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Erschienen in: Journal of Nephrology 4/2019

01.08.2019 | Original Article

Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial

verfasst von: Alejandra Muñoz de Morales, Marian Goicoechea, Eduardo Verde, Javier Carbayo, Diego Barbieri, Andrés Delgado, Ursula Verdalles, Ana Perez de Jose, José Luño

Erschienen in: Journal of Nephrology | Ausgabe 4/2019

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Abstract

Background

Pentoxifylline could reduce proteinuria and slow renal disease progression. We previously conducted a single-blind, randomized, controlled trial that showed that pentoxifylline decreases inflammatory markers and stabilizes renal function.

Setting and Participants

91 participants (46 in the pentoxifylline group and 45 in the control group) followed up for 7 additional years.

Study design

Post hoc analysis of a long-term follow-up after completion of the 12-months trial.

Intervention

Pentoxifylline treatment (400 mg/twice a day) or standard treatment.

Outcome

Renal event (defined as starting dialysis therapy and/or doubling serum creatinine and/or ≥ 50% decrease in estimated glomerular filtration rate) and cardiovascular mortality.

Results

During follow-up, a renal event was recorded in 24 patients from control group (13 initiated dialysis therapy and serum creatinine doubled in 11) and 11 patients from PTF group (7 initiated dialysis and serum creatinine doubled in 4) (log Rank: 5.822, p = 0.016). The possible protector effect of PTF was more significant in albuminuric patients and was independently of diabetes mellitus presence. Treatment with PTF reduced the renal events by 35% compared to the control group in a Cox model adjusted for diabetes mellitus, albuminuria and basal renal function (HR 0.65 (0.45–0.94), p = 0.022). Cardiovascular mortality was significantly reduced in PTF treatment (2 patients vs. 10 in control group) (log Rank 5.0977, p = 0.024). PTF treatment reduced cardiovascular mortality in 55% adjusted for diabetes mellitus and age (HR 0.45 (0.21–0.98), p = 0.044) (Table 3).

Limitations

Small sample size, single center, not double blind and post hoc follow-up analysis.

