Efficacy and safety of combining pentoxifylline with angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker in diabetic nephropathy: a meta-analysis

Tian, Maolu; Shen, Yan; Sun, Zhaolin; Zha, Yan

doi:10.1007/s11255-015-0968-2

Cited by 25 publications

(24 citation statements)

References 34 publications

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“…A systematic review and meta-analysis showed pentoxifylline had an enhanced anti-proteinuric effect, in combination with RAS inhibition, and was associated with some improvement in renal function without significant adverse effects. 67,68 However, the supportive data are methodologically flawed, of short follow-up duration and in small sample sizes. There is insufficient evidence at present to recommend its widespread use.…”

Section: Anti-fibrotic and Anti-inflammatory Targeted Therapiesmentioning

confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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Chronic kidney disease (CKD) is associated with significant morbidity and mortality, impacted not alone by progression to end-stage kidney disease, but also by the high associated incidence of cardiovascular events and related mortality. Despite our current understanding of the pathogenesis of CKD and the treatments available, the reported incidence of CKD continues to rise worldwide, and is often referred to as the silent public healthcare epidemic. The significant cost to patient wellbeing and to the economy of managing the later stages of CKD have prompted efforts to develop interventions to delay the development and progression of this syndrome. In this article, we review established and novel agents that may aid in delaying the progression of CKD and improve patient outcomes. KEYWORDS: Chronic kidney disease, progression, drug therapy IntroductionChronic kidney disease (CKD), as defined by proteinuria or a reduced glomerular filtration rate (GFR) below 90 mL/min/1.73 m 2 persisting for greater than 3 months, is reported to affect 13% of US adults.1 There is a significantly higher prevalence in the elderly and those with hypertension or diabetes, and with these comorbidities increasing in prevalence and the population ageing, CKD is projected to affect up to 16% of adults by 2030.2,3 Even in its early stages, CKD is associated with accelerated cardiovascular disease and increased mortality, with an exponential increase in attributable risk as GFR declines to end-stage kidney disease (ESKD). 4,5 The mortality rate in ESKD patients maintained on dialysis is striking, with a life expectancy less than one-third that of their counterparts without ESKD, and a 5-year survival rate on dialysis of only 40%. 6 There is also a substantial healthcare cost associated with provision of ESKD care, currently estimated at $33 billion annually in the US, ABSTRACT equating to 6.3% of the Medicare Budget. 6 Hence, there may be significant healthcare and economic benefits to be garnered from halting or delaying CKD progression. In this article, we discuss recent evidence for established and emerging therapies that may alter the progression of CKD. Non disease-specific drug therapies Sodium bicarbonateCKD is associated with a metabolic acidosis, particularly at lower levels of GFR <25 mL/min/1.73 m 2 , which is predominantly attributed to reduced hydrogen ion excretion as titratable acids or ammonium in the urine. Chronic metabolic acidosis exacerbates CKD-related mineral bone disease, leads to muscle atrophy, and is associated with other complications such as abnormal albumin synthesis, thyroid dysfunction and insulin resistance. 7,8 Observational data demonstrate a strong risk of progression of CKD in those with a lower serum bicarbonate level, as well as an increased mortality risk. 9,10 Possible mechanisms for the deleterious effect of acidosis on GFR may be the inadvertent pro-fibrotic effects of inducing regulatory mechanisms in the kidney, such as increased renal ammonium production, endothelin-A receptor activation and pr...

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Section: Anti-fibrotic and Anti-inflammatory Targeted Therapiesmentioning

confidence: 99%

Drug therapies to delay the progression of chronic kidney disease

2015

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“…Further studies revealed that enhanced AT 1 receptor signaling in podocytes leads to proteinuria and FSGS 23 , and inhibition of AT receptors is effective against proteinuria 24, 25 .…”

Section: Introductionmentioning

confidence: 99%

The Role of Angiotensin II in Glomerular Volume Dynamics and Podocyte Calcium Handling

Ilatovskaya

Palygin

Levchenko

et al. 2017

Sci Rep

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Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca2+ flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II–dependent stimulation of Ca2+ influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs). Application of Ang(1–7) had no effect on intracellular calcium. Ang II-induced calcium flux was decreased upon inhibition of TRPC channels with SAR7334, SKF 96365, clemizole hydrochloride and La3+, but not ML204. Using a novel 3D whole-glomerulus imaging ex vivo assay, we revealed the involvement of both ATRs in controlling glomerular permeability; additionally, using specific inhibitors and activators of TRPC6, we showed that these channels are implicated in the regulation of glomerular volume dynamics. Therefore, we provide evidence demonstrating the critical role of Ang II/TRPC6 axis in the control of glomeruli function, which is likely important for the development of glomerular diseases.

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“…133 133 The second review (2016) included 26 randomized and quasi-randomized trials, 24 of which focused on diabetic nephropathy (1049 patients with type 2 diabetes). Results showed that albuminuria was reduced in subgroup analysis of patients with higher (≥500 mg/day) baseline proteinuria (mean difference −0.38 g/day, −0.63 to −0.14) and in studies comparing pentoxifylline with RAAS blockers (−0.42, −0.76 to −0.08).…”

Section: Pentoxifyllinementioning

confidence: 99%