Table 1.
Main clinical and experimental studies on the use of pentoxifylline in DKD
| Ref. | Type of study | Type of intervention | Population | Treatment | Main effects of PTF |
|---|---|---|---|---|---|
| Clinical studies | |||||
| [84] | RCT | PTF versus untreated | DM patients, n = 169 Albuminuria >30 mg/24 h, eGFR 60–15 mL/min/1.73 m2 |
1200 mg/day, 2 years. Background RAS blockade | Improvements in GFR decay and in proteinuria. Decrease of urinary levels of TNFα |
| [95] | Open-label RCT | PTF versus untreated | DM patients, n = 24 Albuminuria >300 mg/24 h; creatinine clearance <35 mL/min |
400 mg/day, 6 months | Decrease in proteinuria and TNFα levels |
| [96] | Open-label RCT | PTF versus captopril | DM patients, n = 39 Albuminuria >300 mg/24 h; eGFR >60 mL/min/1.73 m2 |
1200 mg/day, 8 weeks | Both PTF and captopril decreased proteinuria |
| [97] | Open-label RCT | PTF versus captopril | DM patients, n = 130 UAE 20–200 μg/min |
1200 mg/day, 6 months | Both PTF and captopril decreased proteinuria |
| [98] | Open-label RCT | PTF versus untreated | DM patients, n = 61 Albuminuria >300 mg/24 h; eGFR >90 mL/min/1.73 m2 |
1200 mg/day, 4 months. Background RAS blockade |
Decrease in serum and urinary TNFα levels. TNFα changes related to UAE |
| [99] | Double-blind RCT | PTF versus placebo | DM patients, n = 40 UAE 20–200 μg/min |
1200 mg/day, 4 months |
Decrease in urinary levels of high and low molecular weight proteins |
| [100] | Double-blind RCT | PTF versus placebo | Patients with GN, n = 18 proteinuria >500 mg/24 h, mean eGFR 71.2 ± 30.6 mL/min/1.73 m2 |
800–1200 mg/day, 6 months. Background RAS blockade |
Decrease of proteinuria without affecting GFR |
| [101] | Open-label, controlled trial | PTF versus untreated | Diabetic GE patients, n = 14 Proteinuria >1.5 g/24 h; Cr clearance >15 mL/min |
400–800 mg/day, 1 year. Background RAS blockade | PTF did not decrease proteinuria or improved renal function |
| [102] | Double-blind RCT | PTF versus placebo | CKD patients, n = 40 Mean eGFR 29.5 ± 10.1 mL/min/1.73 m2 Proteinuria >1 g/24 h |
800 mg/day, 1 year Background RAS blockade |
PTF stabilized GFR. No decrease of proteinuria |
| [103] | RCT | PTF versus untreated | CKD patients, n = 91 albuminuria >300 mg/24 h, eGFR <60 mL/min/1.73 m2 |
800 mg/day, 1 year. Background RAS blockade | PTF stabilized GFR. No decrease of proteinuria. Decrease in TNFα, fibrinogen and hsCRP |
| [104] | RCT | PTF versus untreated | CKD patients, n = 56 Proteinuria >500 mg/g of Cr; eGFR 10–60 mL/min/1.73 m2 |
400–800 mg/day, 1 year. Background RAS blockade | Decrease of proteinuria and stabilization of GFR. Decrease in TNFα and MCP1 levels |
| [105] | Prospective trial | All in PTF | Patients with GN; non-diabetic, n = 17. Spot proteinuria >1.5 g/g Cr; eGFR 24–115 mL/min/1.73 m2 | 800 mg/day, 6 months | Decrease in spot and 24 h proteinuria (g/g Cr) and in MCP-1 levels |
| [106] | Single-centre retrospective study | PTF versus untreated | CKD patients, n = 661 Mean proteinuria 1102 mg/g of Cr, eGFR <45 mL/min/1.73 m2 |
400–800 mg/day, 1 year. Background RAS blockade |
Better renal outcome in patients with higher proteinuria |
| [107] | Prospective trial | All in PTF | CAN patients, n = 17 UAE 20–200 μg/min, mean eGFR 38 ± 8 mL/min/1.73 m2 |
1200 mg/day, 6 months | Decrease of proteinuria at 3rd month and improved graft survival. Decrease in CD4 + cells bearing TNFα and IL10 |
| [85] | RCT post-hoc analysis | PTF versus untreated | DM patients, n = 166 Albuminuria >30 mg/24 h, eGFR 60–15 mL/min/1.73 m2 |
1200 mg/day, 2 years. Background RAS blockade |
Increments in serum and urine Klotho. Changes in TNFα associated with changes of urinary Klotho |
| Ref. | Experimental model | Treatment conc. | Main effects of PTF | ||
| Experimental studies | |||||
| [108] | RAW 264.7 macrophages | 100 µg/mL, 1 h before the addition of LPS | Inhibition of endotoxin-induced TNFα synthesis | ||
| [109] | Rat model of crescentic GN | Intravenous 0.1 g/kg/day | Suppression of progressive renal injury through inhibition of renal TNFα, ICAM-1, RANTES, MCP-1 and OPN | ||
| [110] | Streptozotocin-induced diabetic rat model | Intraperitoneal 25 mg/kg/day | Decrease in renal TNFα and IL6 and amelioration of renal hypertrophy and sodium retention | ||
| [111] | Alloxan-induced diabetic rat model | Oral 25, 50 or 100 mg/kg/day | Decrease in renal TNFα and IL6 | ||
| [85] | Renal tubular cells | 4, 40, 200, 400 or 800 µg/mL, 1 h before the addition of albumin | Upregulation and prevention of albuminuria-induced downregulation of expression of Klotho | ||
RCT, randomized controlled trial; PTF, pentoxifylline; DM, diabetes mellitus; CKD, chronic kidney disease; RAS, renin-angiotensin aldosterone system; TNF, tumour necrosis factor; GE, glomeruloesclerosis; GN, glomerulonephritis; GFR, glomerular filtration rate; hsCRP, high sensitivity C-reactive protein; MCP1, monocyte chemoattractant protein 1; ICAM-1, intercellular adhesion molecule-1; OPN, osteopontin; CAN, chronic allograft nephropathy; UAE, urinary albumin excretion.