Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study

Mehmet Tonkaz; Abdulkadir Kaya; Meltem Hazel Şimşek; Özgür Önal; Nagihan Ayaz Naycı; Gülsüm Yitik Tonkaz; Duygu Erkal; Gökhan Tonkaz

Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study

Abstract

Aims: To evaluate the association between lithium and renal structure using computed tomography (CT)-based volumetric methods in smoking patients with bipolar disorder, and its relationship with renal function indicators. Methods: This retrospective, cross-sectional, single-center study included 165 participants with contrast-enhanced abdominal CT: smoking patients with bipolar disorder receiving lithium (n=55), lithium-naïve smoking patients with bipolar disorder (n=55), and smoking controls without known psychiatric or renal disease (n=55). Renal parenchymal volume, dimensions, cortical thickness at four sites, and cystic changes were assessed by two radiologists using 3D Slicer software; volumes were normalized to body surface area (BSA). Serum creatinine, estimated glomerular filtration rate (eGFR), and other biochemical parameters were recorded. Results: Interobserver agreement was high (ICC=0.81). In unadjusted analysis, eGFR differed among groups (p=0.037) and was lower in the lithium group than in controls (difference between group medians, 8.8 ml/min/1.73 m²; p=0.011), but this difference was no longer significant after adjustment for age, gender, body-mass index (BMI), and pack-years (p=0.503); creatinine did not differ (p=0.586). In unadjusted comparisons, renal parenchymal volume, dimensions, and BSA-normalized volume did not differ among groups (all p>0.09). Right lower-pole cortical thickness showed an isolated unadjusted difference between the lithium and non-lithium groups (p=0.016) that did not survive correction for the four regional comparisons. Renal cyst frequency was similar among groups (p=0.572). Total renal volume correlated positively with height, weight, and BMI. In these adjusted models, BSA-normalized renal volume was significantly lower in the lithium group than in controls (B=-22.8 cm³/m², 95% CI -41.0 to -4.7; p=0.014), a difference not apparent in the unadjusted comparison. Conclusion: Although unadjusted eGFR was lower in lithium-treated patients with bipolar disorder than in controls, this difference did not persist after covariate adjustment for age, gender, BMI, and smoking exposure. Renal parenchymal volume, dimensions, and cyst frequency did not differ significantly on unadjusted comparison, although BSA-normalized renal volume was significantly lower in the lithium group after covariate adjustment. These findings suggest that the unadjusted eGFR difference is not robust to adjustment for baseline demographic and clinical characteristics, while a confounder-adjusted difference in normalized renal volume between the lithium group and controls represents a novel finding that warrants confirmation in prospective studies.

Keywords

Supporting Institution

No external funding was received for this study.

Ethical Statement

This study was conducted in accordance with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Giresun University Clinical Research Ethics Committee (Date: 18.05.2026; Decision No: 13.05.2026/07). Written informed consent was obtained from all participants prior to inclusion in the study.

Thanks

None.

