Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment.Serum creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function.Here,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney function.We used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 m2.We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum creatinine.The estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all equations.Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 m2.We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients.Therefore,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Is fat-free mass-based gentamicin dosing regimen preferable than whole-body weight in neonates?

Importance:Body fluid dynamics and renal maturation status vary during the neonatal period.We hypothesized that differences in peak and trough gentamicin concentrations could be expected.Objective:To predict the peak and trough gentamicin concentrations in critically ill neonates and to predict the changes in the predicted peak plasma concentrations of gentamicin following fat-free mass dosing.Methods:Critically ill neonates that received gentamicin and have gentamicin concentration measured were recruited.Fat mass was estimated using skinfold thicknesses.Changes in the peak plasma concentrations(Cmax)using whole-body weight(estimated using the current dosing regimen)and predicted concentrations following the fat-free mass-based dosing were the outcome measures.Results:Eighty-nine critically ill neonates were recruited.Sub-therapeutic Cmax was estimated using the current dosing regimen in 32.6%,and 22.5%neonates following the first and second doses of gentamicin.Preterm neonates had significantly higher fat mass compared to term neonates.All except one had Cmax above 12μg/ml after the first dose and all had after the second gentamicin dose following the predicted fat-free massbased gentamicin dosing.The recommended doses are as follows:extreme preterm:7.95 mg/kg every 48 h;very preterm:7.30 mg/kg every 36-48 h;late preterm:5.90 mg/kg every 36-48 h;and term neonates at 5.10 mg/kg every 24 h.Interpretation:Fat-free mass dosing may be considered for obtaining optimal therapeutic effects in the neonatal population.