OBJECTIVETo lessen the occurrence of contrast-induced nephropathy (CIN), the preventive measures of CIN were reviewed.

DATA SOURCESThe data used in this review were from PubMed with relevant English articles and from Chinese Knowledge Information (CNKI) published from 1989 to 2009. The search terms were "contrast medium", "contrast-induced nephropathy" and "prevention". Articles involved in prevention of CIN were selected.

STUDY SELECTIONCIN is the third most common cause of acute kidney injury and is associated with an unfavorable prognosis. The best treatment is prophylaxis because CIN can not be reversed or ameliorated.

RESULTSThirty articles were included. Among various preventive measures, pericatheterization hydration is almost universally accepted as an appropriate and safe measure to prevent CIN, although there is no agreement as to composition, amount, and timing of hydration. Based on the use of concomitant nephrotoxic agents or high doses of contrast medium (CM) is one of risk factors for CIN, discontinuation of potentially nephrotoxic drugs 2 - 3 days before and after the procedure until renal function recover, and using the lowest possible dose of CM can decrease the risk of CIN. It is promising that removing the majority of CM from the coronary sinus, before it enters the systemic circulation, during coronary angiography can reduce the risk for CIN in animal studies and in limited clinical trials. Inconsistent data exist with respect to application of some vasodilators (endothelin antagonists and adenosine antagonists) and antioxidants (N-acetylcysteine and statins) in preventing CIN in high-risk patients, and new vasodilators and antioxidants continue to be tested.

CONCLUSIONSPericatheterization hydration, discontinuation of nephrotoxic drugs, and using the lowest possible dose of CM are effective measures to lessen the risk for CIN. Other prophylactic strategies and some drugs are promising, but further confirmation is required.

Contrast Media ; adverse effects ; Humans ; Iodine ; adverse effects ; Kidney Diseases ; chemically induced ; prevention & control

OBJECTIVETo compare the effects of different contrast media on the renal function in children, and to investigate the prophylactic efficacy of hydration.

METHODSSixty patients on whom either intravenous pyelography (IVP) or enhanced CT scan was required were divided into high osmolality contrast media (HOCM) group (n = 27) and low osmolality contrast media (LOCM) group (n = 33), and each group was randomly subdivided into hydration group (HG) and non-hydration group (NHG). In HOCM group, HG had 14 cases and NHG had 13 cases; while in LOCM group, HG had 18 cases and NHG had 15 cases. A 1/5-tonic solution at a dose of 20 ml/kg was intravenously given immediately after the exposure to a contrast medium within 3 hours in the HG, while the NHG cases were not given any infusion.

RESULTSThere were no significant difference between HG and NHG in baseline serum creatinin (SCr) and creatinin clearance (Ccr). After exposure, in HOCM group, SCr of NHG (59.71 +/- 12.49) micromol/L significantly increased as compared with baseline (49.91 +/- 6.09) micromol/L (P < 0.05), while Ccr (97.81 +/- 15.10)ml/(min x 1.73 m(2)) decreased compared with baseline (71.33 +/- 7.51) ml/(min x 1.73 m(2)) (P < 0.05). No significant changes of SCr and Ccr were observed in the HG before (48.37 +/- 7.11) micromol/L, (99.81 +/- 15.41) ml/(min x 1.73 m(2)) and after (49.63 +/- 6.84) micromol/L, (88.29 +/- 12.75) ml/(min x 1.73 m(2)) (P > 0.05) the exposure to contrast medium. Contrast medium-associated nephropathy (CAN) was found in 3 cases in NHG (23.1%, 3/13) but none in HG (P > 0.05). In the LOCM group, there was no significant difference in SCr and Ccr before and after the exposure to the contrast media. The incidence of CAN was 6.7% (1/15) in the NHG and 11.1% (2/18) in the HG (P > 0.05). The average increase of SCr in HOCM group was significantly higher than that in LOCM group (Z = -2.42, P < 0.05). The average decrease of Ccr in HOCM group was significantly higher than that in LOCM group (Z = -2.83, P < 0.05). The SCr and Ccr of the 6 CAN cases in both HOCM and LOCM groups returned to baseline level within 2 weeks.

CONCLUSIONS(1) Children can develop reversible CAN after the exposure to high or low osmolality contrast medium. (2) The high osmolality contrast medium seemed to have more serious toxicity in renal function than low osmolality contrast medium. (3) The prophylactic use of hydration can effectively prevent CAN in patients who will expose to high osmolality contrast medium. (4) Children can develop reversible CAN after the exposure to low osmolality contrast medium even after hydration.

Child ; Contrast Media ; adverse effects ; Creatinine ; blood ; Fluid Therapy ; Humans ; Infusions, Intravenous ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Function Tests ; Osmolar Concentration

We investigated the effect of urinary alkalinization accomplished by intraperitoneal injection of sodium bicarbonate and acetazolamide on gentamicin nephrotoxicity in male Fisher 344rats. Forty rats (body weight 200-300g) were divided into four groups: control (gentamicin 20mg/kg, bid), high sodium load (gentamicin 20mg/kg, 25cc of saline, bid), low bicarbonate (gentamicin 20mg/kg, 25cc of sodium bicarbonate 100mEq/L, 2.5mg of Diamox, bid) and high bicarbonate (gentamicin 20mg/kg, 10cc of sodium bicarbonate 250mEq/L, 2.5mg of Diamox, bid) groups. All drugs and electrolyte solutions as mentioned above were administered intraperitoneally twice a day for seven days and changes in renal functions were studied. While salt loading failed to influence the severity of gentamicin nephrotoxicity, urinary alkalinization induced by bicarbonate and acetazolamide injection showed remarkable ameliorating effects on gentamicin nephrotoxicity. The high bicarbonate group exhibited more beneficial effects than the low bicarbonate group on gentamicin nephrotoxicity. So, urinary alkalinization seems to be an effective method for the prevention of gentamicin nephrotoxicity in rats.
Animal ; Bicarbonates/*administration and dosage ; Carbon Dioxide/urine ; Gentamicins/*toxicity ; Kidney Diseases/chemically induced/*prevention and control ; Male ; Random Allocation ; Rats ; Rats, Inbred F344

Cyclosporine (CsA) has improved patient and graft survival rates following solid-organ transplantation and has been increasingly applied with significant clinical benefits in the management of autoimmune diseases. However, the clinical use of CsA is often limited by acute and chronic nephrotoxicity, which remains a major problem. Acute nephrotoxicity depends on the dosage of CsA and seems to be caused by a reduction in renal blood flow related to afferent arteriolar vasoconstriction. However, the mechanisms underlying chronic CsA nephrotoxicity are not fully understood. Activation of the intrarenal renin-angiotensin system, increased release of endothelin-1, dysregulation of nitric oxide (NO) and NO synthase, upregulation of transforming growth factor-beta1, inappropriate apoptosis, stimulation of inflammatory mediators, and enhanced immunogenecity have all been implicated in the pathogenesis of chronic CsA nephrotoxicity. Reducing the CsA dose or withdrawing it and using combined nephroprotective drugs (mycophenolate mofetil, losartan, and pravastatin) may ameliorate chronic CsA-induced renal injury. This review discusses new insights and preventive strategies for this clinical dilemma.
Animals ; Chronic Disease ; Cyclosporine/*poisoning/therapeutic use ; Humans ; Immunosuppressive Agents/*poisoning/therapeutic use ; Kidney Diseases/*chemically induced/*prevention & control ; *Organ Transplantation ; Research Support, Non-U.S. Gov't

To systemically evaluate the efficacy and safety of salvianolate intravenous drip in combination with hydration against contrast-induced nephropathy( CIN),and guide clinical medication. Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,VIP,Wan Fang database,CNKI) were retrieved to collect the randomized controlled trials( RCTs) about the efficacy of salvianolate intravenous drip in combination with hydration( trial group) vs routine hydration( control group) in the prevention of contrastinduced nephropathy. The methodological quality of the RCTs was evaluated by using the Cochrane 5. 1. 0 Bias Risks Assessment Tool.The data were extracted and Meta-analysis was conducted by Reviewer Manager 5. 3. Egger's test and non-parametric clipping method were used to evaluate publication bias. A total of 9 RCTs with 2 186 participants were included. RESULTS:: of Meta-analysis showed that the incidence of contrast-induced nephropathy of trial group was significantly higher than that of control group( RR = 0. 46,95% CI[0. 35,0. 59],P<0. 001). Subgroup analysis showed that the incidences of CIN in patients with acute coronary syndrome( ACS) undergoing PCI,in patients with the average age≥65 years,in patients who received mean contrast volume ≥200 m L,in patients with serum creatinine( Scr) ≥ 80 μmol,or in patients who received intraoperative administration of salvianolate or PCI were higher than those in control group,with statistically significant differences( P<0. 05). The experimental group was superior to the control group in improving the indexes of renal function after operation,and the difference was statistically significant( P<0. 05). No study reported the incidence of adverse reactions( ADRs). The funnel plots of the incidence of CIN showed potential publication bias. The results of Egger's linear regression showed that there was certain publication bias. Sensitivity analysis,funnel plot,and " trim and fill" showed that the results of this study were stable and reliable. Salvianolate combined with routine hydration showed definite clinical efficacy in the prevention of contrast-induced nephropathy. However,exact conclusion should be further verified by additional high-quality,multi-centre,and large-scale RCT studies.
Contrast Media ; adverse effects ; Humans ; Kidney Diseases ; chemically induced ; prevention & control ; Percutaneous Coronary Intervention ; Plant Extracts ; therapeutic use ; Randomized Controlled Trials as Topic

Aged ; Animals ; Cyclosporine ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Graft Rejection ; drug therapy ; prevention & control ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Diseases ; chemically induced ; prevention & control ; Kidney Transplantation ; Phytotherapy

