Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model.

摘要: Introduction Metformin can accumulate and cause lactic acidosis in patients with renal insufficiency. is known to inhibit mitochondria, while secretion of the drug by proximal tubules indirectly requires energy. We investigated whether addition metformin before or during ex vivo isolated normothermic machine perfusion (NMP) porcine rat kidneys affects its elimination. Research design methods First, Lewis rats were pretreated saline day nephrectomy. Subsequently, NMP kidney was performed for 90 min. added fluid one three different concentrations (none, 30 mg/L 300 mg/L). Second, increasing doses 4 hours kidneys. concentration determined urine liquid chromatography-tandem mass spectrometry. Results clearance approximately 4-5 times higher than creatinine both models, underscoring drug. at end perfused lower without (both p Conclusions secreted Excretion decreased under metformin, which might be explained saturation transporters rather a self-inhibitory effect. It remains unknown effect contributes accumulation humans longer exposure times.