Erythropoiesis-Stimulating Agents (ESA) for Preventing the Progression of Chronic Kidney Disease: A Meta-Analysis of 19 Studies

Covic, Adrian; Nistor, Ionuţ; Donciu, Mihaela-Dora; Dumea, Raluca; Bolignano, Davide; Goldsmith, David

doi:10.1159/000366025

Cited by 25 publications

(15 citation statements)

References 40 publications

(117 reference statements)

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“…A meta-analysis with patients at risk for AKI showed no benefit of ESAs on incidence of AKI [58]. Another meta-analyses of effects of ESAs on CKD patients also showed no clear benefit on progression to RRT, comparing ESA treatment to no treatment [59] or comparing high vs low Hb targets [60, 61], nor was there was an association between ESA dose and annual GFR change or progression to ESRD [62]. …”

Section: Discussionmentioning

confidence: 99%

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

2017

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BackgroundErythropoiesis stimulating agents (ESAs) were proposed to enhance survival of renal tissues through direct effects via activation of EPO receptors on renal cells resulting in reduced cell apoptosis, or indirect effects via increased oxygen delivery due to increased numbers of Hb containing red blood cells. Thus through several mechanisms there may be benefit of ESA administration on kidney disease progression and kidney function in renal patients. However conflicting ESA reno-protection outcomes have been reported in both pre-clinical animal studies and human clinical trials. To better understand the potential beneficial effects of ESAs on renal-patients, meta-analyses of clinical trials is needed.MethodsLiterature searches and manual searches of references lists from published studies were performed. Controlled trials that included ESA treatment on renal patients with relevant renal endpoints were selected.ResultsThirty two ESA controlled trials in 3 categories of intervention were identified. These included 7 trials with patients who had a high likelihood of AKI, 7 trials with kidney transplant patients and 18 anemia correction trials with chronic kidney disease (predialysis) patients. There was a trend toward improvement in renal outcomes in the ESA treated arm of AKI and transplant trials, but none reached statistical significance. In 12 of the anemia correction trials, meta-analyses showed no difference in renal outcomes with the anemia correction but both arms received some ESA treatment making it difficult to assess effects of ESA treatment alone. However, in 6 trials the low Hb arm received no ESAs and meta-analysis also showed no difference in renal outcomes, consistent with no benefit of ESA/ Hb increase.ConclusionsMost ESA trials were small with modest event rates. While trends tended to favor the ESA treatment arm, these meta-analyses showed no reduction of incidence of AKI, no reduction in DGF or improvement in 1-year graft survival after renal transplantation and no significant delay in progression of CKD. These results do not support significant clinical reno-protection by ESAs.

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Section: Discussionmentioning

confidence: 99%

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

2017

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“…Various triggers that lead to the activation of T cells and monocytes are directly or indirectly involved in the release of inflammatory cytokines [24]. Nevertheless, results of many published studies of anaemia correction are complicated by various factors including methodological concerns such as open-label designs instead of double-blind studies [25,26,27,28,29]. But according to a number of studies, complete correction of anaemia is not always beneficial and in some cases is associated with adverse effects.…”

Section: Hfmentioning

confidence: 99%

The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure

Ebner

Jankowska

Ponikowski

et al. 2016

International Journal of Cardiology

105

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“…[22][23][24] There is also no evidence that ESA use influences the rate of progression of CKD at any stage. 25 There has been increased interest in non-ESA anaemia therapies in particular CKD cohorts. There is a growing recognition of the high prevalence of iron deficiency in chronic heart failure (CHF) patients, and the benefit of iron administration in terms of myocardial function and cardiac clinical endpoints.…”

Section: Sodium Bicarbonatementioning

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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Erythropoiesis-Stimulating Agents (ESA) for Preventing the Progression of Chronic Kidney Disease: A Meta-Analysis of 19 Studies

Cited by 25 publications

References 40 publications

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

Erythropoiesis stimulating agents and reno-protection: a meta-analysis

The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the Studies Investigating Co-morbidities Aggravating Heart Failure

Drug therapies to delay the progression of chronic kidney disease

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