contrast induced nephropathy

Abstract: Contrast induced nephropathy (CIN) remains to be a potentially serious complication following coronary angiography. CIN has become the third leading cause of hospital acquired acute renal failure. This clinical trial was performed to assess the preventive effects of oral nicorandil against CIN in type 2 diabetics undergoing coronary angiography. A total of 150 type 2 diabetics were randomly divided into three groups, basic treatment group (n=51), standard nicorandil therapy group (n=49, nicorandil 5 mg, 3 times/d were used 2 days before and 3 days after an- giography), and intensive nicorandil therapy group (n=50, nicorandil 10 mg, 3 times/d were used 2 days before and 3 days after angiography). Renal functions were assessed at the time of hospital admission and on days 1, 2, and 3 after angiography. CIN occurred in 13 of 150 patients (8.67%). The incidence of CIN was lower in the nicorandil treatment groups than in the basic treatment group (8.16% vs 11.76%, 6% vs 11.76%, P<0.05), and a more signifi- cant decrease in the incidence of CIN in the intensive nicorandil therapy group (6% vs 11.76%, P<0.01). Compared with the basic treatment group, a lower proportion of patients in the nicorandil treatment groups had an eGFR decrease of 25% or greater (10.2% vs 13.73%, 8% vs 13.73%, P<0.05); patients with an eGFR decrease of 25% or greater accounted for an even lower proportion in the intensive nicorandil therapy group (8% vs 13.73%, P<0.01). Multiple Logistic Regression showed that administration of nicorandil, advanced age, lower eGFR levels, and higher dose of contrast volume were independent risk factors of CIN. In conclusion, prophylactic treatment with nicorandil in type 2 diabetics undergoing coronary angiography could effectively prevent CIN, and intensive nicorandil therapy could be more effective.

Abstract: Objective: In order to evaluate the efficacy of ischemic post-conditioning (IPTC) for the contrast induced nephropathy on patients with acute coronary syndrome. Methods: One-hundred and ninety-four patients with acute coronary syndrome and percutaneous coronary intervention (PCI) were enrolled and analyzed retrospectively. De- pending on whether or not performing IPTC, the patients were divided into control group (101 cases) and IPTC group (93 cases). In the control group, PCI was used directly for the patients. Whereas in the IPTC group, IPTC method was employed firstly as follows: 1 minute after the reconnection of infarcted coronary artery, the balloon was inflated and deflated repeatedly at the occluded area under low pressure for 3 times. Then the PCI was performed on the patients. The clinical baseline data, renal function index, incidences of contrast induced nephropathy and major adverse cardiovascular events were recorded and compared. Results: There was no significant difference on basic clinical information (including gender, age, body mass index, clinical disease, number of coronary lesion vessels, dosage of contrast agent and left ventricular ejection fraction) between two groups (all P>0.05). For the serum creatinine (Scr), cystatin C (CysC), estimated glomerular filtration rate (eGFR) and urine neutrophil gelatinase as- sociated lipocalin (NGAL) levels before the surgery, there were also no significant differences between two groups (all P>0.05). Forty-eight hours after the surgery, the levels of Scr, CysC and NGAL in IPTC group were all significantly lower than that in control group (all P<0.05). There was significantly higher eGFR level in IPTC group than that in control group (P<0.05). For the incidences of contrast induced nephropathy and major adverse cardiovascular events, there were significantly lower rates in IPTC group (5.38% and 7.53%, respectively) than that in control group (21.78% and 30.69% respectively, both P<0.05). Conclusion: IPTC could promote the protection on renal function for the patients with acute coronary syndrome and PCI treatment, decrease the incidence of contrast induced nephropathy, and played a positive role in prognosis improvement. This approach deserves more researches and applications in the future.

contrast media are cleared from the plasma at the rate of 50-70 mL/min, approximately about 80% are cleared from the plasma in about four to five hours of hemodialysis. Many studies done to see the effect of hemodialysis, in patients already having chronic kidney disease after they got exposed to contrast media, to decrease the effect on renal function, did not show any promising effect. Also studies done to see the effect of prophylactic hemodialysis, which was done just after patient got exposed to contrast did not decrease the incidence of CIN or other adverse effects⁽⁸⁶’⁸⁷⁾.But in one study, where patients where given adequate hydration versus hydration and hemodialysis immediately after contrast exposure. Here, prophylactic hemodialysis showed less creatinine increase and decreased requirement of further renal replacement therapy⁽⁸⁸⁾.

