Article Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder Tayfun Turan a, *, Ertug ˘rul Es ¸el a , Bu ¨lent Tokgo ¨z b , Suat Aslan a , Seher Sofuog ˘lu a , Cengiz Utas ¸ b , Fahrettin Keles ¸timur c a Department of Psychiatry, Erciyes University School of Medicine, Talas Road, 38039 Kayseri, Turkey b Department of Nephrology, Erciyes University School of Medicine, Talas Road, 38039 Kayseri, Turkey c Department of Endocrinology, Erciyes University School of Medicine, Talas Road, 38039 Kayseri, Turkey Abstract Lithium (Li) carbonate has been reported to be able to cause some reversible functional changes in the kidney. In this study, the authors aimed to investigate whether the duration of Li treatment is the primary determinant of the changes in renal functioning due to the Li treatment. For this purpose, 10 Li-naı ¨ve (mean age ± S.D.: 34.50 ± 4.85), 10 short-term (mean age ± S.D.: 31.77 ± 7.61) and 10 long-term (mean age ± S.D.: 36.60 ± 10.15) Li-treated bipolar patients were included in the study. Serum blood urea nitrogen (BUN) and creatinine, urine creatinine levels, creatinine clearance, urine osmolality before and after 8-h water deprivation and urine osmolality after desmopressin injection were measured in all patients. Serum BUN and creatinine levels were within the normal limits and not statistically different among the groups. Creatinine clearance of the long-term Li-treated group was significantly lower than both that of the Li-naı ¨ve group and that of the short-term Li-treated group. After 8-h water deprivation and also after desmopressin injection, no difference was found among the groups in terms of urine osmolality. However, when each patient was evaluated individually in terms of their renal concentrating ability, partial nephrogenic diabetes insipidus was diagnosed in four patients on long-term and in two patients on short-term Li treatment. To our surprise, hypothalamic diabetes insipidus was also diagnosed in other two patients on long-term Li treatment. These results demonstrate that long-term Li treatment may cause impairment in renal concentrating ability, some of which may originate from the effects of Li on vasopressin on hypothalamic level, and a decrease in glomerular filtration rate (GFR). In the light of these data, we can conclude that long-term administration of Li may be a risk factor for Li-induced renal impairment, which is a progressive effect in nature. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Bipolar mood disorder; Creatinine clearance; Diabetes insipidus; Lithium; Renal concentrating ability 1. Introduction Lithium (Li) may cause functional changes in kidney, which have been reported to be typically benign and revers- ible (Gitlin, 1999). One of the well-documented renal side effects of Li is polyuria. Li-induced polyuria is associated with impaired renal concentrating ability, which is possibly due to a resistance of the collecting ducts to antidiuretic hormone (ADH) (Hansen et al., 1982; Cos ˛kunol et al., 1997). Li-induced impairment in renal concentrating ability has been reported to be associated with a longer duration of Li treatment and higher plasma Li levels (DePaulo et al., 1986), or a multiple daily dosing schedule (Hetmar et al., 1991; Kusalic and Engelsmann, 1996). Deterioration in glomerular filtration rate (GFR) due to Li has rarely been reported (Lokkegaard et al., 1985). In humans, precise site of the inhibitory effect of Li on the action of ADH is thought to be the distal tubular cells, which is likely to be at the level of ADH-sensitive adenylate cyclase activity (Vestergaard et al., 1979). Animal studies have confirmed that Li might affect ADH-induced generation of cyclic AMP in both distal and proximal tubules (Beck and Davis, 1975). In addition to this, it has been reported that the production of ADH might also be inhibited by Li so that the condition will be with mixed renal and hypothalamic origin (Martines- Maldonado et al., 1975). 0278-5846/01/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII:S0278-5846(01)00308-6 Abbreviations: ADH, antidiuretic hormone; BUN, blood urea nitrogen; GFR, glomerular filtration rate; Li, lithium * Corresponding author. Tel./fax: +90-352-4375702. E-mail address: tayfunturan@hotmail.com (T. Turan). Progress in Neuro-Psychopharmacology & Biological Psychiatry 26 (2002) 561 – 565