Radiocontrast Media-Induced Renal Injury – Saline Is Effective in Prevention

Advances in imaging techniques have reduced our reliance on iodinated contrast agents and X-ray studies. However, use of intravenous or arterial X-ray contrast agents is still widespread, and likely to continue for sometime. Radiocontrast-induced nephropathy (RCIN) is a well-described, accepted risk of such a procedure. The incidence of RCIN is difficult to quantify due to definitions, but it is a significant cause of renal morbidity. In an unselected patient population undergoing coronary angiography the incidence approached 15% [1]. After a contrast procedure, a rise in creatinine usually reaches an azimuth at 3–5 days, but often returns to baseline by day 10 [2]. Risk factors for development of RCIN include previous chronic renal impairment, diabetes mellitus, cirrhosis, congestive cardiac failure and possibly multiple myeloma. Patients with underlying renal disease have more than six times the risk of developing renal impairment. In addition, risk factors appear multiplicative and the severity of RCIN is also related to the total dose of iodinated contrast media together with the properties of the contrast agent. Most cases are mild, asymptomatic and most (∼70%) recover completely without dialysis. However, some only partially recover (∼10%) and some never recover (∼20%) [3].After contrast infusion there is initial vasodilatation of the renal vasculature followed by intense and prolonged vasoconstriction. This is not consistent in all tissue beds, for instance in muscle the reverse occurs. There are also changes within the kidney and studies of intrarenal haemodynamics suggest a reduction in medullary perfusion, possible through medullary ‘steal’. Some of the vasoconstriction may be explained by tubuloglomerular feedback mechanisms stimulated by the large osmotic load delivered to the juxtaglomerular apparatus after a contrast load [4]. However, a number of other mediators of vascular changes have been implicated, including adenosine, angiotensin II, calcium, endothelins, prostanoids, nitric oxide and oxidant stress. In addition to the vascular effects there is also evidence that contrast media causes direct tubulotoxicity, resulting in tubular vacuolation and cellular degeneration as well as enzymuria with N-acetyl-β-glucosamine, β2-microglobulin and alkaline phosphatase [2].There have been a number of attempts to develop agents to protect the kidney from contrast-induced injury. Studies have examined the effects of dopamine, diuretics, calcium antagonist, mannitol, endothelin antagonists, atrial natriuretic peptide and N-acteylcysteine. However, the most conceptually simple and attractive hypotheses has been the administration of saline to volume expand patients prior to the administration of contrast media. Indeed most animal models employ dehydration as a strategy for enhancing contrast injury in the study of this condition, with good evidence that the vascular changes are more pronounced in these animals [5]. In many centres, pre-hydration is standard, despite the lack of good prospective, randomized, controlled studies demonstrating the benefit of this approach. Some papers have suggested benefit of saline hydration [6]while others do not support this treatment [7]. Some randomized control studies looking at other agents are disadvantaged by the lack of ‘no-hydration’ controls [8].This issue of Nephron Clinical Practice includes a paper that studies the potential benefit of pre-contrast hydration and adds much needed evidence in a field where anecdote and tradition have long prevailed The study was initially designed to enrol 160 patients in order to detect a 10% incidence of contrast-induced events, enough to validate the hypothesis that there was no difference between the saline hydration and no-hydration groups. However, the study was terminated early with a sample size of n = 53 because interim analysis revealed a significantly lower level of events in the hydration group and it was presumably felt to be unethical to continue with the no-hydration control group. Thus, 27 patients were given 1 ml/kg/h normal saline for 24 h, starting 12 h prior to the procedure, while 26 patients received no hydration. There was an approximately 4% incidence of RCIN in the saline group compared to nearly 35% in the no-hydration group (p = 0.005). However, it should be noted that the control incidence was rather high compared to historical data, an observation the authors suggest may be due to higher co-morbidity in their patients. Nevertheless, these results are statistically compelling and the implications are large.Since saline is relatively cheap and safe, this study suggests that saline hydration should be considered in all patients undergoing investigations involving the use of iodinated contrast media. This is especially true for patients with pre-existing risk factors for the development of RCIN. If one accepts that rehydration is a valid goal, then ancillary questions include what fluid should be used for hydration and how much hydration is enough? The first question has been addressed in a study comparing 0.9 and 0.45% saline in the prevention of RCIN. This study suggests that the former is superior, because it expands intravascular volume more effectively [9]. Further work needs to be performed to establish the duration of therapy. While some authors have suggested that providing oral rehydration prior to a procedure is sufficient [10], it is not known whether an intravenous infusion for a shorter time would be more effective. Clearly this is important information for the development of protocols and to minimize risk to patients who are not in hospital prior to the procedure.