The effect of a methylxanthine vasodilator: pentoxifylline on the treatment of diabetic nephropathy-a meta-analysis.
Diabetic nephropathy
Inflammation, Proteinuria
Meta-analysis
Pentoxifylline
Serum creatinine
Journal
Naunyn-Schmiedeberg's archives of pharmacology
ISSN: 1432-1912
Titre abrégé: Naunyn Schmiedebergs Arch Pharmacol
Pays: Germany
ID NLM: 0326264
Informations de publication
Date de publication:
21 Nov 2023
21 Nov 2023
Historique:
received:
11
09
2023
accepted:
08
11
2023
medline:
21
11
2023
pubmed:
21
11
2023
entrez:
21
11
2023
Statut:
aheadofprint
Résumé
This meta-analysis aimed to comprehensively evaluate the efficacy and safety of pentoxifylline (PTF) in the treatment of diabetic nephropathy (DN) and to offer fresh perspectives and evidence-based references for this condition. Meta-analysis. Relevant randomized controlled trials (RCTs) were searched from PubMed, Embase, Cochrane Library, China Knowledge Network (CNKI), Wanfang, and China Biomedical Literature Database. All trials were screened for compliance with the inclusion and exclusion criteria, and relevant data were extracted after quality evaluation. Eighteen studies with a total of 1280 patients were finally included. Compared to the control group, high sensitivity C-reactive protein (hsCRP) was improved (MD = - 0.23. 95% CI = [- 0.41, - 0.05], P = 0.01); urinary albumin excretion (UAE) rate was reduced (MD = - 16.50, 95% CI = [- 18.87, - 14.13], P<0.00001); the change of serum creatinine (Scr) from baseline was reduced (MD = - 0.05, 95%CI = [- 0.08, - 0.01], P = 0.009); fasting plasma glucose (FPG) was decreased (MD = - 5.66, 95% CI = [- 9.79, - 1.53], P = 0.007); and the improvement of glomerular filtration rate (eGFR) from baseline was increased (MD = 4.38, 95% CI = [3.28, 5.48], P<0.00001) in the treatment group. No significant difference was observed between the two groups concerning systolic blood pressure, diastolic blood pressure, total cholesterol, and triglycerides. And in terms of safety, the use of PTF was relatively safe with some self-limiting adverse events. FPG was decreased by PTF more effectively, but there was no effect of PTF on glycated hemoglobin (HbA1c). PTF could improve hsCRP, decrease UAE and Scr, and raise eGFR in the treatment of DN.
Identifiants
pubmed: 37987795
doi: 10.1007/s00210-023-02842-6
pii: 10.1007/s00210-023-02842-6
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
An Z, Dong X, Guo Y et al (2015) Effects and clinical significance of pentoxifylline on the oxidative stress of rats with diabetic nephropathy. J Huazhong Univ Sci Technolog Med Sci 3:356–361. https://doi.org/10.1007/s11596-015-1437-y
doi: 10.1007/s11596-015-1437-y
Bell D (2021) Are the protean effects of pentoxifylline in the therapy of diabetes and its complications still relevant? Diabetes Ther 12:3025–3035. https://doi.org/10.1007/s13300-021-01168-x
doi: 10.1007/s13300-021-01168-x
Bonner R, Albajrami O, Hudspeth J et al (2020) Diabetic kidney disease. Prim Care 4:645–659. https://doi.org/10.1016/j.pop.2020.08.004
doi: 10.1016/j.pop.2020.08.004
Dal Canto E, Ceriello A, Ryden L et al (2019) Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur. J Prev Cardiol (2_suppl):25–32. https://doi.org/10.1177/2047487319878371
de Morales AM, Goicoechea M, Verde E et al (2019) Pentoxifylline, progression of chronic kidney disease (CKD) and cardiovascular mortality: long-term follow-up of a randomized clinical trial. J Nephrol 4:581–587. https://doi.org/10.1007/s40620-019-00607-0
doi: 10.1007/s40620-019-00607-0
DiPetrillo K, Gesek FA (2004) Pentoxifylline ameliorates renal tumor necrosis factor expression, sodium retention, and renal hypertrophy in diabetic rats. Am J Nephrol 3:352–359. https://doi.org/10.1159/000079121
doi: 10.1159/000079121
Donate-Correa J, Ferri CM, Sanchez-Quintana F et al (2020a) Inflammatory cytokines in diabetic kidney disease: pathophysiologic and therapeutic implications. Front Med (Lausanne): 628289. https://doi.org/10.3389/fmed.2020.628289
Donate-Correa J, Luis-Rodriguez D, Martin-Nunez E et al (2020b) Inflammatory targets in diabetic nephropathy. J Clin Med 2. https://doi.org/10.3390/jcm9020458
