Abstract
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.
Highlights
Most bipolar patients experience a reduction in urinary concentrating ability within a few weeks of starting lithium treatment
In some patients receiving lithium for 10 to 20 years, chronic interstitial nephropathy may develop, which results in increased serum creatinine and a reduction in the glomerular filtration rate (GFR)
Measurements of kidney function The following investigations, regarded for the use of this study as the phenotypes of kidney function were carried out: urine examination with specific gravity evaluation performed in a sample collected after overnight hydropenia, serum creatinine concentration, and estimated GFR evaluation, as well as two markers of kidney injury: the serum concentration of neutrophil gelatinase-associated lipocalin (NGAL) and the urinary concentration of β2-MG
Summary
Most 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 serum level of the neutrophil gelatinase-associated lipocalin (NGAL) may be a biomarker for glomerular filtration and correlates with the severity of the damage in patients with chronic kidney disease. Another marker is beta2microglobulin (β2-MG), the concentration of which in the urine may be correlated with the degree of tubular reabsorption impairment (Lisowska-Myjak 2010; Adiyanti and Loho 2012)
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