References

Malhi GS, Gessler D, Outhred T. The use of lithium for the treatment of bipolar disorder: recommendations from clinical practice guidelines. J Affect Disord. 2017;217:266-280. doi:10.1016/j.jad.2017.03.052
Ercis M, Gonzalez Suarez ML, Singh B. Lithium and kidney disease. Mayo Clin Proc. 2025;100(1):19-25. doi:10.1016/j.mayocp.2024.10.008
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):721-728. doi:10.1016/S0140-6736(11)61516-X
Rodrigo C, de Silva NL, Gunaratne R, Rajapakse S, De Silva VA, Hanwella R. Lower estimated glomerular filtration rates in patients on long term lithium: a comparative study and a meta-analysis of literature. BMC Psychiatry. 2014;14(1):4. doi:10.1186/1471-244X-14-4
Shine B, McKnight RF, Leaver L, Geddes JR. Long-term effects of lithium on renal, thyroid, and parathyroid function: a retrospective analysis of laboratory data. Lancet. 2015;386(9992):461-468. doi:10.1016/S0140-6736(14)61842-0
Bocchetta A, Ardau R, Fanni T, et al. Renal function during long-term lithium treatment: a cross-sectional and longitudinal study. BMC Med. 2015;13:12. doi:10.1186/s12916-014-0249-4
Macaron MM, Abou Rjeily M, Macaron R, et al. Lithium nephrotoxicity: a systematic review and meta-analysis of lithium versus non-lithium control studies in patients with affective disorders. Ther Adv Psychopharmacol. 2026;16:20451253261419633. doi:10.1177/20451253261419633
Schoretsanitis G, de Filippis R, Brady BM, Homan P, Suppes T, Kane JM. Prevalence of impaired kidney function in patients with long-term lithium treatment: a systematic review and meta-analysis. Bipolar Disord. 2022;24(3):264-274. doi:10.1111/bdi.13154

Gislason G, Indridason OS, Sigurdsson E, Palsson R. Risk of chronic kidney disease in individuals on lithium therapy in Iceland: a nationwide retrospective cohort study. Lancet Psychiatry. 2024;11(12):1002-1011. doi:10.1016/S2215-0366(24)00324-9
Van Alphen AM, Bosch TM, Kupka RW, Hoekstra R. Chronic kidney disease in lithium-treated patients, incidence and rate of decline. Int J Bipolar Disord. 2021;9(1):1. doi:10.1186/s40345-020-00204-2
Hayes JF, Osborn DPJ, Francis E, et al. Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder. BMC Med. 2021;19(1):99. doi:10.1186/s12916-021-01964-z
Farres MT, Ronco P, Saadoun D, et al. Chronic lithium nephropathy: MR imaging for diagnosis. Radiology. 2003;229(2):570-574. doi:10.1148/radiol.2292020758
Tuazon J, Casalino D, Syed E, Batlle D. Lithium-associated kidney microcysts. ScientificWorldJournal. 2008;8:828-829. doi:10.1100/tsw.2008.112
Karaosmanoğlu AD, Butros SR, Arellano R. Imaging findings of renal toxicity in patients on chronic lithium therapy. Diagn Interv Radiol. 2013;19(4):299-303. doi:10.5152/dir.2013.097
Eid HA, Moazen EM, Elhussini M, et al. The influence of smoking on renal functions among apparently healthy smokers. J Multidiscip Healthc. 2022;15:2969-2978. doi:10.2147/JMDH.S392848
Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604-612. doi:10.7326/0003-4819-150-9-200905050-00006
Bosi A, Clase CM, Ceriani L, et al. Absolute and relative risks of kidney outcomes associated with lithium vs valproate use in Sweden. JAMA Netw Open. 2023;6(7):e2322056. doi:10.1001/jamanetworkopen.2023.22056
Fransson F, Werneke U, Harju V, et al. Kidney function in patients with bipolar disorder with and without lithium treatment compared with the general population in northern Sweden: results from the LiSIE and MONICA cohorts. Lancet Psychiatry. 2022;9(10):804-814. doi:10.1016/S2215-0366(22)00265-6
Golic M, Aiff H, Attman PO, et al. Lifetime risk of severe kidney disease in lithium-treated patients: a retrospective study. Int J Bipolar Disord. 2023;11(1):39. doi:10.1186/s40345-023-00319-2
Beunon P, Barat M, Dohan A, et al. MRI-based kidney radiomic analysis during chronic lithium treatment. Eur J Clin Invest. 2022;52(5):e13756. doi:10.1111/eci.13756