Donate-Correa J, Tagua VG, Ferri C et al (2019) Pentoxifylline for renal protection in diabetic kidney disease. A Model of Old Drugs for New Horizons. J Clin Med 3. https://doi.org/10.3390/jcm8030287
Feng Z, Zhen J (2017) Analysis of effect of valsartan combined with pentoxifylline on diabetic nephropathy. J Anhui Med College 05:61–62
Ferrari E, Fioravanti M, Patti AL et al (1987) Effects of long-term treatment (4 years) with pentoxifylline on haemorheological changes and vascular complications in diabetic patients. Pharmatherapeutica 1:26–39
Gan N, Kong Y, Liu S (2003) Clinical observation of pentoxifylline in reducing proteinuria in patients with diabetic nephropathy. J Pract Med 12
Garcia FA, Reboucas JF, Balbino TQ et al (2015) Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase. J Inflamm (Lond) 33. https://doi.org/10.1186/s12950-015-0080-5
Gheith O, Farouk N, Nampoory N et al (2016) Diabetic kidney disease: world wide difference of prevalence and risk factors. J Nephropharmacol 1:49–56
Ghorbani A, Omidvar B, Beladi-Mousavi S et al (2012) The effect of pentoxifylline on reduction of proteinuria among patients with type 2 diabetes under blockade of angiotensin system: a double blind and randomized clinical trial. Nefrologia 6. https://doi.org/10.3265/Nefrologia.pre2012.Jun.11242
Han S, Kim H, Kim D et al (2015) Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes. Diabetologia 1:S343–S344. https://doi.org/10.1007/s00125-015-3687-4
doi: 10.1007/s00125-015-3687-4
Inacio MD, Costa MC, Lima T et al (2020) Pentoxifylline mitigates renal glycoxidative stress in obese mice by inhibiting AGE/RAGE signaling and increasing glyoxalase levels. Life Sci 118196. https://doi.org/10.1016/j.lfs.2020.118196
Liu D, Wang LN, Li HX et al (2017) Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic kidney disease: a meta-analysis. J Int Med Res 2:383–398. https://doi.org/10.1177/0300060516663094
doi: 10.1177/0300060516663094
Lv J, Lv L, and Zhao Y et al (2012) VaIsartan combined with pentoxifylline in the treatment of diabetic retinopathy and diabetic nephropathy. Rec Adv Ophthalmol 10:945–948. https://doi.org/10.13389/j.cnki.rao.2012.10.005
Maruno S, Tanaka T, Nangaku M (2022) Exploring molecular targets in diabetic kidney disease. Kidney Res Clin Pract. https://doi.org/10.23876/j.krcp.21.251
McCormick BB, Sydor A, Akbari A et al (2008) The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am J Kidney Dis 3:454–463. https://doi.org/10.1053/j.ajkd.2008.01.025
doi: 10.1053/j.ajkd.2008.01.025
Mehanna OM, El AA, Al-Shehri S et al (2018) Effect of phosphodiesterase inhibitors on renal functions and oxidant/antioxidant parameters in streptozocin-induced diabetic rats. Arch Physiol Biochem 5:424–429. https://doi.org/10.1080/13813455.2017.1419267
doi: 10.1080/13813455.2017.1419267
Microvascular Complications Group Of Chinese Diabetes Society, Xue Y, Zhu D (2021) Clinical guideline for the prevention and treatment of diabetic kidney disease in China (2021 edition). Chin J Diabetes Mellitus 08:762–784
Moosaie F, Rabizadeh S, Fallahzadeh A et al (2022) Effects of pentoxifylline on serum markers of diabetic nephropathy in type 2 diabetes. Diabetes Therapy 5:1023–1036. https://doi.org/10.1007/s13300-022-01250-y
doi: 10.1007/s13300-022-01250-y
Mostafa-Hedeab G, Al-Kuraishy HM, Al-Gareeb AI et al (2022) A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19. Inflammopharmacology 3:799–809. https://doi.org/10.1007/s10787-022-00993-1
doi: 10.1007/s10787-022-00993-1
Navarro J, Mora C, Muros M et al (2003) Effects of pentoxifylline administration on urinary N-acetyl-beta-glucosaminidase excretion in type 2 diabetic patients: a short-term, prospective, randomized study. Ame J kidney Dis 2. https://doi.org/10.1016/s0272-6386(03)00651-6
Navarro J, Mora C, Muros M et al (2005) Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial. J Ame Soc Nephrol: JASN 7. https://doi.org/10.1681/ASN.2005010001
Navarro J, Mora C, Rivero A et al (1999) Urinary protein excretion and serum tumor necrosis factor in diabetic patients with advanced renal failure: effects of pentoxifylline administration. Ame J Kidney Dis 3. https://doi.org/10.1016/s0272-6386(99)70182-4
