Pentoxifylline for diabetic kidney disease

Dan Shan; Hong Mei Wu; Qi Yuan Yuan; Jun Li; Rong Le Zhou; Guan J Liu

doi:10.1002/14651858.CD006800.pub2

Pentoxifilina para la nefropatía diabética

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Referencias

References to studies included in this review

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estudios excluidos
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Aminorroaya A, Janghorbani M, Rezvanian H, Aminian T, Gharavi M, Amini M. Comparison of the effect of pentoxifylline and captopril on proteinuria in patients with type 2 diabetes mellitus. Nephron 2005;99(3):c73‐7. [MEDLINE: 15665549]

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References to other published versions of this review

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estudios incluidos
estudios excluidos
otras referencias

Wu HM, Yuan QY, Zhou RL, Li J, Liu GJ. Pentoxifylline for diabetic kidney disease. Cochrane Database of Systematic Reviews 4, Issue 2007. [DOI: 10.1002/14651858.CD006800]

PubMed

Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos

Aminorroaya 2005a

Methods	Study type: cross‐over RCT
Participants	Country: Iran Setting: one centre (hospital) Inclusion criteria: negative urine culture; no previous treatment; no serious intracranial or retinal haemorrhage, AMI or hypertension Number of patients randomised/analysed: 39/39 Age range: 34 to 75 years Males: 61% DM type: Type 2 DM duration: NS DKD stage: 4 (macroalbuminuria)
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d; oral Routine treatment Glycaemic control; antihypertensive drugs; weight management diet Duration: 2 months Control group Captopril Dose: 25 mg; 3 times/d; oral Routine treatment Glycaemic control; antihypertensive drugs; weight management diet Duration: 2 months
Outcomes	Change in kidney function: SCr, CrCl, proteinuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not describe sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not describe allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not describe blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided

Gan 2003

Methods	Study design: parallel RCT
Participants	Country: China Setting: inpatients and outpatients at one centre Number of patients randomised/analysed: 40/40 Age range: 49 to 71 years Males: 57% DM type: unclear DM duration: 6 to 18 years DKD stage: 3 and 4 (microalbuminuria and macroalbuminuria) Exclusion criteria: patients on dialysis; kidney transplantation wait lists
Interventions	Treatment group Pentoxifylline Dose: 100 mg; 4 times/d; oral Routine treatment: NS Duration: 6 months Control group Routine treatment: NS Duration: 6 months
Outcomes	Changes in kidney function: SCr, proteinuria/albuminuria
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not describe sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not describe allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not describe blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data
Selective reporting (reporting bias)	Unclear risk	Insufficient information. Some clinically important outcomes, such as adverse events, not reported
Other bias	Unclear risk	Insufficient information provided

Guerrero‐Romero 1995a

Methods	Study type: parallel RCT
Participants	Country: Mexico Setting: outpatients, 1 centre Number of patients randomised/analysed: 86/80 Age range: 20 to 71 years Males: 50% DM type: type 1 and type 2 DM duration: 2 to 18 years DKD stage: 3 and 4 (microalbuminuria or macroalbuminuria) Inclusion and exclusion criteria: not reported in detail
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d; oral Routine treatment Glycaemic control; weight maintaining diet Duration: 4 months Control group Placebo Routine treatment Glycaemic control; weight maintaining diet Duration: 4 months Patients were stratified based on DKD stage Type 1 microalbuminuria Type 1 overt proteinuria Type 2 microalbuminuria Type 2 overt proteinuria
Outcomes	Changes in kidney function: CrCl, proteinuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	Participants randomised = 86, but number analysed = 80. ITT analysis not conducted
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided

Harmankaya 2003

Methods	Study type: parallel RCT
Participants	Country: Turkey Setting: one centre Number of patients randomised/analysed: 50/50 Age range: 47 to 73 years Males: 62% DM: type 2 DM duration: 8 to 15 years DKD stage: 3 (microalbuminuria) Exclusion criteria: participants with history of MI, CVA and malignant hypertension
Interventions	Treatment group Pentoxifylline Dose: 600 mg/d; oral Routine treatment Lisinopril: 10 mg/d Glycaemic control Duration: 9 months Control group Routine treatment Lisinopril: 10 mg/d Glycaemic control Duration: 9 months
Outcomes	Change in kidney function: SCr, albuminuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided

