lithium-chloride and Acute-Kidney-Injury

Lithium promotes the phosphorylation of glycogen synthase kinase-3β (GSK3β), and this reaction protects against acute kidney injury mediated by renal apoptosis. Lithium is considered to be reabsorbed by sodium-phosphate cotransporters and sodium-proton exchanger NHE3. This study evaluated the relation between the lithium reabsorption and the phosphorylation of GSK3β, by using acetazolamide, an NHE3 inhibitor. In rats infused with lithium chloride, the plasma concentration of lithium was 4.77 mEq/l, and the renal clearance of lithium and its fractional excretion were calculated to be 2.29 ml/min/kg and 0.405, respectively. Coadministration of acetazolamide decreased creatinine clearance and the reabsorption rate of lithium, increased the fractional excretion of lithium, and did not affect its plasma concentration. Western blot analysis exhibited the facilitation of GSK3β phosphorylation in the kidney cortex by lithium infusion, and acetazolamide inhibited the lithium-induced phosphorylation of GSK3β. Lithium did not affect GSK3β phosphorylation in the liver and did not affect Akt in the kidney cortex and liver. These data show that lithium reabsorption contributes to GSK3β phosphorylation in the kidney cortex.

Topics: Acetazolamide; Acute Kidney Injury; Animals; Apoptosis; Glycogen Synthase Kinase 3 beta; Kidney; Lithium; Lithium Chloride; Male; Phosphorylation; Rats; Rats, Wistar

Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.. El litio sigue siendo el tratamiento de elección en el trastorno bipolar. La intoxicación aguda por litio (IAL) es un cuadro potencialmente grave. Se presenta un estudio observacional, retrospectivo de las IAL observadas durante un periodo de 52 meses. Se definió como IAL cuando se registró una concentración de litio en sangre 1,5 mEq/L. Se analizaron sus características clínicas, epidemiológicas y su tratamiento de 70 episodios de IAL (densidad de incidencia: 1,76 IAL por cada 100 pacientes tratados-año). La causa más frecuente de IAL fue un proceso patológico intercurrente (46%). La mayoría fueron de carácter leve (74,2 %), con sintomatología neurológica en el 40,3%. En 8 IAL hubo alteraciones electrocardiográficas, 23 IAL (37,1%) se asociaron con fracaso renal agudo, la mayoría de carácter leve y 11 precisaron hemodiálisis. Se concluye que la IAL es una complicación infrecuente, pero es necesario disminuir su riesgo advirtiendo al paciente ante la existencia de procesos intercurrentes, errores en la posología o polimedicación.

Topics: Acute Disease; Acute Kidney Injury; Aged; Antidepressive Agents; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Chloride; Male; Middle Aged; Nervous System Diseases; Poisoning; Renal Dialysis; Retrospective Studies

The altered electrolyte handling of the choroid plexus was investigated in rats with acute renal failure (ARF) using lithium and rubidium as surrogate markers for sodium and potassium, respectively. Firstly, the transport of these two markers from the plasma to cerebrospinal fluid (CSF) was evaluated after they were concurrently injected into the femoral vein. As a result, their disposition from the plasma to CSF was shown to decrease in ARF rats, but the relationship profile between those two markers was not different from that observed in normal rats, indicating that the decreased disposition of lithium and rubidium occurs without affecting the stoichiometric balance. To clarify the mechanisms accounting for the decreased disposition, an inhibition study was then performed. When bumetanide, an inhibitor of the Na(+) /K(+) /2Cl(-) co-transporter, was directly introduced into the cerebroventricle prior to lithium and rubidium being intravenously administered, a marked increase in the markers' disposition was observed. However, such an increased disposition did not occur when bumetanide was injected into the femoral vein. Other inhibitors, such as amiloride for the Na(+) /H(+) exchanger and ouabain for Na(+) /K(+) -ATPase, did not show any effects on marker disposition regardless of the inhibitor being administered into either the cerebroventricle or femoral vein. These findings suggest that the decreased marker disposition in ARF rats is due to an increased efflux process of the choroid plexus mediated by the Na(+) /K(+) /2Cl(-) co-transporter. That is, electrolyte efflux from the CSF to plasma increases, and thereby the electrolyte influx from the plasma to CSF is counteracted.

Topics: Acute Kidney Injury; Animals; Area Under Curve; Bumetanide; Chlorides; Choroid Plexus; Electrolytes; Glycerol; Ion Transport; Lithium Chloride; Male; Potassium; Rats; Rats, Wistar; Rubidium; Sodium; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 2

The lithium disposition to cerebrospinal fluid (CSF) was evaluated in rats with acute renal failure (ARF) to examine whether electrolyte homeostasis of the CSF is perturbed by kidney dysfunction. In addition, the effects of renal failure on choroid plexial expressions of the Na+-K+-2Cl- co-transporter (NKCC1) and Na+/H+ exchanger (NHE1) were also studied.. After lithium was intravenously administered at a dose of 4 mmol/kg, its concentration profile in plasma was evaluated by collecting plasma specimens, while that in CSF was monitored with a microdialysis probe in the lateral ventricles. NKCC1 and NHE1 expressions were measured via the Western immunoblot method using membrane specimens prepared from the choroid plexus in normal and ARF rats.. The lithium concentration in CSF of ARF rats was 30% lower than that of normal rats, while their plasma lithium profiles were almost the same, indicating that the lithium disposition to CSF was decreased in ARF rats. It was revealed that the choroid plexial expression of NKCC1 was increased by 40% in ARF rats, but that of NHE1 was unchanged.. ARF decreases the lithium disposition to CSF, possibly by promoting lithium efflux from CSF due to increased NKCC1 expression in the choroid plexus.

Topics: Acute Kidney Injury; Animals; Choroid Plexus; Disease Models, Animal; Glycerol; Injections, Intravenous; Lithium Chloride; Male; Microdialysis; Rats; Rats, Wistar; Sodium-Hydrogen Exchanger 1; Sodium-Hydrogen Exchangers; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 2; Water-Electrolyte Balance