BackgroundConcerns about potential adverse effects of long-term exposure to lithium as a mood-stabilizing treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of lithium dose, serum concentration, and duration of treatment; relative effects of lithium exposure vs. aging; and contributions of sex and other factors all remain unclear.MethodsAccordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling.ResultsOverall, 29.5% of subjects experienced at least one low value of eGFR (<60 mL/min/1.73 m2), most after ≥15 years of treatment and age > 55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer lithium treatment, lower lithium dose, higher serum lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting lithium at age ≥ 40 years.LimitationsControl data for age-matched subjects not exposed to lithium were lacking.ConclusionsLong-term lithium treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum lithium level, longer lithium treatment, lower initial eGFR, and medical comorbidity, as well as older age.

These results confirm the greater susceptibility of female subjects for disturbances of thyroid hormones during lithium therapy, with one-fifth of them showing some features of hypothyroidism. Abnormally high levels of anti-TPO and anti-TG antibodies were shown in a significant proportion of patients. However, in contrast to the effect of lithium on kidney function, our results do not show an association between the duration of lithium therapy and thyroid dysfunction.

Lithium treatment causes an impairment of kidney function reflected also by abnormal levels of novel markers of kidney injury. Of these, urinary β2-MG, as a marker of tubular function seems to be better predictor than serum NGAL in lithium-treated patients because it shows multiple clinical and biochemical correlations, especially in men.

BackgroundMost bipolar patients experience a reduction in urinary concentrating ability within a few weeks of starting lithium treatment. This phenomenon may be connected with the effect of lithium on the glycogen synthase kinase-3beta (GSK-3β) present in the renal tubules. The GSK-3β gene is located on chromosome 3q13 and possesses a functional -50 C/T polymorphism. In the present study, we estimated this polymorphism in a group of long-term lithium-treated patients and assessed its association with various parameters of kidney function, including novel markers of kidney injury such as serum neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta2-microglobulin (β2-MG).MethodsThe study comprised 78 patients with bipolar mood disorder (25 males, 53 females), aged 36 to 82 (60 ± 11) years. The mean duration of bipolar illness was 6 to 50 (24 ± 10) years, and the patients have been receiving lithium for 5 to 38 (16 ± 9) years. All the patients had the following features, regarded as the phenotypes of kidney functions measured: urine examination for specific gravity evaluation, serum creatinine concentration, and estimated glomerular filtration rate (eGFR) evaluation, as well as the serum concentrations of NGAL and urinary β2-MG. Genotyping of GSK-3β gene -50 C/T polymorphism was done by polymerase chain reaction analysis.Results and discussionThirty-four patients (6 males, 28 females) had the T/T genotype, 37 patients (16 males, 21 females) had the T/C genotype, and 7 patients (3 males, 4 females) had the C/C genotype. Patients homozygous for C allele had significantly higher urine specific gravities (1.019 ± 0.008) compared to the remaining genotypes (1.013 ± 0.007) (p = 0.035), with no influence of the duration of lithium treatment. Other parameters of kidney function (serum creatinine, eGFR, serum NGAL, and urinary β2-MG levels) were not different between genotypes and, again, were not affected by the duration of lithium treatment. There was no correlation between urine specific gravity and other kidney function parameters. The results of our study indicate that the GSK-3β genotype may be connected with lithium-induced impairment of renal concentrating ability in long-term lithium-treated bipolar patients. Limitations of the study include small size of the sample, small number of C/C genotype patients, and a lack of multiple testing analysis of genotypic differences in various measures of kidney function.

Począwszy od roku 1963 stosowanie litu stanowi najbardziej udokumentowany sposób postępowania długoterminowego w chorobie afektywnej dwubiegunowej (ChAD), zarówno dla zapobiegania epizodom depresyjnym, jak i maniakalnym, a także zmniejszania ryzyka samobójstwa. W ChAD czynność gruczołu tarczowego i osi podwzgórze-przysadka-tarczyca (PPT) ma istotne znaczenie dla patofizjologii, przebiegu klinicznego i leczenia tej choroby. Wpływ litu na gruczoł tarczowy stanowi jedno z najważniejszych działań niepożądanych długotrwałej terapii tym lekiem. Lit jest gromadzony w tarczycy w stężeniu 3 do 4 razy większym niż w osoczu, a w wyniku jego stosowania dochodzi do zmniejszenia produkcji i hamowania uwalniania hormonów tarczycy oraz zmian w procesach immunologicznych dotyczących tego gruczołu. Najczęstszymi objawami ubocznymi związanymi z działaniem długotrwałego stosowania litu na tarczycę jest wole i niedoczynność tarczycy. Rzadkim powikłaniem stosowania litu jest nadczynność tarczycy. Lit może też powodować wzrost autoimmunizacji tarczycy, zwłaszcza, jeśli jest ona obecna przed rozpoczęciem leczenia oraz zmiany strukturalne tego gruczołu. W artykule omówiono również postępowanie w opisanych wyżej powikłaniach oraz zasady monitorowania czynności tarczycy u osób otrzymujących długotrwałą terapię litem.