Ischemic preconditioning to reduce ischemia-reperfusion injury of the kidney

Contains fulltext : 176474.pdf (publisher's version ) (Open Access)Radboud University, 26 oktober 2017Promotor : Goor, H. van Co-promotores : Warle, M.C., Wever, K.E.207 p

Response to "Re: Remote Ischemic Preconditioning to Reduce Contrast-induced Nephropathy: A Randomized Controlled Trial"

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Regarding "Remote and local ischemic preconditioning equivalently protects rat skeletal muscle mitochondrial function during experimental aortic cross-clamping".

Item does not contain fulltext1 september 201

Preclinical Evidence for the Efficacy of Ischemic Postconditioning against Renal Ischemia-Reperfusion Injury, a Systematic Review and Meta-Analysis

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a major cause of kidney damage after e.g. renal surgery and transplantation. Ischemic postconditioning (IPoC) is a promising treatment strategy for renal IRI, but early clinical trials have not yet replicated the promising results found in animal studies. METHOD: We present a systematic review, quality assessment and meta-analysis of the preclinical evidence for renal IPoC, and identify factors which modify its efficacy. RESULTS: We identified 39 publications studying >250 control animals undergoing renal IRI only and >290 animals undergoing renal IRI and IPoC. Healthy, male rats undergoing warm ischemia were used in the vast majority of studies. Four studies applied remote IPoC, all others used local IPoC. Meta-analysis showed that both local and remote IPoC ameliorated renal damage after IRI for the outcome measures serum creatinine, blood urea nitrogen and renal histology. Subgroup analysis indicated that IPoC efficacy increased with the duration of index ischemia. Measures to reduce bias were insufficiently reported. CONCLUSION: High efficacy of IPoC is observed in animal models, but factors pertaining to the internal and external validity of these studies may hamper the translation of IPoC to the clinical setting. The external validity of future animal studies should be increased by including females, comorbid animals, and transplantation models, in order to better inform clinical trial design. The severity of renal damage should be taken into account in the design and analysis of future clinical trials

Ischaemic preconditioning for the reduction of renal ischaemia reperfusion injury

Item does not contain fulltextBACKGROUND: Ischaemia reperfusion injury can lead to kidney dysfunction or failure. Ischaemic preconditioning is a short period of deprivation of blood supply to particular organs or tissue, followed by a period of reperfusion. It has the potential to protect kidneys from ischaemia reperfusion injury. OBJECTIVES: This review aimed to look at the benefits and harms of local and remote ischaemic preconditioning to reduce ischaemia and reperfusion injury among people with renal ischaemia reperfusion injury. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 5 August 2016 through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: We included all randomised controlled trials measuring kidney function and the role of ischaemic preconditioning in patients undergoing a surgical intervention that induces kidney injury. Kidney transplantation studies were excluded. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality; data were extracted by two independent authors. We collected basic study characteristics: type of surgery, remote ischaemic preconditioning protocol, type of anaesthesia. We collected primary outcome measurements: serum creatinine and adverse effects to remote ischaemic preconditioning and secondary outcome measurements: acute kidney injury, need for dialysis, neutrophil gelatinase-associated lipocalin, hospital stay and mortality. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: We included 28 studies which randomised a total of 6851 patients. Risk of bias assessment indicated unclear to low risk of bias for most studies. For consistency regarding the direction of effects, continuous outcomes with negative values, and dichotomous outcomes with values less than one favour remote ischaemic preconditioning. Based on high quality evidence, remote ischaemic preconditioning made little or no difference to the reduction of serum creatinine levels at postoperative days one (14 studies, 1022 participants: MD -0.02 mg/dL, 95% CI -0.05 to 0.02; I2 = 21%), two (9 studies, 770 participants: MD -0.04 mg/dL, 95% CI -0.09 to 0.02; I2 = 31%), and three (6 studies, 417 participants: MD -0.05 mg/dL, 95% CI -0.19 to 0.10; I2 = 68%) compared to control.Serious adverse events occurred in four patients receiving remote ischaemic preconditioning by iliac clamping. It is uncertain whether remote ischaemic preconditioning by cuff inflation leads to increased adverse effects compared to control because the certainty of the evidence is low (15 studies, 3993 participants: RR 3.47, 95% CI 0.55 to 21.76; I2 = 0%); only two of 15 studies reported any adverse effects (6/1999 in the remote ischaemic preconditioning group and 1/1994 in the control group), the remaining 13 studies stated no adverse effects were observed in either group.Compared to control, remote ischaemic preconditioning made little or no difference to the need for dialysis (13 studies, 2417 participants: RR 0.85, 95% CI 0.37 to 1.94; I2 = 60%; moderate quality evidence), length of hospital stay (8 studies, 920 participants: MD 0.17 days, 95% CI -0.46 to 0.80; I2 = 49%, high quality evidence), or all-cause mortality (24 studies, 4931 participants: RR 0.86, 95% CI 0.54 to 1.37; I2 = 0%, high quality evidence).Remote ischaemic preconditioning may have slightly improved the incidence of acute kidney injury using either the AKIN (8 studies, 2364 participants: RR 0.76, 95% CI 0.57 to 1.00; I2 = 61%, high quality evidence) or RIFLE criteria (3 studies, 1586 participants: RR 0.91, 95% CI 0.75 to 1.12; I2 = 0%, moderate quality evidence). AUTHORS' CONCLUSIONS: Remote ischaemic preconditioning by cuff inflation appears to be a safe method, and probably leads to little or no difference in serum creatinine, adverse effects, need for dialysis, length of hospital stay, death and in the incidence of acute kidney injury. Overall we had moderate-high certainty evidence however the available data does not confirm the efficacy of remote ischaemic preconditioning in reducing renal ischaemia reperfusion injury in patients undergoing major cardiac and vascular surgery in which renal ischaemia reperfusion injury may occur

