Aspirin and Renal Disease Progression in Patients With Type 2 Diabetes
Status:
Unknown status
Trial end date:
2018-09-01
Target enrollment:
Participant gender:
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.