Kontrast madde ilişkili nefropatiyi önlemede statin kullanım mekanizmalarının sıçanlar üzerinde araştırılması

MESUT M. (2023). Investigation Of The Mechanisms Of Statin Use In Prevention Of Contrast Induced Nephropathy In Rats. Yeditepe University, Institute of Health Science, Department of Pharmaceutical Toxicology PhD thesis, İstanbul. AIM: The use of contrast media in diagnostic and other procedural settings has been increasing exponentially, which increases the incidence of a state of iatrogenic kidney function impairment called contrast induced acute kidney injury (CI-AKI). Roughly one third of all hospital acquired kidney injury has been attributed to exposure to radiographic contrast media. The most widely accepted definition of contrast induced nephropathy (CIN) is either a 25% or more increase from the baseline value of serum creatinine or a 0.5 mg/dl or more absolute elevation within 24 to 72 hours of contrast media administration. CI-AKI greatly increases the mortality risk and hospital stay of patients which creates a need for preventative strategies against this condition. Many studies have suggested that alongside their cholesterol lowering properties, statins may exert pleiotrophic effects, including renoprotection, and significantly lower the incidence of CI-AKI. The aim of this study is to observe the efficacy of statins in preventing CI-AKI and demonstrate their mechanism of action. Material & Method For our animal experiment protocol, 30 adult male Spraque-Dawley rats were used. The subjects were equally divided into 5 groups: Rosuvastatin group (rosuvastatin + iohexol + furosemide + dehydration), Atorvastatin group (atorstatin + iohexol + furosemide + dehydration), CFD group (iohexol + furosemide + dehydration), FD group (furosemide + dehydration) and D group (dehydration). For generation of acute kidney injury, the fluid intake of subjects was restricted. CI-AKI was created by administering iohexol 15 ml/kg to three groups. Two of these were selected and they received 20 mg/kg/day Atorvastatin and 10 mg/kg Rosuvastatin, respectively. The renal tissues of all groups were studied histopathologically. From the blood samples, erythrocytes were used to determine the formation of malondialdehyde (MDA), activities of the enzymes glutathione peroxidase (GPx) and catalase (CAT). These parameters were measured spectrophotometrically. Serum creatinine levels were used for the diagnosis of AKI and serum neutrophil gelatinase associated lipocalin (NGAL) levels were measured with ELISA Kit to evaluate tubular damage. Results: 3 out of 5 groups that received contrast media, had higher average values of serum creatinine compared to the control groups. There was a statistically significant difference in serum creatinine levels of the CFD group, compared to Atorvastatin, FD and D groups. There was no statistically significant difference between creatinine levels of Rosuvastatin and CFD groups. Concerning the erythrocyte MDA level and erythrocyte GPx and CAT enzyme activities of all groups, no statistically significant difference was observed. In the histopathological examination, medullary congestion and tubular damage scores were evaluated and there was no statistically significant correlation detected. Conclusion: While atorvastatin is effective in preventing contrast media induced acute kidney injury, the same reno-protective property is not applicable to Rosuvastatin. Although atorvastatin prevented the elevation of serum creatinine in response to contrast media, the same correlation was not evident with prevention of tubular injury or increase in oxidative stress, which were associated with contrast media in priorly published literature.