Chronic kidney disease induced by lithium in an animal model.

OSSANI, GEORGINA; UCEDA ANA; ACOSTA JUAN MANUEL; REPETTO MARISA; LAGO, NÉSTOR; MARTINO DIEGO; TOBLLI JORGE

Congreso; LXII Reunión Científica 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 maintenancetreatment of bipolar disorder. Interest in the risk of chronic kidneydisease and Li-induced renal failure is renewed due to findingssuggesting that both complications would be more frequent thanpreviously estimated. The aim of this work was to evaluate renaldamage due to chronic exposure to Li. Wistar male rats (n=39) werefed standard diet (Control -C-) or a containing 60 mmol Li/kg diet(Experimental -E-) ad libitum and sacrificed after 1 or 3 months oftreatment (1 or 3). Clearance of creatinine (CrCl), lithemia, urin proteinexcretion (UPE) and fractional excretion of sodium (FENa) weremeasured. Kidney samples were processed for: 1-histology andmorphometric analysis (PAS and H&E); 2-oxidative stress (TBARsand 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 after3 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 ofthe cortical collecting tubules (CCT), identified with AQP2 positivestaining. Some CCT had hypertrophy with enlarged, binucleatedcells, protruding into lumen and other CCT had atrophy with flattenedcells. Glomerular area -mm2- was smaller in E rats (C1=11333±2067vs E1=9757±2178; t=1.58, p=0.135 and C3=13103±1494 vsE3=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 andC3=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 andC3=0.24±0.07 vs E3=0.36±0.10; t=-3.24, p=0.005) was observedin both E groups. Exposure to Li from 1 to 3 months induced renal