Leyva‐Jimenez 2009

Methods	Study type: parallel RCT
Participants	Country: Mexico Setting: hospital, 1 centre Number of patients randomised/analysed: 37/34 Age range: 30 to 65 years Males: 82.3% DM: type 2 DM duration: > 7 years DKD stage: 3 or 4 (microalbuminuria or macroalbuminuria) Exclusion criteria: patients with hypertension and use of ACEi/ARB by the time of the study period or during the last 12 months
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d; oral Routine treatment Glycaemic control; diet control Duration: 12 months Control group Placebo Routine treatment Glycaemic control; diet control Duration:12 months Patients were stratified based on DKD stage Early DKD (microalbuminuria) Established DKD (macroalbuminuria or overt proteinuria)
Outcomes	Change in kidney function: UAE, CrCl
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Low risk	Participants and outcome assessors were blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	Participants randomised = 37, but number analysed = 34. ITT analysis not conducted
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided: adverse events not reported
Other bias	Unclear risk	Insufficient information provided

Navarro 1999a

Methods	Study type: parallel RCT
Participants	Country: Spain Setting: NS Number of patients randomised/analysed: 24/24 Age range: 53 to 77 years Males: 67% DM: type 1 DM duration: NS DKD stage: 4 (macroalbuminuria) Exclusion criteria: patients had no other significant known diseases
Interventions	Treatment group Pentoxifylline Dose: 400 mg/d; oral Routine treatment Glycaemic control; antihypertensive drugs (not including ACEi); diet control Duration: 2 months Control group Routine treatment Glycaemic control; antihypertensive drugs (not including ACEi); diet control Duration: 2 months
Outcomes	Change in kidney function: SCr, proteinuria BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided: e.g., adverse events were not reported
Other bias	Unclear risk	Insufficient information provided

Navarro 2003a

Methods	Study type: parallel RCT
Participants	Country: Spain Setting: outpatient Number of patients randomised/analysed: 45/45 Age range: 53 to 75 years Males: 53% DM: type 2 DM duration: 7 to 16 years DKD stage: 3 (microalbuminuria) Exclusion criteria: current acute illness (including infectious diseases); severe proteinuria (urinary protein excretion > 3 g/24 h); UTI; renal insufficiency (SCr > 132.6 μmol/L); CVD history (cardiac, cerebral, or peripheral vascular disease)
Interventions	Treatment group Pentoxifylline Dose: 1200 mg/d; oral Routine treatment Glycaemic control (insulin injection); antihypertensive drugs; diet control Duration: 4 months Control group Routine treatment Glycaemic control (insulin injection); antihypertensive drugs; diet control Duration: 4 months
Outcomes	Change in kidney function: SCr, proteinuria BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	After basal measurements, patients with DM were randomly assigned using a computer‐generated random‐number table to either a control (no treatment) or pentoxifylline (treatment) group based on a 1:2 split
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided: e.g. adverse events were not reported
Other bias	Unclear risk	Insufficient information provided

Navarro 2005a

Methods	Study type: parallel RCT
Participants	Country: Spain Setting: one centre Number of patients randomised/analysed: 61/61 Age range: 49 to 68 years Males: 51% DM: type 1 DM duration: 10 to 15 years Inclusion criteria: patients with no other kidney or urinary tract disease; presence of diabetic retinopathy; normal BP; normal kidney function (GFR ≥ 90 mL/min) and insufficient response to conventional therapy were included DKD stage: 4 (macroalbuminuria) Exclusion criteria: current acute illness (including infectious disease); CVD history (cardiac, cerebral, or peripheral vascular disease); history of cigarette smoking
Interventions	Treatment group Pentoxifylline Dose: 600 mg; twice/d; oral Routine treatment ARB; glycaemic control (insulin injection); diet control Duration: 4 months Control group Routine treatment ARB; glycaemic control (insulin injection); diet control Duration: 4 months
Outcomes	Change in kidney function: SCr, albuminuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	After an initial 2 weeks run‐in period, patients were randomised using a computer‐generated random‐number table into a control group or an active treatment group
Allocation concealment (selection bias)	Unclear risk	Study did not report on allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report on blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided

