Drug-induced nephrotoxicity (DIN) accounts for up to sixty percent of hospital acquired acute kidney injury. Several efforts have been made to reduce drug-induced renal damage; however, DIN remains a matter of concern, with substantial impact on patients and the health system. Silymarin is a drug that has been used for many years in alternate and modern medicine for treating hepatic diseases. Its antioxidant, anti-inflammatory and anti-apoptotic effects make it an interesting herbal medicine, and these properties have implicated this compound as a potential renoprotective agent. Based on the findings from animal studies, this review concluded that silymarin might exert significant protective or ameliorative effects against drug-induced kidney disease, especially against cisplatin-induced renal damage. Whether the protective administration of silymarin could be an effective clinical pharmacological strategy to prevent DIN is a question that remains to be answered in clinical trials. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

This article reviews mechanisms, incidences, risk factors and preventive modalities of colistin toxicity as well as colistin use in special populations and through special routes. All clinical studies that examined the pharmacokinetic/pharmacodynamic, efficacy and side effects of colistin in the management of multidrug-resistant organisms in different patient population including pediatrics, adults, obese, critically ill, burn or cancer patients with any route of drug administration were considered. Compared with older recommended doses, current dosing approach improves cure rate without significant increase in the rate of colistin-induced nephrotoxicity. Efficacy and safety of high doses of colistin should be considered in the future studies. Also comparing efficacy and safety of different doses of aerosolized colistin and defining the appropriate dose in different populations is another open area of future researches.

Background: Acute kidney injury (AKI) commonly occurs in critically ill patients. Estimation of renal function and antibiotics dose adjustment in patients with AKI is a challenging issue.Methods: Urinary creatinine clearance was measured in a 6-hour urine collection from patients with acute kidney injuries. The correlations between different formulas including the modified Cockcroft-Gault, modification of diet in renal disease, chronic kidney disease-epidemiology collaboration, Jelliffe, kinetic-glomerular filtration rate (GFR), Brater, and Chiou formulas were considered. The pattern of the prescribed antimicrobial agents was also compared with the patterns in the available resources.Results: Ninety-five patients with acute kidney injuries were included in the research. The mean age of the participants was 63.11±17.58 years old. The most patients (77.89%) were in stage 1 of AKI according to the Acute Kidney Injury Network criteria, followed by stage 2 (14.73%) and stage 3 (7.36), respectively. None of the formulations had a high or very high correlation with the measured creatinine clearance. In stage 1, Chiou (r=0.26), and in stage 2 and 3, kinetic-GFR (r=0.76 and r=0.37) had the highest correlation coefficient. Antibiotic over- and under-dosing were frequently observed in the study.Conclusions: The results showed that none of the static methods can predict the measured creatinine clearance in the critically ill patients. The dynamic methods such as kinetic-GFR can be helpful for patients who do not receive diuretics and vasopressors. Further studies are needed to confirm our results.

Septic shock may occur in critically ill patients and despite antimicrobial treatment, it is associated with a high mortality rate. It is reasonable to look for new treatment modalities that might improve outcome. This is a randomized, double-blind control trial aiming at critically-ill septic patients in a tertiary hospital. Patients with quick sofa score of 2 and with organ dysfunction were included in this study. The intervention group received high doses of vitamin C at a dose of 50 mg/kg/four times daily along with thiamine at a dose of 200 mg/ twice daily) and the control group received normal saline for four days. The dose of vasopressors, procalcitonin and lactate clearance, and mean sequential organ failure assessment (SOFA) score were examined in the two groups. Patients were followed for 28 days. One hundred patients were allocated into two equal groups, and there was no difference between the two groups regarding baseline characteristics. Mean lactate concentration, SOFA score, days of antimicrobial therapy, and mortality at 28 days were similar between them. However, the mean procalcitonin concentration, and mean vasopressor treatment hours were significantly lower in the intervention group (p<0.05). Although Days of ICU stay were lower in the intervention group, It did not reach statistical significance. The results of this study showed that treatment with high dose vitamin C Reduces the vasopressor requirement without any effects on other parameters. Further studies with larger sample size are required for more generalizable results.