Pre-existing renal failure worsens the outcome after intestinal ischaemia and reperfusion in rats.
BACKGROUND
Chronic kidney disease (CKD) serves as a risk factor in the development of acute kidney injury (AKI) requiring renal replacement therapy. Furthermore, superimposed AKI on CKD is associated with an increased mortality and risk of progression to end-stage renal disease. We aim to examine whether CKD increases the morbidity and mortality of AKI induced by intestinal ischaemia and reperfusion (I-I/R).


METHODS
A novel two-stage rat model was developed for CKD induced by 5/6 nephrectomy followed by AKI induced by lethal I-I/R in male rats. All rats initially underwent either 5/6 nephrectomy or sham operation. After 2 weeks, half of each group were subjected to clamping of the superior mesenteric artery for 45 min. The rats were placed in metabolic cages for measurements of water intake and urine output.


RESULTS
Fourteen days after 5/6 nephrectomy, polyuria, polydipsia, azotaemia and proteinuria were seen. Furthermore, urinary excretion of neutrophil gelatinase-associated lipocalin was increased in rats with CKD. Earlier death was observed in rats with AKI superimposed on CKD compared with rats with AKI superimposed on normal renal function (the average time to death during reperfusion after intestinal ischaemia: 71.0 ± 7.1 vs 112.4 ± 11.0 min, P < 0.05). Shortly after reperfusion of the intestine, mean arterial pressure dropped to pre-shock levels, which were partly compensated, although to a larger extent, in the sham-operated rats compared with the rats with CKD.


CONCLUSIONS
The results suggest that even mild CKD has a critical impact on survival during the development of multiple organ failure induced by AKI.
Skott
Martin
M
The Water and Salt Research Centre, University of Aarhus, Aarhus, Denmark.
Nørregaard
Rikke
R
Sorensen
Hanne Birke
HB
Kwon
Tae-Hwan
TH
Frøkiaer
Jørgen
J
Nielsen
Søren
S
D058186:Acute Kidney Injury / Q000401:mortality*; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D002908:Chronic Disease; D004195:Disease Models, Animal; D006339:Heart Rate; D007422:Intestines / Q000098:blood supply*; D007511:Ischemia / Q000150:complications*; D007674:Kidney Diseases / Q000150:complications*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D009102:Multiple Organ Failure / Q000401:mortality; D009392:Nephrectomy; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D015427:Reperfusion Injury / Q000150:complications*
D000209:Acute-Phase Proteins; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins