A Comparative Randomized and Placebo-controlled Short-term Trial of Aspirin and Dipyridamole for Overt Type-2 Diabetic Nephropathy

Khajehdehi, Parviz; Roozbeh, Jamshid; Mostafavi, H

doi:10.1080/003655902753679454

Cited by 30 publications

(14 citation statements)

References 17 publications

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“…A randomized, placebo-controlled, short-term trial of aspirin and dipyridamole for overt T2DM nephropathy demonstrated that a combination of the two drugs significantly reduces proteinuria [95]. In patients with peripheral artery disease and diabetes picotamide reduced the relative risk of vascular events [93].…”

Section: Antiplatelet Drugs: Results From Clinical Trialsmentioning

confidence: 99%

“…Other antiplatelet drugs such as indobufen, dipyridamole or picotamide have been investigated over the years in clinical practice [92][93][94][95]. A randomized, placebo-controlled, short-term trial of aspirin and dipyridamole for overt T2DM nephropathy demonstrated that a combination of the two drugs significantly reduces proteinuria [95].…”

Section: Antiplatelet Drugs: Results From Clinical Trialsmentioning

confidence: 99%

See 1 more Smart Citation

Platelet activation in type 2 diabetes mellitus

Ferroni¹,

Basili

Falco

et al. 2004

Journal of Thrombosis and Haemostasis

396

288

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The abnormal metabolic state that accompanies diabetes renders arteries susceptible to atherosclerosis, being capable of altering the functional properties of multiple cell types, including endothelium and platelets. In particular, an altered platelet metabolism and changes in intraplatelet signaling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. A variety of mechanisms may be responsible for enhanced platelet aggregation. Among them, hyperglycemia may represent a causal factor for in vivo platelet activation, and may be responsible for nonenzymatic glycation of platelet glycoproteins, causing changes in their structure and conformation, as well as alterations of membrane lipid dynamics. Furthermore, hyperglycemia-induced oxidative stress is responsible for enhanced peroxidation of arachidonic acid to form biologically active isoprostanes, which represents an important biochemical link between impaired glycemic control and persistent platelet activation. Finally, increased oxidative stress is responsible for activation of transcription factors and expression of redox-sensitive genes leading to a phenotypic switch of endothelium toward an adhesive, prothrombotic condition, initial platelet activation, adhesion and subsequent platelet aggregate formation. All this evidence is strengthened by the results of clinical trials documenting the beneficial effects of metabolic control on platelet function, and by the finding that aspirin treatment may even be more beneficial in diabetic than in high-risk non-diabetic patients. Attention to appropriate medical management of diabetic patients will have great impact on long-term outcome in this high-risk population. © 2004 International Society on Thrombosis and Haemostasis

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Section: Antiplatelet Drugs: Results From Clinical Trialsmentioning

confidence: 99%

Section: Antiplatelet Drugs: Results From Clinical Trialsmentioning

confidence: 99%

Platelet activation in type 2 diabetes mellitus

Ferroni¹,

Basili

Falco

et al. 2004

Journal of Thrombosis and Haemostasis

396

288

View full text Add to dashboard Cite

show abstract

“…Later studies showed that the administration of dipyridamole alone or combined with aspirin to patients with type 2 diabetes and DN resulted in 14.8% and 37.3% reductions in proteinuria, respectively. 30 A study has shown that PTF does not affect the arachidonic acid-induced thromboxane formation by human platelets. 31 However, an experimental study using an isolated perfused kidney model demonstrated that PTF had a protective renal effect during sepsis by modulating arachidonic acid metabolism within the kidney.…”

Section: Discussionmentioning

confidence: 99%

Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease

Navarro‐González

Mora‐Fernández

Fuentes

et al. 2015

Journal of the American Society of Nephrology

186

130

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Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean6SEM of 2.160. patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m 2 per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P,0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, 20.3% to 11.1%) in the control group and 214.9% (95% CI, 220.4% to 29.4%) in the PTF group (P=0.001). Urine TNF-a decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P,0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria. 26: 220-229, 201526: 220-229, . doi: 10.1681 Diabetic kidney disease (DKD) is the most frequent cause of CKD, and ESRD in type 2 diabetes is considered a medical catastrophe. 1 Strong evidence supports the blockade of the renin-angiotensin system (RAS), most commonly with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptors blockers (ARBs), as an established standard of care in these patients to reduce the risk of developing ESRD. 2 However, these therapies do not provide complete renal protection, 3 and diabetic patients continue to show a high renal risk, which is positively associated with residual albuminuria. 4 Unfortunately, recent studies evaluating new strategies to delay the progression of diabetic nephropathy (DN) have had little success. Trials with pyridoxamine or sulodexide failed to detect a renoprotective effect in patients with type 2 diabetes and renal impairment. 5,6 Meanwhile, studies with the endothelin antagonist avosentan, 7 J Am Soc Nephrol

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“…também avaliaram o uso de aspirina (1000 mg/dia) associada ou não ao dipiridamol em pacientes com DM tipo 2 e EUA ≥ 500 mg/dia, comparado com placebo, e observaram uma redução significativa de 15%, 14% e 37% na EUA nos grupos usando aspirina, dipiridamol ou a associação de ambos, respectivamente (40).…”

Section: Aspirina Em Pacientes Com Diabete Melitounclassified

Aspirina em baixa dosagem em pacientes com diabete melito: riscos e benefícios em relação às complicações macro e microvasculares

Camargo

Gross²,

Weinert³

et al. 2007

Arq Bras Endocrinol Metab

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RESUMOO uso de aspirina é recomendado como estratégia de prevenção cardiovascular em pacientes com diabete melito. Em decorrência do risco de eventos hemorrágicos e da hipótese de que poderia haver um agravamento das complicações microvasculares associado ao uso da aspirina, tem havido importante sub-utilização dessa terapia. Entretanto, está definido que o uso de aspirina não piora a retinopatia diabética e existem evidências de que também não afeta a função renal em doses usuais (150 mg/dia). Por outro lado, pacientes com diabete melito parecem necessitar de doses maiores do agente antiplaquetário, o que sugere que esses indivíduos apresentem a chamada "resistência à aspirina". Os mecanismos dessa resistência ainda não estão completamente esclarecidos, estando provavelmente relacionados à atividade plaquetária intrínseca anormal. Portanto, o emprego de terapêuticas antiplaquetárias alternativas ou a administração de doses maiores de aspirina (150-300 mg/dia) devem ser melhor avaliados em relação a um aumento da eficácia na prevenção da doença cardiovascular e também a possíveis efeitos nas complicações microvasculares no diabete melito. Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.

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A Comparative Randomized and Placebo-controlled Short-term Trial of Aspirin and Dipyridamole for Overt Type-2 Diabetic Nephropathy

Abstract: Short-term trial of aspirin and/or dipyridamole significantly reduces proteinuria of type-2 diabetic nephropathy, with the most prominent effect seen with combination of the 2 drugs.

Cited by 30 publications

References 17 publications

Platelet activation in type 2 diabetes mellitus

Platelet activation in type 2 diabetes mellitus

Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease

Aspirina em baixa dosagem em pacientes com diabete melito: riscos e benefícios em relação às complicações macro e microvasculares

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