Genetic background determines renal response to chronic lithium treatment in female mice.
Physiol Genomics
; 53(9): 406-415, 2021 09 01.
Article
em En
| MEDLINE
| ID: mdl-34378418
Chronic lithium treatment for bipolar disease causes mainly side effects in the kidney. A subset of lithium users develops nephrogenic diabetes insipidus (NDI), a urinary concentrating disorder, and chronic kidney disease (CKD). Age, lithium dose, and duration of treatment are important risk factors, whereas genetic background might also play an important role. To investigate the role of genetics, female mice of 29 different inbred strains were treated for 1 year with control or lithium chow and urine, blood, and kidneys were analyzed. Chronic lithium treatment increased urine production and/or reduced urine osmolality in 21 strains. Renal histology showed that lithium increased interstitial fibrosis and/or tubular atrophy in eight strains, whereas in none of the strains glomerular injury was induced. Interestingly, lithium did not elevate urinary albumin-creatinine ratio (ACR) in any strain, whereas eight strains even demonstrated a lowered ACR. The protective effect on ACR coincided with a similar decrease in urinary IgG levels, a marker of glomerular function, whereas the adverse effect of lithium on interstitial fibrosis/tubular atrophy coincided with a severe increase in urinary ß2-microglobulin (ß2M) levels, an indicator of proximal tubule damage. Genetic background plays an important role in the development of lithium-induced NDI and chronic renal pathology in female mice. The strong correlation of renal pathology with urinary ß2M levels indicates that ß2M is a promising biomarker for chronic renal damage induced by lithium.
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Base de dados:
MEDLINE
Assunto principal:
Diabetes Insípido Nefrogênico
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Insuficiência Renal Crônica
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Patrimônio Genético
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Lítio
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article