Cyclosporine (CsA) has improved patient and graft survival rates following solid-organ transplantation and has shown significant clinical benefits in the management of autoimmune diseases. However, the clinical use of CsA is often limited by acute or chronic nephropathy, which remains a major problem. Acute nephropathy depends on the dosage of CsA and appears to be caused by a reduction in renal blood flow related to afferent arteriolar vasoconstriction. However, the mechanisms underlying chronic CsA nephropathy are not completely understood. Activation of the intrarenal renin-angiotensin system (RAS), increased release of endothelin-1, dysregulation of nitric oxide (NO) and NO synthase, up-regulation of transforming growth factor-beta1 (TGF-beta1), inappropriate apoptosis, stimulation of inflammatory mediators, enhanced innate immunity, endoplasmic reticulum stress, and autophagy have all been implicated in the pathogenesis of chronic CsA nephropathy. Reducing the CsA dosage or using other renoprotective drugs (angiotensin II receptor antagonist, mycophenolate mofetil, and statins, etc.) may ameliorate chronic CsA-induced renal injury. This review discusses old and new concepts in CsA nephropathy and preventive strategies for this clinical dilemma
Animals ; Chronic Disease ; Cyclosporine/*adverse effects ; Humans ; Immunosuppressive Agents/*adverse effects ; Kidney/*drug effects/immunology/metabolism/pathology ; Kidney Diseases/*chemically induced/immunology/metabolism/pathology/prevention & control ; Risk Factors ; Signal Transduction/*drug effects

OBJECTIVETo investigate the effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with chronic cyclosporine A nephropathy.

METHODSMale Sprague-Dawley rats on low-salt diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000 U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy model. Masson staining was used to examine fibrin deposition. Western blotting and reversal transcription polymerase chain reaction were employed to evaluate urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene expressions, respectively.

RESULTSCsA can increase fibrin deposition and the expression of TGF-beta1 in the renal tissue, which were significantly reduced after uPA treatment (P<0.05).

CONCLUSIONContinuous low-dose uPA treatment can reduce renal interstitial fibrosis in rats possibly in association with its inhibitory effect on TGF-beta1 expression.

Animals ; Cyclosporine ; Fibrosis ; prevention & control ; Kidney ; pathology ; Kidney Diseases ; chemically induced ; drug therapy ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Urokinase-Type Plasminogen Activator ; pharmacology ; therapeutic use

OBJECTIVETo study the prevention effect of salidroside on contrast-induced-nephropathy (CIN) and its underlying mechanism.

METHODSA total of 24 Wistar rats were randomly divided into 4 groups with 6 in each group. Rats were firstly administrated with normal saline (control and model groups), N-acetylcysteine (NAC, NAC group) and salidroside (salidroside group) for 7 days before model establishment in each group, respectively. Histopathological analysis was performed by periodic acid-Schiff (PAS) staining. Oxidative stress related parameters including superoxide dismutase (SOD) and methane dicarboxylic aldehyde (MDA), nitric oxide (NO), angiotensin II (Ang II), 8-hydroxy-2'-deoxyguanosine (8-OHdG), mRNA and protein levels of endothelial nitric oxide synthase (eNOS), and nitric oxide synthase (NOS) activity were measured.

RESULTSCompared with the control group, the levels of MDA, Ang II and 8-OHdG were all significantly increased and levels of SOD, NO, and eNOS mRNA and protein were decreased significantly in the model group (P<0.05). Meanwhile, the NOS activity was also significantly decreased in the model group (P<0.05). In addition, the levels of these parameters were all improved in the NAC (P<0.05) and salidroside groups and no significant different was found between these two groups (P>0.05).

CONCLUSIONSalidroside can be the potential substitute of NAC to prevent CIN. The underlying mechanism may be associated with oxidative stress damage caused by contrast agents.

Acetylcysteine ; pharmacology ; Animals ; Contrast Media ; adverse effects ; Cytoprotection ; drug effects ; Glucosides ; pharmacology ; Kidney ; drug effects ; pathology ; Kidney Diseases ; chemically induced ; prevention & control ; Oxidative Stress ; drug effects ; Phenols ; pharmacology ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects

PURPOSE: To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing coronary angiography. MATERIALS AND METHODS: This randomized 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 intravenously 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 compared 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 between the two groups. The incidence of CIN also did not differ between the nicorandil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference between 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). CONCLUSION: Prophylactic intravenous infusion of nicorandil did not decrease the incidence of CIN in patients with renal dysfunction undergoing coronary angiography.
Administration, Intravenous ; Aged ; Contrast Media/*adverse effects ; Coronary Angiography/*adverse effects/methods ; Creatinine/blood ; Female ; Glomerular Filtration Rate ; Humans ; Incidence ; Kidney Diseases/*chemically induced/epidemiology/physiopathology/*prevention & control ; Male ; Middle Aged ; Nicorandil/*administration & dosage/therapeutic use