evaluating the association between hyperuricemia and

SM Journal of Nephrology and Therapeutics

Gr upSM

How to cite this article Abdallah E, Mosbah O, El-Shistawy S, Khalifa G, Badr M and Amin AA. Evaluating the Association between Hyperuricemia and Contrast Induced-Acute Kidney Injury in Patients with Acute ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention. SM J Nephrol Therap.

2016; 1(1): 1003. https://dx.doi.org/10.36876/smjnt.1003

OPEN ACCESS

ISSN: 2573-3613

IntroductionContrast-Induced Acute Kidney Injury (CI-AKI) is the third most common cause of in-hospital

acute kidney injury (AKI) and accounts for 10% of total cases [1]. CI-AKI continues to be one of the most common major adverse side effect of cardiac catheterization, and is associated with short- and long-term morbidity and mortality [2,3]. This is particularly true in the population presenting with acute ST-Elevation Myocardial Infarction (STEMI). A recent study evaluating the epidemiology of CI-AKI in over 8000 patients undergoing PCI found that CI-AKI occurred in 12% of STEMI, which was significantly higher compared with patients undergoing non-emergent catheterization (9.2% in unstable angina and NSTEMI patients and 4.5% undergoing elective PCI). Even in patients with baseline Glomerular Filtration Rate (GFR)>60, the incidence of CI-AKI in the STEMI patients was 9.2% [4]. Such a high incidence of this complication invokes the need to define measures to decrease the occurrence of CI-AKI in patients presenting with STEMI.

In addition to prophylactic intravenous volume expansion with isotonic crystalloid solution, few prophylactic strategies for CI-AKI are clearly effective [5]. The most important step in reducing the risk of CI-AKI is identifying at-risk patients as old age, Chronic Kidney Disease (CKD), Diabetes Mellitus (DM), hypertension, metabolic syndrome, hypovolemia, Congestive Heart Failure (CHF), an Ejection Fraction (EF) of less than 40%, hypotension, and Intra-Aortic Balloon Counterpulsation (IABP) use. Procedure-related risk factors are as urgent versus elective, arterial versus venous contrast. Contrast-related risk factors are as contrast volume, contrast characteristics, including osmolarity, ionicity, molecular structure, and viscosity. The single most important patient-related risk factor is preexisting CKD, even more so than DM [6]. Patients with CKD in the setting of DM

Research Article

Evaluating the Association between Hyperuricemia and Contrast Induced-Acute Kidney Injury in Patients with Acute ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary InterventionAbdallah E*1, Mosbah O1, El-Shistawy S1, Khalifa G1, Badr M2 and Amin AA3

1Nephrology Department, Theodor Bilharz Research Institute, Egypt2Intensive Care Unit, Theodor Bilharz Research Institute, Egypt3Cardiology Care Unit, National Heart Institute, Egypt

Article Information

Received date: Aug 08, 2016 Accepted date: Oct 15, 2016 Published date: Oct 21, 2016

*Corresponding author

Emad Abdallah, Nephrology Department, Theodor Bilharz Research Institute, Cairo, Egypt; Phone: 00201005767492; Fax: 20235409125; Email: [email protected]

Distributed under Creative Commons CC-BY 4.0

Keywords Acute kidney injury; Acute myocardial infarction; Uric acid

Article DOI 10.36876/smjnt.1003

Abstract

Background: The association between Hyperuricemia (HUA) and Contrast Induced-Acute Kidney Injury (CI-AKI) has not been extensively studied. The aim of our study was to evaluate the association between HUA and CI-CKD in patients with acute ST-Elevation Myocardial Infarction (STEMI) undergoing Percutanious Coronary Intervention (PCI).

Methods: We prospectively studied 146 patients with acute STEMI undergoing PCI. According to serum uric acid (SUA), patients were divided into 2 groups, normouricemic group (Group 1, n=68) and hyperuricemic group (Group 11, n=78). HUA was defined as a SUA concentration of more than 7.0mg/dL in men and 6.0mg/dL in women. Medical records of both groups of patients were reviewed for the occurrence of AKI. Multi-variate regression analysis was used to define independent risk predictors of AKI.

Results: AKI was found in 11 of 78 (14.1%) in Group I1 of patients and in 2 of 68 (2.94%) in Group 1 of patients (p=0.0436), baseline Serum Creatinine (SCr) and Estimated Glomerular Filtration Rate (eGFR) were comparable between the two groups. There was positive significant correlation between admission SUA and SCr 48h after PCI in the studied patients. According to regression analysis, SUA, age, Left Ventricular Ejection Fraction (LVEF), multi-vessel disease and volume of Contrast Media (CM) were found to be independent risk factors of AKI. After adjusting for age, sex, LVEF, multi-vessel disease, and volume of CM, SUA remained as an independent risk factor for CI-AKI.

Conclusion: Elevated uric acid was associated with higher risk for AKI in STEMI patients with normal SCr treated with PCI.

https://creativecommons.org/licenses/by/4.0/

https://creativecommons.org/licenses/by/4.0/

https://dx.doi.org/10.36876/smjnt.1003

Citation: Abdallah E, Mosbah O, El-Shistawy S, Khalifa G, Badr M and Amin AA. Evaluating the Association between Hyperuricemia and Contrast Induced-Acute Kidney Injury in Patients with Acute ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention. SM J Nephrol Therap. 2016; 1(1):

1003. https://dx.doi.org/10.36876/smjnt.1003

/5

Gr upSM Copyright Abdallah E

have a 4-fold increase in the risk of CI-AKI compared with patients without DM or preexisting CKD [6].

The association between Hyperuricemia (HUA) and CI-AKI has not been extensively studied. It has been suggested that tubular obstruction by uric acid plays a role in the pathogenesis of CI-AKI [7,8]. HUA is accompanied by enhanced synthesis of Reactive Oxygen Species (ROS), activation of the renin-angiotensin-aldosterone system, an increase in Endothelin-1, and inhibition of the nitric oxide system; all of these factors play a role in the pathogenesis of CI-AKI [9-11]. However, there are no adequate clinical studies to demonstrate whether HUA further increases the risk of CI-AKI. Accordingly, in our study, we evaluated, the association between HUA and AKI occurrence in patients with normal kidney function and STEMI undergoing Coronary Angiography (CAG) and primary PCI.

Patients and MethodsThis a prospective study conducted on 146 patients admitted

during the period from January 2013 to April 2016 at National Heart Institute and Theodor Bilharz Research Institute, Cairo, Egypt, with acute STEMI for CAG and treated by PCI. STEMI was diagnosed as patients had typical chest pain, serial elevation of cardiac troponin with Electrocardiogram (ECG) and echo-heart changes. Primary PCI was performed on patients with symptoms from 12-24h duration. Contrast Media (CM) used in procedures was iodixanol (Visipaque, GE healthcare, Ireland) or iohexol (Omnipaque, GE healthcare, Ireland). Following CAG and PCI procedures, normal saline (0.9%) was given intravenously at a rate of 1ml/kg/h for 12h after contrast exposure. The hydration rate was reduced in patients with volume overload as patients with heart failure. Left Ventricular Ejection Fraction (LVEF) was assessed in all patients within the first 48h of

admission. Patients with DM, Estimated Glomerular Filtration Rate (eGFR) <60ml/min/1.73m2 and critically ill patients on mechanical ventilation or IABP were excluded from the study. Informed consent was obtained from all patiehts. The study was approved by an institutional review committee and was performed in accordance with the Declaration of Helsinki.

According to Serum Uric Acid (SUA), patients were divided into 2 groups, normouricemic group (Group-I, n=68) and hyperuricemic group (Group-II, n=78). HUA was defined as SUA concentration of more than 7.0mg/dL in men and 6.0mg/dL in women [12].