Details

Primary Language

English

Subjects

Psychiatry, Radiology and Organ Imaging

Journal Section

Research Article

Authors

Mehmet Tonkaz ^*
0000-0002-8746-4443
Türkiye

Abdulkadir Kaya
0009-0007-8660-9798
Türkiye

Meltem Hazel Şimşek
0000-0002-3323-4116
Türkiye

Özgür Önal
0000-0001-6514-2120
Türkiye

Nagihan Ayaz Naycı
0000-0002-0865-2818
Türkiye

Gülsüm Yitik Tonkaz
0000-0001-7195-2293
Türkiye

Duygu Erkal
0000-0002-8201-1568
Türkiye

Gökhan Tonkaz
0000-0001-5759-0206
Türkiye

Publication Date

October 25, 2026

Submission Date

July 23, 2026

Acceptance Date

September 7, 2026

Published in Issue

Year 2026 Volume: 8 Number: 6

IZ

https://izlik.org/JA46UB96TH

Cite

RIS / Bibtex

APA

Tonkaz, M., Kaya, A., Şimşek, M. H., Önal, Ö., Ayaz Naycı, N., Yitik Tonkaz, G., Erkal, D., & Tonkaz, G. (2026). Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study. Anatolian Current Medical Journal, 8(6), 1269-1278. https://izlik.org/JA46UB96TH

AMA

1.Tonkaz M, Kaya A, Şimşek MH, et al. Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study. Anatolian Curr Med J / ACMJ / acmj. 2026;8(6):1269-1278. https://izlik.org/JA46UB96TH

Chicago

Tonkaz, Mehmet, Abdulkadir Kaya, Meltem Hazel Şimşek, et al. 2026. “Effects of Lithium Use on Renal Structure in Smoking Patients With Bipolar Disorder: A Computed Tomography-Based Volumetric Study”. Anatolian Current Medical Journal 8 (6): 1269-78. https://izlik.org/JA46UB96TH.

EndNote

Tonkaz M, Kaya A, Şimşek MH, Önal Ö, Ayaz Naycı N, Yitik Tonkaz G, Erkal D, Tonkaz G (October 1, 2026) Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study. Anatolian Current Medical Journal 8 6 1269–1278.

IEEE

[1]M. Tonkaz et al., “Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study”, Anatolian Curr Med J / ACMJ / acmj, vol. 8, no. 6, pp. 1269–1278, Oct. 2026, [Online]. Available: https://izlik.org/JA46UB96TH

ISNAD

Tonkaz, Mehmet - Kaya, Abdulkadir - Şimşek, Meltem Hazel - Önal, Özgür - Ayaz Naycı, Nagihan - Yitik Tonkaz, Gülsüm - Erkal, Duygu - Tonkaz, Gökhan. “Effects of Lithium Use on Renal Structure in Smoking Patients With Bipolar Disorder: A Computed Tomography-Based Volumetric Study”. Anatolian Current Medical Journal 8/6 (October 1, 2026): 1269-1278. https://izlik.org/JA46UB96TH.

JAMA

1.Tonkaz M, Kaya A, Şimşek MH, Önal Ö, Ayaz Naycı N, Yitik Tonkaz G, Erkal D, Tonkaz G. Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study. Anatolian Curr Med J / ACMJ / acmj. 2026;8:1269–1278.

MLA

Tonkaz, Mehmet, et al. “Effects of Lithium Use on Renal Structure in Smoking Patients With Bipolar Disorder: A Computed Tomography-Based Volumetric Study”. Anatolian Current Medical Journal, vol. 8, no. 6, Oct. 2026, pp. 1269-78, https://izlik.org/JA46UB96TH.

Vancouver

1.Mehmet Tonkaz, Abdulkadir Kaya, Meltem Hazel Şimşek, Özgür Önal, Nagihan Ayaz Naycı, Gülsüm Yitik Tonkaz, Duygu Erkal, Gökhan Tonkaz. Effects of lithium use on renal structure in smoking patients with bipolar disorder: a computed tomography-based volumetric study. Anatolian Curr Med J / ACMJ / acmj [Internet]. 2026 Oct. 1;8(6):1269-78. Available from: https://izlik.org/JA46UB96TH