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Meta-Analysis
. 2012 Feb 15;2012(2):CD006800.
doi: 10.1002/14651858.CD006800.pub2.

Pentoxifylline for diabetic kidney disease

Dan Shan  1 , Hong Mei Wu, Qi Yuan Yuan, Jun Li, Rong Le Zhou, Guan J Liu
Affiliations
Meta-Analysis

Pentoxifylline for diabetic kidney disease

Dan Shan et al. Cochrane Database Syst Rev. .

Abstract

Background: Diabetic kidney disease (DKD) is associated with increased morbidity and mortality, mostly relating to cardiovascular complications. The relevance of inflammation in the pathogenesis of DKD has been investigated in recent years, and it has been shown that inflammatory markers are higher in people with DKD compared with the wider population. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with favourable anti-inflammatory effects and immunoregulatory properties. The anti-inflammatory effects conferred by pentoxifylline may be beneficial in the management of DKD.

Objectives: To assess the benefits and harms of pentoxifylline for treating people with DKD.

Search methods: We searched the Cochrane Renal Group's specialised register (January 2012), CENTRAL (Issue 12, 2011), MEDLINE, EMBASE and four Chinese biomedical literature databases (CBM-disc, 1979 to July 2009), Chinese Science and Technique Journals Database (VIP, until July 2009), China National Knowledge Infrastructure (CNKI, until July 2009) and WanFang database (until July 2009).

Selection criteria: All randomised controlled trials (RCTs) and quasi-RCTs studying the benefits and harms of pentoxifylline for DKD.

Data collection and analysis: Data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome in sufficiently similar patients. Results of dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Mean differences (MD) were calculated to assess the effects of treatment where outcomes were expressed on continuous scales, and standardised mean differences (SMD) calculated where different scales were used. Data was pooled using the random effects model. Adverse effects were assessed using descriptive techniques and where possible, risk differences (RD) with 95% CI.

Main results: We identified 17 studies that included a total of 991 participants with DKD which met our inclusion criteria. Overall, the methodological quality of included studies was low: 4/17 reported the method of randomisation, 13/17 did not; no study described the method of random allocation; 4/17 studies were considered to be at high risk of bias and 13/17 were considered to have unclear risk for incomplete outcome data reporting; 9/17 studies were at low risk bias and in 8/17 the risk of bias was unclear for selective outcome reporting.Compared with placebo, pentoxifylline significantly reduced serum creatinine (SCr) (MD -0.10 mg/dL, 95% CI -0.17 to -0.03), albuminuria (SMD -2.28, 95% CI -3.85 to -0.70) and overt proteinuria (MD -428.58 µg/min, 95% CI -661.65 to -195.50), but there was no difference in creatinine clearance (CrCl) (MD -5.18 mL/min, 95% CI -15.55 to 5.19). When compared with routine treatment alone, pentoxifylline did not significantly reduce SCr (MD 0.00 mg/dL, 95% CI -0.06 to 0.07) or blood pressure (systolic (SBP): MD -0.28 mm Hg, 95% CI -2.20 to 1.63; diastolic (DBP): MD -0.15 mm Hg, 95% CI -1.44 to 1.14), but did significantly reduce albuminuria (SMD 0.62, 95% CI 0.18 to 1.07) and proteinuria (MD 0.46 g/24 h, 95% CI 0.17 to 0.74). There was no significant difference in SCr (MD 0.00 mg/dL, 95% CI -0.08 to 0.07), albuminuria (MD -8.79 µg/min, 95% CI -27.18 to 9.59), proteinuria (MD -0.01 g/24 h, 95% CI -0.03 to 0.01) or blood pressure (SBP: MD 1.46 mm Hg, 95% CI -0.57 to 3.50; DBP: MD 1.37 mm Hg, 95% CI -0.23 to 2.98) between pentoxifylline and the active comparator (captopril or clonidine/methyldopa) for patients with type 1 and type 2 DKD. CrCl was significantly increased when pentoxifylline was compared to clonidine/methyldopa (MD 10.90 mL/min, 95% CI -1.40 to 20.40) but not with captopril (MD 3.26 mL/min, 95% CI -1.05 to 7.59). No data were available on the incidence of end-stage kidney disease (ESKD), time to ESKD, quality of life, or all-cause mortality. The adverse events of pentoxifylline were mild; no serious adverse events were reported in any of the included studies.

Authors' conclusions: From the available evidence, pentoxifylline seems to offer some beneficial effects in renal function improvement and reduction in albuminuria and proteinuria, with no obvious serious adverse effects for patients with DKD. However, most studies were poorly reported, small, and methodologically flawed. Evidence to support the use of pentoxifylline for DKD was insufficient to develop recommendations for its use in this patient population. Rigorously designed, randomised, multicentre, large scale studies of pentoxifylline for DKD are needed to further assess its therapeutic effects.

PubMed Disclaimer

Conflict of interest statement

  1. Dan Shan: None known

  2. Hong Mei Wu: None known

  3. Qi Yuan Yuan: None known

  4. Jun Li: None known

  5. Rong Le Zhou: None known

  6. Guan J Liu: None known

Figures

1
1
Study flow diagram: pentoxifylline for diabetic kidney disease (DKD)
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 1 Serum creatinine at end of treatment.
1.2
1.2. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
1.3
1.3. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 3 Albuminuria at end of treatment.
1.4
1.4. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 4 Overt proteinuria at end of treatment.
1.5
1.5. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 5 Systolic BP at end of treatment.
1.6
1.6. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 6 Diastolic BP at end of treatment.
1.7
1.7. Analysis
Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 7 Any adverse events at end of treatment.
2.1
2.1. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 1 Serum creatinine at end of treatment.
2.2
2.2. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 2 Change in albuminuria.
2.3
2.3. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 3 Change in proteinuria.
2.4
2.4. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 4 Systolic BP at end of treatment.
2.5
2.5. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 5 Diastolic BP at end of treatment.
2.6
2.6. Analysis
Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 6 Any adverse events at end of treatment.
3.1
3.1. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 1 Serum creatinine at end of treatment.
3.2
3.2. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
3.3
3.3. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 3 Albuminuria at end of treatment.
3.4
3.4. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 4 Proteinuria at end of treatment.
3.5
3.5. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 5 Systolic BP at end of treatment.
3.6
3.6. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 6 Diastolic BP at end of treatment.
3.7
3.7. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 7 Plasma fibrinogen at end of treatment.
3.8
3.8. Analysis
Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 8 Adverse events at end of treatment.
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD006800

References

References to studies included in this review

Aminorroaya 2005a {published data only}
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Gan 2003 {published data only}
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Guerrero‐Romero 1995a {published data only}
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Harmankaya 2003 {published data only}
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Navarro 2003a {published data only}
    1. Navarro JF, Mora C, Muros M, Maca M, Garca J. Effects of pentoxifylline administration on urinary N‐acetyl‐beta‐glucosaminidase excretion in type 2 diabetic patients: a short‐term, prospective, randomized study. American Journal of Kidney Diseases 2003;42(2):264‐70. [MEDLINE: ] - PubMed
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References to studies excluded from this review

Cen 2005 {published data only}
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Demir 2007 {published data only}
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Diao 2003 {published data only}
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Diskin 2007 {published data only}
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