Adis Tasanarong

Side Effects of Radiographic Contrast Media: Pathogenesis, Risk Factors, and Prevention

Radiocontrast media (RCM) are medical drugs used to improve the visibility of internal organs and structures in X-ray based imaging techniques. They may have side effects ranging from itching to a life-threatening emergency, known as contrast-induced nephropathy (CIN). We define CIN as acute renal failure occurring within 24–72 hrs of exposure to RCM that cannot be attributed to other causes. It usually occurs in patients with preexisting renal impairment and diabetes. The mechanisms underlying CIN include reduction in medullary blood flow leading to hypoxia and direct tubule cell damage and the formation of reactive oxygen species. Identification of patients at high risk for CIN is important. We have reviewed the risk factors and procedures for prevention, providing a long list of references enabling readers a deep evaluation of them both. The first rule to follow in patients at risk of CIN undergoing radiographic procedure is monitoring renal function by measuring serum creatinine and calculating the eGFR before and once daily for 5 days after the procedure. It is advised to discontinue potentially nephrotoxic medications, to choose radiocontrast media at lowest dosage, and to encourage oral or intravenous hydration. In high-risk patients N-acetylcysteine may also be given.

New strategy of α- and γ-tocopherol to prevent contrast-induced acute kidney injury in chronic kidney disease patients undergoing elective coronary procedures

BACKGROUND Contrast-induced acute kidney injury (CI- AKI) increases the likelihood of patient morbidity and mortality following coronary procedures. Volume supplement with saline is the standard treatment to prevent CI-AKI. Additional antioxidant prophylaxis has often yielded conflicting results. The present study was conducted to examine the role of novel application vitamin E (tocopherol) in preventing CI-AKI. METHODS This prospective, double-blind, randomized and placebo-controlled trial was carried out in 305 patients with chronic kidney disease (CKD) undergoing coronary procedures. All patients were randomly assigned to prophylaxis administration with 0.9% saline infusions plus daily oral medication comprised of either (i) placebo (n = 101), (ii) α-tocopherol (n = 102) or (iii) γ-tocopherol (n = 102) starting 5 days before and ending 2 days after coronary procedures. The CI-AKI risk score of each patient was calculated. All coronary procedures were performed using a low-osmolar, non-ionic contrast agent. RESULTS CI-AKI developed in 14.9% in the placebo group, 4.9% in the α-tocopherol group (P = 0.02 versus the placebo group) and 5.9% in the γ-tocopherol group (P = 0.04 versus the placebo group). In patients with diabetes, hypertension, anaemia, aged over 55 years, male gender or with contrast agent dosages >120 mL, α-tocopherol showed a larger effect than γ-tocopherol when compared with the placebo group (P < 0.05). CONCLUSIONS Prophylaxis administration with oral α- or γ-tocopherol in combination with 0.9% saline is effective in protecting against CI-AKI in CKD patients undergoing elective coronary procedures.

Pharmacological Strategies to Prevent Contrast-Induced Acute Kidney Injury

Contrast-induced acute kidney injury (CI-AKI) is the most common iatrogenic cause of acute kidney injury after intravenous contrast media administration. In general, the incidence of CI-AKI is low in patients with normal renal function. However, the rate is remarkably elevated in patients with preexisting chronic kidney disease, diabetes mellitus, old age, high volume of contrast agent, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion. Consequently, CI-AKI particularly in high risk patients contributes to extended hospitalizations and increases long-term morbidity and mortality. The pathogenesis of CI-AKI involves at least three mechanisms; contrast agents induce renal vasoconstriction, increase of oxygen free radicals through oxidative stress, and direct tubular toxicity. Several strategies to prevent CI-AKI have been evaluated in experimental studies and clinical trials. At present, intravascular volume expansion with either isotonic saline or sodium bicarbonate solutions has provided more consistent positive results and was recommended in the prevention of CI-AKI. However, the proportion of patients with risk still develops CI-AKI. This review critically evaluated the current evidence for pharmacological strategies to prevent CI-AKI in patients with a risk of developing CI-AKI.

Protective effect of alpha tocopherol on contrast-induced nephropathy in rats

BACKGROUND Contrast-induced nephropathy (CIN) is a prominent cause of in-hospital acute kidney injury occurring after the administration of intravenous radiocontrast medium. Oxidative stress has been proposed as one of the more important mechanisms in the pathogenesis of CIN. The aim of the present study has been to determine the effect of alpha tocopherol on the reduction of renal damage in a rat model of CIN. METHODS Male Sprague Dawley rats were subjected into six groups pretreated with alpha-tocopherol (250 or 500 mg/kg/day) or the vehicle tweeen80 for 5 days before the induction of CIN. Renal function and oxidative stress markers; level of malondialdehyde (MDA), total antioxidant capacity (TAC), superoxide dismutase (SOD) activity were determined. Kidney tissues were sectioned for pathohistological examination. RESULTS In the contrast media (CM) group, an increase in serum urea and creatinine was found. Tubular necrosis and peritubular capillary congestion were demonstrated in this group. Also, an imbalance of oxidative stress markers; an increase in MDA and a decreased SOD activity in kidney were shown. On the contrary, in CIN-induced rats administrated with alpha-tocopherol group, a significant reduction of renal function and renal MDA, together with a significant increase of renal SOD, were observed. Interestingly, a reduction in MDA and an increase of TAC in serum, along with prevention of tubular injury, were demonstrated in this group, as compared to the CM group. CONCLUSION This present study demonstrated that alpha tocopherol showed protective effect on the rat renal damage induced CIN. Therefore, this vitamin could be used as an antioxidant to attenuate the radiocontrast oxidative damage.

Dual Inhibiting Senescence and Epithelial-to-Mesenchymal Transition by Erythropoietin Preserve Tubular Epithelial Cell Regeneration and Ameliorate Renal Fibrosis in Unilateral Ureteral Obstruction

This study aims to investigate the renoprotective effect of recombinant human erythropoietin (rhEPO) treatment could preserve tubular epithelial cell regeneration and ameliorate renal fibrosis by dual inhibition of stress-induced senescence and EMT in unilateral ureteric obstruction (UUO) mouse model. UUO or sham-operated mice were randomly assigned to receive rhEPO or vehicle treatment and were sacrificed on days 3, 7, and 14. Kidney specimens were fixed for histopathological and immunohistochemical study. The expression of S100A4, TGF-β1, BMP-7, Smad2/3, Smad1/5/8, and p16INK4a was determined by western blot and real-time RT-PCR. Vehicle treated UUO mice had increased tubular atrophy and interstitial fibrosis within 3 to 14 days. An increase in TGF-β1, Smad2/3, S100A4, and p16INK4a expression and a decrease in BMP-7 and Smad1/5/8 expression were observed in the obstructed kidneys. p16INK4a was positively correlated with TGF-β1/Smad2/3 and negatively correlated with BMP-7/Smad1/5/8 in UUO mice. rhEPO treatment significantly suppressed the upregulation of TGF-β, Smad2/3, S100A4, and p16INK4a and preserved the downregulation of BMP-7 and Smad1/5/8, resulting in markedly reduced TA/IF compared to the vehicle treated mice. The renoprotective effects of rhEPO could ameliorate renal TA/IF by modulating senescence and EMT which could be a part of therapeutic option in patients with chronic kidney disease.