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      The renoprotective effects of mannitol and udenafil in renal ischemia-reperfusion injury model

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          Abstract

          Purpose

          The aim of this study was to investigate and compare the effects of udenafil and mannitol in an experimental renal ischemia-reperfusion (I/R) injury model.

          Materials and Methods

          A total of 64 female Wister Albino rats were used. Right nephrectomy was performed in all groups. In the control group; I/R injury was not performed. In the I/R group; left renal pedicle was clamped for 45 minutes and then underwent 60 minutes and 24 hours of reperfusion. In the mannitol group; 1 mL 20% mannitol was given intravenously 15 minutes before clamping. In the udenafil group; 10-mg/kg udenafil was given orally 1 hour before clamping. Creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, malondialdehyde, neutrophil gelatinase associated lipocalin (NGAL), histological examination and DNA damage (Comet Assay method) levels were compared in tissue, serum and urine samples.

          Results

          Udenafil had a better protective effect than mannitol according to biochemical parameters (Cr, BUN, Cr clearance, and NGAL levels) and histopathological findings when compared with the I/R group. In the Comet sampling analysis no significant difference was detected.

          Conclusions

          Udenafil has a better renoprotective effect than mannitol against I/R injury and this effect supports more functional improvements. Further clinical trials are needed to demonstrate those effects and clinical utility of udenafil for that purpose in humans.

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          Most cited references29

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          Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey.

          Orfeas Liangos, Ron Wald, John O'Bell … (2006)
          The aim of this study was to provide a broad characterization of the epidemiology of acute renal failure (ARF) in the United States using national administrative data and describe its impact on hospital length of stay (LOS), patient disposition, and adverse outcomes. Using the 2001 National Hospital Discharge Survey, a nationally representative sample of discharges from nonfederal acute care hospitals in the United States, new cases of ARF were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Multivariate regression analyses were used to explore the relation of ARF to hospital LOS and mortality as well as discharge disposition. Review of discharge data on a projected total of 29,039,599 hospitalizations identified 558,032 cases of ARF, with a frequency of 19.2 per 1000 hospitalizations. ARF was more commonly coded for in older patients; men; black individuals; and the setting of chronic kidney disease, congestive heart failure, chronic lung disease, sepsis, and cardiac surgery. ARF was associated with an adjusted prolongation of hospital LOS by 2 d (P < 0.001) and an adjusted odds ratio of 4.1 for hospital mortality and of 2.0 for discharge to short- or long-term care facilities. In a US representative sample of hospitalized patients, the presence of an ICD-9-CM code for ARF in discharge records is associated with prolonged LOS, increased mortality, and, among survivors, a greater requirement for posthospitalization care. These findings suggest that in the United States, ARF is associated with increased in-hospital and post-hospitalization resource utilization.
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            Diuretics in acute kidney injury.

            W Mansour, V Karajala, J Kellum (2009)
            In an acute care setting, diuretics are often prescribed to maintain or increase urine output in patients presenting with acute kidney injury (AKI). The rationale behind giving diuretics is that they may protect the kidney from ischemic injury by maintaining a nonoliguric state. There have been many studies both supporting and criticizing diuretic use in AKI for improving overall patient outcomes. A systematic review of the literature was conducted to evaluate the role of diuretics including osmotics, loop diuretics, and nesiritide in modifying AKI. There was no evidence to suggest that the use of loop diuretics in AKI reduces mortality, the need for dialysis, the number of dialysis sessions, or length of Intensive Care Unit/hospital stay or that it increases the recovery of renal function. There is no benefit for the use of mannitol as an osmotic diuretic over hydration in rhabdomyolysis. In contrast, mannitol was found to cause more harm and to induce nephropathy. Nesiritide did not improve renal function in patients with decompensated heart failure and mild chronic renal insufficiency. Nesiritide may be effective in the prevention of AKI when applied in lower doses for a prolonged period of time in patients with mild to moderate renal insufficiency. Diuretics have been shown to be ineffective in the prevention of AKI or for improving outcomes once AKI occurs. At best, diuretics can help decrease symptoms of pulmonary edema secondary to volume overload.
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              Ischaemic preconditioning protects against ischaemia/reperfusion injury: emerging concepts.

              S Homer-Vanniasinkam, S Pasupathy (2005)
              Ischaemic preconditioning (IP) has emerged as a powerful method of ameliorating ischaemia/reperfusion (I/R) injury to the myocardium. This review investigates whether this phenomenon is universally applicable in modulating I/R injury to other tissues. A Medline search was conducted to identify both animal and human studies that described IP-induced protection from I/R injury in a variety of non-cardiac organ systems. Particular emphasis was placed on elucidation of underlying physiological concepts. IP utilises endogenous mechanisms in skeletal muscle, liver, lung, kidney, intestine and brain in animal models to convey varying degrees of protection from I/R injury. To date there are few human studies, but recent reports suggest that human liver, lung and skeletal muscle acquire similar protection after IP. Specifically, preconditioned tissues exhibit reduced energy requirements, altered energy metabolism, better electrolyte homeostasis and genetic re-organisation, giving rise to the concept of 'ischaemia tolerance'. IP also induces 'reperfusion tolerance' with less reactive oxygen species and activated neutrophils released, reduced apoptosis and better microcirculatory perfusion compared to non-preconditioned tissue. Systemic I/R injury is also diminished by preconditioning. IP is ubiquitous but more research is required to fully translate these findings to the clinical arena.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Investig Clin Urol
                Journal ID (iso-abbrev): Investig Clin Urol
                Journal ID (publisher-id): ICU
                Title: Investigative and Clinical Urology
                Publisher: The Korean Urological Association
                ISSN (Print): 2466-0493
                ISSN (Electronic): 2466-054X
                Publication date (Print): July 2017
                Publication date (Electronic): 27 June 2017
                Volume: 58
                Issue: 4
                Pages: 289-295
                Affiliations
                [1 ]Denizli State Hospital, Urology Clinic, Denizli, Turkey.
                [2 ]Department of Urology, Pamukkale University School of Medicine, Denizli, Turkey.
                [3 ]Department of Biochemistry, Pamukkale University School of Medicine, Denizli, Turkey.
                [4 ]Department of Physiology, Pamukkale University School of Medicine, Denizli, Turkey.
                [5 ]Department of Pathology, Pamukkale University School of Medicine, Denizli, Turkey.
                Author notes
                Corresponding Author: Yusuf Özlülerden. Denizli State Hospital, Urology Clinic, Denizli 20100, Turkey. TEL: +90-506-9680184, FAX: +90-258-2619206, yusufozlu35@ 123456hotmail.com
                Article
                DOI: 10.4111/icu.2017.58.4.289
                PMC ID: 5494354
                SO-VID: 86d1abe9-92ea-447f-9110-ba5e4643df4a
                Copyright © © The Korean Urological Association, 2017
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 06 February 2017
                Date accepted : 14 March 2017
                Funding
                Funded by: Pamukkale University, CrossRef http://dx.doi.org/10.13039/501100004214;
                Award ID: 2014TPF009
                Categories
                Subject: Original Article
                Subject: Basic and Translational Research

                Keywords: comet assay,ischemia reperfusion injury,mannitol,ngal protein,udenafil
                Data availability:
                Keywords: comet assay, ischemia reperfusion injury, mannitol, ngal protein, udenafil

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