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Study flow diagram: pentoxifylline for diabetic kidney disease (DKD)
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Figure 1

Study flow diagram: pentoxifylline for diabetic kidney disease (DKD)

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 1 Serum creatinine at end of treatment.
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Analysis 1.1

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 1 Serum creatinine at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
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Analysis 1.2

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 2 Creatinine clearance at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 3 Albuminuria at end of treatment.
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Analysis 1.3

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 3 Albuminuria at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 4 Overt proteinuria at end of treatment.
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Analysis 1.4

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 4 Overt proteinuria at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 5 Systolic BP at end of treatment.
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Analysis 1.5

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 5 Systolic BP at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 6 Diastolic BP at end of treatment.
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Analysis 1.6

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 6 Diastolic BP at end of treatment.

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 7 Any adverse events at end of treatment.
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Analysis 1.7

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 7 Any adverse events at end of treatment.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 1 Serum creatinine at end of treatment.
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Analysis 2.1

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 1 Serum creatinine at end of treatment.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 2 Change in albuminuria.
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Analysis 2.2

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 2 Change in albuminuria.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 3 Change in proteinuria.
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Analysis 2.3

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 3 Change in proteinuria.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 4 Systolic BP at end of treatment.
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Analysis 2.4

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 4 Systolic BP at end of treatment.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 5 Diastolic BP at end of treatment.
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Analysis 2.5

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 5 Diastolic BP at end of treatment.

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 6 Any adverse events at end of treatment.
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Analysis 2.6

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 6 Any adverse events at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 1 Serum creatinine at end of treatment.
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Analysis 3.1

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 1 Serum creatinine at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
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Analysis 3.2

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 2 Creatinine clearance at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 3 Albuminuria at end of treatment.
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Analysis 3.3

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 3 Albuminuria at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 4 Proteinuria at end of treatment.
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Analysis 3.4

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 4 Proteinuria at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 5 Systolic BP at end of treatment.
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Analysis 3.5

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 5 Systolic BP at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 6 Diastolic BP at end of treatment.
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Analysis 3.6

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 6 Diastolic BP at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 7 Plasma fibrinogen at end of treatment.
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Analysis 3.7

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 7 Plasma fibrinogen at end of treatment.

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 8 Adverse events at end of treatment.
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Analysis 3.8

Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 8 Adverse events at end of treatment.

Comparison 1. Pentoxifylline + routine treatment versus placebo + routine treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Serum creatinine at end of treatment Show forest plot

2

117

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.17, ‐0.03]

2 Creatinine clearance at end of treatment Show forest plot

1

94

Mean Difference (IV, Random, 95% CI)

‐5.18 [‐15.55, 5.18]

2.1 Type 2 microalbuminuria

1

30

Mean Difference (IV, Random, 95% CI)

‐12.0 [‐27.42, 3.42]

2.2 Type 2 proteinuria

1

22

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐21.66, 19.66]

2.3 Type 1 albuminuria

1

18

Mean Difference (IV, Random, 95% CI)

2.0 [‐21.59, 25.59]

2.4 Type 1 proteinuria

1

24

Mean Difference (IV, Random, 95% CI)

1.0 [‐31.19, 33.19]

3 Albuminuria at end of treatment Show forest plot

2

117

Std. Mean Difference (IV, Random, 95% CI)

‐2.28 [‐3.85, ‐0.70]

4 Overt proteinuria at end of treatment Show forest plot

1

46

Mean Difference (IV, Random, 95% CI)

‐428.58 [‐661.65, ‐195.50]

4.1 Type 2 proteinuria

1

22

Mean Difference (IV, Random, 95% CI)

‐552.0 [‐656.57, ‐447.43]

4.2 Type 1 proteinuria

1

24

Mean Difference (IV, Random, 95% CI)

‐314.0 [‐367.36, ‐260.64]

5 Systolic BP at end of treatment Show forest plot

2

126

Mean Difference (IV, Random, 95% CI)

‐1.29 [‐11.80, 9.23]

5.1 Type 2 microalbuminuria

2

62

Mean Difference (IV, Random, 95% CI)