The local institutional review board approved the study protocol, and we obtained written informed consent from all patients. Between Jan- uary 2005 and March 2007, a total of 100 consecutive patients were included in the study. The patients were referred by our in-house stroke unit. Patients with clinical signs of acute cerebral ischemia first undergo plain cranial CT examination, which is followed by a con- trast-enhanced CT perfusion study (CTP) of the brain if results of the plain scan show no early signs of ischemic infarction or hemorrhage. Precontrast SCr samples were obtained on admission, but CM was administered without knowledge of these values or of any informa- tion on the pre-existing renal function, either by the referring physi- cian or by the radiologist. Patients were ineligible for the study if they had known hypersensitivity to iodine-containing contrast agents, hy- perthyroidism, or thyroid malignant tumors. Also, nursing and preg- nant patients were excluded, as were patients scheduled to receive any medication to prevent CIN or patients undergoing hemodialysis. Co- morbidities such as diabetes and hypertension—as potential risk fac- tors for CIN—were initially not registered because contrast adminis- tration in the clinical setting of stroke was performed regardless of pre-existing renal function. Possible risk factors influencing CIN 10,22,27 were then evaluated retrospectively by analysis of the pa-

of delayed renal impairment in 8.2% of patients (6/73) at 6 months after CAS was also in agreement with that in these previous reports. Although CIN occurred in 7 patients, only 1 developed delayed renal impairment. Krol et al 24 reported that a late rise in SCr level may not have been solely due to the contrast use; many factors such as dehydration, drugs, and hemodynamic complications might have contributed to a late increase in SCr level. All patients who exhibited delayed renal impairment had a preoperative decrease in eGFR (moderate or more in CKD stage III), so there is an increased probability that renal disease had progressed due to new or worsening medical conditions rather than contrast exposure.

The study was a prospective, double-blind, placebo con- trolled, randomized clinical trial. The patients were ran- domly assigned on a 1:1 fashion via the balanced block randomization method using computer generated ran- dom numbers to receive NAC or placebo by randomly drawing sealed envelopes containing either the active drug or matching placebo. NAC and placebo were pre- pared by Darmanyab Co. (agency of Zambon Group S.p.A, Milan, Italy) matched in appearance, packing, and way of use. NAC was orally administered at the dose of 600 mg twice a day, starting 24 h before the procedure (two doses before and two doses after the procedure). The patients were hydrated orally and intravenously. All the patients were encouraged to drink fluids like water and fruit juice for at least 8 glasses over 12 h before the proce- dure and memorize the number of glasses. The oral pre- procedural hydration was estimated by multiplying the number of glasses drunk by 200 mL (estimated volume of a glass). In addition, the patients were hydrated intrave- nously by 1 L of 0.9 normal saline, which was com- menced in the catheterization laboratory. Serum creatinine and urea nitrogen concentrations were meas- ured prior to coronary angiography and 48 h after the pro- cedure. Serum creatinine concentration prior to coronary angiography was referred to as the baseline level. Creati- nine clearance (CrCl) was estimated with the Cockcroft- Gault formula, where CrCl = ([140-age]*weight(kg)/ serum creatinine(mg/dL)*72), with adjustment for female sex (CrCl female = CrCl*0.85)[38]. Coronary angiog- raphies were performed with the low osmolar nonionic contrast medium Iohexol (Omnipaque; Amersham Health, Co. Cork, Ireland) or the iso-osmolar nonionic contrast medium Iodixanol (Visipaque;GE Healthcare, Co. Cork, Ireland) and/or the high osmolar ionic medium Diatrizoate meglumine/sodium (Urografin; Schering AG, Berlin, Germany).

Purpose: To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dys- function undergoing coronary angiography. Materials and Methods: This ran- domized controlled multicenter study enrolled a total of 166 patients (nicorandil n=81; control n=85) with an estimated glomerular filtration rate <60 mL/min. Nicorandil 12 mg dissolved in 100 mL of 0.9% saline was administered intrave- nously for 30 minutes just prior to coronary angiography in the nicorandil group. The same volume of only saline was given to the control group. The primary end- point was the incidence of CIN, defined as >0.5 mg/dL increase or >25% rise in serum creatinine (SCr) concentration within 48 hours of contrast exposure com- pared to baseline. Results: The final analysis included 149 patients (nicorandil n=73; control n=76). The baseline characteristics and the total volume of the used contrast (Iodixanol, 125.6±69.1 mL vs. 126.9±74.6 mL, p=0.916) were similar be- tween the two groups. The incidence of CIN also did not differ between the nicor- andil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference be- tween the two groups in the relative change in SCr from baseline to peak level within 48 hours after coronary angiography (-1.58±24.07% vs. 0.96±17.49%, p=0.464), although the nicorandil group showed less absolute change in SCr than the control group (-0.01±0.43 mg/mL vs. 0.02±0.31 mg/mL, p=0.005). Conclu- sion: Prophylactic intravenous infusion of nicorandil did not decrease the inci- dence of CIN in patients with renal dysfunction undergoing coronary angiography.