Pang 2003

Methods	Study type: parallel RCT
Participants	Country: China Setting: inpatients and outpatients Number of patients randomised/analysed: 60/60 Age range: 28 to 64 years Males: 62% DM: NS DM duration: 6 to 20 years DKD stage: 3 (microalbuminuria) Exclusion criteria: NS
Interventions	Treatment group Pentoxifylline Dose: 100 mg/d; IV; gtt Routine treatment Glycaemic control; antihypertensive drugs; diet control Duration: 21 days Control group Routine treatment Glycaemic control; antihypertensive drugs; diet control Duration: 21 days
Outcomes	Change in kidney function: albuminuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process.
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided

Pantoja 2003

Methods	Study type: parallel RCT
Participants	Country: Brazil Setting: NS Number of patients randomised/analysed: 14/14 Age range: 38 to 62 years Males: 50% DM: NS DM duration: NS DKD stage: 4 (macroalbuminuria) Exclusion criteria: NS
Interventions	Treatment group Pentoxifylline Dose: 400 mg/d; oral Routine treatment Glycaemic control; antihypertensive drugs (furosemide, amlodipine, enalapril); diet control Duration: 6 months Control group Routine treatment Glycaemic control; antihypertensive drugs (furosemide, amlodipine, enalapril); diet control Duration: 6 months
Outcomes	Change in kidney function: SCr, proteinuria BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment method
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Study did not report some important clinical outcomes, such as possible adverse events of pentoxifylline
Other bias	Unclear risk	Insufficient information provided

Rodriguez‐Moran 2005

Methods	Study type: parallel RCT
Participants	Country: Mexico Setting: outpatients Number of patients randomised/analysed: 130/130 Age range: 46 to 71 years Males: NS DM: type 2 DM duration: 2 to 16 years DKD stage: 3 (microalbuminuria) Exclusion criteria: hypertension and/or kidney failure and receiving ACEi or pentoxifylline
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d; oral Routine treatment 3 months before the study, all subjects received diet control and physical activity interventions, drug intervention included glibenclamide and metformin. Hypoglycaemic drug was not changed when the study began Duration: 6 months Control group Captopril Dose: 25 mg; 3 times/d Routine treatment 3 months before the study, all subjects received diet control and physical activity interventions, drug intervention included glibenclamide and metformin. Hypoglycaemic drug was not changed when the study began Duration: 6 months
Outcomes	Change in kidney function: SCr, albuminuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers were used to assign participants to pentoxifylline or captopril groups
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Low risk	Outcomes assessors were blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided for assessment

Rodriguez‐Moran 2006

Methods	Study type: parallel RCT
Participants	Country: Mexico Setting: NS Number of patients randomised/analysed: 40/40 Age range: 44 to 66 years Males: NS DM: type 2 DM duration: 4 to 12 years DKD stage: 3 (microalbuminuria) Exclusion criteria: hypertensive patients receiving ACEi, ARB and CCB, and those who previously received pentoxifylline; kidney failure or reduced kidney function; pregnancy; UTI; diuretic therapy; smoking
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d Routine treatment Glycaemic control; pretreatment serum glucose stabilisation 6 months before the study Duration: 4 months Control group Placebo Routine treatment Glycaemic control; pretreatment serum glucose stabilisation 6 months before the study Duration: 4 months
Outcomes	Change in kidney function: SCr, albuminuria Adverse events BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers used to assign participants to pentoxifylline or placebo groups
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Low risk	All participants and outcomes assessors were blinded to group assignment
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided for assessment

