Antioxidants for chronic kidney disease

Min Jun, Vinod Venkataraman, Mona Razavian, Bruce Cooper, Sophia Zoungas, Toshiharu Ninomiya, Angela C. Webster, Vlado Perkovic

Research output: Contribution to journalReview article

71 Citations (Scopus)

Abstract

Background: Chronic kidney disease (CKD) is a significant risk factor for premature cardiovascular disease and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor for some cardiovascular diseases. Antioxidant therapy may reduce cardiovascular mortality and morbidity in people with CKD. Objectives: To examine the benefits and harms of antioxidant therapy on mortality and cardiovascular events in people with CKD stages 3 to 5; dialysis, and kidney transplantation patients. Search methods: We searched the Cochrane Renal Group's specialised register (July 2011), CENTRAL (Issue 6, 2011), MEDLINE (from 1966) and EMBASE (from 1980). Selection criteria: We included all randomised controlled trials (RCTs) investigating the use of antioxidants for people with CKD, or subsets of RCTs reporting outcomes for participants with CKD. Data collection and analysis: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using the random effects model and expressed as either risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results: We identified 10 studies (1979 participants) that assessed antioxidant therapy in haemodialysis patients (two studies); kidney transplant recipients (four studies); dialysis and non-dialysis CKD patients (one study); and patients requiring surgery (one study). Two additional studies reported the effect of an oral antioxidant inflammation modulator in patients with CKD (estimated glomerular filtration rate (eGFR) 20 to 45 mL/min/1.73 m2), and post-hoc findings from a subgroup of people with mild-to-moderate renal insufficiency (serum creatinine ≥125 μmol/L) respectively. Interventions included different doses of vitamin E (two studies); multiple antioxidant therapy (three studies); co-enzyme Q (one study); acetylcysteine (one study); bardoxolone methyl (one study); and human recombinant superoxide dismutase (two studies). Compared with placebo, antioxidant therapy showed no clear overall effect on cardiovascular mortality (RR 0.95, 95% CI 0.70 to 1.27; P = 0.71); all-cause mortality (RR 0.93, 95% CI 0.76 to 1.14; P = 0.48); cardiovascular disease (RR 0.78, 95% CI 0.52 to 1.18; P = 0.24); coronary heart disease (RR 0.71, 95% CI 0.42 to 1.23; P = 0.22); cerebrovascular disease (RR 0.91, 95% CI 0.63 to 1.32; P = 0.63); or peripheral vascular disease (RR 0.54, 95% CI 0.26 to 1.12; P = 0.10). Subgroup analyses found no evidence of significant heterogeneity based on proportions of males (P = 0.99) or diabetes (P = 0.87) for cardiovascular disease. There was significant heterogeneity for cardiovascular disease when studies were analysed by CKD stage (P = 0.003). Significant benefit was conferred by antioxidant therapy for cardiovascular disease prevention in dialysis patients (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001), although no effect was observed in CKD patients (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Antioxidant therapy was found to significantly reduce development of end-stage of kidney disease (ESKD) (RR 0.50, 95% CI 0.25 to 1.00; P = 0.05); lowered serum creatinine levels (MD 1.10 mg/dL, 95% CI 0.39 to 1.81; P = 0.003); and improved creatinine clearance (MD 14.53 mL/min, 95% CI 1.20 to 27.86; P = 0.03). Serious adverse events were not significantly increased by antioxidants (RR 2.26, 95% CI 0.74 to 6.95; P = 0.15). Risk of bias was assessed for all studies. Studies that were classified as unclear for random sequence generation or allocation concealment reported significant benefits from antioxidant therapy (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001) compared with studies at low risk of bias (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Authors' conclusions: Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD.

Original languageEnglish
Article numberCD008176
JournalCochrane Database of Systematic Reviews
Volume2012
Issue number10
DOIs
Publication statusPublished - Oct 17 2012
Externally publishedYes

Fingerprint

Chronic Renal Insufficiency
Antioxidants
Confidence Intervals
Odds Ratio
Cardiovascular Diseases
Dialysis
Therapeutics
Creatinine
Mortality
Chronic Kidney Failure
Randomized Controlled Trials
Kidney
Cerebrovascular Disorders
Peripheral Vascular Diseases
Acetylcysteine
Serum
Glomerular Filtration Rate
Vitamin E
MEDLINE
Kidney Transplantation

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

Jun, M., Venkataraman, V., Razavian, M., Cooper, B., Zoungas, S., Ninomiya, T., ... Perkovic, V. (2012). Antioxidants for chronic kidney disease. Cochrane Database of Systematic Reviews, 2012(10), [CD008176]. https://doi.org/10.1002/14651858.CD008176.pub2

Antioxidants for chronic kidney disease. / Jun, Min; Venkataraman, Vinod; Razavian, Mona; Cooper, Bruce; Zoungas, Sophia; Ninomiya, Toshiharu; Webster, Angela C.; Perkovic, Vlado.

