Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes

Summary

The pathophysiology of diabetes is multifactorial. Beyond genetic susceptibility loci, a lot of acquired risk factors are involved in the development and progression of the disease. Chronic complications of diabetes can be divided into vascular and nonvascular. The risk of developing complications increases with the duration of hyperglycemia, and usually become apparent in the second decade of hyperglycemia. Vascular complications are further subdivided into microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, peripheral arterial disease, cerebrovascular disease). It is estimated that the annual decline of estimated glomerular filtration rate (eGFR) in diabetic adults is about 2.1-2.7 ml/min.

While there is consolidated evidence about the use of aspirin (ASA) for secondary prevention in diabetic patients, there is no consensus on the use in primary prevention; the use of ASA in these patients is at physician discretion.

ASA is an effective antithrombotic agent that inhibits the production of thromboxane (Tx) A2 and other prostaglandins by blocking cyclooxygenase (COX). In patients treated with aspirin, serum TxB₂ level is the most reliable in vivo indicator of COX-1 inhibition than TxA2, due to its short half-life and artifacts associated with platelet activation ex vivo.

COX are present in the kidney in the macula densa, in the medulla and in the interstitium. Experimental animals models have demonstrated that COX are involved in regulation of renal blood flow. In particular, in a murine animal model, after the administration of COX inhibitors such as aspirin and celecoxib, it was observed an improvement in renal plasma flow and eGFR, suggesting a role for Tx in the progression of renal damage However, data on the relationship between aspirin and renal function in humans are scarce. In a recent work lead on a large cohort of 800 patients with non-valvular atrial fibrillation, ASA use was associated with a reduced progression of eGFR \<45 ml/min during 2 years of follow-up. Furthermore, basal levels of urinary excretion of TxB2, correlated inversely with the use of aspirin and with the decrease of eGFR at follow-up.

The aim of the study is to evaluate the decline in renal function in diabetic patients treated with low-dose aspirin (100 mg/day) vs. untreated diabetic patients.

Conditions

• Diabetes

Interventions

DRUG

Aspirin

Patients suffering from type 2 diabetes will be randomized to receive 100 mg/day or placebo for one year

OTHER

Placebo

Patients in this arm will be treated with placebo

Sponsors & Collaborators

• University of Roma La Sapienza

  lead OTHER

Principal Investigators

• Francesco Violi, MD · University of Roma La Sapienza

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-01-31

Primary Completion

2018-01-31

Completion

2018-09-30

Countries

• Italy

Study Locations