Allopurinol for the treatment of chronic kidney disease: asystematic review

Fleeman, Nigel; Pilkington, Gerlinde; Dündar, Yenal; Dwan, Kerry; Boland, Angela; Dickson, Rumona; Anijeet, Hameed; Kennedy, Tom D.; Pyatt, Jason

doi:10.3310/hta18400

Cited by 22 publications

(17 citation statements)

References 53 publications

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“…Three other meta-analyses already approached this issue in the past, providing scant or indefinite conclusions and partial disagreement among findings reported [ 9 , 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Notwithstanding such strong biological premises and a wealth of positive experimental and uncontrolled clinical studies, previously published meta-analyses of randomized controlled trials (RCTs) focusing on Allopurinol showed no effects or only slight improvements in renal function in individuals with overt CKD receiving this therapy [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Pisano

Cernaro

Gembillo

et al. 2017

IJMS

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Background: Accruing evidence suggests that Xanthine Oxidase inhibitors (XOis) may bring direct renal benefits, besides those related to their hypo-uricemic effect. We hence aimed at performing a systematic review of randomized controlled trials (RCTs) to verify if treatment with XOis may improve renal outcomes in individuals with chronic kidney disease (CKD). Methods: Ovid-MEDLINE, PubMed and CENTRAL databases were searched for RCTs comparing any XOi to standard therapy or placebo. The primary endpoint of interest was progression to End-Stage Kidney Disease (ESKD); secondary endpoints were changes in serum creatinine, glomerular filtration rate (eGFR), proteinuria and albuminuria. Results: XOis treatment significantly reduced the risk of ESKD compared to the control (3 studies, 204 pts; RR = 0.42; 95% CI, 0.22, 0.80) and also improved eGFR in data pooled from RCTs with long follow-up times (>3 mo.) (4 studies, 357 pts; mean difference (MD) 6.82 mL/min/1.73 m2; 95% CI, 3.50, 10.15) and high methodological quality (blind design) (3 studies, 400 pts; MD 2.61 mL/min/1.73 m2; 95% CI, 0.23, 4.99). Conversely, no definite effects were apparently noticed on serum creatinine, proteinuria and albuminuria. Conclusions: XOis may represent a promising tool for retarding disease progression in CKD patients. Future trials are awaited to confirm the generalizability of these findings to the whole CKD population.

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“…Three other meta-analyses already approached this issue in the past, providing scant or indefinite conclusions and partial disagreement among findings reported [ 9 , 10 , 11 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Pisano

Cernaro

Gembillo

et al. 2017

IJMS

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“…38 However, two recent meta-analysis and systematic review studies of allopurinol use in CKD patients did not demonstrate clear evidence of retarding progression of CKD or reducing cardiovascular events, although therapy appears to be safe. 39,40 Current clinical guidelines are ambivalent regarding the benefit of urate-lowering therapy in CKD and do not specifically recommend this strategy at present. 41 Renin-angiotensin system inhibition Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), and perhaps direct renin inhibitors, are standard of care treatment in proteinuric CKD, with a role in delaying progression of CKD compared to other antihypertensive medications, although unfortunately the risk of CKD progression still remains high.…”

Section: Urate-lowering Therapymentioning

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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“…Allopurinol supplementation has been reported to retard the rate of progression of chronic kidney disease and reduction in the overall cardiovascular risk in subjects with kidney disease [85,91]. The potential benefit of Allopurinol was attributed to its amelioration of OS and subsequent reduction in the levels of inflammatory markers.…”

Section: The Therapeutic Potential Of Allopurinolmentioning

confidence: 96%

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

Singh¹,

Farrington²

2015

J Diabetes Metab

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Vascular calcification contributes significantly to the vascular damage burden in type 2 diabetes. Chronic hyperglycaemia is the driver of initiation and progression of vascular damage in these subjects. Enhanced oxidative stress is widespread in these subjects due to complex metabolic, cytokine, inflammatory and ageing factors, on the background of chronic hyperglycaemia. All these factors together contribute to an increased risk of vascular damage leading to atherosclerosis and vascular calcification. The xanthine oxidase system is a major contributor to the development of enhanced oxidative stress through generation of excessive free radicals. Current standard therapy is focused on controlling hyperglycaemia and screening/treatment of known co-morbidities. However, these therapies do not target oxidative stress. Allopurinol, a potent xanthine oxidase inhibitor has demonstrated beneficial effects on several parameters of vascular health such as reduction in oxidative stress, proteinuria, reversal of vascular damage, regression of ventricular hypertrophy and arresting the rate of progression of chronic kidney disease. A randomised clinical trial of Allopurinol for amelioration of oxidative stress, endothelial cell dysfunction and vascular calcification in subjects with type 2 DM may be helpful to explore its potential in this area.

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Allopurinol for the treatment of chronic kidney disease: asystematic review

Cited by 22 publications

References 53 publications

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Xanthine Oxidase Inhibitors for Improving Renal Function in Chronic Kidney Disease Patients: An Updated Systematic Review and Meta-Analysis

Drug therapies to delay the progression of chronic kidney disease

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

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