SERUM ANGIOPOIETIN 1 AND 2 ARE ELEVATED IN DECEASED BRAIN DEAD DONORS AND PREDICT RENAL FUNCTION AFTER TRANSPLANTATION.

Abstract Background: Acute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (MV - microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and / or the secretome alone.Methods: AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v. injected post-ischemia. Mice were analyzed 48 hours later.Results: IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: MV+Ang-1, MV+BMP-5, MV+melatonin, and MV+secretome+Ang-1.Conclusion: Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

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Donor dopamine treatment in brain dead rats is associated with an improvement in renal function early after transplantation and a reduction in renal inflammation

Transplant International ◽

10.1111/j.1432-2277.2008.00725.x ◽

2008 ◽

pp. ???-??? ◽

Cited By ~ 4

Author(s):

Simone Hoeger ◽

Anke Reisenbuechler ◽

Uwe Gottmann ◽

Fabian Doyon ◽

Claude Braun ◽

...

Keyword(s):

Renal Function ◽

Renal Inflammation ◽

Brain Dead

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Effects of Terlipressin on Management of Hypotensive Brain-Dead Patients Who are Potential Organ Donors: A Retrospective Study

Frontiers in Pharmacology ◽

10.3389/fphar.2021.716759 ◽

2021 ◽

Vol 12 ◽

Author(s):

Donghua Zheng ◽

Genglong Liu ◽

Li Chen ◽

Wenfeng Xie ◽

Jiaqi Sun ◽

...

Keyword(s):

Renal Function ◽

Retrospective Study ◽

Liver Function ◽

Estimated Glomerular Filtration Rate ◽

Organ Procurement ◽

Venous Pressure ◽

Organ Donors ◽

Hemodynamic Stability ◽

Norepinephrine Dose ◽

Brain Dead

Background: Administration of terlipressin can reverse hypotension in potential organ donors with norepinephrine-resistance. The aim of this study was to determine the effects of terlipressin on the hemodynamics, liver function, and renal function of hypotensive brain-dead patients who were potential organ donors.Methods: A retrospective study was conducted by using the ICU database of one hospital. 18 patients in a total of 294 brain-dead cases were enrolled and administered terlipressin intravenously. All physiological parameters of recruited patients were obtained at baseline, 24 and 72 h after administration, and immediately before organ procurement.Results: Terlipressin induced significant increases in mean arterial pressure (MAP) from 69.56 ± 10.68 mm Hg (baseline) to 101.82 ± 19.27 mm Hg (immediately before organ procurement) and systolic blood pressure (SBP) from 89.78 ± 8.53 mm Hg (baseline) to 133.42 ± 26.11 mm Hg (immediately before organ procurement) in all patients. The increases in MAP were accompanied by significant decreases in heart rate (HR) from 113.56 ± 28.43 bpm (baseline) to 83.89 ± 11.70 bpm (immediately before organ procurement), which resulted in the decrease of norepinephrine dose over time from 0.8 ± 0.2 μg/kg/min (baseline) to 0.09 ± 0.02 μg/kg/min (immediately before organ procurement). There were no changes in central venous pressure, liver function including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin. Renal function, assessed by serum creatinine (SCr), urine output (UOP), creatinine clearance rate (CCr), and estimated glomerular filtration rate (eGFR), improved significantly.Conclusion: Our analysis of brain-dead patients with hypotension indicates that administration of terlipressin can significantly increases MAP, SBP, UOP, CCr, and eGFR, while decreases HR and Scr. Terlipressin appears to help maintain hemodynamic stability, reduce vasoactive support, and improve renal function.

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PAC-mediated AKI protection is critically mediated but does not exclusively depend on cell-derived microvesicles

10.1101/2020.04.23.057760 ◽

2020 ◽

Author(s):

H. Dihazi ◽

K. Schwarze ◽

S. Patschan ◽

G.A. Müller ◽

O. Ritter ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Bone Morphogenetic Protein ◽

Extracellular Vesicles ◽

Cystatin C ◽

Kidney Injury ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Morphogenetic Protein ◽

Angiopoietin 1

AbstractAcute Kidney Injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as reliable option for improving AKI outcomes in experimental AKI. Own studies focused on so-called Proangiogenic Cells (PACs). Mechanisms that contribute to PAC-mediated AKI protection include production / secretion of extracellular vesicles (MV - microvesicles). In addition, the cells most likely act by paracrinic processes (secretome). The current study evaluated whether AKI may be preventable by the administration of either PAC-derived MV and / or the secretome alone. AKI was induced in male C57/Bl6N mice (8-12 weeks) by bilateral renal ischemia (IRI - 40 minutes). Syngeneic murine PACs were stimulated with either melatonine, Angiopoietin-1 or -2, or with Bone Morphogenetic Protein-5 (BMP-5) for one hour, respectively. PAC-derived MV and the vesicle-depleted supernatant were subsequently collected and i.v. injected post-ischemia. Mice were analyzed 48 hours later. IRI induced significant kidney excretory dysfunction as reflected by higher serum cystatin C levels. The only measure that improved AKI was the injection of MV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: MV+Ang-1, MV+BMP-5, MV+melatonin, and MV+secretome+Ang-1. Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived MV. However, since previous data showed improved AKI-protection by PACs after cell preconditioning with certain mediators (Ang-1 and -2, melatonine, BMP-5), other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

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