The Effect of Long-Term Lithium Use on Renal Functions in Patients with Bipolar Disorder

The Effect of Long-Term Lithium Use on Renal Functions in Patients with Bipolar Disorder

It is known that especially glomerular side effects of lithium lead to serious consequences such as end-stage renal disease. Therefore, it is critical to evaluate patients on long-term lithium therapy for glomerular pathologies. The present study investigated the changes in renal functions, prevalence of renal failure and progress in patients have been followed up for at least six years with bipolar disorders (BD) and on regular lithium treatment. 51 patients with BD and 38 age and sex matched healthy controls were enrolled for the study. The serum blood urea nitrogen (BUN), creatinine, uric acid, electrolytes, calcium (Ca), phosphorus (P), vitamin D (25-OH D3), parathyroid hormone (PTH) and eGFR levels were measured to compare the kidney functions of patients and control group. The relation between the renal functions and mean serum lithium levels and duration of lithium treatment were also investigated. Mean eGFR level, 25-OH D3 and urine density of patients with were significantly lower whereas creatinine, uric acid, Ca and PTH were significantly higher than that of controls.. The duration of lithium treatment and mean lithium levels were negatively correlated with eGFR level. Eight of 51 patients have critical eGFR level as lover than 60ml/minute thus further nephrological investigation was needed. The study revealed that the renal functions of the patient group was significantly lower than controls. The findings suggested that both duration of lithium treatment and high serum lithium levels may have a negative impact on renal functions. These findings suggest that it is important to clarify the response type to lithium in patients who are on long term treatment with lithium and maintain the treatment with the lowest possible therapeutic serum levels and carefully monitoring the renal functions in patients with good response to lithium.

___

  • Nielsen RE, Kessing LV, Nolen WA, Licht RW. Lithium and Renal Impairment: A Review on a Still Hot Topic. Pharmacopsychiatry. 2018;51(5):200-205.
  • Yatham LN, Kennedy SH, Parikh SV, et al. The evolution of CANMAT Bipolar Disorder Guidelines: past, present, and future. Bipolar Disord. 2013;15(1):58-60.
  • Azab AN, Shnaider A, Osher Y, Wang D, Bersudsky Y, Belmaker RH. Lithium nephrotoxicity. Int J Bipolar Disord. 2015;3(1):28.
  • Hestbech J, Hansen HE, Amdisen A, Olsen S. Chronic renal lesions following long-term treatment with lithium. Kidney Int. 1977;12(3):205-13.
  • Markowitz GS, Radhakrishnan J, Kambham N, et al. Lithium nephrotoxicity: a progressive combined glomerular and tubulointerstitial nephropathy. J Am Soc Nephrol. 2000;11(8):1439-1448.
  • Golshayan D, Nseir G, Venetz JP, Pascual M, Barbey F. MR imaging as a specific diagnostic tool for bilateral microcysts in chronic lithium nephropathy. Kidney Int. 2012;81(6):601.
  • Wells JE, Cross NB, Savage RL, Parkin L, Horsburgh S, Richardson AK. Renal replacement therapy associated with lithium nephrotoxicity in New Zealand. N Z Med J. 2015;128(1425):77-83
  • Davis J, Desmond M, Berk M. Lithium and nephrotoxicity: a literature review of approaches to clinical management and risk stratification. BMC Nephrol. 2018;19(1):305.
  • Johnson GFS, Hunt GE, Duggin GG, Horvath JS, Tiller DJ. Renal function and lithium treatment: Initial and follow-up tests in manic-depressive patients. J Affect Disord. 1984;6(3–4) :249-63.
  • Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis. 1987;10(5):329-45.
  • McCann SM, Daly J, Kelly CB. The impact of long-term lithium treatment on renal function in an outpatient population. *. 2008;77(2):102-5.
  • Bendz H, Aurell M, Balldin J, Mathé AA, Sjödin I. 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(9):1250-4.
  • Lepkifker E, Sverdlik A, Iancu I, Ziv R, Segev S, Kotler M. Renal insufficiency in long-term lithium treatment. J Clin Psychiatry. 2004;65(6):850-6.
  • Clos S, Rauchhaus P, Severn A, Cochrane L, Donnan PT. Long-term effect of lithium maintenance therapy on estimated glomerular filtration rate in patients with affective disorders: a population-based cohort study. Lancet Psychiatry. 2015;2(12):1075-83.
  • McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-8.
  • Fogo AB, Lusco MA, Andeen NK, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: Lithium Nephrotoxicity. Am J Kidney Dis. 2017;69(1):e1-e2.
  • Presne C, Fakhouri F, Noël LH, et al. Lithium-induced nephropathy: Rate of progression and prognostic factors. Kidney Int. 2003;64(2):585-92.
  • Matsushita K, Mahmoodi BK, Woodward M, et al. Chronic Kidney Disease Prognosis Consortium. Comparison of risk prediction using the CKD-EPI equation and the MDRD study equation for estimated glomerular filtration rate. JAMA. 2012; 9;307(18):1941-51.
  • Aiff H, Attman PO, Aurell M, Bendz H, Schön S, Svedlund J. End-stage renal disease associated with prophylactic lithium treatment. Eur Neuropsychopharmacol. 2014;24(4):540-4.
  • Tredget J, Kirov A, Kirov G. Effects of chronic lithium treatment on renal function. J Affect Disord. 2010;126(3):436-40.
  • González-Buitrago JM, Ferreira L, Lorenzo I. Urinary proteomics. Clin Chim Acta. 2007;375(1-2):49-56.
  • McPherson RA, Ben-Ezra J. Basic Examination of Urine. In: Henry’s Clinical Diagnosis and Management by Laboratory Methods. 2011.
  • D'Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int. 2003;63(3):809-25.
  • Kehoe RF. A cross-sectional study of glomerular function in 740 unselected lithium patients. Acta Psychiatr Scand. 1994;89(1):68-71.
  • Kirkham E, Skinner J, Anderson T, Bazire S, Twigg MJ, Desborough JA. One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database. BMJ Open. 2014;4(11):e006020.
  • Ott M, Stegmayr B, Salander Renberg E, Werneke U. Lithium intoxication: Incidence, clinical course and renal function - a population-based retrospective cohort study. J Psychopharmacol. 2016;30(10):1008-19.
  • Bendz H, Sjödin I, Toss G, Berglund K. Hyperparathyroidism and long-term lithium therapy--a cross-sectional study and the effect of lithium withdrawal. J Intern Med. 1996;240(6):357-65.
  • Albert U, De Cori D, Aguglia A, et al. Effects of maintenance lithium treatment on serum parathyroid hormone and calcium levels: a retrospective longitudinal naturalistic study. Neuropsychiatr Dis Treat. 2015;11:1785-91.
  • Meehan AD, Humble MB, Yazarloo P, Järhult J, Wallin G. The prevalence of lithium-associated hyperparathyroidism in a large Swedish population attending psychiatric outpatient units. J Clin Psychopharmacol. 2015;35(3):279-85.
  • Boudou P, Ibrahim F, Cormier C, Sarfati E, Souberbielle JC. A very high incidence of low 25 hydroxy-vitamin D serum concentration in a French population of patients with primary hyperparathyroidism. J Endocrinol Invest. 2006;29(6):511-5.