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: Evidence suggests the possibility that pre-existing chronic kidney (CKD) disease may result in a more severe outcome of acute kidney injury (AKI). The aim of this study was to examine whether CKD enhances the inflammatory response in the kidney, as well as other organs, in response to AKI in rats. CKD was induced by 5/6 nephrectomy (Nx) and AKI by intestinal ischaemia and reperfusion (IIR). For 6 weeks following Nx there was a progressive increase in serum creatinine with associated development of albuminuria. The increment in creatinine above baseline determination 90 min following IIR was comparable in 5/6 Nx and in the sham 5/6 Nx. Similarly, increased levels of serum alanine transaminase and histomorphological changes in the lungs were observed in the rats exposed to IIR compared to those exposed to sham IIR, with no additional significant impact of 5/6 Nx. In kidney tissue the levels of cytokines/chemokines were equally elevated regardless of exposure to sham IIR or IIR. In lung and liver tissue the levels of cytokines/chemokines were equally elevated in the rats that were exposed to IIR, regardless of exposure to sham Nx or Nx. We conclude that the immediate severity of AKI induced by IIR in rats with CKD is similar to that induced in rats without CKD. However, the impact of Nx on the cytokine/chemokine response after AKI is not uniform in kidney, lung or liver tissue.Nephrology 04/2014; · 1.69 Impact Factor
- Journal of cardiothoracic and vascular anesthesia 10/2013; · 1.06 Impact Factor
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ABSTRACT: The role of an impaired estimated glomerular filtration rate (eGFR) at hospital admission in the outcome of acute kidney injury (AKI) after acute myocardial infarction (AMI) has been underreported. The aim of this study was to assess the influence of an admission eGFR<60 mL/min/1.73 m(2) on the incidence and early and late mortality of AMI-associated AKI. A prospective study of 828 AMI patients was performed. AKI was defined as a serum creatinine increase of ≥ 50% from the time of admission (RIFLE criteria) in the first 7 days of hospitalization. Patients were divided into subgroups according to their eGFR upon hospital admission (MDRD formula, mL/min/1.73 m(2)) and the development of AKI: eGFR ≥ 60 without AKI, eGFR<60 without AKI, eGFR ≥ 60 with AKI and eGFR<60 with AKI. Overall, 14.6% of the patients in this study developed AKI. The admission eGFR had no impact on the incidence of AKI. However, the admission eGFR was associated with the outcome of AMI-associated AKI. The adjusted hazard ratios (AHR, Cox multivariate analysis) for 30-day mortality were 2.00 (95% CI 1.11-3.61) for eGFR<60 without AKI, 4.76 (95% CI 2.45-9.26) for eGFR ≥ 60 with AKI and 6.27 (95% CI 3.20-12.29) for eGFR<60 with AKI. Only an admission eGFR of <60 with AKI was significantly associated with a 30-day to 1-year mortality hazard (AHR 3.05, 95% CI 1.50-6.19). AKI development was associated with an increased early mortality hazard in AMI patients with either preserved or impaired admission eGFR. Only the association of impaired admission eGFR and AKI was associated with an increased hazard for late mortality among these patients.PLoS ONE 01/2012; 7(4):e35496. · 3.53 Impact Factor