Solerte 1986

Methods	Study type: parallel RCT
Participants	Country: Italy Setting: outpatients Number of patients randomised/analysed: 82/82 Age range: 26 to 52 years Males: 48% DM: types 1 and 2 DM duration: 2 to 5 years DKD stage: 3 and 4 (microalbuminuria and macroalbuminuria) Exclusion criteria: NS
Interventions	Treatment group Pentoxifylline Dose: 1200 mg/d; oral Routine treatment Glycaemic control including insulin injection, tolbutamide, glibenclamide, glicazide, metformin Duration: 6 months Control group Routine treatment Glycaemic control including insulin injection, tolbutamide, glibenclamide, glicazide, metformin Duration: 6 months
Outcomes	Change in kidney function: proteinuria, albuminuria
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided: e.g., adverse events were not reported
Other bias	Unclear risk	Insufficient information provided for assessment

Solerte 1987

Methods	Study type: parallel RCT
Participants	Country: Italy Setting: outpatients: 1 centre Number of patients randomised/analysed: 21/21 Age range: 43 to 53 years Males: 38% DM: type 1 DM duration: 11 to 13 years DKD stage: 4 (macroalbuminuria) Exclusion criteria: NS
Interventions	Treatment group Pentoxifylline Dose:1200 mg/d; oral Routine treatment Glycaemic control: insulin injection Duration: 1 year Control group Other drugs Antihypertensive therapy Clonidine: 0.6 mg/d (8 patients) Methyldopa 1000 mg/d (3 patients) Routine treatment: Glycaemic control: insulin injection Duration: 1 year
Outcomes	Change in kidney function: CrCl Plasma fibrinogen
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided e.g. adverse events were not reported
Other bias	Unclear risk	Insufficient information provided for assessment

Sui 1999

Methods	Study type: parallel RCT
Participants	Country: China Setting: inpatients Number of patients randomised/analysed: 72/69 Age range: 38 to 76 years Males: 51% DM type: 2 DM duration: 6 to 21 years DKD stage: 3 or 4 (microalbuminuria or macroalbuminuria) Exclusion criteria: NS
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d; oral Routine treatment: NS Duration: 4 months Control group Routine treatment: NS Duration: 4 months
Outcomes	Change in kidney function: proteinuria, albuminuria Pentoxifylline adverse events
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	Participants randomised = 72, but number analysed = 69. ITT analysis not conducted
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided for assessment

Zang 1999

Methods	Study type: parallel RCT
Participants	Country: China Setting: NS Number of patients randomised: 84/77 Age range: 34 to 51 years Males: 55% DM type: 2 DM duration: NS Stage of DKD: 3 (microalbuminuria) Exclusion criteria: hypertension; lipid disorders; hepatic; kidney function damage; infectious diseases; other primary and secondary kidney or urological diseases
Interventions	Treatment group Pentoxifylline Dose: 400 mg; 3 times/d Routine treatment Glycaemic control Duration: 6 months Control group Placebo Routine treatment Glycaemic control Duration: 6 months
Outcomes	Change in kidney function: SCr, albuminuria Adverse events BP (mean arterial pressure)
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	High risk	Participants randomised = 84, but number analysed = 77. ITT analysis was not conducted
Selective reporting (reporting bias)	Low risk	Free of selective reporting
Other bias	Unclear risk	Insufficient information provided for assessment

Zhang 2001

Methods	Study type: parallel RCT
Participants	Country: China Setting: NS Number of patients randomised/analysed: 106/106 Age range: 56 to 72 years Males: 57% DM type: 2 DM duration: 5 to 17 years DKD stage: 3 (microalbuminuria) Exclusion criteria: severe complications (heart, brain, lung, liver and kidney damage); bleeding and receiving anticoagulation therapy; ACEi
Interventions	Treatment group Pentoxifylline Dose: 400 mg; twice/d; oral Routine treatment Glycaemic control; antihypertensive drugs Duration: 6 months Control group Captopril Dose: 2.5 mg; 3 times/d Routine treatment Glycaemic control; antihypertensive drugs Duration: 6 months
Outcomes	Change in kidney function: CrCl, proteinuria/albuminuria BP
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Study did not report sequence generation process
Allocation concealment (selection bias)	Unclear risk	Study did not report allocation concealment
Blinding (performance bias and detection bias) All outcomes	Unclear risk	Study did not report blinding
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcomes data reported
Selective reporting (reporting bias)	Unclear risk	Insufficient information provided: e.g. adverse events were not reported
Other bias	Unclear risk	Insufficient information provided for assessment

