Abstract
Despite the availability of alternative agents, lithium continues to be the standard against which all mood stabilisers, prescribed for acute and maintenance treatment of bipolar (and, to a lesser extent, unipolar) mood disorders, are compared. As a medication often used on a maintenance basis for a lifelong disorder, the potential for lithium to cause long term organ toxicity has generated appropriate concern. Foremost among these concerns are its renal effects.
Lithium adversely affects renal tubular function, causing polyuria secondary to a deficit in urine concentrating ability. This effect is probably progressive for the first decade of lithium therapy, i.e. it correlates with duration of lithium therapy. Although this effect of lithium is probably functional and reversible early in treatment, it may become structural and irreversible over time. In contrast, the effect of lithium on glomerular function is not progressive.
Conclusions in this area are hampered by the evidence that patients with psychiatric disorders who are not receiving lithium also show defects in certain aspects of renal function. Despite the generally sanguine data on glomerular function, a very small group of patients may develop renal insufficiency due to lithium (possibly in conjunction with other somatic factors) in the form of interstitial nephritis. However, for the vast majority of patients, the renal effects of lithium are benign.
Current strategies for minimising the renal effects of lithium include: (i) assiduously avoiding episodes of renal toxicity; (ii) monitoring serum lithium concentrations in order to achieve optimal efficacy at the lowest possible concentration; (iii) monitoring serum creatinine levels on a yearly basis, getting further medical evaluation when the serum creatinine level consistently rises above 140 mmol/L (1.6 mg/dl); and (iv) possibly administering lithium once a day.
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References
American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder. Am J Psychiatry 1994, 151: 1–31
Hestbech J, Hansen HE, Amdisen A, et al. Chronic renal lesions following long-term treatment with lithium. Kidney Int 1977; 12: 205–13
Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis 1987, 5: 329–45
Schou M. Effects of long-term lithium treatment on kidney function: an overview. J Psychiatr Res 1988; 22: 287–96
Waller DG, Edwards JG. Lithium and the kidney: an update. Psychol Med 1989; 19: 825–31
Thomsen K. Renal handling of lithium: basic concepts and present status. In: Christensen S, editor. Lithium and the kidney: lithium therapy monographs. Vol. 3. New York (NY): Karger, 1990: 2–18
Leyssac P P, Frederiksen O, Holstein-Rathlou NH. Renal tubular transport of lithium. In: Christensen S, editor. Lithium and the kidney: lithium therapy monographs. Vol. 3. New York (NY): Karger, 1990: 19–33
Singer I, Oster JR, Fishman LM. The management of diabetes insipidus in adults. Arch Intern Med 1997; 157: 1293–301
Wahlin A, Bucht G, Von Knorring L, et al. Kidney function in patients with affective disorders with and without lithium therapy. Int Pharmacopsychiatry 1980; 16: 253–9
Coppen A, Bishop ME, Bailey JE, et al. Renal function in lithium and non-lithium-treated patients with affective disorders. Acta Psychiatr Scand 1980; 62: 343–55
Gelenberg AJ, Wojcik JD, Falk WE, et al. Effects of lithium on the kidney. Acta Psychiatr Scand 1987; 75: 29–34
Vestergaard P, Amdisen A. Lithium treatment and kidney function. Acta Psychiatr Scand 1981; 63: 333–45
DePaulo Jr RJ, Correa EI, Sapir DG. Renal function and lithium: a longitudinal study. Am J Psychiatry 1986; 143: 892–5
Hetmar O, Clemmesen L, Ladefoged J, et al. Lithium: long-term effects on the kidney. Acta Psychiatr Scand 1987; 75: 251–8
Johnson GFS, Hunt GE, Daggin GG, et al. Renal function and lithium treatment: initial and follow-up tests in manic-depressive illness. J Affect Disord 1984; 6: 249–63
Smigan L, Gucht G, Von Knorring L, et al. Long-term lithium treatment and renal functions. Neuropsychobiology 1984; 11: 33–8
Waller DG, Edwards JG, Papsthatis-Papayanni S. Longitudinal assessment of renal function during treatment with lithium. Q J Med 1988; 68: 553–8
Bendz H, Aurell M, Balldin J, et al. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant 1994; 9: 1250–4
