Pentoxifylline for Anemia in Chronic Kidney Disease: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Pentoxifylline (PTX) is a promising therapeutic approach for reducing inflammation and improving anemia associated to various systemic disorders. However, whether this agent may be helpful for anemia management also in CKD patients is still object of debate.</p><p>Study Design</p><p>Systematic review and meta-analysis.</p><p>Population</p><p>Adults with CKD (any KDOQI stage, including ESKD patients on regular dialysis) and anemia (Hb<13 g/dL in men or < 12 g/dL in women).</p><p>Search Strategy and Sources</p><p>Cochrane CENTRAL, EMBASE, Ovid-MEDLINE and PubMed were searched for studies providing data on the effects of PTX on anemia parameters in CKD patients without design or follow-up restriction.</p><p>Intervention</p><p>PTX derivatives at any dose regimen.</p><p>Outcomes</p><p>Hemoglobin, hematocrit, ESAs dosage and resistance (ERI), iron indexes (ferritin, serum iron, TIBC, transferrin and serum hepcidin) and adverse events.</p><p>Results</p><p>We retrieved 11 studies (377 patients) including seven randomized controlled trials (all comparing PTX to placebo or standard therapy) one retrospective case-control study and three prospective uncontrolled studies. Overall, PTX increased hemoglobin in three uncontrolled studies but such improvement was not confirmed in a meta-analysis of seven studies (299 patients) (MD 0.12 g/dL, 95% CI -0.22 to 0.47). Similarly, there were no conclusive effects of PTX on hematocrit, ESAs dose, ferritin and TSAT in pooled analyses. Data on serum iron, ERI, TIBC and hepcidin were based on single studies. No evidence of increased rate of adverse events was also noticed.</p><p>Limitations</p><p>Small sample size and limited number of studies. High heterogeneity among studies with respect to CKD and anemia severity, duration of intervention and responsiveness/current therapy with iron or ESAs.</p><p>Conclusions</p><p>There is currently no conclusive evidence supporting the utility of pentoxifylline for improving anemia control in CKD patients. Future trials designed on hard, patient-centered outcomes with larger sample size and longer follow-up are advocated.</p></div

Study selection flow.

<p>Study selection flow.</p

Effects of pentoxifylline vs. placebo/standard treatment on ferritin.

<p>Effects of pentoxifylline vs. placebo/standard treatment on ferritin.</p

Effects of pentoxifylline vs. placebo/standard treatment on TSAT.

<p>Effects of pentoxifylline vs. placebo/standard treatment on TSAT.</p

Effects of pentoxifylline vs. placebo/standard treatment on hematocrit.

<p>Effects of pentoxifylline vs. placebo/standard treatment on hematocrit.</p

Antioxidant agents for delaying diabetic kidney disease progression: A systematic review and meta-analysis

<div><p>Background</p><p>Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression.</p><p>Study design</p><p>Systematic review and meta-analysis.</p><p>Population</p><p>Adults with DKD (either secondary to type 1 or 2 diabetes mellitus)</p><p>Search strategy and sources</p><p>Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction.</p><p>Intervention</p><p>Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination.</p><p>Outcomes</p><p>Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function.</p><p>Results</p><p>From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m²; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking.</p><p>Limitations</p><p>Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy.</p><p>Conclusions</p><p>In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression.</p></div

Effect of antioxidants vs. control on renal function (GFR).

<p>Effect of antioxidants vs. control on renal function (GFR).</p

Summary of findings (GRADE) table.

<p>Summary of findings (GRADE) table.</p

Effect of antioxidants vs. control on urinary albumin (2a); sensitivity analyses on separate effects by Vitamin E (2b) and Vitamin C supplements (2c).

<p>Effect of antioxidants vs. control on urinary albumin (2a); sensitivity analyses on separate effects by Vitamin E (2b) and Vitamin C supplements (2c).</p

Publication bias (funnel plot) for urinary albumin.

<p>Publication bias (funnel plot) for urinary albumin.</p