Renal concentrating ability and glomerular filtration rate in lithium-treated patients

J. Doornebal, A. Diepenbroek, M. W. M. van de Luijtgaarden, E. G. T. M. Hartong, K. P. Grootens, R. W. Kupka, U. M. H. Klumpers, P. M. T. Deen, C. A. Gaillard, J. F. M. Wetzels

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background. Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. Methods. 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. Results. A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/ kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60ml/min/1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B =-6.1, 95%-CI:-9.4,-2.9, p < 0.001) and eGFR (B =-0.6, 95%-CI: 0.2,-3.3; p < 0.01). Conclusions. RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.
Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalNetherlands Journal of Medicine
Volume77
Issue number4
Publication statusPublished - 1 May 2019

Cite this

Doornebal, J., Diepenbroek, A., van de Luijtgaarden, M. W. M., Hartong, E. G. T. M., Grootens, K. P., Kupka, R. W., ... Wetzels, J. F. M. (2019). Renal concentrating ability and glomerular filtration rate in lithium-treated patients. Netherlands Journal of Medicine, 77(4), 139-149.
Doornebal, J. ; Diepenbroek, A. ; van de Luijtgaarden, M. W. M. ; Hartong, E. G. T. M. ; Grootens, K. P. ; Kupka, R. W. ; Klumpers, U. M. H. ; Deen, P. M. T. ; Gaillard, C. A. ; Wetzels, J. F. M. / Renal concentrating ability and glomerular filtration rate in lithium-treated patients. In: Netherlands Journal of Medicine. 2019 ; Vol. 77, No. 4. pp. 139-149.
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title = "Renal concentrating ability and glomerular filtration rate in lithium-treated patients",
abstract = "Background. Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. Methods. 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. Results. A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/ kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51{\%}) had an impaired RCA and 17 patients (17{\%}) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19{\%}) had an eGFR ≤ 60ml/min/1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B =-6.1, 95{\%}-CI:-9.4,-2.9, p < 0.001) and eGFR (B =-0.6, 95{\%}-CI: 0.2,-3.3; p < 0.01). Conclusions. RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.",
keywords = "Chronic kidney disease, Glomerular filtration rate, Lithium, Mood disorders, Nephrogenic diabetes insipidus, Renal concentrating ability",
author = "J. Doornebal and A. Diepenbroek and {van de Luijtgaarden}, {M. W. M.} and Hartong, {E. G. T. M.} and Grootens, {K. P.} and Kupka, {R. W.} and Klumpers, {U. M. H.} and Deen, {P. M. T.} and Gaillard, {C. A.} and Wetzels, {J. F. M.}",
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Doornebal, J, Diepenbroek, A, van de Luijtgaarden, MWM, Hartong, EGTM, Grootens, KP, Kupka, RW, Klumpers, UMH, Deen, PMT, Gaillard, CA & Wetzels, JFM 2019, 'Renal concentrating ability and glomerular filtration rate in lithium-treated patients' Netherlands Journal of Medicine, vol. 77, no. 4, pp. 139-149.

Renal concentrating ability and glomerular filtration rate in lithium-treated patients. / Doornebal, J.; Diepenbroek, A.; van de Luijtgaarden, M. W. M.; Hartong, E. G. T. M.; Grootens, K. P.; Kupka, R. W.; Klumpers, U. M. H.; Deen, P. M. T.; Gaillard, C. A.; Wetzels, J. F. M.

In: Netherlands Journal of Medicine, Vol. 77, No. 4, 01.05.2019, p. 139-149.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Renal concentrating ability and glomerular filtration rate in lithium-treated patients

AU - Doornebal, J.

AU - Diepenbroek, A.

AU - van de Luijtgaarden, M. W. M.

AU - Hartong, E. G. T. M.

AU - Grootens, K. P.

AU - Kupka, R. W.

AU - Klumpers, U. M. H.

AU - Deen, P. M. T.

AU - Gaillard, C. A.

AU - Wetzels, J. F. M.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Background. Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. Methods. 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. Results. A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/ kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60ml/min/1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B =-6.1, 95%-CI:-9.4,-2.9, p < 0.001) and eGFR (B =-0.6, 95%-CI: 0.2,-3.3; p < 0.01). Conclusions. RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.

AB - Background. Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium. Methods. 134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA. Results. A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/ kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and < 600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60ml/min/1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B =-6.1, 95%-CI:-9.4,-2.9, p < 0.001) and eGFR (B =-0.6, 95%-CI: 0.2,-3.3; p < 0.01). Conclusions. RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.

KW - Chronic kidney disease

KW - Glomerular filtration rate

KW - Lithium

KW - Mood disorders

KW - Nephrogenic diabetes insipidus

KW - Renal concentrating ability

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M3 - Article

VL - 77

SP - 139

EP - 149

JO - Netherlands Journal of Medicine

JF - Netherlands Journal of Medicine

SN - 0300-2977

IS - 4

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Doornebal J, Diepenbroek A, van de Luijtgaarden MWM, Hartong EGTM, Grootens KP, Kupka RW et al. Renal concentrating ability and glomerular filtration rate in lithium-treated patients. Netherlands Journal of Medicine. 2019 May 1;77(4):139-149.