Repeated remote ischemic preconditioning and isoflurane anesthesia in an experimental model of renal ischemia-reperfusion injury

BACKGROUND: In animal studies, remote ischemic preconditioning (RIPC) and anesthetic preconditioning are successful in reducing renal ischemia reperfusion injury (IRI), however the protective effect of RIPC may be improved by repeating the RIPC stimulus. METHODS: Sprague-Dawley rats underwent unilateral nephrectomy followed by 30 min of renal pedicle clamping. Animals were allocated into six groups: sham, control (IRI), RepISO (daily isoflurane anesthesia), RIPC (single dose isoflurane anesthesia and single dose RIPC), RepISO + RIPC (7-day isoflurane anesthesia and single dose RIPC) and RepISO + RepRIPC (7-day isoflurane anesthesia with 7-day RIPC). RIPC was applied by 3x5 min of cuff inflation on both thighs. Serum creatinine and urea levels were measured and histology was obtained at day two. RESULTS: RepISO diminished renal IRI, as reflected by a significant reduction in serum creatinine levels as compared to the control group, 170 +/- 74 resp. 107 +/- 29 mumol/L. The other preconditioning protocols showed similar reduction in serum creatinine levels as compared to the control group. No significant differences were observed between the different preconditioning protocols. For urea levels, only RepISO + RIPC resulted in significantly lower levels as compared to the control group, 14 +/- 4 resp. 22 +/- 7 mmol/L (p = 0.010). In the preconditioning groups only RepISO showed less histological damage as compared to controls 1.73 +/- 1.19 resp. 2.91 +/- 1.22 (p = 0.032). CONCLUSIONS: In this study no additional protective effect of repeated ischemic preconditioning was observed as compared to single dose RIPC. Repeated administration of isoflurane provided stronger protection against renal IRI as compared to single dose isoflurane

Remote Ischemic Preconditioning To Reduce Contrast-Induced Nephropathy: A Randomized Controlled Trial

Item does not contain fulltextBACKGROUND: Despite the increasing use of pre- and post-hydration protocols and low osmolar instead of high osmolar iodine containing contrast media, the incidence of contrast induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia reperfusion injury of the renal medulla. Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low cost method to reduce ischemia reperfusion injury. The aim of this study is to investigate whether RIPC, as an adjunct to standard preventive measures, reduces contrast induced acute kidney injury in patients at risk of CIN. METHODS: The RIPCIN study is a multicenter, single blinded, randomized controlled trial in which 76 patients at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary outcome measure was the change in serum creatinine from baseline to 48 to 72 hours after contrast administration. RESULTS: With regard to the primary endpoint, no significant effect of RIPC was found. CIN occurred in four patients (2 sham and 2 RIPC). A pre-defined subgroup analysis of patients with a Mehran risk score >/=11, showed a significantly reduced change in serum creatinine from baseline to 48 to 72 hours in patients allocated to the RIPC group (Delta creatinine -3.3 +/- 9.8 mumol/L) compared with the sham group (Delta creatinine +17.8 +/- 20.1 mumol/L). CONCLUSION: RIPC, as an adjunct to standard preventive measures, does not improve serum creatinine levels after contrast administration in patients at risk of CIN according to the Dutch guideline. However, the present data indicate that RIPC might have beneficial effects in patients at a high or very high risk of CIN (Mehran score >/= 11). The RIPCIN study is registered at: http://www.controlled-trials.com/ISRCTN76496973

Alice Lane, Ettie Lane and one unidentified figure in orchard

BACKGROUND: Despite the increasing use of pre- and posthydration protocols and low-osmolar instead of high-osmolar iodine-containing contrast media, the incidence of contrast-induced nephropathy (CIN) is still significant. There is evidence that contrast media cause ischemia-reperfusion injury of the medulla. Remote ischemic preconditioning (RIPC) is a non-invasive, safe, and low-cost method to reduce ischemia-reperfusion injury. METHODS: The RIPCIN study is a multicenter, single-blinded, randomized controlled trial in which 76 patients at risk of CIN will receive standard hydration combined with RIPC or hydration with sham preconditioning. RIPC will be applied by four cycles of 5 min ischemia and 5 min reperfusion of the forearm by inflating a blood pressure cuff at 50 mmHg above the actual systolic pressure. The primary outcome measure will be the change in serum creatinine from baseline to 48 to 72 h after contrast administration. DISCUSSION: A recent pilot study reported that RIPC reduced the incidence of CIN after coronary angioplasty. The unusual high incidence of CIN in this study is of concern and limits its generalizability. Therefore, we propose a randomized controlled trial to study whether RIPC reduces contrast-induced kidney injury in patients at risk for CIN according to the Dutch guidelines. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76496973