SUA was measured on admission. Renal function tests {Serum Creatinine (SCr), blood urea, serum potassium, serum sodium} were measured on hospital admission, and at least once a daily. Random blood sugar, glycosylated hemoglobin (HbA1c), total cholesterol and triglycerides, C – Reactive Protein (C-RP), and Creatine Phosphokinase (C-PK) were measured from blood samples taken within 24h of hospital admission using standad methods. Echocardiography was used to measure LVEF. The eGFR was estimated using the abbreviated Modification of Diet in Renal Disease equation (MDRD). [13] Baseline renal insufficiency was categorized as admission eGFR of <60ml/min/1.73m2. AKI was determined using Kidney Disease Improving Global Outcome (KDIGO) guidelines and defined as increase in SCr by 0.3mg/dl (26.5umol/l) within 48h of admission [14].

Statistical AnalysisAll data were analysed as mean±standard deviation or as number

(%). Continuous variables were compared using the independent sample t test (using GraphPad QuickCalcs). The p-values for the categorical variables were calculated with the chi square test. Spearman

Table 1: Demographic, clinical and laboratory characteristics of studied patients.

Variables Group-I (uric acid<7mg/dL) No.68 Group-II (uric acid≥7mg/dL) No.78 P-value

Age (years) 57.8±11.4 60.7±12.5 0.1474

Gender (M/F) 46/22(67.6%/32.4%) 57/21(73.1%/26.9) 0.5856

Systolic BLP (mm/Hg) 130.96±24.7 135.8±27.6 0.2690

Diastolic BLP (mm/Hg) 87.8±19.2 89.7±19.3 0.5529

Glucose level at admission (mg/dL) 109.8±11.6 112.7± 9.3 0.0960

HbA1c (%) 5.6±1.3 5.8±1.4 0.3749

Total cholesterol (mg/dL) 168.6±38.4 169.3±41.1 0.9159

Triglycerides (mg/dL) 87.8±15.9 89.2±21.3 0.6573

Serum uric acid (mg/dL) 6.23±0.73 8.92±1.87 0.0001

Personal history of MI 11(16.2%) 21(26.9%) 0.1743

Family history of CAD 18(26.5%) 31(39.7%) 0.1312

No.of stenosed coronary arteries

1 19(23.4%) 18(23.1%) 0.8779

2 23(34.04%) 22(28.2%) 0.5605

3 26(42.6%) 38(48.7%) 0.5677

Time to reperfusion (h) 8.6±4.1 9.1±3.2 0.4099

C-RP (mg/L) 18.3±4.6 19.2±3.9 0.2028

C-PK (units/L) 1371.2±429.8 1425.3±469.2 0.4711

LVEF (%) 49.4±8.2 47.9±6.8 0.0701

BLP: Blood Pressure; HbA1c: Glycosylated Hemoglobin; MI: Myocardial Infarction; CAD: Coronary Artery Disease; C-RP: C-Reactive Protein; C-PK: Creatine Phosphokinase; LVEF: Left Ventricular Ejection Fraction.



/5


rank correlation test was used to analyse the correlation between uric acid and serum creatinine (MedCalc software). Multivariable linear regression model was used to identify risk factors for CI-AKI. A two-tailed p value of <0.05 was considered significant. All analysis was performed with the SPSS software (SPSS Inc., Chicago, IL).

ResultsThe patients included in this study were 146 patients with mean

age 59.7±10.9 (70.5 % males), 68 of whom (46.6%) had SUA <7mg/dL in men (46; 67.6%) and <6mg/dL in women (22; 32.4%) and 78 of whom (53.4%) had SUA level ≥7mg/dL in men (57; 73.1%) and ≥6mg/dL in women (21; 26.9%). The baseline demographic, clinical and laboratory characteristics of patients according to SUA levels are presented in (Table 1). The two groups were comparable regarding age, gender, blood pressure, dyslipidemia, blood glucose, HbA1c, total cholesterol and triglycerides, C-RP, C-PK, LVEF, time of reperfusion and extent of coronary artery disease. (Table 2).

Table-2 Compares SCr changes, CM volume applied and the occurrence of AKI according to SUA levels. Baseline SCr and eGFR were comparable between the two groups. The total volume of CM was not statistically different between the two groups. SCr change at 48h after PCI and on discharge was highly significant in Group-II compared with Group-I of patients. AKI was found in 11 of 78 (14.1%) in Group I1 of patients and in 2 of 68 (2.94%) in Group-I of patients (p = 0.0436).