Navarro-González J, Mora-Fernández C, de Fuentes MM et al (2015) Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Ame Soc Nephrol: JASN 1. https://doi.org/10.1681/ASN.2014010012
Nisi A, Panfili M, De Rosa G et al (2013) Pharmacokinetics of pentoxifylline and its main metabolites in patients with different degrees of heart failure following a single dose of a modified-release formulation. J Clin Pharmacol 1:51–57. https://doi.org/10.1177/0091270011433435
doi: 10.1177/0091270011433435
Oliaei F, Hushmand S, Khafri S et al (2011) Efficacy of pentoxifylline for reduction of proteinuria in type II diabetic patients. Caspian J Inter Med 4:309–313
Paap CM, Simpson KS, Horton MW et al (1996) Multiple-dose pharmacokinetics of pentoxifylline and its metabolites during renal insufficiency. Ann Pharmacother 7-8:724–729. https://doi.org/10.1177/106002809603000702
doi: 10.1177/106002809603000702
Pang J, Zhang X, Zhi Z (2003) Effect of pentoxifylline in the treatment of early diabetic nephropathy. Clin focus 20
Rabizadeh S, Dehghani Firouzabadi F, Noshad S et al (2018) Beneficial effects of pentoxifylline plus losartan dual therapy in type 2 diabetes with nephropathy. Ame J Med Sci 5. https://doi.org/10.1016/j.amjms.2017.12.015
Rodriguez-Morán M, González-González G, Bermúdez-Barba M et al (2006) Effects of pentoxifylline on the urinary protein excretion profile of type 2 diabetic patients with microproteinuria: a double-blind, placebo-controlled randomized trial. Clin Nephrol 1. https://doi.org/10.5414/cnp66003
Roozbeh J, Banihashemi M, Ghezlou M et al (2010) Captopril and combination therapy of captopril and pentoxifylline in reducing proteinuria in diabetic nephropathy. Renal Failure 2. https://doi.org/10.3109/08860221003602645
Sagoo MK, Gnudi L (2020) Diabetic nephropathy: an overview. Methods Mol Biol 3-7. https://doi.org/10.1007/978-1-4939-9841-8_1
Samsu N (2021) Diabetic nephropathy: challenges in pathogenesis, diagnosis, and treatment. Biomed Res Int 1497449. https://doi.org/10.1155/2021/1497449
Setiadi A, Korim WS, May CN et al (2020) Systemic administration of pentoxifylline attenuates the development of hypertension in renovascular hypertensive rats. Hypertens Res 7:667–678. https://doi.org/10.1038/s41440-020-0412-6
doi: 10.1038/s41440-020-0412-6
Shan D, Wu H, Yuan Q et al (2012) Pentoxifylline for diabetic kidney disease. Cochrane Database Syst Rev 2:CD006800. https://doi.org/10.1002/14651858.CD006800.pub2
doi: 10.1002/14651858.CD006800.pub2
Sui C, Sheng H, Yang Y (1999) Effect of pentoxifylline on diabetic nephropathy. Shanghai journal of preventive medicine 10
Świerczek A, Wyska E, Baś S et al (2017) PK/PD studies on non-selective PDE inhibitors in rats using cAMP as a marker of pharmacological response. Naunyn Schmiedebergs Arch Pharmacol 10:1047–1059. https://doi.org/10.1007/s00210-017-1406-z
doi: 10.1007/s00210-017-1406-z
Thomas B (2019) The global burden of diabetic kidney disease: time trends and gender gaps. Curr Diab Rep 4:18. https://doi.org/10.1007/s11892-019-1133-6
doi: 10.1007/s11892-019-1133-6
Tian ML, Shen Y, Sun ZL et al (2015) Efficacy and safety of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a meta-analysis. Int Urol Nephrol 5:815–822. https://doi.org/10.1007/s11255-015-0968-2
doi: 10.1007/s11255-015-0968-2
Valente EG, Vernet D, Ferrini MG et al (2003) L-arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie's fibrotic plaque and related fibroblast cultures. Nitric Oxide 4:229–244. https://doi.org/10.1016/j.niox.2003.12.002
doi: 10.1016/j.niox.2003.12.002
Zang Q, Su R (1999) The effect of pentoxifylline in the treatment of early diabetic nephropathy. Tianjin medicine 4
Zhao F, Gao J, Yang D et al (2019) Effects of pentoxifylline on glucose metabolism and renal function in patients with early type 2 diabetic nephropathy. Modern J Integrat Tradition Chinese Western Med 35:3881–3883+3918
Zhen G, Ren G, Zhao Z (2020) Pharmacological mechanism and research advance of pentoxifylline on cardiovascular disease. World Clin Drugs 11:905–909