Background : Percutaneous coronary intervention is now the best way of man- agement of acute coronary syndrome (ACS). Contrast induced nephropathy is a serious complication and greatly dependent on several factors. It is still unclear whether the vascular access migrates CIN risk. Objective : To study the impact of Radial Access (RA) compared with Femoral Access (FA) on developing con- trast-induced nephropathy (CIN) in patients undergoing invasive management of acute coronary syndrome (ACS). Methods : Sixty patients eligible for invasive management of ACS at cardiology department (Menoufia University hospital and National Heart Institute) were randomized into two groups. Group I: in- cluded 30 patients with femoral approach and Group II: included 30 patients with radial approach. The occurrence of CIN estimated by KDIGO definition (absolute increase in serum creatinine (SCr) by ≥0.5 mg/dl within 48 hours; or increase in SCr to ≥25% of baseline) was estimated in both groups. Results : On- ly 9 patients (15%) developed CIN, 5 patients (55.6%) of them underwent PCI through FA without statistically significant difference between the two ap- proaches. Conclusion : CIN is considered a potential complication of percuta- neous coronary intervention (PCI). Our study did not show the preference of using an approach over the other.

Active mediators such as nitric oxide and prostaglandins play an active role in the regulation of renal perfusion. The intrarenal production of these vasodilators is responsible for the maintenance of perfusion and oxygen supply in the medulla; therefore, reductions in the availability of these mediators can promote nephropathy. It has been suggested that a number of factors are implicated in this decrease in nitric oxide concentration during CIN, although the role of CM hyperosmolality or of cellular necrosis subsequent to the administration of CM is still doubtful. According to some recent studies, CM could induce a depletion of cofactors involved in nitric oxide synthesis, such as tetrahydrobiopterin, or modify substrates, such as L- arginine (22) , or interfere with its synthesis through the nuclear factor κB (NFκB), which inhibits

Perhaps more importantly, we could not study patients with RCM exposures shortly after ICU admission, since we required a pre-scan urine collection. These patients may well differ from those scanned later in their ICU stays. For example, there might be salutary effects of the markedly positive pre-scan fluid balances among estab- lished ICU patients. We therefore cannot exclude a possi- bly substantial CIN risk for patients just arriving to the ICU. We also could not study patients whose physicians felt the risk of RCM exposure outweighed the benefits. However, scanning with contrast was judged preferable from an imaging standpoint for fewer than 10% of patients scanned without contrast, including those who could not be matched.

Iodixanol, an intravenous contrast media, significantly increases adenosine receptor gene expression in normal mice. Since the adenosine release and adenosine receptor stimulation were proposed to be pathophysiologic factors in the development of CIN [2], although the CIN was not induced in the normal mice, we presume that the adeno- sine receptor expression increase we found in normal mice may play a role in the CIN development by exac- erbating adenosine-induced vasoconstriction. Further stu- dy should focus on whether this alteration really plays a role in CIN development using animal models that actu- ally developed CIN. We plan to use db/db and hyperten- sion mice treated with Iodixanol or other contrast media to do this further study.

Contrast-induced nephropathy is a common complica- tion after coronary or peripheral angiography. Patients at increased risk include those with previous renal failure, diabetes mellitus, heart failure, shock states and elderly. [4] Acetylcystine represents a simple, non-toxic, low-cost, and wide available intervention. The majority of previous trials that tested this intervention had small sample sizes, inadequate methodology, have reached conflicting results, and have not assessed patient-important out- comes. At present there is limited evidence that acetyl- cysteine together with hydration may be useful as standard prophylactic procedure in patients at high risk for CIN. Therefore, a well designed trial with adequate sta- tistical power is needed to resolve the question of acetyl- cysteine for the prevention of CIN.

CIN was defined as relative increase by 25% of serum creatinine from the baseline value within 5 days [24]. CT scans were performed according to the institute’s stand- ard protocol with the use of the same agent, iopamidol, a low osmolarity, non ionic, iodinated contrast medium (Iopamiro 370, Bracco). The quantity of infused contrast agent was determined by the radiologists depending on the type of CT imaging, and patients related characteris- tics and was recorded in a dedicated chart. The dose of contrast medium for contrast-enhanced CT was gener- ally 0.5–2 ml/Kg of body weight. The minimum used dose was 100 ml and 150 ml was the maximum dose that was given. Measurement of serum cystatin-C and 8- isoprostane were performed with commercial enzyme- linked immunoassay kits (Cayman CC, USA).

