Abstract Rationale Several medications used in critical care medicine are cleared by the kidneys via tubular secretion, including penicillins, digoxin, and furosemide. Studies in animals and human subjects have shown that invasive mechanical ventilation is associated with a reduction in urine output, natriuresis, and renal clearance; however, the impact of mechanical ventilation on renal secretion is unknown. Methods Sixteen rats were sedated and randomized to mechanical ventilation (MV) with modest ventilator settings (TV 8 cc/kg, PEEP = 3 cm H2O) or spontaneous breathing (SB) for 4 hours. Plasma and urine were collected at the end of the experiment. Liquid chromatography tandem mass spectrometry was used to quantify the secretion of 19 endogenous compounds secreted by kidney tubules. Among these, urine-to-plasma ratios (UPRs) were used to calculate a composite secretion index. Linear regression was used with each UPR as the dependent variable, and MV vs. SB as an independent variable, adjusting for urine creatinine to account for urine tonicity. Results Of the 19 endogenous secretion measures, 12 were detected in the urine and plasma. Rats receiving MV had higher secretion of 10 of the 12 metabolites compared to SB rats; 8 of these were statistically significantly higher in unadjusted analyses. The composite secretion index was significantly higher in those undergoing MV when compared to SB (p = 0.043, Figure). Adjusting for urine tonicity attenuated, but did not fully eliminate, these differences. Conclusions Mechanical ventilation acutely increases kidney tubule secretion in rats, as illustrated by the composite secretion index. Future studies should determine if MV impacts secretion and kidney drug elimination in humans with critical illness. This abstract is funded by: T32 GM121318
Epler et al. (Fri,) studied this question.