In: Cochrane Database of Systematic Reviews, Vol. 2012, No. 10, CD008176, 17.10.2012.

Research output: Contribution to journalReview article

Jun, M, Venkataraman, V, Razavian, M, Cooper, B, Zoungas, S, Ninomiya, T, Webster, AC & Perkovic, V 2012, 'Antioxidants for chronic kidney disease', Cochrane Database of Systematic Reviews, vol. 2012, no. 10, CD008176. https://doi.org/10.1002/14651858.CD008176.pub2
Jun M, Venkataraman V, Razavian M, Cooper B, Zoungas S, Ninomiya T et al. Antioxidants for chronic kidney disease. Cochrane Database of Systematic Reviews. 2012 Oct 17;2012(10). CD008176. https://doi.org/10.1002/14651858.CD008176.pub2
Jun, Min ; Venkataraman, Vinod ; Razavian, Mona ; Cooper, Bruce ; Zoungas, Sophia ; Ninomiya, Toshiharu ; Webster, Angela C. ; Perkovic, Vlado. / Antioxidants for chronic kidney disease. In: Cochrane Database of Systematic Reviews. 2012 ; Vol. 2012, No. 10.
@article{38404dab6bf84d2bbb72565b13b8d0fb,
title = "Antioxidants for chronic kidney disease",
abstract = "Background: Chronic kidney disease (CKD) is a significant risk factor for premature cardiovascular disease and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor for some cardiovascular diseases. Antioxidant therapy may reduce cardiovascular mortality and morbidity in people with CKD. Objectives: To examine the benefits and harms of antioxidant therapy on mortality and cardiovascular events in people with CKD stages 3 to 5; dialysis, and kidney transplantation patients. Search methods: We searched the Cochrane Renal Group's specialised register (July 2011), CENTRAL (Issue 6, 2011), MEDLINE (from 1966) and EMBASE (from 1980). Selection criteria: We included all randomised controlled trials (RCTs) investigating the use of antioxidants for people with CKD, or subsets of RCTs reporting outcomes for participants with CKD. Data collection and analysis: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using the random effects model and expressed as either risk ratios (RR) or mean difference (MD) with 95{\%} confidence intervals (CI). Main results: We identified 10 studies (1979 participants) that assessed antioxidant therapy in haemodialysis patients (two studies); kidney transplant recipients (four studies); dialysis and non-dialysis CKD patients (one study); and patients requiring surgery (one study). Two additional studies reported the effect of an oral antioxidant inflammation modulator in patients with CKD (estimated glomerular filtration rate (eGFR) 20 to 45 mL/min/1.73 m2), and post-hoc findings from a subgroup of people with mild-to-moderate renal insufficiency (serum creatinine ≥125 μmol/L) respectively. Interventions included different doses of vitamin E (two studies); multiple antioxidant therapy (three studies); co-enzyme Q (one study); acetylcysteine (one study); bardoxolone methyl (one study); and human recombinant superoxide dismutase (two studies). Compared with placebo, antioxidant therapy showed no clear overall effect on cardiovascular mortality (RR 0.95, 95{\%} CI 0.70 to 1.27; P = 0.71); all-cause mortality (RR 0.93, 95{\%} CI 0.76 to 1.14; P = 0.48); cardiovascular disease (RR 0.78, 95{\%} CI 0.52 to 1.18; P = 0.24); coronary heart disease (RR 0.71, 95{\%} CI 0.42 to 1.23; P = 0.22); cerebrovascular disease (RR 0.91, 95{\%} CI 0.63 to 1.32; P = 0.63); or peripheral vascular disease (RR 0.54, 95{\%} CI 0.26 to 1.12; P = 0.10). Subgroup analyses found no evidence of significant heterogeneity based on proportions of males (P = 0.99) or diabetes (P = 0.87) for cardiovascular disease. There was significant heterogeneity for cardiovascular disease when studies were analysed by CKD stage (P = 0.003). Significant benefit was conferred by antioxidant therapy for cardiovascular disease prevention in dialysis patients (RR 0.57, 95{\%} CI 0.41 to 0.80; P = 0.001), although no effect was observed in CKD patients (RR 1.06, 95{\%} CI 0.84 to 1.32; P = 0.63). Antioxidant therapy was found to significantly reduce development of end-stage of kidney disease (ESKD) (RR 0.50, 95{\%} CI 0.25 to 1.00; P = 0.05); lowered serum creatinine levels (MD 1.10 mg/dL, 95{\%} CI 0.39 to 1.81; P = 0.003); and improved creatinine clearance (MD 14.53 mL/min, 95{\%} CI 1.20 to 27.86; P = 0.03). Serious adverse events were not significantly increased by antioxidants (RR 2.26, 95{\%} CI 0.74 to 6.95; P = 0.15). Risk of bias was assessed for all studies. Studies that were classified as unclear for random sequence generation or allocation concealment reported significant benefits from antioxidant therapy (RR 0.57, 95{\%} CI 0.41 to 0.80; P = 0.001) compared with studies at low risk of bias (RR 1.06, 95{\%} CI 0.84 to 1.32; P = 0.63). Authors' conclusions: Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD.",
author = "Min Jun and Vinod Venkataraman and Mona Razavian and Bruce Cooper and Sophia Zoungas and Toshiharu Ninomiya and Webster, {Angela C.} and Vlado Perkovic",
year = "2012",
month = "10",
day = "17",
doi = "10.1002/14651858.CD008176.pub2",
language = "English",
volume = "2012",
journal = "Cochrane Database of Systematic Reviews",
issn = "1361-6137",
publisher = "John Wiley and Sons Ltd",
number = "10",

