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

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

10.1101/2020.04.23.057745 ◽

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

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PAC-Mediated AKI Protection Is Critically Mediated but Does Not Exclusively Depend on Cell-Derived Microvesicles

International Journal of Nephrology ◽

10.1155/2021/8864183 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

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

Introduction. Acute kidney injury (AKI) significantly worsens the prognosis of hospitalized patients. In recent years, cell-based strategies have been established as a reliable option for improving AKI outcomes in experimental AKI. Our previous studies focused on the 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 melatonin, 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 after 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 after 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, melatonin, BMP-5), mechanisms other than exclusively vesicle-dependent mechanisms must be involved in PAC-mediated AKI protection.

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P0548PAC-MEDIATED AKI PROTECTION IS CRITICALLY MEDIATED BUT DOES NOT EXCLUSIVELY DEPEND ON CELL-DERIVED MICROVESICLES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0548 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Daniel Patschan ◽

Katrin Schwarze ◽

Oliver Ritter ◽

Susann Patschan ◽

Gerhard Anton Müller

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Kidney Injury ◽

Serum Cystatin C ◽

Intact Cells ◽

Serum Cystatin ◽

Morphogenetic Protein ◽

Ischemic Tissue ◽

Mere Presence ◽

Angiopoietin 1

Abstract Background and Aims 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 (EV). 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 EV and / or the secretome alone. Method 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. The four mediators were chosen since previous own studies showed improved PAC-mediated AKI protection after cell preconditioning with these substances. PAC-derived EV 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 EV, collected from native PACs. The following conditions worsened post-ischemic renal function even further: EV+Ang-1, EV+BMP-5, EV+melatonin, and EV+secretome+Ang-1. Conclusion Together, our data show that PAC-mediated AKI protection substantially depends on the availability of cell-derived EV. The secretome, either collected from native or preconditioned cells does not prevent mice from ischemia-induced dysfunction. 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. We suggest, that the mere presence of intact cells in the post-ischemic tissue is necessary for improving functional and structural outcome parameters under certain conditions.

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Serum cystatin C as a marker of renal function in detection of early acute kidney injury

Indian Journal of Nephrology ◽

10.4103/0971-4065.111840 ◽

2013 ◽

Vol 23 (3) ◽

pp. 180 ◽

Cited By ~ 31

Author(s):

M. S. N. Murty ◽

UK Sharma ◽

VB Pandey ◽

SB Kankare

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Cystatin C ◽

Kidney Injury ◽

Serum Cystatin C ◽

Serum Cystatin

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Estimated Glomerular Filtration Rate Correlates Poorly with Four-Hour Creatinine Clearance in Critically Ill Patients with Acute Kidney Injury

Critical Care Research and Practice ◽

10.1155/2013/406075 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 4

Author(s):

Christopher J. Kirwan ◽

Barbara J. Philips ◽

Iain A. M. MacPhee

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Critically Ill ◽

Cystatin C ◽

Critically Ill Patients ◽

Filtration Rate ◽

Kidney Injury ◽

Serum Cystatin C ◽

Serum Cystatin

Introduction.RIFLE and AKIN provide a standardised classification of acute kidney injury (AKI), but their categorical rather than continuous nature restricts their use to a research tool. A more accurate real-time description of renal function in AKI is needed, and some published data suggest that equations based on serum creatinine that estimate glomerular filtration rate (eGFR) can provide this. In addition, incorporating serum cystatin C concentration into estimates of GFR may improve their accuracy, but no eGFR equations are validated in critically ill patients with AKI.Aim.This study tests whether creatinine or cystatin-C-based eGFR equations, used in patients with CKD, offer an accurate representation of 4-hour creatinine clearance (4CrCl) in critically ill patients with AKI.Methods.Fifty-one critically ill patients with AKI were recruited. Thirty-seven met inclusion criteria, and the performance of eGFR equations was compared to 4CrCl.Results.eGFR equations were better than creatinine alone at predicting 4CrCl. Adding cystatin C to estimates did not improve the bias or add accuracy. The MDRD 7 eGFR had the best combination of correlation, bias, percentage error and accuracy. None were near acceptable standards quoted in patients with chronic kidney disease (CKD).Conclusions.eGFR equations are not sufficiently accurate for use in critically ill patients with AKI. Incorporating serum cystatin C does not improve estimates. eGFR should not be used to describe renal function in patients with AKI. Standards of accuracy for validating eGFR need to be set.

