Hyperglycaemia, inflammation, RAS activation: three culprits to blame for acute kidney injury emerging in healthy rats during general anaesthesia.
OBJECTIVE
Major surgery under general anaesthesia might evoke acute kidney injury (AKI), sometimes culminating in end stage renal disease. We investigated the roles of hyperglycaemia, inflammation and renin-angiotensin system (RAS) activation in induction of AKI following anaesthesia by different anaesthetic drugs and/or regimens.


METHODS
Ninety-four Sprague-Dawley rats underwent 1 h-anaesthesia by various protocols, including repeated blood glucose and insulin measurements. Blood samples and kidneys were allocated at sacrifice, for evaluation of renal function, inflammatory status and Angiotensin-II availability.


RESULTS
Hyperglycaemia emerged in unconscious rats irrespective of anaesthetic drug choice or anaesthesia regimen. Insulin increase correlated with hyperglycaemia levels. Levels of Cystatin-C, as well as serum and urine neutrophil gelatinase-associated lipocain (NGAL), were significantly augmented. Serum transforming growth factor beta (TGF-β) and interleukins (IL)-1β, -4, -6, and -10 were significantly increased. Intra-renal Angiotensin-II, TGF-β, IL-6 and-10 were significantly increased. IL-1 was decreased. IL-4 remained unaltered.


CONCLUSIONS
Acute hyperglycaemia, systemic and intra-renal inflammation and RAS activation were independently triggered by induction of anaesthesia. Each confounder aggravated the impacts of the others, bringing about concomitant deterioration of renal function. Increased insulin secretion attenuated but did not abolish hyperglycaemia. Systemic inflammation was counterforced by anti-inflammatory cytokines, whereas intra-renal inflammation persisted, so that AKI progressed unopposed.
Nephrology Division Research & Development Unit, Assaf Harofeh Medical Center, Zerifin, Sackler Faculty of Medicine, Tel Aviv University, Israel. efratishai@013
Shai
S
Efrati
Sylvia
S
Berman
Ramzia
R
Abu Hamad
Ranin
R
El Nakib
Michael
M
Chanimov
Yariv
Y
Siman-Tov
Joshua
J
Weissgarten
D058186:Acute Kidney Injury / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D000768:Anesthesia, General / Q000009:adverse effects* / Q000379:methods; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000209:etiology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology / Q000652:urine; D018836:Inflammation Mediators / Q000097:blood / Q000652:urine; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System; D012307:Risk Factors; D013997:Time Factors
D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D018836:Inflammation Mediators; D007328:Insulin