Eur J Vasc Endovasc Surg (2015)
-,
1
INVITED COMMENTARY
Commentary on ‘Remote Ischemic Preconditioning to Reduce Contrast Induced Nephropathy: A Randomized Controlled Trial’ A. Lejay, N. Chakfe
*
Department of Vascular Surgery and Kidney Transplantation, University Hospital of Strasbourg, Strasbourg, France
In their paper, Menting et al.1 evaluated the potential role of remote ischemic preconditioning (RIPC) to reduce contrast induced nephropathy (CIN) through a randomized clinical trial. The trial failed to demonstrate any improvement of serum creatinine level in the RIPC arm, but found that RIPC might have beneficial effects in patients at high risk of CIN. This is an extremely interesting topic that might help in clinical practice since more and more endovascular procedures are performed in an ageing population presenting more and more comorbidities, including impaired renal function. Menting et al.1 considered the change in serum creatinine from baseline to 48e72 hours after contrast administration as the primary outcome. Although creatinine is widely used, it is a suboptimal marker of renal injury because it does not rapidly reflect the altered glomerular filtration rate or degree of tubular injury.2 In CIN, the creatinine level increases from 24 to 48 hours after contrast exposure and peaks within 2e5 days. Furthermore, renal function must decrease by more than half before an increase in serum creatinine is detected. Urinary excretion of liver type fatty acid binding protein (L-FABP) as been showed to be an early biomarker that reflects tubulo-interstitial damage, including ischemic and toxic injury, and peaks within 24 hours after contrast administration, justifying the use of urinary L-FABP for the early detection of contrast induced nephropathy.3 Igarashi et al.3 showed that RIPC attenuated the prevalence of LFABP based contrast induced nephropathy after angiographic procedures in patients with low to moderate risk, without any difference in the serum creatinine level between the RIPC and control groups. In their trial, Menting et al.1 failed to demonstrate any improvement of serum creatinine level in the RIPC arm, but the use of both serum creatinine level and urinary LFABP might have been interesting. The second point is that contrast induced vasoconstriction is not the only factor involved in CIN. The mechanism of CIN is actually multifactorial, and the pathogenesis involves combined hypoxic and toxic renal tubular damage with renal endothelial dysfunction and decreased intrarenal microcirculation. The DOI of original article: http://dx.doi.org/10.1016/j.ejvs.2015.04.002 * Corresponding author. Department of Vascular Surgery, Les Hôpitaux Universitaires de Strasbourg, B.P. 426, 67091 Strasbourg Cedex, France. E-mail address: [email protected] (N. Chakfe). 1078-5884/Ó 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejvs.2015.05.001
infusion of contrast medium with the attendant increase in osmotic load and viscosity elicits hypoxia of the renal medulla and leads to renal free radical production via post-ischemic oxidative stress. Free radicals are a double edged sword. They can be harmful by inducing oxidative stress leading to protein carboxylation, lipid peroxidation, and DNA damage, but can be beneficial via the cell signaling involved in the antioxidant defense network when produced in smaller amounts.4 In the control group, patients received sham preconditioning by inflation of the blood pressure cuff to 10 mmHg below the actual diastolic pressure for 5 minutes followed by 5 minutes of reperfusion (four cycles). Even if the level of ischemia induced by this sham treatment can be considered to be negligible, a certain influence cannot be ruled out. The last point in this study is the proportion of diabetic patients in the trial (28% in the sham group, and 22% in the RIPC group). Oxidative stress plays a central role in contrast induced nephropathy, and the mechanism of ischemic conditioning includes the activation of intracellular pro-survival pathways. There are numbers of studies showing that these pro-survival pathways are impaired in the diabetic state.5 However, these studies have been conducted in the cardiac field, and it is well known that the diabetic state is a limiting factor in ischemic conditioning. In conclusion, this paper investigates a very interesting topic, highlighting the need for new strategies including ischemic conditioning to prevent contrast induced nephropathy, especially in high risk patients.
REFERENCES 1 Menting T, Sterenborg T, de Waal Y, Donders R, Waver K, Lemson S, et al. Remote ischemic preconditioning to reduce contrast-induced nephropathy: a randomized controlled trial. Eur J Vasc Endovasc Surg 2015 [in press]. 2 Waikar SS, Bonventre JV. Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol 2009;20:672e9. 3 Igarashi G, Iiono K, Hiroyushi W, Hiroshi I. Remote ischemic preconditioning alleviates contrast-induced acute kidney injury in patients with moderate chronic kidney disease. Circ J 2013;77: 3037e44. 4 Lejay A, Meyer A, Schlagowsi AI, Charles AL, Singh F, Bouitbir J, et al. Mitochondria: mitochondrial participation in ischemia reperfusion injury in skeletal muscle. Int J Biochem Cell Biol 2014;50:101e5. 5 Wider J, Przyklenk K. Ischemic conditioning: the challenge of protecting the diabetic heart. Cardiovasc Diagn Ther 2014;4: 383e96.