Conclusions

Long-term treatment with pentoxifylline may slow the rate of progression of kidney disease and reduce cardiovascular risk.
Literatur
1.
Zurück zum Zitat Goicoechea M, García de Vinuesa S, Quiroga B, Verdalles U, Barraca D, Yuste C et al (2012) Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial. J Nephrol 25(6):969–975CrossRef Goicoechea M, García de Vinuesa S, Quiroga B, Verdalles U, Barraca D, Yuste C et al (2012) Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial. J Nephrol 25(6):969–975CrossRef
2.
Zurück zum Zitat Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, Chahin J, Méndez ML, Gallego E et al (2015) Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease the PREDIAN trial. J Am Soc Nephrol 26(1):220–229CrossRef Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, Chahin J, Méndez ML, Gallego E et al (2015) Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease the PREDIAN trial. J Am Soc Nephrol 26(1):220–229CrossRef
3.
Zurück zum Zitat Lin SL, Chen YM, Chiang WC, Tsai TJ, Chen WY (2004) Pentoxifylline: a potential therapy for chronic kidney disease. Nephrology (Carlton) 9(4):198–204CrossRef Lin SL, Chen YM, Chiang WC, Tsai TJ, Chen WY (2004) Pentoxifylline: a potential therapy for chronic kidney disease. Nephrology (Carlton) 9(4):198–204CrossRef
4.
Zurück zum Zitat Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ (2002) Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol 13(12):2916–2929CrossRef Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ (2002) Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol 13(12):2916–2929CrossRef
5.
Zurück zum Zitat Lai TS, Chiang WC, Chen YM (2016) Pentoxifylline: evidence strong enough for renoprotection? J Formos Med Assoc 115(8):591–592CrossRef Lai TS, Chiang WC, Chen YM (2016) Pentoxifylline: evidence strong enough for renoprotection? J Formos Med Assoc 115(8):591–592CrossRef
6.
Zurück zum Zitat Badri S, Dashti-Khavidaki S, Lessan-Pezeshki M, Abdollahi M (2011) A review of the potential benefits of pentoxifylline in diabetic and non-diabetic proteinuria. J Pharm Pharm Sci 14(1):128–137CrossRef Badri S, Dashti-Khavidaki S, Lessan-Pezeshki M, Abdollahi M (2011) A review of the potential benefits of pentoxifylline in diabetic and non-diabetic proteinuria. J Pharm Pharm Sci 14(1):128–137CrossRef
7.
Zurück zum Zitat Jiang X, Zhou S, Yao J, Kong X, Cui M (2016) Effect of pentoxifylline in proteinuric chronic kidney disease: a systematic review and meta-analysis. J Nephrol 29(5):653–662CrossRef Jiang X, Zhou S, Yao J, Kong X, Cui M (2016) Effect of pentoxifylline in proteinuric chronic kidney disease: a systematic review and meta-analysis. J Nephrol 29(5):653–662CrossRef
8.
Zurück zum Zitat McCormick BB, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G (2008) The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am J Kidney Dis 52(3):454–463CrossRef McCormick BB, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G (2008) The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am J Kidney Dis 52(3):454–463CrossRef
9.
Zurück zum Zitat Lin SL, Chen YM, Chiang WC, Wu KD, Tsai TJ (2008) Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: a 12-month randomized trial. Am J Kidney Dis 52(3):464–474CrossRef Lin SL, Chen YM, Chiang WC, Wu KD, Tsai TJ (2008) Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: a 12-month randomized trial. Am J Kidney Dis 52(3):464–474CrossRef
10.
Zurück zum Zitat Wu PC, Wu CJ, Lin CJ, Pan CF, Chen CY, Huang TM et al (2015) Pentoxifylline decreases dialysis risk in patients with advanced chronic kidney disease. Clin Pharmacol Ther 98(4):442–449CrossRef Wu PC, Wu CJ, Lin CJ, Pan CF, Chen CY, Huang TM et al (2015) Pentoxifylline decreases dialysis risk in patients with advanced chronic kidney disease. Clin Pharmacol Ther 98(4):442–449CrossRef
11.
Zurück zum Zitat Chen PM, Lai TS, Chen PY, Lai CF, Wu V, Chiang WC et al (2014) Renoprotective effect of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in advanced chronic kidney disease. J Formos Med Assoc 113(4):219–226CrossRef Chen PM, Lai TS, Chen PY, Lai CF, Wu V, Chiang WC et al (2014) Renoprotective effect of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in advanced chronic kidney disease. J Formos Med Assoc 113(4):219–226CrossRef
12.
Zurück zum Zitat Kuo KL, Hung SC, Liu JS, Chang YK, Hsu CC, Tarng DC (2015) Add-on protective effect of pentoxifylline in advanced chronic kidney disease treated with renin-angiotensin-aldosterone system blockade—a nationwide database analysis. Sci Rep 5:17150CrossRef Kuo KL, Hung SC, Liu JS, Chang YK, Hsu CC, Tarng DC (2015) Add-on protective effect of pentoxifylline in advanced chronic kidney disease treated with renin-angiotensin-aldosterone system blockade—a nationwide database analysis. Sci Rep 5:17150CrossRef
