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Abstract: FR-PO091

A Single Dose of Lithium Attenuates Rhabdomyolysis-Associated AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Shimizu, Maria HM, Faculty of Medicine - University of Sao Paulo, São Paulo, São Paulo, Brazil
  • de Braganca, Ana Carolina, Faculty of Medicine - University of Sao Paulo, São Paulo, São Paulo, Brazil
  • Canale, Daniele, Faculty of Medicine - University of Sao Paulo, São Paulo, São Paulo, Brazil
  • Volpini, Rildo A., Faculty of Medicine - University of Sao Paulo, São Paulo, São Paulo, Brazil
  • Seguro, Antonio C., Faculty of Medicine - University of Sao Paulo, São Paulo, São Paulo, Brazil
Background

Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis. Evidence suggests that glycogen synthase kinase 3β (GSK3β) inhibition protects against AKI. Treatment with a single dose of lithium, a selective inhibitor of GSK3β, accelerated recovery of renal function in models of cisplatin and ischemia/reperfusion- induced AKI. The aim of this study was to evaluate the efficacy of a single dose of lithium in the treatment of rhabdomyolysis-induced AKI in rats.

Methods

Male Wistar rats aged 3 months were allocated to four groups: 1- Control: received saline 0.9% intraperitoneal (IP ); 2- Lithium: rats treated with a single IP injection of lithium chloride 80 mg/Kg body weight (BW) ; 3- Glycerol (50%, 5 ml/kg intramuscular,IM); 4- Glycerol plus Lithium: glycerol 50%, 5 ml/kg IM + lithium chloride 80 mg/kg IP injected 2 hours after glycerol administration. After 24 h the animals were anesthetized to measure inulin clearance (GFR, ml/min/100g BW). At the end of the clearance experiments the rats were euthanized, blood and kidney were collected to evaluate plasma levels of creatine phosphokinase (CPK), expression of GSK3β in renal tissue and kidney histological damage score.

Results

As described in the table below, glycerol-injected rats showed markedly reduction of GFR, increase of CPK levels, exaggerated increase of GSK3β renal expression and higher kidney injury score. A single dose of lithium administration ameliorated all these alterations.

Conclusion

Lithium treatment attenuated renal dysfunction in a model of rhabdomyolysis-associated AKI by improving inulin clearance and reducing kidney injury score. These therapeutic effects were due to an inhibition of renal GSK3β and were associated with a decrease in muscle injury. This may represent a new therapeutic approach for rhabdomyolysis-induced AKI. (FAPESP 2015/11933-3; 2015/05513-1)

ParametersControl
n=6
Lithium
n=6
Glycerol
n=6
Glycerol+
Lithium
n=7
GFR
ml/min/
100gBW
1.01±0.070.86±0.070.36±0.06a0.86±0.06f
CPK
U/L
247±26146±24721±87ad268±19f
GSK 3β
%
99±9120±11646±71ad328±53cef
Renal Injury
score
0.08±0.020.08±0.021.62±0.25ad0.87±0.30ceg

Data are expressed as mean±SEM. a p<0.001, c p<0.05 vs Control; d p<0.001, e p<0.01 vs Lithium ;f p<0.001, g p<0.05 vs Glycerol.