AI Article Synopsis

  • Chronic lithium treatment for bipolar disorder primarily impacts kidney health, leading to conditions like nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), with age, dosage, and treatment duration as key risk factors.
  • A study with 29 different inbred strains of female mice showed significant increases in urine production and kidney damage markers associated with lithium treatment, affecting 21 strains' urine concentration abilities.
  • Genetic differences among the mouse strains significantly influenced their response to lithium, with urinary β2-microglobulin levels emerging as a potential biomarker for assessing lithium-induced chronic kidney damage.

Article Abstract

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 β2-microglobulin (β2M) 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 β2M levels indicates that β2M is a promising biomarker for chronic renal damage induced by lithium.

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Source
http://dx.doi.org/10.1152/physiolgenomics.00149.2020DOI Listing

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