}

TY - JOUR

T1 - Antioxidants for chronic kidney disease

AU - Jun, Min

AU - Venkataraman, Vinod

AU - Razavian, Mona

AU - Cooper, Bruce

AU - Zoungas, Sophia

AU - Ninomiya, Toshiharu

AU - Webster, Angela C.

AU - Perkovic, Vlado

PY - 2012/10/17

Y1 - 2012/10/17

N2 - Background: Chronic kidney disease (CKD) is a significant risk factor for premature cardiovascular disease and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor for some cardiovascular diseases. Antioxidant therapy may reduce cardiovascular mortality and morbidity in people with CKD. Objectives: To examine the benefits and harms of antioxidant therapy on mortality and cardiovascular events in people with CKD stages 3 to 5; dialysis, and kidney transplantation patients. Search methods: We searched the Cochrane Renal Group's specialised register (July 2011), CENTRAL (Issue 6, 2011), MEDLINE (from 1966) and EMBASE (from 1980). Selection criteria: We included all randomised controlled trials (RCTs) investigating the use of antioxidants for people with CKD, or subsets of RCTs reporting outcomes for participants with CKD. Data collection and analysis: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using the random effects model and expressed as either risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results: We identified 10 studies (1979 participants) that assessed antioxidant therapy in haemodialysis patients (two studies); kidney transplant recipients (four studies); dialysis and non-dialysis CKD patients (one study); and patients requiring surgery (one study). Two additional studies reported the effect of an oral antioxidant inflammation modulator in patients with CKD (estimated glomerular filtration rate (eGFR) 20 to 45 mL/min/1.73 m2), and post-hoc findings from a subgroup of people with mild-to-moderate renal insufficiency (serum creatinine ≥125 μmol/L) respectively. Interventions included different doses of vitamin E (two studies); multiple antioxidant therapy (three studies); co-enzyme Q (one study); acetylcysteine (one study); bardoxolone methyl (one study); and human recombinant superoxide dismutase (two studies). Compared with placebo, antioxidant therapy showed no clear overall effect on cardiovascular mortality (RR 0.95, 95% CI 0.70 to 1.27; P = 0.71); all-cause mortality (RR 0.93, 95% CI 0.76 to 1.14; P = 0.48); cardiovascular disease (RR 0.78, 95% CI 0.52 to 1.18; P = 0.24); coronary heart disease (RR 0.71, 95% CI 0.42 to 1.23; P = 0.22); cerebrovascular disease (RR 0.91, 95% CI 0.63 to 1.32; P = 0.63); or peripheral vascular disease (RR 0.54, 95% CI 0.26 to 1.12; P = 0.10). Subgroup analyses found no evidence of significant heterogeneity based on proportions of males (P = 0.99) or diabetes (P = 0.87) for cardiovascular disease. There was significant heterogeneity for cardiovascular disease when studies were analysed by CKD stage (P = 0.003). Significant benefit was conferred by antioxidant therapy for cardiovascular disease prevention in dialysis patients (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001), although no effect was observed in CKD patients (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Antioxidant therapy was found to significantly reduce development of end-stage of kidney disease (ESKD) (RR 0.50, 95% CI 0.25 to 1.00; P = 0.05); lowered serum creatinine levels (MD 1.10 mg/dL, 95% CI 0.39 to 1.81; P = 0.003); and improved creatinine clearance (MD 14.53 mL/min, 95% CI 1.20 to 27.86; P = 0.03). Serious adverse events were not significantly increased by antioxidants (RR 2.26, 95% CI 0.74 to 6.95; P = 0.15). Risk of bias was assessed for all studies. Studies that were classified as unclear for random sequence generation or allocation concealment reported significant benefits from antioxidant therapy (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001) compared with studies at low risk of bias (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Authors' conclusions: Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD.