There was positive significant correlation between admission SUA levels and SCr levels 48h after PCI in the studied patients Figure 1.

Multivariate linear regression analysis was used to define independent risk factors of AKI. According to regression analysis, SUA, age, LVEF, multi-vessel disease and volume of CM were found to be independent risk factors of AKI. After adjusting for age, sex, LVEF, multi-vessel disease, and volume of CM, SUA remained as an independent risk factor for CI-AKI (Table 3).

DiscussionOur study demonstrated that the incidence of CI-AKI was

statistically significantly high in hyperuricemic patients compared with normouricemic patients (14.1% vs. 2.94%, p=0.0436) and the admission SUA level is correlated with the increased incidence of CI-AKI in patients with normal serum creatinine and acute STEMI undergoing PCI.

Previous reports have showed that elevated SUA is a risk factor for developing AKI in specific circumstances. Preoperative and postoperative HUA has been linked to a higher incidence of postoperative AKI, especially in cardiovascular surgery settings [15-19]. Moreover, HUA has also been shown to increase the risk of contrast-induced AKI after PCI [20,21]. SUA measurement has been proposed as a novel marker for early detection of AKI [22,23].

Toprak et al. conducted the most rigorous observational study of the value of HUA for predicting the risk of CI-AKI in patients with CKD (SCr≥1.2mg/dL) who were considered at high risk of developing CI-AKI and concluded that the hyperuricemic patients were at risk of developing CI-AKI [24]. The results of the present study were consistent with those obtained by Toprak and colleagues. Recently, Park et al. also concluded that HUA was independently associated with an increased risk of in-hospital mortality and CI-AKI in patients treated with PCI, although they performed a retrospective analysis that used a different definition of CI-AKI (an increase in SCr≥0.5mg/dL or ≥50% over baseline within seven days of PCI) [21]. Consequently, the incidence of CI-AKI in our study was lower than the incidence in previous studies [21,24].

Table 2: Serum creatinine changes, contrast media volume applied and the occurrence of AKI according to serum uric acid levels.

Variables Group-I (uric acid<7mg/dL) N=68 Group-II (uric acid≥7mg/dL) N=78 P-value

Serrum creatinine at admission (mg/dL) 0.99±0.21 1.02±0.29 0.4810

eGFR (mL/min/1.73 m2) 78.31±17.2 74.62±13.9 0.1541

Contast volume (mL) 138.6±16.7 141.3±17.2 0.3392

Serum creatinine 48h after PCI 1.28±0.56 1.62±0.74 0.0024

Serum creatinine at discharge 1.17±0.46 1.37±0.62 0.0304

AKI 2(2.94%) 11(14.1%) 0.0384

eGFR: Estimated Glomerular Filtation Rate; PCI: Percutaneous Coronary Intervention; AKI: Acute Kidney Injury

Table 3: Multi-variate regression analysis of the risk factors for CI-AKI.

Variables β P-value

Uric acid 0.71 0.019

LVEF - 0.46 0.050

Age 0.62 0.023

Contrast volume 0.68 0.021

Multi-vessels disease 0.51 0.038

LVEF: Left Ventricular Ejection Fraction.

Figure 1: Correlation coefficient between admission serum uric acid levels (SUA) and serum creatinine levels (SCr) 48h after percutanious coronary intervention in the studied patients (r=0.293, 95% confidence interval for rho 0.130 to 0.441, p=0.0006).



/5


The patients with normal SCr values, however, did not receive any prophylaxis, as they are typically thought to be at low risk. Chong et al. observed that subgroups of patients with normal baseline SCr who were undergoing PCI were at risk of developing CI-AKI, which results in higher mortality [25]. Therefore, despite normal baseline SCr values, the subgroups of patients undergoing PCI may be at higher risk of developing CI-AKI. In our study, HUA has been identified as one of independent risk predictor of CI-AKI in addition to age, LVEF and volume of CM. Hence, the patients with normal baseline SCr values who have the risk factors for CI-AKI should be considered for additional renal prophylaxis treatment.

