Search

Purpose The aim of the study was to analyze sonographic (US) renal findings in lithium-treated bipolar patients and to correlate them with renal function. Methods Renal US and renal function tests were performed on 120 patients with bipolar disorder. Ninety patients (30 males, 60 females), aged 36–82 years, had received lithium therapy for an average of 16 years, whereas 30 patients (10 males, 20 females), aged 35–85 years, who had never been exposed to lithium, served as controls. Results In the lithium-treated group, patients with macrocysts (22%) had poorer renal function with higher creatinine serum concentrations, lower estimated glomerular filtration rates, and lower urine specific gravity, compared with the patients without macrocysts. The US changes characteristic for lithium nephropathy (punctate hyperechoic foci, microcysts < 2 mm, and increased echogenicity) were seen in three patients. These patients had been treated with lithium for more than 20 years and had impaired renal function. Sixteen percent of patients in the control group had macrocysts; however, no correlation between their presence and impaired renal function was found. Conclusions The presence of macrocysts in the kidneys of lithium-treated bipolar patients is associated with impaired renal function. The US changes characteristic for lithium nephropathy are rare, and in our study, were only found in patients treated with lithium for 20 years or more. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound, 2016

Objectives We assessed kidney function in long-term lithium-treated bipolar patients compared with age-matched patients not taking lithium, including novel markers of kidney injury such as plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary beta-2 microglobulin (β2-MG) Methods The study comprised 120 patients with bipolar disorder of which 90 (30 males and 60 females) have been receiving lithium for 5–38 (mean 16) years, and 30 (10 males and 20 females) have never been exposed to lithium. Results Lithium-treated patients, both men and women, showed significantly higher plasma NGAL and urinary β2-MG and lower urine specific gravity and estimated glomerular filtration rate (eGFR), compared with patients not taking lithium. In these patients, serum NGAL did not correlate with any clinical feature or other parameter of kidney function. Urinary β2-MG correlated with serum creatinine and eGFR in the whole group of lithium-treated patients and in addition, in males, with duration of illness, duration of lithium treatment, and urine specific gravity. Conclusions 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. Copyright © 2013 John Wiley & Sons, Ltd.

Background Concerns 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. Methods Accordingly, 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. Results Overall, 29.5% of subjects experienced at least one low value of eGFR ( 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. Limitations Control data for age-matched subjects not exposed to lithium were lacking. Conclusions Long-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.

We present the cases of five patients (two men aged 64 years and 79 years) and three women (aged 64 years, 65 years and 75 years) who have received lithium treatment for 40–45 years, with particular regard to kidney and thyroid functions, hypercalcaemia and cognition, in the context of disease course and overall functioning. Lithium was initiated in the early phase of the illness (in three patients within the first 2 years). In four patients, lithium concentration was between 0.60 and 0.65 mmol/l and in one patient, between 0.7 and 0.8 mmol/l. Four were very good lithium responders. One man had stage 3 chronic kidney disease, and the other stage 2/3 chronic kidney disease. All three women had asymptomatic stage 2 chronic kidney disease. One woman had severe thyroid dysfunction (Hashimoto’s disease) with extremely high levels of antithyroid peroxidase antibodies and antithyroglobulin antibodies and was receiving thyroxine. Serum calcium levels were normal or borderline in all five patients, and most cognitive functions were comparable to healthy persons of similar gender, age and years of education. All the patients were professionally active until 55–65 years and their family and social functioning were satisfactory. It was concluded that, in good lithium responders, ultra-long-term treatment with lithium enables good professional and psychosocial functioning, and the possible somatic side effects are manageable.

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.

Objectives An important side effect of lithium therapy is an influence on thyroid function. It is unclear whether there is a significant association between thyroid function and duration of lithium administration. The aim of the present cross-sectional study was to measure levels of thyroid hormones and antibodies in patients with bipolar disorder receiving lithium for more than ten years. Methods The study was performed in 66 patients (21 males, 45 females) with bipolar mood disorder, receiving lithium for 10–44 (21 ± 9; mean ± standard deviation) years. Thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) were measured by the microparticle enzyme immunoassay. Thyroid peroxidase (TPO) antibodies, thyroglobulin (TG) antibodies, and TSH receptor (TSH-R) antibodies were measured by the radioimmunoassay. Results Some features of hypothyroidism were found in ten (22%) female patients (seven received levothyroxine and three had increased TSH). No abnormality in thyroid hormones was found in male patients. A significant percentage of patients had abnormally high levels of anti-TPO, and anti-TG antibodies, which correlated with TSH and fT3 concentrations. There were no differences in thyroid function between patients receiving lithium for 10–20 years and those taking the drug for more than 20 years. Conclusions 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.

Summary Background Lithium is the most effective therapeutic modality for the prevention of recurrences in bipolar disorder. An important adverse effect of lithium, especially with long-term treatment, is a possibility of a toxic effect on kidney function. Therefore, the aim of the study was to assess kidney function in a group of long-term lithium-treated patients. Material/Methods The study comprised 80 patients with bipolar mood disorder (26 male, 54 female), aged 60±11 years. They had been receiving lithium for 5–38 (16±9) years. Random urine sample was examined for albumin and creatinine excretion, and urinary albumin to creatinine ratio (UACR) was calculated. Specific gravity of the urine sample was recorded. Serum concentration of creatinine was measured and estimated glomerular filtration rate (eGFR) was calculated. Serum concentration of albumin was also measured. Results Decreased eGFR values 30 mg/g) were found in 25% of men and 12% of women, respectively. Serum albumin concentration >52 g/l was detected in 19% of patients (17% of men and 20% of women). Specific gravity of the urine, equal to or below 1.005, was recorded in 21% of men and 14% of women. Conclusions The results confirm the opinion that screening for the markers of kidney damage should be performed in long-term lithium-treated patients for identification of persons with impaired kidney function. Male sex seems to be the risk factor for the development of kidney damage during long-term lithium treatment.