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ASSESSMENT OF SERUM CYSTATIN C AS AN EARLY PREDICTOR OF ACUTE KIDNEY INJURY IN PRETERM NEONATES WITH RESPIRATORY DISTRESS SYNDROME

10.26226/morressier.57d034d2d462b80292383764 ◽

2016 ◽

Author(s):

Abdelmoneim khashana

Keyword(s):

Acute Kidney Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Cystatin C ◽

Distress Syndrome ◽

Kidney Injury ◽

Preterm Neonates ◽

Serum Cystatin C ◽

Serum Cystatin ◽

Early Predictor

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A nomogram based on serum cystatin C for predicting acute kidney injury in patients with traumatic brain injury

Renal Failure ◽

10.1080/0886022x.2021.1871919 ◽

2021 ◽

Vol 43 (1) ◽

pp. 206-215

Author(s):

Ruo Ran Wang ◽

Min He ◽

Xiying Gui ◽

Yan Kang

Keyword(s):

Traumatic Brain Injury ◽

Acute Kidney Injury ◽

Brain Injury ◽

Cystatin C ◽

Kidney Injury ◽

Serum Cystatin C ◽

Serum Cystatin

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Acute Kidney Injuries in Children with Severe Malaria

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.2020.20.04.006 ◽

2020 ◽

Vol 20 (4) ◽

pp. e312-317

Author(s):

Folake M. Afolayan ◽

Olanrewaju T. Adedoyin ◽

Mohammed B. Abdulkadir ◽

Olayinka R. Ibrahim ◽

Sikiru A. Biliaminu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Severe Malaria ◽

Diagnostic Criteria ◽

Cystatin C ◽

Filtration Rate ◽

Kidney Injury ◽

Serum Cystatin C ◽

Serum Cystatin

Objectives: Serum creatinine levels are often used to diagnose acute kidney injury (AKI), but may not necessarily accurately reflect changes in glomerular filtration rate (GFR). This study aimed to compare the prevalence of AKI in children with severe malaria using diagnostic criteria based on creatinine values in contrast to cystatin C. Methods: This prospective cross-sectional study was performed between June 2016 and May 2017 at the University of Ilorin Teaching Hospital, Ilorin, Nigeria. A total of 170 children aged 0.5–14 years old with severe malaria were included. Serum cystatin C levels were determined using a particle-enhanced immunoturbidmetric assay method, while creatinine levels were measured using the Jaffe reaction. Renal function assessed using cystatin C-derived estimated GFR (eGFR) was compared to that measured using three sets of criteria based on creatinine values including the Kidney Disease: Improved Global Outcomes (KDIGO) and World Health Organization (WHO) criteria as well as an absolute creatinine cut-off value of >1.5 mg/dL. Results: Mean serum cystatin C and creatinine levels were 1.77 ± 1.37 mg/L and 1.23 ± 1.80 mg/dL, respectively (P = 0.002). According to the KDIGO, WHO and absolute creatinine criteria, the frequency of AKI was 32.4%, 7.6% and 16.5%, respectively. In contrast, the incidence of AKI based on cystatin C-derived eGFR was 51.8%. Overall, the rate of detection of AKI was significantly higher using cystatin C compared to the KDIGO, WHO and absolute creatinine criteria (P = 0.003, <0.001 and <0.001, respectively). Conclusion: Diagnostic criteria for AKI based on creatinine values may not indicate the actual burden of disease in children with severe malaria. Keywords: Biomarkers; Acute Kidney Injury; Renal Failure; Glomerular Filtration Rate; Cystatin C; Creatinine; Malaria; Nigeria.

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