How is lithium associated with chronic tubulointerstitial nephritis?
Long-term lithium ingestion may cause chronic tubulointerstitial nephritis, nephrogenic diabetes insipidus (NDI), RTA, and hypercalcemia. Lithium enters the collecting tubule cells via the luminal epithelial sodium channels and accumulates intracellularly where it interferes with antidiuretic hormone (ADH)-mediated water reabsorption. An incomplete distal (type 1) RTA, secondary to lithium-induced decreased H+ATPase pump activity in the distal tubule, has been described. Lithium has also been associated with hypercalcemia caused by morphologic changes in the parathyroid glands.
Lithium-induced nephropathy is characterized by the formation of microcysts in the distal convoluted tubules and collecting ducts.
Typically, kidney dysfunction secondary to chronic lithium use is mild to moderate. Amiloride, a potassium-sparing diuretic, has been shown to reduce polyuria and to block lithium uptake in the sodium channels of the collecting duct. Those with serum creatinine levels greater than 2.5 mg/dL at the time of presentation may progress to end-stage kidney disease (ESKD) even after the cessation of lithium. The average latent period between the initiation of lithium therapy and the onset of ESKD is 20 years.
For those patients receiving chronic maintenance therapy with lithium, regular follow-up of serum creatinine is recommended. Elevations in creatinine should lead to either dose reduction or complete withdrawal of the drug.