Coskunol H, Vahip S, Mees ED, et al. Renal side-effects of long-term lithium treatment. J Affect Disord 1997; 43: 5–10
Conte G, Vazzola A, Sacchetti E. Renal function in chronic lithium-treated patients. Acta Psychiatr Scand 1989; 79: 503–4
Nilsson A, Axelsson R. Effects of long-term lithium treatment on thyroid and renal function (serum creatinine and maximal urine osmolality) — a prospective study in psychiatric patients. Curr Ther Res 1989; 46: 85–102
Jorkasky DK, Amsterdam JD, Oler J, et al. Lithium-induced renal disease: a prospective study. Clin Nephrol 1988; 30: 293–302
Hetmar O, Povlsen UJ, Ladefoged J, et al. Lithium: long-term effects on the kidney: a prospective follow-up study ten years after kidney biopsy. Br J Psychiatry 1991; 158: 53–8
Kallner G, Peterson U. Renal, thyroid and parathyroid function during lithium treatment: laboratory tests in 207 people treated for 1–30 years. Acta Psychiatr Scand 1995; 91: 48–51
Waller DG, George JG. Lithium and the kidney. Adverse Drug React Acute Poisoning Rev 1984; 3: 65–89
Bucht G, Wahlin A. Renal concentrating capacity in long-term lithium treatment and after withdrawal of lithium. Acta Med Scand 1980; 207: 309–14
Bendz H. Kidney function in a selected lithium population: a prospective, controlled, lithium-withdrawal study. Acta Psychiatr Scand 1985; 72: 451–63
Bendz H, Sjodin I, Aurell M. Renal function on and off lithium in patients treated with lithium for 15 years or more: a controlled, prospective lithium-withdrawal study. Nephrol Dial Transplant 1996; 11: 457–60
Schuster VL, Seldin DW. Renal clearance. In: Seldin DW, Giebisch G, editors. The kidney: physiology and pathophysiology. 2nd ed. New York, (NY): Raven Press, 1992: 943–78
Gaspari F, Perico N, Remuzzi G. Measurement of glomerular filtration rate. Kidney Int 1997; 52: S151–4
Bendz H, Andersch S, Aurell M. Kidney function in an unselected lithium population. Acta Psychiatr Scand 1983; 68: 325–34
Bosquet S, Descombes E, Gauthier T, et al. Nephrotic syndrome during lithium therapy. Nephrol Dialysis Transplant 1997; 12: 2728–31
Gill DS, Chhetri M, Milne JR. Nephrotic syndrome associated with lithium therapy. Am J Psychiatry 1997; 154: 1318–9
Hansen HE, Hestbech J, Sorensen JL, et al. Chronic interstitial nephropathy in patients on long-term lithium treatment. Q J Med 1979; 192: 577–91
Albrecht J, Kampf D, Muller-Oberlinghausen B. Renal function and biopsy in patients on lithium-therapy. Pharmacopsychiatry 1980; 13: 228–34
Aurell M, Svalander C, Wallin L, et al. Renal function and biopsy findings in patients on long-term lithium treatment. Kidney Int 1981; 20: 663–70
Walker RG, Bennett WM, Davis BM. Structural and functional aspect of long-term lithium therapy. Kidney Int 1982; 21: 513–9
Walker RG, Dowling JF, Alcorn D, et al. Renal pathology associated with lithium therapy. Pathology 1983; 15: 404–11
Jørgensen F, Larsen S, Spanager E, et al. Kidney function and quantitative histological changes in patients on long-term lithium therapy. Acta Psychiatr Scand 1984; 70: 347–55
Davies B, Kincaid-Smith P. Renal biopsy studies of lithium and prelithium patients and comparison with cadaver transplant kidneys. Neuropharmacology 1979; 18: 1001–2
Walker RG, Escott M, Birchall I, et al. Chronic progressive renal lesions induced by lithium. Kidney Int 1986; 29: 875–81
Løkkegaard H, Andersen NF, Henriksen E, et al. Renal function in 153 manic-depressive patients treated with lithium for more than five years. Acta Psychiatr Scand 1985; 71: 347–55
Stancer HC, Forbath N. Hyperparathyroidism, hypothyroidism and impaired renal function after 10 to 20 years of lithium treatment. Arch Intern Med 1989; 149: 1042–5
Gitlin MJ. Lithium-induced renal insufficiency. J Clin Psychopharmacol 1993; 13: 276–9
Von Knorring L, Wahlin A, Nystrom K, et al. Uraemia induced by long-term lithium treatment. Lithium 1990; 1: 251–3
Chugh S, Yager H. End stage renal disease following lithium therapy. J Clin Psychopharmacol 1997; 17: 495–7
Bucht G, Wahlin A, Wentzel, et al. Renal function and morphology in long-term lithium and combined lithium-neuroleptic treatment. Acta Med Scand 1980; 208: 381–5
Lessen E, Vestergaard P, Thomsen K. Renal function of patients in long-term treatment with lithium citrate alone or in combination with neuroleptics and antidepressant drugs. Arch Gen Psychiatry 1986; 43: 481–2