In our study, the incidence of CI-AKI was statistically significantly high in hyperuricemic patients compared with normouricemic patients (14.1% Vs. 2.94%, p=0.0436) and no patients who developed AKI need renal replacement therapy. Our results are in agreement with the study of Liu et al. who concluded that the incidence of CI-AKI was significantly higher in the hyperuricemic group than in the normouricemic group (8.1% Vs. 1.4%, p<0.001) in patients with relatively normal serum creatinine after percutaneous coronary interventions. However, Liu et al demonstrated that, in hospital mortality and the need for renal replacement therapy were significantly higher in the hyperuricemic group [26].

There are many explanations for the increased AKI risk in patients with elevated SUA values. Uric acid has been proposed to play a role in AKI via crystal-independent mechanisms, as well as crystal-dependent pathways [27]. Elevated SUA can induce renal vasoconstriction and impair auto-regulation, which results in reduced renal blood flow and GFR. Sanchez-Lozada et al. showed that even a mild elevation of SUA can cause renal vasoconstriction in rats without evidence of intra-tubular crystal precipitation [27-30]. Furthermore, HUA has been shown to worsen renal injury via pro-inflammatory pathways involving chemokine expression with leukocyte infiltration, as well as proliferation of vascular smooth muscle cells and inhibition of endothelial function [28,31-33]. AKI-related crystal-dependent pathways can also occur in renal stones and acute urate nephropathy associated with tumor lysis syndrome [29,34-37].

The results of our study showed a prognostic effect of admission SUA level on the CI-AKI development. Previous attempts to identify effective interventions to prevent CI-AKI have been largely unsuccessful [38]. Using the admission SUA level in clinical practice may help identify patients with a high risk of CI-AKI during hospitalization in order to promptly prevent AKI events. Several clinical trials have examined the efficacy of uric acid-lowering agents, such as allopurinol, in cardiovascular surgery and found a reduction in the production of ROS [39,40]. Rasburicase has also been studied in a prospective, double-blind, placebo-controlled, randomized trial of 26 hyperuricemic patients undergoing cardiac surgery [41]. Despite no observed benefit on postoperative SCr, markers of structural renal injury such as urine neutrophil-associated lipocalin tended to be lower in rasburicase-treated patients.

ConclusionOur study has some limitations. First, this is a single-center,

prospective study. Second, small sample of patients is included in our study, so further bigger multicenter prospective studies are required to address these limitations.

In conclusion, this study showed that elevated admission SUA is associated with an increased risk of CI-AKI in patients with STEMI and normal SCr undergoing PCI.

References

1. Gallagher S, Knight C. Contrast-induced nephropathy in primary percutaneous coronary intervention. Heart. 2011; 97: 1723-1725.

2. Marenzi G, Lauri G, Assanelli E, Campodonico J, De Metrio M, et al. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol. 2004; 44: 1780-1785.

3. Rihal CS, Textor SC, Grill DE, Berger PB, Henry H. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 2002; 105: 2259-2264.

4. Chong E, Poh KK, Liang S, Soon CY, Tan HC. Comparison of risks and clinical predictors of contrast-induced nephropathy in patients undergoing emergency versus nonemergency percutaneous coronary interventions. J Interv Cardiol. 2010; 23: 451-459.

5. Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, et al. Prevention of contrast-associated nephropathy. Arch Intern Med. 2002; 162: 329-336.

6. Toprak O. Risk markers for contrast-induced nephropathy. Am J Med Sci. 2007; 334: 283-290.

7. Postlethwaite AE, Kelley WN. Uricosuric effect of radiocontrast agents. A study in man of four commonly used preparations. Ann Intern Med. 1971; 74: 845-852.

8. Mudge GH. Uricosuric action of cholecystographic agents: possible nephrotoxicity. N Engl J Med. 1971; 284: 929-933.

9. Kang DH, Nakagawa T. Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease. Semin Nephrol. 2005; 25: 43-49.

10. Dincer HE, Dincer AP, Levinson DJ. Asymptomatic hyperuricemia: to treat or not to treat. Cleve Clin J Med 2002; 69: 594, 597, 600-602.