13.
Zurück zum Zitat Navarro JF, Milena FJ, Mora C, León C, García J (2006) Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol 26(6):562–570CrossRef Navarro JF, Milena FJ, Mora C, León C, García J (2006) Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. Am J Nephrol 26(6):562–570CrossRef
14.
Zurück zum Zitat Renke M, Tylicki L, Rutkowski P, Knap N, Zietkiewicz M, Neuwelt A et al (2010) Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease—placebo controlled, randomized, cross-over study. Acta Biochim Pol 57(1):119–123CrossRef Renke M, Tylicki L, Rutkowski P, Knap N, Zietkiewicz M, Neuwelt A et al (2010) Effect of pentoxifylline on proteinuria, markers of tubular injury and oxidative stress in non-diabetic patients with chronic kidney disease—placebo controlled, randomized, cross-over study. Acta Biochim Pol 57(1):119–123CrossRef
15.
Zurück zum Zitat Sönmez MF, Dündar M (2016) Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney. Ren Fail 38(4):605–613CrossRef Sönmez MF, Dündar M (2016) Ameliorative effects of pentoxifylline on NOS induced by diabetes in rat kidney. Ren Fail 38(4):605–613CrossRef
16.
Zurück zum Zitat Navarro-González JF, Sánchez-Niño MD, Donate-Correa J, Martín-Núñez E, Ferri C, Pérez-Delgado N et al (2018) Effects of pentoxifylline on Soluble Klotho concentrations and renal tubular cell expression in diabetic kidney disease. Diabetes Care 41(8):1817–1820CrossRef Navarro-González JF, Sánchez-Niño MD, Donate-Correa J, Martín-Núñez E, Ferri C, Pérez-Delgado N et al (2018) Effects of pentoxifylline on Soluble Klotho concentrations and renal tubular cell expression in diabetic kidney disease. Diabetes Care 41(8):1817–1820CrossRef
17.
Zurück zum Zitat Perkins RM, Aboudara MC, Uy AL, Olson SW, Cushner HM, Yuan CM (2009) Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis 53(4):606–616CrossRef Perkins RM, Aboudara MC, Uy AL, Olson SW, Cushner HM, Yuan CM (2009) Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis 53(4):606–616CrossRef
18.
Zurück zum Zitat Diskin CJ (2009) The promise of pentoxifylline and interference with the renin-angiotensin system in diabetic nephropathy. Am J Kidney Dis. 53(2):355CrossRef Diskin CJ (2009) The promise of pentoxifylline and interference with the renin-angiotensin system in diabetic nephropathy. Am J Kidney Dis. 53(2):355CrossRef
19.
Zurück zum Zitat Zhang M, Xu YJ, Saini HK, Turan B, Liu PP, Dhalla NS (2005) Pentoxifylline attenuates cardiac dysfunction and reduces TNF-alpha level in ischemic-reperfused heart. Am J Physiol Heart Circ Physiol 289(2):H832–H839CrossRef Zhang M, Xu YJ, Saini HK, Turan B, Liu PP, Dhalla NS (2005) Pentoxifylline attenuates cardiac dysfunction and reduces TNF-alpha level in ischemic-reperfused heart. Am J Physiol Heart Circ Physiol 289(2):H832–H839CrossRef
20.
Zurück zum Zitat Skudicky D, Bergemann A, Sliwa K, Candy G, Sareli P (2001) Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study. Circulation 103(8):1083–1088CrossRef Skudicky D, Bergemann A, Sliwa K, Candy G, Sareli P (2001) Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study. Circulation 103(8):1083–1088CrossRef
21.
Zurück zum Zitat Sliwa K, Woodiwiss A, Candy G, Badenhorst D, Libhaber C, Norton G et al (2002) Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 90(10):1118–1122CrossRef Sliwa K, Woodiwiss A, Candy G, Badenhorst D, Libhaber C, Norton G et al (2002) Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol 90(10):1118–1122CrossRef
22.
Zurück zum Zitat Watanabe H, Furukawa Y, Chiba S (1982) Cardiovascular effects of aminophylline and pentoxifylline on intact dogs and isolated dog atria. Jpn Heart J 23(2):235–243CrossRef Watanabe H, Furukawa Y, Chiba S (1982) Cardiovascular effects of aminophylline and pentoxifylline on intact dogs and isolated dog atria. Jpn Heart J 23(2):235–243CrossRef
23.
Zurück zum Zitat Zhang X, Meng F, Song J, Zhang L, Wang J, Li D et al (2016) Pentoxifylline ameliorates cardiac fibrosis, pathological hypertrophy, and cardiac dysfunction in angiotensin ii-induced hypertensive rats. J Cardiovasc Pharmacol 67(1):76–85CrossRef Zhang X, Meng F, Song J, Zhang L, Wang J, Li D et al (2016) Pentoxifylline ameliorates cardiac fibrosis, pathological hypertrophy, and cardiac dysfunction in angiotensin ii-induced hypertensive rats. J Cardiovasc Pharmacol 67(1):76–85CrossRef
Metadaten
Titel
Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial
verfasst von
Alejandra Muñoz de Morales
Marian Goicoechea
Eduardo Verde
Javier Carbayo
Diego Barbieri
Andrés Delgado
Ursula Verdalles
Ana Perez de Jose
José Luño
Publikationsdatum
01.08.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Nephrology / Ausgabe 4/2019
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-019-00607-0

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