Pre-existing renal failure worsens the outcome after intestinal ischaemia and reperfusion in rats
ABSTRACT 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).
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.
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.
The results suggest that even mild CKD has a critical impact on survival during the development of multiple organ failure induced by AKI.
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ABSTRACT: Objectives: To examine retrospectively the relationship between acute kidney injury (AKI) and acute myocardial infarction (AMI), and the association between estimated glomerular filtration rate (eGFR) at admission and AKI outcome. Methods: AKI was defined as an increase in serum creatinine (SCr) by >= 0.3 mg/dl within 48 h or an increase in SCr to >= 1.5 times baseline within the first 7 days of hospitalization. Patients with AMI were divided into subgroups according to their eGFR at admission and the development of AKI. Results: This study enrolled 396 patients with AMI; 48 (12.1%) developed AKI. In-hospital mortality was 39.6% (19/48) for patients with AKI compared with 7.5% (26/348) in those without AKI (odds ratio [OR] 8.11; 95% confidence interval [CI] 4.02, 16.39). The mortality rate was 35.7% (five of 14) in the eGFR >= 60 ml/min/1.73m(2) with AKI group (OR 6.21, 95% CI 1.50, 25.69) and 41.2% (14/34) in the eGFR <60 ml/min/1.73m(2) with AKI group (OR 12.62, 95% CI 5.54, 28.74). Conclusions: AKI development was common and associated with mortality in AMI patients with either preserved or impaired eGFR levels.The Journal of international medical research 07/2014; 42(5). DOI:10.1177/0300060514541254 · 1.10 Impact Factor
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ABSTRACT: Background The primary aim of the study was to investigate the cytokine/chemokine response in the kidney, lung, and liver following acute kidney injury (AKI). The secondary aim was to test whether α-melanocyte-stimulating hormone (α-MSH) could prevent a reduction in organ function, and attenuate the inflammatory cytokine/chemokine response within the kidney, lung, and liver following AKI in rats with or without preexisting chronic kidney disease (CKD). Methods A two-stage animal model, in which AKI was induced in rats with preexisting CKD, induced by 5/6 nephrectomy (Nx), was used. Six weeks later, AKI was induced by intestinal ischemia and reperfusion (IIR). Sham procedures [S(Nx) and S(IIR)] were also performed. Results Increasing levels of serum creatinine (sCr) demonstrated progressive development of CKD in response to Nx, and following IIR sCr levels increased further significantly, except in the S(Nx) group treated with α-MSH. However, no significant differences in the fractional increase in sCr were observed between any of the groups exposed to IIR. In kidney, lung, and liver tissue the levels of interleukin (IL)-1β were significantly higher in rats undergoing IIR when compared to the S(IIR) and control rats. The same pattern was observed for the chemokine MCP-1 in lung and liver tissue. Furthermore, kidney IL-1β and RANTES levels were significantly increased after IIR in the Nx rats compared to the S(Nx) rats. Conclusion Both the functional parameters and the cytokine/chemokine response are as dramatic when AKI is superimposed onto CKD as onto non-CKD. No convincing protective effect of α-MSH was detected.06/2014; 33(2). DOI:10.1016/j.krcp.2014.02.002
06/2014; 33(2). DOI:10.1016/j.krcp.2014.04.005