Lithium concentrations during cisplatin-based chemotherapy: evidence for renal interaction

Abstract

We read with interest the report of J. H. Beijnen etal . [1] concerning lithium pharmacokinetics during cisplatin-based chemotherapy [1]. However, we do not agree with their interpretation of the transient decrease in serum lithium concentration. Lithium clearance is widely used in view of estimating the distal tubular sodium delivery, because of its absorption at the same rate as sodium in the proximal tubule and, normally, no more beyond the thick ascending limb [2]. This is true only in normovolemic states. In case of water and/or sodium depletion, some lithium is reabsorbed in the thick ascending limb and the collecting duct. Under osmotic diuresis as usually done during cisplatin-based chemotherapy, these phenomena do not occur [3]. Therefore, the two major factors influencing renal lithium clearance include not only the glomerular filtration rate but also variations in the tubular reabsorption of sodium and water. It cannot be interpreted at face value because of its variation with creatinine clearance and sodium intake. The necessity of correction for total sodium excretion and creatinine clearance so as to obtain the true value has been established [4]. Large variations in sodium loading before, during, and after treatment of the patient as reported by Beijnen et al. [1] may account for variation in lithium concentrations without a significant difference in noncorrected lithium clearance. As for sodimn, the transport of lithium along the proximal tubule is due mainly to an active phenomenon [5]. The mechanism of renal dysfunction during cisplatin therapy remains unclear. In a recent report suggesting a protective effect of glycine [6], it has been proven that toxic intracellular platinum species are formed early after injection. The main site of such formation is the $3 part of the