Risk factors for Amphotericin B Nephrotoxicity among children six months to eighteen years old admitted at the Philippine Children’s Medical Center

BACKGROUND@#Amphotericin B is used in pediatrics for severe fungal infections despite its known nephrotoxic side effects. Tubular injury and renal vasoconstriction range from 15-58% with exact risk factors that predispose children to developing these complications still undefined.@*OBJECTIVES@#To determine the risk factors for nephrotoxicity with deoxycholate Amphotericin B treatment among children 6 months-18 years old at the Philippine Children‘s Medical Center from 2006-2017@*METHODS@#This is a retrospective case-control study of 150 patients. Cases had decrease in eGFR by at least 25% and/or developed hypokalemia after at least one dose of Amphotericin. Those who did not develop nephrotoxicity were considered controls. Risk factors evaluated were age, sex, nutritional status, underlying medical condition, cumulative dose, concomitant use of nephrotoxic drugs used, treatment with diuretics and intravenous hydration. Results were analyzed using univariate and multivariate regression models.@*RESULTS@#Using logistic regression, underlying malignancy had the highest odds ratio of 33.1 and nutritional status of z score=0 showed the lowest at 0.158. Duration of treatment >14 days had 1.75 times chance of developing nephrotoxicity while total cumulative dose >7.1 mg/kg had 1.5 times more chance of developing nephrotoxicity. Subjects given diuretics had 5.5 times more odds, while those not given concomitant nephrotoxic medications were 5.33% less likely to develop renal toxicity.@*CONCLUSION@#Risk factors for nephrotoxicity were malignancy as an underlying medical condition, duration of amphotericin treatment of >14 days, cumulative dose >7.1 mg/kg and diuretic use. Normal nutritional status and no other concomitant nephrotoxic medication use had lesser odds of developing nephrotoxicity.@*RECOMMENDATIONS@#Clinicians should consider these risk factors, institute measures to monitor occurrence of nephrotoxicity and the need for alternative fungal therapy in these children. With identification of the population at risk, prospective research on determining the specific onset of renal effects and possible intervention is recommended.

Effect of vitamin C deficiency and excess on the liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet.

When guinea pigs were kept on a restricted vitamin C intake of only 0.5 mg daily, their serum ascorbic acid fell to 0.16 +/- 0.06 mg/d1 in 16 weeks as compared to 0.73 +/- 0.11 in control. This was associated with significant increase in liver cholesterol and triglycerides. When they were simultaneously challenged with a high cholesterol load, this fat accumulation was markedly exaggerated. The weight of the liver now increased by almost two-and-half times. Liver cholesterol rose to 12.90 +/- 2.63 mg/gm as compared to 3.23 +/- 0.56 mg/gm with low vitamin C alone. Histopathology showed marked distension and vacuolation of hepatocytes, focal necrosis and fibroplasia. Administration of excess vitamin C (100 mg daily) significantly countered these changes. The vitamin C-lipid relationship has important clinical bearings and liver could be an important site of vitamin C action.