Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol

Abstract

BackgroundContrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease.Methods/DesignWe designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance.DiscussionContrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials.Trial registrationClinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study

“…The beneficial effect of NAC is mostly observed in patients with pre-existing renal dysfunction, particularly in cases of contrast-induced nephropathy [10,12]. In the current study, where patients had no baseline renal impairment, a resolution of AKI in patients receiving adjuvant NAC during COL therapy was not demonstrated clearly.…”

“…NAC is commonly used as a mucolytic agent, but it has powerful anti-inflammatory and antioxidant activities [9]. The protective effect of NAC against oxidative stress has been demonstrated in different types of conditions, such as sepsis, chronic obstructive pulmonary disease (COPD), and contrastinduced nephropathy [10][11][12]. Beneficial effects of NAC, in terms of the resolution of renal injury, have also been demonstrated [8].…”

Measurement of renal function in patients with chronic kidney disease

“…While inulin continues to be useful particularly for mechanistic studies, especially when coupled with measurement of renal clearance of para‐aminohippuric acid (PAH) to assess renal plasma flow , it is seldom used nowadays, partly due to the complex methodology described above but also as a result of limitations in the supply of this agent. Nevertheless, the classic urinary inulin clearance method remains the benchmark by which newer, and often simpler, methods of GFR assessment are compared.…”

Screening of Renal Function in Patients with Chronic Kidney Disease

“…As a result, serum inulin concentrations are often lower than expected, which in turn leads to an overestimation of GFR, frequently exceeding urinary inulin clearance by ∼5-10 ml min −1 [17,19]. While inulin continues to be useful particularly for mechanistic studies, especially when coupled with measurement of renal clearance of para-aminohippuric acid (PAH) to assess renal plasma flow [20,21], it is seldom used nowadays, partly due to the complex methodology described above but also as a result of limitations in the supply of this agent. Nevertheless, the classic urinary inulin clearance method remains the benchmark by which newer, and often simpler, methods of GFR assessment are compared.…”