Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: a 12-month randomized trial.
BACKGROUND
Pentoxifylline potently inhibits cell proliferation, inflammation, and extracellular matrix accumulation. Human studies have proved its antiproteinuric effect in patients with glomerular diseases. Its benefit in addition to angiotensin receptor blockade in patients with chronic kidney disease is not clear.


METHODS
Randomized controlled study.


METHODS
85 patients with estimated glomerular filtration rate (eGFR) of 10 to 60 mL/min/1.73 m(2) and proteinuria with protein greater than 500 mg/g of creatinine on treatment with losartan, 100 mg/d, for longer than 6 months were screened in National Taiwan University Hospital.


METHODS
In the first stage (12 months), group 1 served as control and group 2 was administered pentoxifylline. In the second stage (6 months), both groups were administered pentoxifylline. The pentoxifylline dose was 400 mg twice daily for patients with eGFR of 30 to 60 mL/min/1.73 m(2) or once daily for patients with eGFR of 10 to 29 mL/min/1.73 m(2).


RESULTS
Proteinuria and eGFR.


METHODS
Proteinuria was assessed as total protein-creatinine ratio, eGFR was computed by using the Modification of Diet in Renal Disease Study equation.


RESULTS
27 and 29 patients were randomly assigned to groups 1 and 2, respectively. In the first stage, pentoxifylline decreased median proteinuria from 1,140 to 800 mg/g (median change, -23.9%) compared with 1,410 to 1,810 mg/g (median change, 13.8%) in the control group. The difference between groups was 38.7% (95% confidence interval, 25.7 to 51.6; P < 0.001). The change in proteinuria was related to the change in urinary tumor necrosis factor alpha and monocyte chemoattractant protein 1 excretion (R = 0.64 and R = 0.55, respectively; P < 0.001 for both). In the second stage, pentoxifylline reproduced the change in proteinuria in group 1.


CONCLUSIONS
Small sample size, disease of late stages, open-labeled study.


CONCLUSIONS
Pentoxifylline added to losartan therapy for 1 year decreased proteinuria in patients with CKD stages 3 to 5. A large-scale clinical trial is necessary to confirm this result.
Lin
Shuei-Liong
SL
Renal Division, Department of Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Yung-Ming
YM
Chiang
Wen-Chih
WC
Wu
Kwan-Dun
KD
Tsai
Tun-Jun
TJ
D000450:Aldosterone / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000652:urine; D002908:Chronic Disease; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000652:urine
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000450:Aldosterone; D019808:Losartan; D010431:Pentoxifylline