Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Am J Kidney Dis. 2017 Aug;70(2):290-296. doi: 10.1053/j.ajkd.2016.12.010. Epub 2017 Feb 20.
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy.
二甲双胍中毒合并乳酸性酸中毒是一种潜在致命的疾病,当药物剂量不当和/或清除率降低时,糖尿病患者可能会发生。由于首发时出现非特异性症状,诊断和治疗可能会延迟,严重的阴离子间隙代谢性酸中毒和血清肌酐值升高是最突出的实验室发现。确认需要通过高效液相色谱-串联质谱法测量血清中的二甲双胍,但该技术仅在专门的机构中可用,不能作为立即治疗的指导。因此,基于强烈的临床怀疑,必须迅速开始肾脏替代治疗以实现有效的药物清除和纠正代谢性酸中毒。然而,由于二甲双胍在长时间治疗后会在细胞内隔室中积累,因此在透析结束时会由于再分布而导致血清浓度反弹。我们报告了一例患有慢性肾脏病 3 期的糖尿病患者发生二甲双胍中毒、严重乳酸性酸中毒和急性肾损伤的病例,该患者经持续低效透析治疗有效。我们讨论了其病理生理学、鉴别诊断和治疗选择,并强调了在选择适当的肾脏替代治疗方式时应考虑的特定药代动力学问题。