High fat feeding promotes obesity and renal inflammation and protects against post cardiopulmonary bypass acute kidney injury in swine

Abstract

IntroductionObesity confers a survival advantage in the critically ill and in patients undergoing cardiac surgery. We explored whether an obesogenic high fat diet could confer protection against post cardiopulmonary bypass (CPB) acute kidney injury (AKI) in a swine model.MethodsIn this study, 28 anaesthetised adult female Landrace White swine (55 to 70 kg) were allocated into a 4 group design to either 2.5 hours of CPB or Sham operation with or without pre-procedural high fat (HF) feeding containing 15% lard, 1.5% cholesterol and 1% cholic acid for 12-weeks (Groups: Sham, CPB, CPB + HF and Sham + HF). Our primary endpoint was creatinine clearance measured at 1.5 and 24 hours post intervention. This is a validated index of the glomerular filtration rate (GFR) in swine and an endpoint used in our clinical studies. Secondary endpoints included measures of systemic and renal inflammation, endothelial homeostasis, tubular injury and dysfunction, and inflammatory cell signalling. Differences between groups were calculated using analysis of variance with adjustment for baseline differences for repeated measures.ResultsCPB in pigs fed a normal chow diet resulted in AKI. This was characterised by reductions in GFR sustained for up to 24 hours post injury relative to Sham operated pigs fed a normal diet; mean difference 50.2 ml/min (95% CI 5.9 to 94.4). Post CPB AKI was also characterised by renal inflammation, parallel activation of both pro-inflammatory (NF-kB, iNOS) and pro-survival pathways (pAkt, p70s6k, HIF-1α) and apoptosis. Pigs fed a 12-week high fat diet developed obesity and hyperlipidaemia. This was associated with increased redox sensitive pro-inflammatory and anti-apoptotic signalling, and tubular epithelial cell proliferation. High fat feeding also protected swine against post CPB AKI; mean difference in creatinine clearance CPB - CPB + HF −65.3 ml/min (95% CI −106.9 to −23.7), by preserving endothelial homeostasis and function, and preventing the reductions in GFR, loss of ATP and tubular apoptosis that characterise the extension phase of AKI in swine at 24 hours post injury. Reno-protection was not attributed to pAkt signaling.ConclusionsA high fat diet promoted obesity and renal inflammation and prevented post CPB AKI in swine. This study provides insights into the obesity paradox and the failure of anti-inflammatory interventions to improve clinical outcomes in patients at risk of post cardiac surgery AKI.

Role of Body Mass Index in Acute Kidney Injury Patients after Cardiac Surgery

“…However, AKI mortality in our study followed a reversed J shape, indicating that although obese people had an increased mortality risk compared to overweigh patients, their mortality incidence was still lower than for underweight and normal-weight cases, which is similar to the results from a previous report about mortality in nondialyzed advanced chronic kidney disease male patients [32]. The data indicated that in contrast to RRT, obesity was a survival advantage for AKI patients, which supports findings of Sleeman et al [33], according to which obesity had beneficial effects on kidneys by inducing renal inflammation in a CPB swine model.…”

High fat diets alter aerobic exercise and L-arginine effects in ischemia reperfusion induced renal injury in rats: gender related difference

“…This study showed that HFD-supplementation could not impress renal function in renal injury induced by kidney I/R, however this regimen elevated body weight, energy intake and lee index. Although it was indicated that HFD leads to kidney histopathlogical changes, inflammation, oxidative stress (5,20,21) and aggravated kidney I/R induced renal injury (22), one study in parallel with our study reported that HFD for 12 weeks developed overweight and did not affect kidney function and maintained renal blood flow and glomerular filtration rate (GFR), and inhibited kidney injury after cardio bypass surgery (23). The effect of HFD for 2 weeks before surgery indicated no more damage in outcome than normal diet against I/R injury (24).…”

Changes in renal medulla gene expression in a pre-clinical model of post cardiopulmonary bypass acute kidney injury

“…A limitation of our study is that this model only reflects less severe AKI; the changes n renal clearance that we have described equate to the ‘Risk’ stage of the RIFLE classification, now considered as Stage 1 AKI in the recent Kidney Diseases Improving Global Outcomes consensus definition [ 25 ]. Animal recovery with re-evaluation at 24 hours is a key component, and strength of the current model as our previous studies have shown that changes in filtration immediately post CPB are not indicative of later pathophysiology [ 26 , 27 ]. However reproducible recovery mandates that the nature of the injury sustained by study subjects is less severe.…”