Functional and structural rat kidney changes caused by peroral or parenteral lithium treatment

Abstract

Renal functional and structural changes were studied in rats treated with lithium for 5 months. The lithium was administered in two different ways: in the food or as a daily intrapentoned injection. In the perorally treated rats serum lithium was relatively constant during the day. In the injected rats serum lithium reached a high peak value just after the injection followed by a decrease to very low values. In all rats an increased water consumption and a reduced renal concentratia ability were seen during lithium treatment. Light microscopy showed focal degenerative changes in the distal convoluted tubule and collecting ducts. These changes comprised nuclear and cellular polymorphism and tubular dilatation. The functional as well as the structural changes were most pronounced in the rats treated with peroral lithium, and a correlation between the functional and morphological changes was present. It is concluded that lithium is more harmful to the kidney when the administrations give a relatively constant serum lithium level, such as in peroral administration, than when administration causes great variations, including peak values and very low minimum levels in serum lithium. The reason for this might be that a number of regenerative processes occur only in periods with low lithium concentrations.

Lithium in the Kidney: Friend and Foe?

“…19 Serum lithium levels were not determined, but the mice were injected daily with 4 mg lithium chloride (approximately 120 mg/kg body wt), which likely resulted in lithium levels within the therapeutic range (0.6-1.0 mM). 86 It remains to be determined why this dose improved the kidney function of lupus mice, whereas it causes renal disease in other animals and humans. 86 Finally, rats that were injected 30 minutes before ischemia-reperfusion with lithium displayed reduced levels of renal oxidative stress, because they exhibited a diminished mitochondrial membrane depolarization and reactive oxygen species (ROS) production.…”

“…86 It remains to be determined why this dose improved the kidney function of lupus mice, whereas it causes renal disease in other animals and humans. 86 Finally, rats that were injected 30 minutes before ischemia-reperfusion with lithium displayed reduced levels of renal oxidative stress, because they exhibited a diminished mitochondrial membrane depolarization and reactive oxygen species (ROS) production. 13 In addition, a 30-day pretreatment of rats with lithium reduced renal damage induced by ischemia-reperfusion, which was shown by the reduction in BUN and serum creatinine and the improved preservation of the tubular structure.…”

Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats.

“…intake of 0.9% NaCl (18)(19)(20). This regimen prevents intermittent sharp increases in plasma Li above the therapeutic range (17,22) and prevents sodium depletion that leads to acute Li nephrotoxicity (19,20,22).…”

“…In view of these considerations, we analyzed the animal model of Li-induced polyuria, which closely duplicates renal effects of chronic Li administration encountered in humans (17)(18)(19)(20)(21). In this model, the Li is administered to rats orally for at least several weeks in solid food, simultaneously with ad lib.…”

“…Most renal studies of the AVP-dependent cAMP system have been conducted mainly on kidney tissue preparations (9)(10)(11)(12)) that contain at least two types of tubular segments that are both endowed with AVPdependent cAMP metabolism (3,15), specifically medullary collecting tubules (MCT) and the medullary thick ascending limb of Henle's loop (MAL). Moreover, the effects of Li on renal components of urinary concentrating mechanism were examined, usually, only after short periods (I wk) of treatment and/or with Li salt administered parenterally (2,8,16,17). While results of the past studies suggested in principle the mode of Li action, these experimental models are quite remote from the conditions under which the NDI develops after chronic oral consumption of relatively small amounts of Li, as it is employed in management of manic-depressive psychosis (1,2,5,10,12).…”