Mild to severe lithium-induced nephropathy models and urine N-acetyl-beta-D-glucosaminidase in rats

Long-term treatment with lithium induces functional and/or structural disturbances in the kidneys. However, no procedure has been established for the early diagnosis of lithium intoxication. In this study, we prepared mild to severe lithium-induced nephropathy rat models and examined the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) for the early diagnosis of lithium-induced renal insufficiency. Lithium was administered by repeated intraperitoneal injection (1, 2 and 4 mEq/kg/day for 10 days). We also measured the plasma creatinine and paraaminohippuric acid (PAH) clearance, and observed renal histological changes. Lithium pretreatment elevated the plasma creatinine level and decreased PAH clearance in a dose-dependent manner. The NAG level in the lithium 4 mEq/kg group was very high. The levels in the lithium 1 mEq/kg and 2 mEq/kg groups were almost the same and were higher than the control group. A histological examination of the kidney revealed glomerular congestion and/or atrophy and tubular expansion in all of the groups except the control group. These histological changes were dose-dependent. In conclusion, urine NAG may be useful in the early diagnosis of renal side effects caused by lithium therapy. When the urine NAG level becomes high in a patient taking lithium for bipolar disorder, the physician may need to consider lithium-induced renal insufficiency.