Dyslipidemia is common in diabetic patients. Typical dyslipidemia of diabetic patients is hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C) levels, high small and dense low-density lipoprotein (LDL) particles levels [8]. Most of diabetic patients have complications such as retinopathy, nephropathy, and neuropathy. Nearly 40% of diabetic patients have the risk of developing diabetic nephropathy [9]. Diabetic nephropathy is characterized by an increased in albuminuria and a decreased in creatinine clearance. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effective reduce both total and LDL cholesterol. Studies have found unequivocally that lowering LDL-C, particularly with statins, decreases the risk of cardiovascular deaths and events [10]. Recently years, there has been increasing interest in the role of statins in decreasing CIN risk in patients receiving contrast media [11-13]. This is owing to both their ability to anti-inflammatory and improve endothelial function properties, and their anti-apoptotic and anti-oxidant effects [14-16]. Rosuvastatin is a new generation of statin [14], which reduces levels of circulating LDL-C. In addition to its beneficial cholesterol lowering effects, rosuvastatin has been shown to protect against inflammatory, oxidant, and thrombotic effects, and may improve endothelial function. These effects of rosuvastatin have been translated into beneficial effects on atherosclerosis and have resulted in a significant reduc- tion in cardiovascular events [17]. Our recent study reports

It is uncertain whether contrast-induced nephropathy is an important entity in intensive care medicine. Indeed, no data are available on the incidence of contrast-induced nephropathy in the critically ill or on whether it has a profound impact on morbidity and mortality in these patients. However, the critically ill form an important group at risk for development of contrast-induced nephropathy. Renal failure is a common complication of critical illness; the incidence of acute renal failure among intensive care admissions reaches 15–20%, with 4–6% requiring some form of acute renal replacement therapy [71]. Furthermore, the critically ill are often subject to a number of risk factors for the development of contrast-induced nephropathy (e.g. pre-existing renal insufficiency, especially diabetic nephropathy), factors that influence renal perfusion (e.g. hypovolaemia) and administration of concomitant nephrotoxic medication. It has been shown that even modest degrees of acute renal failure without need for haemodialysis increase the risk for death by fivefold [7].

including saline hydration, diuretics, mannitol, calcium channel antagonists, theophylline, endothelin receptor antagonists, and dopamine, have been used in an attempt to prevent CIN [6-9]. Hydration with normal saline solution is the most widely accepted preventive intervention [9,10]. But the nephropathy occurred in 20~30% who received the recommend treatment [11,12], it means current treatments are not enough and the optimal strategy to prevent CIN has not been established.

Contrast induced nephropathy (CIN) is one of the major complications of coronary intervention and has been correlated with mortality. CIN is responsible for approximately 11% of all iatrogenic renal insufficiency and is the third most common cause of hospital-acquired renal failure after decreased renal perfusion and nephrotoxic drugs. CIN is traditionally defined as an increase in serum creatinine of either 0.5 mg/dl or 25% from baseline within 72 h of exposure. The association of term adverse clinical outcomes is well established. To find out occurrence of contrast induced nephropathy in patients undergoing primary PCI and its relation with duration of symptoms and contrast volume.

Apoptosis also contributed to the occurrence of CIN. Cumulative evidence has suggested that CM leads to renal tubular cell apoptosis through the ROS pathway and the intrinsic apoptotic pathway [21, 22]. Our study proved that Caspase-3 activation, in other words, the intrin- sic apoptotic pathway was involved in the CM induced renal injury, as reported in our recent studies [23, 24] and other reports [25]. CS might exert its inhibitory effect on apoptosis via direct inhibition of caspases. The present study demonstrated that CS pre-administration could protect against CIN. Our data indicated that CS ameliorated deterioration of renal function and histopathological kidney injury in CIN rats, Figure 5. Scanning electron microscopic of kidney (×10,000). In the C group,

What it is also interesting about this study is that sev- eral prophylactic measures for CIN were undertaken in some of the examined patients; N-acetylcysteine, bicar- bonate and additional pre-emptive fluids were given in 79% of contrast patients, but none of these methods re- vealed significant improvement of post-CT-scan renal function. Of note, after decades of debate on prevention of CIN, meta-analyses still do not provide significantly effective measures, in most cases advocating significantly larger trials than those currently performed [10]. As sug- gested by Cely and colleagues, critically ill patients undergoing administration of contrast media should be enrolled in most of these studies to definitely clarify the additional CIN risk in this high risk of AKI population [11].

Recent advances in medical sciences, especially in imaging, have dramatically increased the use of contrast agents. The constantly changing nature of medicine and the availability of new informa- tion, such as new pharmaceutical formulations, have necessitated periodic revisions and drafting of new guidelines for the safe use of intravenous contrast agents in radiology. This study examined the majority of guidelines, articles, and authoritative references available on the use of intraven- ous contrast agents in adults to reduce the risk of contrast-induced nephropathy. The search en- gines of PubMed, Web of Science, Scopus, and Google Scholar were used, and relevant English ar- ticles cited at least twice between 1979 and 2014 were studied. Review of the collected papers showed no consensus among them for guidelines on the incidence of contrast-induced nephropa- thy in patients at risk. Different formulas were used to calculate estimated glomerular filtration rate, which could be problematic in some cases. Further studies are needed for unification of ex- isting guidelines.