11. Perlstein TS, Gumieniak O, Hopkins PN, Murphey LJ, Brown NJ, et al. Uric acid and the state of the intrarenal renin-angiotensin system in humans. Kidney Int. 2004; 66:1465-1470.

12. Chiou WK, Wang MH, Huang DH, Chiu HT, Lee YJ, et al. The relationship between serum uric acid level and metabolic syndrome: differences by sex and age in Taiwanese. J Epidemiol. 2010; 20: 219-224.

13. National Kidney Foundation (NKF) kidney disease outcome quality initiative (k/doqi) advisory board. K/doqi clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis . 2002; 39: 1-266.

14. Levin A, Warnock DG, Mehta RL, Kellum JA, Shah SV, et al. Improving outcomes from acute kidney injury: Report of an initiative. Am J Kidney Dis. 2007; 50: 1-4.

15. Lapsia V, Johnson RJ, Dass B Shimada M, Kambhampati G, et al. Elevated uric acid increases the risk for acute kidney injury. Am J Med. 2012; 125: 302. 9-17.

16. Ejaz AA, Beaver TM, Shimada M, Sood P, Lingegowda V, et al. Uric acid: A novel risk factor for acute kidney injury in high-risk cardiac surgery patients? Am J Nephrol. 2009; 30: 425-429.

17. Moguel GB, Wasung de LM, Tella VP, McLoughlin CR, Villa AR, et al. Acute kidney injury in cardiac surgery. Rev Invest Clin. 2013; 65: 467-475.

18. Ejaz AA, Kambhampati G, Ejaz NI, Dass B, Lapsia V, et al. Post-operative serum uric acid and acute kidney injury. J Nephrol. 2012; 25: 497-505.

19. Hillis GS, Cuthbertson BH, Gibson PH, McNeilly JD, Maclennan GS, et al. Uric acid levels and outcome from coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2009; 138: 200-205.

http://heart.bmj.com/content/97/21/1723.extract

http://heart.bmj.com/content/97/21/1723.extract

https://www.ncbi.nlm.nih.gov/pubmed/15519007










https://www.google.co.in/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&cad=rja&uact=8&ved=0ahUKEwiZjLOW6-PPAhXIrI8KHZUwDWQQFgggMAA&url=http%3A%2F%2Fjamanetwork.com%2Fpdfaccess.ashx%3FResourceID%3D298893%26PDFSource%3D13&usg=AFQjCNEmoWiXXAXCSkF1TEdqnts1gfLBvg&bv





http://annals.org/article.aspx?articleid=685554



http://www.nejm.org/doi/full/10.1056/NEJM197104292841701

http://www.nejm.org/doi/full/10.1056/NEJM197104292841701









https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900844/













http://www.karger.com/Article/Pdf/238824







http://www.jtcvsonline.org/article/S0022-5223(09)00498-X/abstract





/5


20. Liu Y, Tan N, Chen J, Zhou Y, Chen L, et al. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine. Clinics. 2013; 68: 19-25.

21. Park SH, Shin WY, Lee EY, Gil HW, Lee SW, et al. The impact of hyperuricemia on in-hospital mortality and incidence of acute kidney injury in patients undergoing percutaneous coronary intervention. Circ J. 2011; 75: 692-697.

22. Lisowska-Myjak B. Serum and urinary biomarkers of acute kidney injury. Blood Purif. 2010; 29: 357-365.

23. Kosmadakis G, Viskaduraki M, Michail S. The validity of fractional excretion of uric acid in the diagnosis of acute kidney injury due to decreased kidney perfusion. Am J Kidney Dis. 2009; 54: 1186-1187.

24. Toprak O, Cirit M, Esi E, Postaci N, Yesil M, et al. Hyperuricemia as a risk factor for contrast-induced nephropathy in patients with chronic kidney disease. Catheter Cardiovasc Interv. 2006; 67: 227-235.

