Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic kidney disease: a meta-analysis

Liu, Dong; Wang, Lina; Huang, Ping; Qu, Liang-bo; Chen, Fei-yan

doi:10.1177/0300060516663094

Cited by 15 publications

(10 citation statements)

References 40 publications

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“…In addition, in a small RCT assessing the effect of the add-on of pentoxifylline to RAS inhibition, not only albuminuria and urinary tumor necrosis factor (TNF)-α but also the decline in eGFR was attenuated in patients with diabetic nephropathy [ 399 ]. A recent meta-analysis of RCTs confirmed this benefit for pentoxifylline combined to RAS inhibition [ 400 ].…”

Section: Pharmacological Treatmentmentioning

confidence: 98%

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

Vanholder

Laecke

Glorieux

et al. 2018

Toxins

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The uremic syndrome, which is the clinical expression of chronic kidney disease (CKD), is a complex amalgam of accelerated aging and organ dysfunctions, whereby cardio-vascular disease plays a capital role. In this narrative review, we offer a summary of the current conservative (medical) treatment options for cardio-vascular and overall morbidity and mortality risk in CKD. Since the progression of CKD is also associated with a higher cardio-vascular risk, we summarize the interventions that may prevent the progression of CKD as well. We pay attention to established therapies, as well as to novel promising options. Approaches that have been considered are not limited to pharmacological approaches but take into account lifestyle measures and diet as well. We took as many randomized controlled hard endpoint outcome trials as possible into account, although observational studies and post hoc analyses were included where appropriate. We also considered health economic aspects. Based on this information, we constructed comprehensive tables summarizing the available therapeutic options and the number and kind of studies (controlled or not, contradictory outcomes or not) with regard to each approach. Our review underscores the scarcity of well-designed large controlled trials in CKD. Nevertheless, based on the controlled and observational data, a therapeutic algorithm can be developed for this complex and multifactorial condition. It is likely that interventions should be aimed at targeting several modifiable factors simultaneously.

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Section: Pharmacological Treatmentmentioning

confidence: 98%

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

Vanholder

Laecke

Glorieux

et al. 2018

Toxins

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“…Most of the included studies were small and of short duration, with the exception of the PREDIAN trial. Metaanalyses by Leporini et al [88] and Liu et al [89], also concluded that there is evidence for some renoprotective effects of PTX but no conclusive data proving the usefulness of this agent for improving renal outcomes in CKD. Moreover, meta-analyses of small trials are insufficient to guide therapy as they tend to overestimate treatment effects compared to large trials, partly due to publication bias.…”

Section: Ptx: Meta-analysesmentioning

confidence: 99%

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

Leehey

2020

Kidney360

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Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) in the U.S. and worldwide. Current treatment for DKD includes strict glycemic control and normalization of blood pressure with renin-angiotensin-aldosterone system (RAAS) blockade. Although RAAS blockers slow progression of disease they do not generally prevent ESRD, and none of the studies with these agents in DKD included non-proteinuric patients, which make up an increasingly large percentage of diabetic patients now seen in clinical practice. Recent studies with glucagon-like peptide-1 receptor agonists and sodium-glucose co-transport-2 (SGLT2) inhibitors have shown beneficial renal effects, and the benefits of SGLT2 inhibitors likely extend to non-proteinuric patients. However, there remains a need to develop new therapies for DKD, particularly in those patients with advanced disease. A role of chronic low-grade inflammation in the microvascular complications in diabetic patients has now been widely accepted.Large clinical trials are being carried out with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress. The FDA-approved non-specific phosphodiesterase inhibitor pentoxifylline (PTX) has been shown to have anti-inflammatory effects in both animal and human studies by inhibiting the production of proinflammatory cytokines. Small randomized clinical trials and meta-analyses indicate that PTX may have therapeutic benefits in DKD, raising the possibility that a clinically available drug may be able to be repurposed to treat this disease. A large multicenter randomized clinical trial to determine whether this agent can decrease time to ESRD or death is currently being conducted, but results will not be available for several years. At the current time, the combination of RAAS blockade plus SGLT2 inhibition is considered standard of care for DKD, but it may be reasonable for clinicians to consider addition of PTX in patients whose disease continues to progress despite optimization of current standard of care therapies.

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“…The renoprotective potential of PTX has been eagerly reviewed [ 10 , 11 , 54 – 56 ] or meta-analyzed [ 57 , 58 ] in recent years. Most such analyses, however, were based on clinical trials with varied study designs and treatment protocols, yielding inconclusive results and hampering the recommendation of PTX to the whole CKD population (Table 3 ).…”

Section: Main Textmentioning

confidence: 99%

“… In a pooled meta-analysis of 10 RCTs (786 pts), PTX was associated with an almost 3-fold higher risk of gastrointestinal symptoms than control treatment. Liu et al, 2017 [ 58 ] CKD of various etiology, N = 705 Meta-analysis (11 RCT as of July 30, 2015) -8: diabetic patients 3: non-diabetic or mixed CKD patients 6: 1200 mg/day 1: 800 mg/day 1: 600 mg/day 1: 400/800 mg/day 2: 400 mg/day Treatment duration: 7: ≦6 months 4: 9 to 24 months. 11 RCTs: compared to ACEI and/or ARB Combination of a RAS blockade and PTX reduces proteinuria & ameliorates eGFR decline in patients with CKD stages 3 to 5.…”

Section: Main Textmentioning

confidence: 99%

Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update

et al. 2017

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Blood pressure control with renin-angiotensin system (RAS) blockade has remained the gold standard for treating patients with proteinuric chronic kidney disease (CKD) up to date. Nevertheless, RAS blockade slows but does not halt the progression of kidney disease, thus highlighting the need to search for additional therapeutic approaches. The nonselective phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) is an old drug that exhibits prominent anti-inflammatory, anti-proliferative and anti-fibrotic activities both in vitro and in vivo. Studies in human subjects have shown that PTX monotherapy decreases urinary protein excretion, and add-on therapy of PTX to background RAS blockade additively reduces proteinuria in patients with CKD of various etiology. More recent studies find that PTX combined with RAS blockade delays the decline of glomerular filtration rate in diabetic patients with mild to moderate CKD, and reduces the risk of end-stage renal disease in diabetic and non-diabetic patients in late stage of CKD with high proteinuria levels. In this review, we update the clinical trial results of PTX as monotherapy, or in conjunction or in comparison with RAS blockade on patients with proteinuria and CKD, and propose a mechanistic scheme explaining the renoprotective activities of this drug.

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Pentoxifylline plus ACEIs/ARBs for proteinuria and kidney function in chronic kidney disease: a meta-analysis

Cited by 15 publications

References 40 publications

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

Deleting Death and Dialysis: Conservative Care of Cardio-Vascular Risk and Kidney Function Loss in Chronic Kidney Disease (CKD)

Targeting Inflammation in Diabetic Kidney Disease: Is There a Role for Pentoxifylline?

Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update

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