ACEi: angiotensin converting enzyme inhibitors; AMI: acute myocardial infarction; ARB: angiotensin receptor blockers; BP: blood pressure; CCB: calcium channel blockers; CrCl: creatinine clearance; CVA: cardiovascular accident; DKD: diabetic kidney disease; DM: diabetes mellitus; GFR: glomerular filtration rate; gtt: guttae (drops); IV: intravenous; MI: myocardial infarction; NS: not stated; RCT: randomised controlled trial; SCr: serum creatinine; UAE: urinary albumin excretion; UTI: urinary tract infection

Characteristics of excluded studies [ordered by study ID]

Ir a:

estudios incluidos

Study	Reason for exclusion
Cen 2005	Questionable randomisation
Chua 1995	Questionable randomisation
Demir 2007	Participants were kidney transplant recipients with unknown underlying kidney diseases
Diao 2003	Questionable randomisation
Diskin 2007	Not RCT
Garg 1998	Participants Included diabetic retinopathy and/or DKD. Separate data not available for DKD
Gonzalez‐Espinoza 2008	Haemodialysis patients
Laczy 2009	Participants diagnosed with type 2 DM and diabetic neuropathy, not DKD
Lin 2008	Participants with moderate‐advanced CKD due to multiple causes. Separate data not available for DKD
Maiti 2007	Participants diagnosed with type 2 DM, not DKD
Mooraki 2006	Questionable randomisation
Navarro 1998	Participants diagnosed with advanced kidney failure due to multiple causes. Separate data not available for DKD
Paap 1996	Not RCT
Perkins 2009	Participants diagnosed with progressive CKD due to multiple causes. Separate data not available for DKD

CKD: chronic kidney disease; DKD: diabetic kidney disease; DM: diabetes mellitus; RCT: randomised controlled trial

Data and analyses

Open in table viewer

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]
Open in figure viewer Analysis 1.1 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 1 Serum creatinine at end of treatment.
2 Creatinine clearance at end of treatment Show forest plot	1	94	Mean Difference (IV, Random, 95% CI)	‐5.18 [‐15.55, 5.18]
Open in figure viewer Analysis 1.2 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
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]
Open in figure viewer Analysis 1.3 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 3 Albuminuria at end of treatment.
4 Overt proteinuria at end of treatment Show forest plot	1	46	Mean Difference (IV, Random, 95% CI)	‐428.58 [‐661.65, ‐195.50]
Open in figure viewer Analysis 1.4 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 4 Overt proteinuria at end of treatment.
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]
Open in figure viewer Analysis 1.5 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 5 Systolic BP at end of treatment.
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]
Open in figure viewer Analysis 1.6 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 6 Diastolic BP at end of treatment.
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]
Open in figure viewer Analysis 1.7 Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 7 Any adverse events at end of treatment.

Open in table viewer

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]
Open in figure viewer Analysis 2.1 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 1 Serum creatinine at end of treatment.
2 Change in albuminuria Show forest plot	4	220	Std. Mean Difference (IV, Random, 95% CI)	0.62 [0.18, 1.07]
Open in figure viewer Analysis 2.2 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 2 Change in albuminuria.
3 Change in proteinuria Show forest plot	5	192	Mean Difference (IV, Random, 95% CI)	0.46 [0.17, 0.74]
Open in figure viewer Analysis 2.3 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 3 Change in proteinuria.
4 Systolic BP at end of treatment Show forest plot	5	240	Mean Difference (IV, Random, 95% CI)	‐0.28 [‐2.20, 1.63]
Open in figure viewer Analysis 2.4 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 4 Systolic BP at end of treatment.
5 Diastolic BP at end of treatment Show forest plot	5	240	Mean Difference (IV, Random, 95% CI)	‐0.15 [‐1.44, 1.14]
Open in figure viewer Analysis 2.5 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 5 Diastolic BP at end of treatment.
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]
Open in figure viewer Analysis 2.6 Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 6 Any adverse events at end of treatment.