25. Chong E, Poh KK, Liang S, Tan HC. Risk factors and clinical outcomes for contrast-induced nephropathy after percutaneous coronary intervention in patients with normal serum creatinine. Ann Acad Med Singapore. 2010; 39: 374-380.

26. Yong Liu, Ning Tan, Jiyan Chen, Yingling Zhou, Liling Chen, et al. The relationship between hyperuricemia and the risk of contrast-induced acute kidney injury after percutaneous coronary intervention in patients with relatively normal serum creatinine. Clinics (Sao Paulo) 2013; 68: 19-25.

27. Ejaz AA, Dass B, Kambhampati G, Ejaz NI, Maroz N, et al. Lowering serum uric acid to prevent acute kidney injury. Med Hypotheses. 2012; 78: 796-799.

28. Kosmadakis G, Viskaduraki M, Michail S. The validity of fractional excretion of uric acid in the diagnosis of acute kidney injury due to decreased kidney perfusion. Am J Kidney Dis. 2009; 54: 1186-1187.

29. Zavada J, Hoste E, Cartin-Ceba R, Calzavacca P, Gajic O, et al. A comparison of three methods to estimate baseline creatinine for RIFLE classification. Nephrol Dial Transplant. 2010; 25: 3911-3918.

30. Sanchez-Lozada LG, Tapia E, Santamaria J, Soto V, Nepomuceno T, et al. Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats. Kidney Int. 2005; 67: 237-247.

31. Roncal CA, Mu W, Croker B, Ouyang X, Tabah-Fisch I, et al. Effect of elevated serum uric acid on cisplatin-induced acute renal failure. Am J Physiol Renal Physiol. 2007; 292: 116-122.

32. Shimada M, Dass B, Ejaz AA. Paradigm shift in the role of uric acid in acute kidney injury. Semin Nephrol. 2011; 31: 453-458.

33. Durante P, Romero F, Perez M, Chávez M, Parra G. Effect of uric acid on nephrotoxicity induced by mercuric chloride in rats. Toxicol Ind Health. 2010; 26: 163-174.

34. Cameron JS, Simmonds HA. Uric acid, gout and the kidney. J Clin Pathol. 1981; 34: 1245-1254.

35. Lameire NH, Flombaum CD, Moreau D, Ronco C. Acute renal failure in cancer patients. Ann Med. 2005; 37: 13-25.

36. Hsu HH, Chen YC, Tian YC, Chan YL, Kuo MC, et al. Role of serum sodium in assessing hospital mortality in cancer patients with spontaneous tumour lysis syndrome inducing acute uric acid nephropathy. Int J Clin Pract. 2009; 63: 751-756.

37. Preitner F, Laverriere LA, Metref S, Da Costa A, Moret C,et al. Urate-induced acute renal failure and chronic inflammation in liver-specific Glut9 knockout mice. Am J Physiol Renal Physiol. 2013; 305: 786-795.

38. Cheng X, Tong J, Hu Q, Chen S, Yin Y, et al. Meta-analysis of the effects of preoperative renin-angiotensin system inhibitor therapy on major adverse cardiac events in patients undergoing cardiac surgery. Eur J Cardiothorac Surg 2015; 47: 958-966.

39. Tarkka MR, Vuolle M, Kaukinen S, Holm P, Eloranta J, et al. Effect of allopurinol on myocardial oxygen free radical production in coronary bypass surgery. Scand Cardiovasc J. 2000; 34: 593-596.

40. Castelli P, Condemi AM, Brambillasca C, Fundarò P, Botta M, et al. Improvement of cardiac function by allopurinol in patients undergoing cardiac surgery. J Cardiovasc Pharmacol. 1995; 25: 119-125.

41. Ejaz AA, Dass B, Lingegowda V, Shimada M, Beaver TM, et al. Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery. Int Urol Nephrol. 2013; 45: 449-458.





https://www.jstage.jst.go.jp/article/circj/75/3/75_CJ-10-0631/_article

























http://ndt.oxfordjournals.org/content/25/12/3911.full.pdf



















http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2007.01264.x/abstract











http://europepmc.org/abstract/med/11214014









evaluating the association between hyperuricemia and

Documents