Please cite this article in press as: Lejay A, Chakfe N, Commentary on ‘Remote Ischemic Preconditioning to Reduce Contrast Induced Nephropathy: A Randomized Controlled Trial’, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.05.001
-,
1
INVITED COMMENTARY
Commentary on ‘Remote Ischemic Preconditioning to Reduce Contrast Induced Nephropathy: A Randomized Controlled Trial’ A. Lejay, N. Chakfe
*
Department of Vascular Surgery and Kidney Transplantation, University Hospital of Strasbourg, Strasbourg, France
In their paper, Menting et al.1 evaluated the potential role of remote ischemic preconditioning (RIPC) to reduce contrast induced nephropathy (CIN) through a randomized clinical trial. The trial failed to demonstrate any improvement of serum creatinine level in the RIPC arm, but found that RIPC might have beneficial effects in patients at high risk of CIN. This is an extremely interesting topic that might help in clinical practice since more and more endovascular procedures are performed in an ageing population presenting more and more comorbidities, including impaired renal function. Menting et al.1 considered the change in serum creatinine from baseline to 48e72 hours after contrast administration as the primary outcome. Although creatinine is widely used, it is a suboptimal marker of renal injury because it does not rapidly reflect the altered glomerular filtration rate or degree of tubular injury.2 In CIN, the creatinine level increases from 24 to 48 hours after contrast exposure and peaks within 2e5 days. Furthermore, renal function must decrease by more than half before an increase in serum creatinine is detected. Urinary excretion of liver type fatty acid binding protein (L-FABP) as been showed to be an early biomarker that reflects tubulo-interstitial damage, including ischemic and toxic injury, and peaks within 24 hours after contrast administration, justifying the use of urinary L-FABP for the early detection of contrast induced nephropathy.3 Igarashi et al.3 showed that RIPC attenuated the prevalence of LFABP based contrast induced nephropathy after angiographic procedures in patients with low to moderate risk, without any difference in the serum creatinine level between the RIPC and control groups. In their trial, Menting et al.1 failed to demonstrate any improvement of serum creatinine level in the RIPC arm, but the use of both serum creatinine level and urinary LFABP might have been interesting. The second point is that contrast induced vasoconstriction is not the only factor involved in CIN. The mechanism of CIN is actually multifactorial, and the pathogenesis involves combined hypoxic and toxic renal tubular damage with renal endothelial dysfunction and decreased intrarenal microcirculation. The DOI of original article: http://dx.doi.org/10.1016/j.ejvs.2015.04.002 * Corresponding author. Department of Vascular Surgery, Les Hôpitaux Universitaires de Strasbourg, B.P. 426, 67091 Strasbourg Cedex, France. E-mail address: [email protected] (N. Chakfe). 1078-5884/Ó 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ejvs.2015.05.001
infusion of contrast medium with the attendant increase in osmotic load and viscosity elicits hypoxia of the renal medulla and leads to renal free radical production via post-ischemic oxidative stress. Free radicals are a double edged sword. They can be harmful by inducing oxidative stress leading to protein carboxylation, lipid peroxidation, and DNA damage, but can be beneficial via the cell signaling involved in the antioxidant defense network when produced in smaller amounts.4 In the control group, patients received sham preconditioning by inflation of the blood pressure cuff to 10 mmHg below the actual diastolic pressure for 5 minutes followed by 5 minutes of reperfusion (four cycles). Even if the level of ischemia induced by this sham treatment can be considered to be negligible, a certain influence cannot be ruled out. The last point in this study is the proportion of diabetic patients in the trial (28% in the sham group, and 22% in the RIPC group). Oxidative stress plays a central role in contrast induced nephropathy, and the mechanism of ischemic conditioning includes the activation of intracellular pro-survival pathways. There are numbers of studies showing that these pro-survival pathways are impaired in the diabetic state.5 However, these studies have been conducted in the cardiac field, and it is well known that the diabetic state is a limiting factor in ischemic conditioning. In conclusion, this paper investigates a very interesting topic, highlighting the need for new strategies including ischemic conditioning to prevent contrast induced nephropathy, especially in high risk patients.
REFERENCES 1 Menting T, Sterenborg T, de Waal Y, Donders R, Waver K, Lemson S, et al. Remote ischemic preconditioning to reduce contrast-induced nephropathy: a randomized controlled trial. Eur J Vasc Endovasc Surg 2015 [in press]. 2 Waikar SS, Bonventre JV. Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol 2009;20:672e9. 3 Igarashi G, Iiono K, Hiroyushi W, Hiroshi I. Remote ischemic preconditioning alleviates contrast-induced acute kidney injury in patients with moderate chronic kidney disease. Circ J 2013;77: 3037e44. 4 Lejay A, Meyer A, Schlagowsi AI, Charles AL, Singh F, Bouitbir J, et al. Mitochondria: mitochondrial participation in ischemia reperfusion injury in skeletal muscle. Int J Biochem Cell Biol 2014;50:101e5. 5 Wider J, Przyklenk K. Ischemic conditioning: the challenge of protecting the diabetic heart. Cardiovasc Diagn Ther 2014;4: 383e96.
Please cite this article in press as: Lejay A, Chakfe N, Commentary on ‘Remote Ischemic Preconditioning to Reduce Contrast Induced Nephropathy: A Randomized Controlled Trial’, European Journal of Vascular and Endovascular Surgery (2015), http://dx.doi.org/10.1016/j.ejvs.2015.05.001
