The Effect of Parathyroid Hormone on Cisplatin Nephrotoxicity

Abstract

The clinical use of cisplatin as an antineoplastic agent is limited by its nephrotoxicity that, in many cases, includes acute tubular necrosis and renal wasting of various electrolytes (1–4). Several studies have been performed to account for the various disorders of renal function induced by cisplatin. The decrease in GFR, for example, has been found to be related to a reduction in renal blood flow and to a lowered effective filtration pressure (5). The reported concentrating defect and the observed impaired sodium reabsorption have been associated to a defect in papillary hypertonicity found in cisplatin treated rats (6), while the potassium wasting effect is in part due to a negative potential difference induced by cisplatin in late distal segments (6). Finally the pathogenesis of cisplatin induced hypomagnesemia has been attributed to pathological changes confined to the straight portion (S₃ segment) of superficial nephrons (7). On the other hand many therapeutic strategies have been tested to reduce its nephrotoxic action: the fall in GFR, for example, can be modified by hydration, mannitol diuresis (8) and by the administration of atrial natriuretic peptide (9); moreover compounds that provide SH groups have been reported to reduce the cisplatin associated renal injury (10).