Bendz H, Sjodin I, Toss G, et al. Hyperparathyroidism and long-term lithium therapy — a cross-sectional study and the effect of lithium withdrawal. J Intern Med 1996: 240: 357–65
Racke F, McHenry CR, Wentworth D. Lithium-induced alterations in parathyroid cell function: insight into the pathogenesis of lithium-associated hyperparathyroidism. Am J Surg 1994; 168: 464–5
Schou M, Amdisen A, Thomsen K, et al. Lithium treatment regimen and renal water handling: the significance of dosage pattern and tablet examination through comparison of results from two clinics and different treatment regimens. Psychopharmacol 1982; 77: 387–90
Plenge P, Mellerup ET, Bolwig TG, et al. Lithium treatment: does the kidney prefer one daily dose instead of two? Acta Psychiatr Scand 1982; 66: 121–8
Plenge P, Mellerup ET. Lithium and the kidney: is one daily dose better than two? Compr Psychiatry 1986; 27: 336–42
Hetmar O, Bolwig, TG, Brun C, et al. Lithium: long-term effects on the kidney. Acta Psychiatr Scand 1986; 73: 574–81
Hetmar O, Brun C, Clemmesen L, et al. Lithium: long-term effects on the kidney: II: structural changes. J Psychiatr Res 1987; 21: 279–88
Bowen RC, Grof CM, Grof E. Less frequent lithium administration and lower urine volume. Am J Psychiatry 1991; 148: 189–92
Plenge P, Mellerup ET, Norgaard T. Functional and structural rat kidney changes caused by peroral or parenteral lithium treatment. Acta Psychiatr Scand 1981; 63: 303–13
Lauritsen BJ, Mellerup E T, Plenge P, et al. Serum lithium concentrations around the clock with different treatment regimens and the diurnal variation of the renal lithium clearance. Acta Psychiatr Scand 1981; 64: 314–9
Amdisen A. Monitoring of lithium treatment through determination of lithium concentration. Dan Med Bull 1975; 22: 277–90
O’Donovan C, Hawkes J, Bowen R. Effect of lithium dosing schedule on urinary output. Acta Psychiatr Scand 1993; 87: 92–5
Abraham G, Waldron JJ, Lawson JS. Are the renal effects of lithium modified by frequency of administration? Acta Psychiatr Scand 1995; 92: 115–8
Muir A, Davidson R, Silverstone T, et al. Two regimens of lithium prophylaxis and renal function. Acta Psychiatr Scand 1989; 80: 579–83
Kusalic M, Engelsmann F. Renal reactions to changes of lithium dosage. Neuropsychobiology 1996; 34: 113–6
Jensen H V, Plenge P, Mellerup ET, et al. Lithium prophylaxis of manic-depressive disorder: daily lithium dosing schedule versus every second day. Acta Psychiatr Scand 1995; 92: 69–74
Jensen H V, Davidsen K, Toftegaard L, et al. Double-blind comparison of the side-effect profiles of daily versus alternate-day dosing schedules in lithium maintenance treatment of manic-depressive disorder. J Affect Disord 1996; 36: 89–93
Vestergaard P, Thomsen K. Renal side effects of lithium: the importance of the serum lithium level. Psychopharmacology 1981; 72: 203–4
Gelenberg AJ, Bassak EL, Schoonover SC. The practitioners guide to psychoactive drugs. 3rd ed. New York (NY): Plenum, 1991
Gitlin M. The psychotherapist’s guide to psychopharmacology. 2nd ed. New York (NY): Free Press, 1996
Schou M. Forty years of lithium treatment. Arch Gen Psychiatry 1997; 54: 9–15
Schou M, Hansen HE, Thomsen K, et al. Lithium treatment in Aarhus: 2: risk of renal failure and of intoxication. Pharmacopsychiatry 1989; 22: 101–3
Harvey NS, Merriman S. Review of clinically important drug interactions with lithium. Drug Saf 1994; 10: 455–63
Jefferson JW. Potassium supplementation in lithium patients: a timely intervention or premature speculation? J Clin Psychiatry 1992; 53: 370–2
Olesen OV. The effects of potassium on the renal actions of lithium in rats. In: Christensen S, editor. Lithium and the kidney: lithium therapy monographs. Vol. 3. New York (NY): Karger, 1990: 164–73
Olesen OV. The effect of potassium on some nephrotoxic actions of lithium in rats. Dan Med Bull 1984; 31: 270–82
Musa MN, Tripuraneni BR. Lithium-induced polyuria ameliorated by potassium supplementation. Lithium 1993; 4: 199–203
Batlle DC, Von Riotte AB, Gaviria M, et al. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med 1985; 312: 409–14
Jefferson JW. Lithium: a therapeutic magic wand. J Clin Psychiatry 1989; 50: 81–6
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Gitlin, M. Lithium and the Kidney. Drug-Safety 20, 231–243 (1999). https://doi.org/10.2165/00002018-199920030-00004
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DOI: https://doi.org/10.2165/00002018-199920030-00004