Monitoring treatment of acute kidney injury with damage biomarkers
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作者:
Pianta, T. J.
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Univ New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Univ Melbourne, Northern Clin Sch, 185Cooper St, Epping, Vic 3076, AustraliaUniv New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Pianta, T. J.
[1
,2
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Succar, L.
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Univ New South Wales, Prince Wales Clin Sch, Randwick, NSW, AustraliaUniv New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Succar, L.
[1
]
Davidson, T.
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Prince Wales Hosp, Anat Pathol, Randwick, NSW, AustraliaUniv New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Davidson, T.
[3
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Buckley, N. A.
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Univ Sydney, Clin Pharmacol, Sydney, NSW 2006, AustraliaUniv New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Buckley, N. A.
[4
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Endre, Z. H.
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Univ New South Wales, Prince Wales Clin Sch, Randwick, NSW, AustraliaUniv New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Endre, Z. H.
[1
]
机构:
[1] Univ New South Wales, Prince Wales Clin Sch, Randwick, NSW, Australia
Background: Damage biomarkers may identify mechanisms and sites of acute kidney injury (AKI). However, the utility of novel AKI biomarkers differs by context, and their utility for monitoring treatment of AKI is unknown. We hypothesized that selected AKI biomarkers would facilitate monitoring of mechanism-specific treatment. We examined this using a panel of biomarkers to monitor cisplatininduced AKI treatment with alpha-lipoic acid (alpha-LA) that has previously been demonstrated to ameliorate cisplatin induced AKI. Methods: AKI was induced in male Sprague Dawley rats using cisplatin (6 mg/kg) in the presence or absence of a single dose of alpha-LA (100 mg/kg). A panel of 12 urinary kidney damage biomarkers (CystatinC, NGAL albumin, alpha-l-acid glycoprotein, clusterin, KIM-1, osteopontin, total protein, cytochrome C, epidermal growth factor, interleukin-18 and malondialdehyde was examined as well as histological injury, serum creatinine and cystatin C, and clinical parameters. Results: Cisplatin treatment modified all parameters, except interleukin-18 and malondialdehyde, with each parameter demonstrating a different temporal profile. alpha-LA treatment attenuated renal tubular injury scores (P < 0.05), decreased peak serum creatinine (p = 0.004) and cystatin C (p = 0.04), and urinary damage biomarkers of proximal tubular injury (Cystatin C, NGAL, albumin, and alpha-l-acid glycoprotein). Other urinary biomarkers were not modified. Neither alpha-LA alone, nor the cisplatin vehicle (DMSO) modified biomarker profiles. Conclusions: alpha-LA treatment ameliorated cisplatin-induced AKI. Protection was demonstrated by reduced structural damage, improved glomerular filtration and reduced excretion of urinary biomarkers of proximal tubular damage. Effective treatment of AKI can be monitored by site and perhaps by mechanism-specific kidney damage biomarkers.(C) 2017 Elsevier B.V. All rights reserved.
机构:
Univ Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, BelgiumUniv Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, Belgium
De Loor, J.
Daminet, S.
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Univ Ghent, Fac Vet Med, Dept Med & Clin Biol Small Anim, B-9820 Merelbeke, BelgiumUniv Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, Belgium
Daminet, S.
Smets, P.
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Univ Ghent, Fac Vet Med, Dept Med & Clin Biol Small Anim, B-9820 Merelbeke, BelgiumUniv Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, Belgium
Smets, P.
Maddens, B.
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Univ Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, BelgiumUniv Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, Belgium
Maddens, B.
Meyer, E.
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Univ Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, BelgiumUniv Ghent, Fac Vet Med, Biochem Lab, Dept Pharmacol Toxicol & Biochem, B-9820 Merelbeke, Belgium
机构:
Univ Oslo, Oslo Renal Res Grp Ulleval, Inst Clin Med, Fac Med, Oslo, Norway
Oslo Univ Hosp, Dept Anaesthesiol, Div Emergencies & Crit Care, POB 4956 Nydalen, N-0424 Oslo, NorwayUniv Oslo, Oslo Renal Res Grp Ulleval, Inst Clin Med, Fac Med, Oslo, Norway
Beitland, S.
Joannidis, M.
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Med Univ Innsbruck, Div Intens Care & Emergency Med, Dept Internal Med, Innsbruck, AustriaUniv Oslo, Oslo Renal Res Grp Ulleval, Inst Clin Med, Fac Med, Oslo, Norway
机构:
Yale Univ, Nephrol Sect, Sch Med, West Haven, CT 06516 USA
Vet Affairs Med Ctr, West Haven, CT 06516 USAYale Univ, Nephrol Sect, Sch Med, West Haven, CT 06516 USA
Parikh, C. R.
Garg, A. X.
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Univ Western Ontario, Div Nephrol, London, ON, CanadaYale Univ, Nephrol Sect, Sch Med, West Haven, CT 06516 USA