AB - Background: Chronic kidney disease (CKD) is a significant risk factor for premature cardiovascular disease and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor for some cardiovascular diseases. Antioxidant therapy may reduce cardiovascular mortality and morbidity in people with CKD. Objectives: To examine the benefits and harms of antioxidant therapy on mortality and cardiovascular events in people with CKD stages 3 to 5; dialysis, and kidney transplantation patients. Search methods: We searched the Cochrane Renal Group's specialised register (July 2011), CENTRAL (Issue 6, 2011), MEDLINE (from 1966) and EMBASE (from 1980). Selection criteria: We included all randomised controlled trials (RCTs) investigating the use of antioxidants for people with CKD, or subsets of RCTs reporting outcomes for participants with CKD. Data collection and analysis: Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using the random effects model and expressed as either risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results: We identified 10 studies (1979 participants) that assessed antioxidant therapy in haemodialysis patients (two studies); kidney transplant recipients (four studies); dialysis and non-dialysis CKD patients (one study); and patients requiring surgery (one study). Two additional studies reported the effect of an oral antioxidant inflammation modulator in patients with CKD (estimated glomerular filtration rate (eGFR) 20 to 45 mL/min/1.73 m2), and post-hoc findings from a subgroup of people with mild-to-moderate renal insufficiency (serum creatinine ≥125 μmol/L) respectively. Interventions included different doses of vitamin E (two studies); multiple antioxidant therapy (three studies); co-enzyme Q (one study); acetylcysteine (one study); bardoxolone methyl (one study); and human recombinant superoxide dismutase (two studies). Compared with placebo, antioxidant therapy showed no clear overall effect on cardiovascular mortality (RR 0.95, 95% CI 0.70 to 1.27; P = 0.71); all-cause mortality (RR 0.93, 95% CI 0.76 to 1.14; P = 0.48); cardiovascular disease (RR 0.78, 95% CI 0.52 to 1.18; P = 0.24); coronary heart disease (RR 0.71, 95% CI 0.42 to 1.23; P = 0.22); cerebrovascular disease (RR 0.91, 95% CI 0.63 to 1.32; P = 0.63); or peripheral vascular disease (RR 0.54, 95% CI 0.26 to 1.12; P = 0.10). Subgroup analyses found no evidence of significant heterogeneity based on proportions of males (P = 0.99) or diabetes (P = 0.87) for cardiovascular disease. There was significant heterogeneity for cardiovascular disease when studies were analysed by CKD stage (P = 0.003). Significant benefit was conferred by antioxidant therapy for cardiovascular disease prevention in dialysis patients (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001), although no effect was observed in CKD patients (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Antioxidant therapy was found to significantly reduce development of end-stage of kidney disease (ESKD) (RR 0.50, 95% CI 0.25 to 1.00; P = 0.05); lowered serum creatinine levels (MD 1.10 mg/dL, 95% CI 0.39 to 1.81; P = 0.003); and improved creatinine clearance (MD 14.53 mL/min, 95% CI 1.20 to 27.86; P = 0.03). Serious adverse events were not significantly increased by antioxidants (RR 2.26, 95% CI 0.74 to 6.95; P = 0.15). Risk of bias was assessed for all studies. Studies that were classified as unclear for random sequence generation or allocation concealment reported significant benefits from antioxidant therapy (RR 0.57, 95% CI 0.41 to 0.80; P = 0.001) compared with studies at low risk of bias (RR 1.06, 95% CI 0.84 to 1.32; P = 0.63). Authors' conclusions: Although antioxidant therapy does not reduce the risk of cardiovascular and all-cause death or major cardiovascular events in people with CKD, it is possible that some benefit may be present, particularly in those on dialysis. However, the small size and generally suboptimal quality of the included studies highlighted the need for sufficiently powered studies to confirm this possibility. Current evidence suggests that antioxidant therapy in predialysis CKD patients may prevent progression to ESKD; this finding was however based on a very small number of events. Further studies with longer follow-up are needed for confirmation. Appropriately powered studies are needed to reliably assess the effects of antioxidant therapy in people with CKD.

UR - http://www.scopus.com/inward/record.url?scp=84871865822&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871865822&partnerID=8YFLogxK

U2 - 10.1002/14651858.CD008176.pub2

DO - 10.1002/14651858.CD008176.pub2

M3 - Review article

C2 - 23076940

AN - SCOPUS:84871865822

VL - 2012

JO - Cochrane Database of Systematic Reviews

JF - Cochrane Database of Systematic Reviews

SN - 1361-6137

IS - 10

M1 - CD008176

ER -