10.15 [‐15.27, 35.58]

5.2 Type 2 proteinuria

1

22

Mean Difference (IV, Random, 95% CI)

5.0 [‐4.19, 14.19]

5.3 Type 1 microalbuminuria

1

18

Mean Difference (IV, Random, 95% CI)

‐6.0 [‐11.08, ‐0.92]

5.4 Type 1 proteinuria

1

24

Mean Difference (IV, Random, 95% CI)

‐22.0 [‐31.41, ‐12.59]

6 Diastolic BP at end of treatment Show forest plot

2

126

Mean Difference (IV, Random, 95% CI)

‐5.75 [‐9.56, ‐1.94]

6.1 Type 2 microalbuminuria

2

62

Mean Difference (IV, Random, 95% CI)

‐3.17 [‐7.98, 1.64]

6.2 Type 2 proteinuria

1

22

Mean Difference (IV, Random, 95% CI)

‐1.0 [‐8.07, 6.07]

6.3 Type 1 microalbuminuria

1

18

Mean Difference (IV, Random, 95% CI)

‐9.0 [‐14.55, ‐3.45]

6.4 Type 1 proteinuria

1

24

Mean Difference (IV, Random, 95% CI)

‐11.0 [‐18.23, ‐3.77]

7 Any adverse events at end of treatment Show forest plot

2

83

Risk Difference (M‐H, Random, 95% CI)

0.10 [‐0.10, 0.30]

Figures and Tables -
Comparison 1. Pentoxifylline + routine treatment versus placebo + routine treatment
Comparison 2. Pentoxifylline + routine treatment versus routine treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Serum creatinine at end of treatment Show forest plot

5

199

Mean Difference (IV, Random, 95% CI)

0.00 [‐0.06, 0.07]

2 Change in albuminuria Show forest plot

4

220

Std. Mean Difference (IV, Random, 95% CI)

0.62 [0.18, 1.07]

3 Change in proteinuria Show forest plot

5

192

Mean Difference (IV, Random, 95% CI)

0.46 [0.17, 0.74]

4 Systolic BP at end of treatment Show forest plot

5

240

Mean Difference (IV, Random, 95% CI)

‐0.28 [‐2.20, 1.63]

5 Diastolic BP at end of treatment Show forest plot

5

240

Mean Difference (IV, Random, 95% CI)

‐0.15 [‐1.44, 1.14]

6 Any adverse events at end of treatment Show forest plot

3

190

Risk Difference (M‐H, Random, 95% CI)

0.11 [‐0.01, 0.22]

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Comparison 2. Pentoxifylline + routine treatment versus routine treatment
Comparison 3. Pentoxifylline + routine treatment versus other drugs + routine treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Serum creatinine at end of treatment Show forest plot

2

166

Mean Difference (IV, Random, 95% CI)

‐0.00 [‐0.08, 0.07]

2 Creatinine clearance at end of treatment Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Compared with ACEi

2

145

Mean Difference (IV, Random, 95% CI)

3.26 [‐1.05, 7.58]

2.2 Compared with clonidine or methyldopa

1

21

Mean Difference (IV, Random, 95% CI)

10.90 [1.40, 20.40]

3 Albuminuria at end of treatment Show forest plot

2

233

Mean Difference (IV, Random, 95% CI)

‐8.79 [‐27.18, 9.59]

4 Proteinuria at end of treatment Show forest plot

2

145

Mean Difference (IV, Random, 95% CI)

‐0.01 [‐0.03, 0.01]

5 Systolic BP at end of treatment Show forest plot

3

272

Mean Difference (IV, Random, 95% CI)

1.46 [‐0.57, 3.50]

6 Diastolic BP at end of treatment Show forest plot

3

272

Mean Difference (IV, Random, 95% CI)

1.37 [‐0.23, 2.98]

7 Plasma fibrinogen at end of treatment Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

8 Adverse events at end of treatment Show forest plot

2

166

Risk Difference (M‐H, Random, 95% CI)

‐0.07 [‐0.15, 0.01]

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Comparison 3. Pentoxifylline + routine treatment versus other drugs + routine treatment