Table 2. Summary of the main characteristics of the randomized studies reviewed.
| Study, year (ref) | Study population | Population characteristics | Duration | Intervention | Comparator | Outcome(s) | Results |
|---|---|---|---|---|---|---|---|
| Navarro et al. 1999 [18] | Anemic patients with advanced CKD (CCr<30 mL/min), no clinical evidence of blood losses and normal iron status (serum ferritin>50 ng/mL and TSAT>20%) | N = 12, Men(%) = 58, Age = 65±7 yrs, Hb (g/dL) = 10±0.6, Ferritin (ng/mL) = 84±12, TSAT(%) = 28±4, CCr(mL/min) = 25±4 | 6 months | Pentoxifylline 400 mg/day (n = 7) | Placebo (n = 5) | Hemoglobin (g/dL) | -Significant increase (from 9.9 ±0.5 to 10.6±0.6, p<0.01) in PTX group-No changes in controls |
| Hematocrit (%) | -Significant increase (from 27.9 ±1.6 to 31.3±1.9, p<0.01) in PTX group-No changes in controls | ||||||
| Perkins et al. 2009 [19] | Hypertensive patients (age>18 yrs) with decreased GFR and proteinuria >1 g/24h treated with RAS blockers | N = 39, Men(%) = 62, Age = 64.3 yrs, Hct (%) = 34.3 | 12 months | Pentoxifylline 400 mg/twice a day (n = 22) | Placebo (n = 17) | Hematocrit (%) | No difference between groups at the end of the study (33±5.9 vs. 34.1±4.9 in PTX vs. PLB, p = 0.3) |
| Gonzalez-Espinoza et al. 2012 [20] | Patients on chronic HD for at least 2 months, age ≥18 yrs | N = 36, Men(%) = 69, Age = 35.3 yrs | 4 months | Pentoxifylline 400 mg/ day (n = 18) | Placebo (n = 18) | ESA dose (IU/Kg) | No difference between groups [50 (0–60) vs. 50 (0–60)] and within groups [50 (0–60) vs. 50 (0–60) and 50 (47–60) vs. 50 (0–60) in PTX and PLB respectively, p = NS] at the end of the study |
| Hemoglobin (g/dL) | No difference between groups (9.6±1.9 vs. 10.5±2.7) and within groups (10.6±1.8 vs 9.6±1.9 and 10.7±2.1 vs. 10.5±2.7 in PTX and PLB respectively, p = NS) at the end of study | ||||||
| Mortazavi et al. 2012 [21] | Patients on chronic HD patients for at least 1 month with Hb <10.7 g/dL at least 2 times | N = 50, Men(%) = 66, Age = 57.2yrs | 6 months | Pentoxifylline 400 mg/a day (n = 25) | Placebo (n = 25) | Hemoglobin(g/dL) | No changes in both groups |
| Serum iron (mg/dL) | Changes at the end of the study were significantly different between groups (-62±56.8 vs -13.2±47.1 in PTX vs PLB, p = 0.005) | ||||||
| TIBC | No difference in changes between groups | ||||||
| Ferritin (ng/mL) | No difference in changes between groups | ||||||
| ESA dose (UI/Kg) | No difference in changes between groups | ||||||
| AIONID 2013 [22] | Chronic HD patients with serum albumin <4.0 g/dL persisting for at least 3 months | N = 43, Men(%) = 58, Age = 61yrs, DM(%) = 67 | 16 weeks | Pentoxifylline 400 mg/day (n = 22) | Placebo (n = 21) | Hemoglobin (g/dL) | Changes at the end of the study were not significantly different between groups |
| Ferritin (ng/mL) | -Increase from 464±301 to 789±396 in PTX group-Decrease from 673±304 to 640±357 in PLB group | ||||||
| TSAT (%) | -Increase from 26±12 to 32±9 in PTX group-Increase from 32±16 to 35±22 in PLB group | ||||||
| Antunes et al. 2014 [23] | Chronic HD patients with CRP≥0.5 mg/dL in screening test | N = 71, Men (%) = 64,Age = 55.7 yrs, DM(%) = 20, Hb (mg/dL) = 10.95, Ferritin (ng/dL) = 328.5, TSAT(%) = 31.4, Hepcidin (ng/mL) = 127.7 | 3 months | Pentoxifylline (400mg/thrice weekly) (n = 35) | Standard therapy (n = 36) | Hemoglobin (g/dL) | No difference between groups at the end of the study |
| TSAT (%) | No difference between groups at the end of the study | ||||||
| Hepcidin (ng/mL) | No difference between groups at the end of the study | ||||||
| HERO 2015 [24] | Patients with CKD stage 4–5, (including HD) with ESA-hyporesponsive anemia (hemoglobin ≤120 g/L and ESA resistance index ≥1.0 IU/kg/wk/g/L for erythropoietin-treated patients and ≥0.005 mg/kg/wk/g/L for darbepoetin-treated patients) | N = 53, Men(%) = 45, Age = 62.1 yrs, DM(%) = 47, Hb (g/L) = 106, Serum ferritin (mcg/L) = 486.5, ESA dose (IU/kg/wk) = 236, ERI (IU/kg/wk/g/L) = 2.37 | 4 months | Pentoxifylline (400 mg/day) (n = 26) | Placebo (n = 27) | ERI (IU/kg/wk/g/L) | No difference between groups (data adjusted for baseline values) |
| Hemoglobin (g/L) | Significant differences between groups (110.9 vs 103.2 in PTX vs PLB, p = 0.01; data adjusted for baseline values) | ||||||
| ESA dose (IU/kg/wk) | No difference between groups (data adjusted for baseline values) | ||||||
| Serum ferritin (mcg/L) | No difference between groups (data adjusted for baseline values) | ||||||
| TSAT (%) | No difference between groups (data adjusted for baseline values) |
Legend: CCr: creatinine clearance, CKD: chronic kidney disease, CRP: C-reactive protein, DM: diabetes mellitus, ERI: erythropoiesis-stimulating agent resistance index, ESA: erythropoiesis-stimulating agent, GFR: glomerular filtration rate, Hb: hemoglobin, Hct: hematocrit, HD: hemodialysis, IU: international units, PLB: placebo, PTX: pentoxifylline, RAS: Renin-Angiotensin-System, TIBC: Total Iron Binding Capacity, TSAT: transferrin saturation.