) changes were significant for both treatments : RBX 4.38 ( 0.75 ) to 1.49 ( 0.38 ) ( p < .001 ) and TPX 7.57 ( 1.3 ) to 4.26 ( 0.95 ) ( p = .036 ) . Changes in QOL-DN large fiber subscores correlated ( Spearman 's rank ) significantly with changes in NTSS-6 ( r = 0.55 ; p < .0001 ) , NSS ( r = 0.31 ; p < .04 ) , neuropathy impairment score ( NIS ) ( r = 0.35 ; p < .02 ) , and TNS ( r = 0.48 ; p < .0006 ) . Changes in QOL-DN small fiber subscores correlated significantly with changes in NTSS-6 total scores ( r = 0.40 ; p < .005 ) and intraepidermal nerve fiber density ( IENFD ) ( r = −0.29 ; p < .05 ) . Conclusion : Ruboxistaurin produced significant improvement in large fiber measures while TPX produced significant changes in small fiber measures . The Norfolk QOL-DN tool differentiated between these changes captured in the fiber-specific domains . Correlations were found between objective measures of neuropathy and total QOL , but those with nerve fiber domain scores were modest and reinforce the need to quantify QOL as an endpoint in neuropathy independent of other measures Background / Aims : Bardoxolone methyl , a novel synthetic triterpenoid , induces Nrf2 , a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules . Methods : This exploratory multi-center , open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes . Patients received 25 mg of bardoxolone methyl daily for 28 days , followed by 75 mg daily for another 28 days . Results : The study achieved its primary efficacy endpoint , as demonstrated by a significant increase from baseline in estimated glomerular filtration rate ( eGFR ) of 7.2 ml/min/1.73 m2 ( p < 0.001 ) . Improvements were seen in approximately 90 % of patients and showed a dose- and time-dependent increase in eGFR . The eGFR change paralleled a significant reduction in serum creatinine ( –0.3 mg/dl ) and blood urea nitrogen ( –4.9 mg/dl ) , along with an increase in creatinine clearance ( + 14.6 ml/min/1.73 m2 ) , without a change in the 24-hour creatinine excretion rate . Markers of vascular injury and inflammation were improved by treatment with bardoxolone .  No life-threatening adverse events or drug-related serious adverse events were reported . Conclusions : The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl , a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function Prior research has shown that in experimental diabetes mellitus , green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway . We investigated the effect of green tea polyphenols ( GTP ) on residual albuminuria of diabetic subjects with nephropathy . We conducted a r and omised , double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio ( UACR ) > 30 mg/g , despite administration of the maximum recommended dose of renin-angiotensin ( RAS ) inhibition . Patients were r and omly assigned to two equal groups to receive either GTP ( containing 800 mg of epigallocatechin gallate , 17 with type 2 diabetes and 4 with type 1 diabetes ) or placebo ( 21 with type 2 diabetes ) for 12 weeks . Treatment with GTP  reduced UACR by 41 % , while the placebo group saw a 2 % increase in UACR ( p = 0.019 ) . Podocyte apoptosis ( p = 0.001 ) and in vitro albumin permeability ( p < 0.001 ) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals . In conclusion , GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS . Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect 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 twice daily in PYR-206 ; PYR-205/207 patients were escalated to 250 mg twice daily . Results : Adverse events were balanced between the groups ( p = NS ) . Slight imbalances , mainly in the PYR-205/207 groups , were noted in deaths ( from diverse causes , p = NS ) and serious adverse events ( p = 0.05 ) that were attributed to pre-existing conditions . In a merged data set , pyridoxamine significantly reduced the change from baseline in serum creatinine ( p < 0.03 ) . In patients similar to the RENAAL/IDNT studies ( bSCr ≧1.3 mg/dl , type 2 diabetes ) , a treatment effect was observed on the rise in serum creatinine ( p = 0.007 ) . No differences in urinary albumin excretion were seen . Urinary TGF-β1 also tended to decrease with pyridoxamine ( p = 0.049 ) as did the CML and CEL AGEs . Conclusion : These data provide a foundation for further evaluation of this AGE inhibitor in DN Inflammation is a central component of progressive chronic kidney disease ( CKD ) .  Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD .  Parenteral iron provokes oxidative stress in patients with CKD ; however , its potential to provoke an inflammatory response is unknown . In 20 veterans with CKD , 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 ( MCP-1 ) were measured at timed intervals over 24 h. Patients were then r and omized to placebo or N-acetyl cysteine ( NAC ) 600 mg b.i.d . and the experiment was repeated at 1 week . Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits ( P < 0.0001 for time effect ) . Urinary excretion peaked at 30 min and plasma concentration at 15 min . Plasma MCP-1 concentration fell from 164 + /- 17.7 to 135 + /- 17.7 pg/ml with NAC , whereas it remained unchanged from 133 + /- 12.5 to 132 + /- 17.7 pg/ml with placebo ( P=0.001 for visit x antioxidant drug interaction ) . There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2 . At the baseline visit , the urinary excretion rate averaged 305 + /- 66 pg/min and at the second visit 245 + /- 67 pg/min ( mean difference 60 + /- 28 pg/min , P = 0.030 ) . There was no improvement in urinary MCP-1 excretion with NAC . In conclusion , iron sucrose causes rapid and transient generation and /or release of MCP-1 plasma concentration and increases urinary excretion rate , and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC . These results may have implication s for the progression of CKD with parenteral iron Background Arterial stiffness is increased in patients with CKD and is a powerful predictor of cardiovascular morbidity and mortality . Use of the xanthine oxidase inhibitor allopurinol has been shown to improve endothelial function , reduce left ventricular hypertrophy and possibly improve cardiovascular outcome . We explored the relationship between use of allopurinol and arterial stiffness in patients with chronic kidney disease ( CKD ) . Methods Cross-sectional observational study of 422 patients with CKD with evidence of , or at high risk of , renal disease progression . Arterial stiffness was determined by carotid-femoral pulse wave velocity ( PWV ) . Results The mean age was 63±16 years , median estimated glomerular filtration rate was 25 ( interquartile range : 19–31 ) ml/min/1.73 m2 and mean PWV was 10.2±2.4 m/s . Seventy-seven patients ( 18 % ) were receiving regular allopurinol , 61 % at a dose of 100 mg/day ( range : 50–400 mg/day ) . Patients receiving allopurinol had significantly lower peripheral pulse pressure , central pulse pressure , central systolic blood pressure , serum uric acid level tissue advanced glycation end product levels but comparable high-sensitivity C-reactive protein levels . Use of allopurinol was associated with lower PWV . After adjusting for age , gender , ethnicity , tissue advanced glycation end product level , peripheral pulse pressure , smoking pack years , presence of diabetes mellitus and use of angiotensin converting enzyme inhibitor or angiotensin II receptor blocker , the use of allopurinol remained a significant independent determinant of PWV ( mean difference : −0.63 m/s ; 95 % CI , −0.09 to −1.17 m/s , p = 0.02 ) . Conclusion In patients with CKD , use of allopurinol is independently associated with lower arterial stiffness . This study provides further justification for a large definitive r and omised controlled trial examining the therapeutic potential of allopurinol to reduce cardiovascular risk in people with CKD Pyridoxamine dihydrochloride ( Pyridorin , NephroGenex ) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls , but whether these actions translate into renoprotective effects is unknown . In this double-blind , r and omized , placebo-controlled trial , we r and omly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo ; Py 
    Output:
    
The findings of this investigation indicate that antioxidant treatment is effective clinical ly for DN treatment in T2DM patient .