Open in table viewer

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]
Open in figure viewer Analysis 3.1 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 1 Serum creatinine at end of treatment.
2 Creatinine clearance at end of treatment Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Subtotals only
Open in figure viewer Analysis 3.2 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 2 Creatinine clearance at end of treatment.
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]
Open in figure viewer Analysis 3.3 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 3 Albuminuria at end of treatment.
4 Proteinuria at end of treatment Show forest plot	2	145	Mean Difference (IV, Random, 95% CI)	‐0.01 [‐0.03, 0.01]
Open in figure viewer Analysis 3.4 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 4 Proteinuria at end of treatment.
5 Systolic BP at end of treatment Show forest plot	3	272	Mean Difference (IV, Random, 95% CI)	1.46 [‐0.57, 3.50]
Open in figure viewer Analysis 3.5 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 5 Systolic BP at end of treatment.
6 Diastolic BP at end of treatment Show forest plot	3	272	Mean Difference (IV, Random, 95% CI)	1.37 [‐0.23, 2.98]
Open in figure viewer Analysis 3.6 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 6 Diastolic BP at end of treatment.
7 Plasma fibrinogen at end of treatment Show forest plot	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.7 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 7 Plasma fibrinogen at end of treatment.
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]
Open in figure viewer Analysis 3.8 Comparison 3 Pentoxifylline + routine treatment versus other drugs + routine treatment, Outcome 8 Adverse events at end of treatment.

Figure 1

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

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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.

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Figure 3

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

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Analysis 1.1

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

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Analysis 1.3

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

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Analysis 1.5

Comparison 1 Pentoxifylline + routine treatment versus placebo + routine treatment, Outcome 5 Systolic 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.

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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.

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Analysis 2.1

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

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Analysis 2.2

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

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Analysis 2.3

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

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Analysis 2.4

Comparison 2 Pentoxifylline + routine treatment versus routine treatment, Outcome 4 Systolic 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.

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Analysis 2.6

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

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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.

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Analysis 3.3

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

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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.

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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.

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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.

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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.

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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]

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

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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]

Comparison 2. Pentoxifylline + routine treatment versus routine treatment

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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]

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

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Referencias

References to studies included in this review

Aminorroaya 2005a {published data only}

Gan 2003 {published data only}

Guerrero‐Romero 1995a {published data only}

Harmankaya 2003 {published data only}

Leyva‐Jimenez 2009 {published data only}

Navarro 1999a {published data only}

Navarro 2003a {published data only}

Navarro 2005a {published data only}

Pang 2003 {published data only}

Pantoja 2003 {published data only}

Rodriguez‐Moran 2005 {published data only}

Rodriguez‐Moran 2006 {published data only}

Solerte 1986 {published data only}

Solerte 1987 {published data only}

Sui 1999 {published data only}

Zang 1999 {published data only}

Zhang 2001 {published data only}

References to studies excluded from this review

Cen 2005 {published data only}

Chua 1995 {published data only}

Demir 2007 {published data only}

Diao 2003 {published data only}

Diskin 2007 {published data only}

Garg 1998 {published data only}

Gonzalez‐Espinoza 2008 {published data only}

Laczy 2009 {published data only}

Lin 2008 {published data only}

Maiti 2007 {published data only}

Mooraki 2006 {published data only}

Navarro 1998 {published data only}

Paap 1996 {published data only}

Perkins 2009 {published data only}

Additional references

ADA 1997

ADA 2004

Aminorroaya 2005b

Bruno 2003

Chantrel 1999

Chen 1996

Chen 1999

Chen 2004

Collins 2005

de Zeeuw 2007

Eijkelkamp 2007

Festa 2000

Guerrero‐Romero 1995b

Han 2010

Higgins 2003

Higgins 2011

Hrobjartsson 2001

Jones 1996

KDOQI 2004

KDOQI 2007

Kjaergard 1999

Lin 2002

McCormick 2008

McCullough 2004

Middleton 2006

Mogensen 1997

Moher 1998

Navaneethan 2009

Navarro 1999b

Navarro 2003b

Navarro 2003c

Navarro 2003d

Navarro 2005b

Navarro 2006

Navarro‐Gonzalez 2008

Olsen 2006

Rabbani 2009

Ritz 1999a

Ritz 1999b

Ritz 2006

Rivero 2009

Robertson 2007

Rochon 1999