Chronic kidney disease induced by lithium in an animal model

MARTINO D.J.; ACOSTA J.M.; TOBLLI J.E.; REPETTO M.G.; LAGO N.R; UCEDA A.M; OSSANI G.P

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2017

Sociedad Argentina de Investigación Clínica

Lithium (Li) is considered as a first-line drug for the maintenance treatment of bipolar disorder. Interest in the risk of chronic kidney disease and Li-induced renal failure is renewed due to findings suggesting that both complications would be more frequent than previously estimated. The aim of this work was to evaluate renal damage due to chronic exposure to Li. Wistar male rats (n=39) were fed standard diet (Control -C-) or a containing 60 mmol Li/kg diet (Experimental -E-) ad libitum and sacrificed after 1 or 3 months of treatment (1 or 3). Clearance of creatinine (CrCl), lithemia, urin protein excretion (UPE) and fractional excretion of sodium (FENa) were measured. Kidney samples were processed for: 1-histology and morphometric analysis (PAS and H&E); 2-oxidative stress (TBARs and carbonyls) evaluation; 3-immunohistochemistry (Aquaporin-2; AQP2). FENa and UPE were within normal values in all groups. Lithemia (mmol/L) reached therapeutic values in both E groups (E1=0.57±0.18 and E3=0.68±0.12). CrCl was markedly reduced after 3 months of Li administration (C3=2.750.47 vs E3=1.550.75; t=4.18, p=0.001). Kidney from both E groups showed dilatation of the cortical collecting tubules (CCT), identified with AQP2 positive staining. Some CCT had hypertrophy with enlarged, binucleated cells, protruding into lumen and other CCT had atrophy with flattened cells. Glomerular area -m2- was smaller in E rats (C1=11333±2067 vs E1=9757±2178; t=1.58, p=0.135 and C3=13103±1494 vs E3=11053±929; t=3.76, p=0.001). A significant increase in TBARs -nmol/mg-(C1=0.36±0.10 vs E1=0.51±0.11; t=-3.02, p=0.008 and C3=0.36±0.08 vs E3=0.58±0.15; t=-4.02, p=0.001) and carbonyls -nmol/mg-(C1=0.23±0.07 vs E1=0.33±0.06; t=-3.27, p=0.004 and C3=0.24±0.07 vs E3=0.36±0.10; t=-3.24, p=0.005) was observed in both E groups. Exposure to Li from 1 to 3 months induced renal damage resulting in histological and functional alterations, changes in glomerular area and increase of oxidative stress and damage.