Mechanism of lithium-induced hypercalciuria in rats.
Chronic administration of lithium salts is associated with hypercalciuria in the rat. To study the renal and extrarenal mechanisms of this phenomenon, we utilized balance and clearance techniques in rats pair-fed diets with or without Li2CO3 (0.5 meq/day per rat). Lithium induced hypercalcemia (mean +/- SE: 5.40 +/- 0.09 VS. 5.06 +/- 0.05 meq/liter) and hypercalciuria (Ca/creatinine = 0.28 +/- 0.04 vs. 0.13 +/- 0.03) only during feeding. When CaCO2 supplement to a calcium-deficient diet was abruptly withdrawn, hypercalciuria was abolished. However, polyuria and polydipsia persisted. No significant changes in serum phosphate, urine phosphate, sodium, pH, or citrate were observed. Chronic parathyroidectomy (PTX) also abolished this effect. During clearance studies, fasting excretion of calcium was similar between treated and control animals. Superimposed acute PTX resulted in comparable changes, hence arguing against primary changes in renal calcium reabsorption or changes in parathyroid hormone effects on the renal tubule. Thus, lithium produces absorptive hypercalciuria by a mechanism dependent on intact parathyroid glands and adequate diet calcium, but independent of urine sodium, phosphate, or pH. The active component of gut calcium transport may be involved, possibly via alterations of vitamin D metabolism.
D000818:Animals; D002118:Calcium / Q000652:urine*; D002136:Calcium, Dietary / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005215:Fasting; D005260:Female; D005919:Glomerular Filtration Rate; D006934:Hypercalcemia / Q000209:etiology; D007444:Inulin / Q000378:metabolism; D008094:Lithium / Q000009:adverse effects*; D010280:Parathyroid Glands / Q000601:surgery; D010281:Parathyroid Hormone / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013268:Stimulation, Chemical
D002136:Calcium, Dietary; D010281:Parathyroid Hormone; D010710:Phosphates; D007444:Inulin; D008094:Lithium; D012964:Sodium; D003404:Creatinine; D002118:Calcium