Ex Vivo Analysis of Kidney Graft Viability Using 31P Magnetic Resonance Imaging Spectroscopy.
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
18
7
2020
medline:
7
10
2020
entrez:
18
7
2020
Statut:
ppublish
Résumé
The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation. To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury. Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury. ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.
Sections du résumé
BACKGROUND
The lack of organs for kidney transplantation is a growing concern. Expansion in organ supply has been proposed through the use of organs after circulatory death (donation after circulatory death [DCD]). However, many DCD grafts are discarded because of long warm ischemia times, and the absence of reliable measure of kidney viability. P magnetic resonance imaging (pMRI) spectroscopy is a noninvasive method to detect high-energy phosphate metabolites, such as ATP. Thus, pMRI could predict kidney energy state, and its viability before transplantation.
METHODS
To mimic DCD, pig kidneys underwent 0, 30, or 60 min of warm ischemia, before hypothermic machine perfusion. During the ex vivo perfusion, we assessed energy metabolites using pMRI. In addition, we performed Gadolinium perfusion sequences. Each sample underwent histopathological analyzing and scoring. Energy status and kidney perfusion were correlated with kidney injury.
RESULTS
Using pMRI, we found that in pig kidney, ATP was rapidly generated in presence of oxygen (100 kPa), which remained stable up to 22 h. Warm ischemia (30 and 60 min) induced significant histological damages, delayed cortical and medullary Gadolinium elimination (perfusion), and reduced ATP levels, but not its precursors (AMP). Finally, ATP levels and kidney perfusion both inversely correlated with the severity of kidney histological injury.
CONCLUSIONS
ATP levels, and kidney perfusion measurements using pMRI, are biomarkers of kidney injury after warm ischemia. Future work will define the role of pMRI in predicting kidney graft and patient's survival.
Identifiants
pubmed: 32675744
doi: 10.1097/TP.0000000000003323
pii: 00007890-202009000-00014
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1825-1831Références
Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2017 annual data report: kidney Am J Transplant. 2019; 19Suppl 219–123. doi:10.1111/ajt.15274
doi: 10.1111/ajt.15274
Aubert O, Reese PP, Audry B, et al. Disparities in acceptance of deceased donor kidneys between the United States and France and estimated effects of increased US acceptance JAMA Intern Med. 2019; 179:1365–1374. doi:10.1001/jamainternmed.2019.2322
doi: 10.1001/jamainternmed.2019.2322
Rege A, Leraas H, Vikraman D, et al. Could the use of an enhanced recovery protocol in laparoscopic donor nephrectomy be an incentive for live kidney donation? Cureus. 2016; 8:e889. doi:10.7759/cureus.889
doi: 10.7759/cureus.889
Heilman RL, Green EP, Reddy KS, et al. Potential impact of risk and loss aversion on the process of accepting kidneys for transplantation. Transplantation. 2017; 101:1514–1517. doi:10.1097/TP.0000000000001715
doi: 10.1097/TP.0000000000001715
Sung RS, Christensen LL, Leichtman AB, et al. Determinants of discard of expanded criteria donor kidneys: impact of biopsy and machine perfusion. Am J Transplant. 2008; 8:783–792. doi:10.1111/j.1600-6143.2008.02157.x
doi: 10.1111/j.1600-6143.2008.02157.x
Port FK, Bragg-Gresham JL, Metzger RA, et al. Donor characteristics associated with reduced graft survival: an approach to expanding the pool of kidney donors. Transplantation. 2002; 74:1281–1286. doi:10.1097/00007890-200211150-00014
doi: 10.1097/00007890-200211150-00014
Dare AJ, Pettigrew GJ, Saeb-Parsy K. Preoperative assessment of the deceased-donor kidney: from macroscopic appearance to molecular biomarkers. Transplantation. 2014; 97:797–807. doi:10.1097/01.TP.0000441361.34103.53
doi: 10.1097/01.TP.0000441361.34103.53
Vajdová K, Graf R, Clavien P-A. ATP-supplies in the cold-preserved liver: a long-neglected factor of organ viability. Hepatology. 2002; 36:1543–1552. doi:10.1053/jhep.2002.37189
doi: 10.1053/jhep.2002.37189
Bruinsma BG, Sridharan GV, Weeder PD, et al. Metabolic profiling during ex vivo machine perfusion of the human liver. Sci Rep. 2016; 6:22415. doi:10.1038/srep22415
doi: 10.1038/srep22415
Miyagi S, Iwane T, Akamatsu Y, et al. The significance of preserving the energy status and microcirculation in liver grafts from non-heart-beating donor. Cell Transplant. 2008; 17:173–178. doi:10.3727/000000008783906874
doi: 10.3727/000000008783906874
Tennankore KK, Kim SJ, Alwayn IP, et al. Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation. Kidney Int. 2016; 89:648–658. doi:10.1016/j.kint.2015.09.002
doi: 10.1016/j.kint.2015.09.002
Chouchani ET, Pell VR, James AM, et al. A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metab. 2016; 23:254–263. doi:10.1016/j.cmet.2015.12.009
doi: 10.1016/j.cmet.2015.12.009
van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med. 2012; 52:1382–1402. doi:10.1016/j.freeradbiomed.2012.01.013
doi: 10.1016/j.freeradbiomed.2012.01.013
Nohl H, Koltover V, Stolze K. Ischemia/reperfusion impairs mitochondrial energy conservation and triggers O2.− release as a byproduct of respiration. Free Radic Res Commun. 1993; 18:127–137. doi:10.3109/10715769309147486
doi: 10.3109/10715769309147486
Lanir A, Jenkins RL, Caldwell C, et al. Hepatic transplantation survival: correlation with adenine nucleotide level in donor liver. Hepatology. 1988; 8:471–475. doi:10.1002/hep.1840080306
doi: 10.1002/hep.1840080306
Kamiike W, Burdelski M, Steinhoff G, et al. Adenine nucleotide metabolism and its relation to organ viability in human liver transplantation. Transplantation. 1988; 45:138–143. doi:10.1097/00007890-198801000-00030
doi: 10.1097/00007890-198801000-00030
Grenier N, Pedersen M, Hauger O. Contrast agents for functional and cellular MRI of the kidney. Eur J Radiol. 2006; 60:341–352. doi:10.1016/j.ejrad.2006.06.024
doi: 10.1016/j.ejrad.2006.06.024
Rusinek H, Kaur M, Lee VS. Renal magnetic resonance imaging. Curr Opin Nephrol Hypertens. 2004; 13:667–673. doi:10.1097/00041552-200411000-00014
doi: 10.1097/00041552-200411000-00014
Laissy JP, Faraggi M, Lebtahi R, et al. Functional evaluation of normal and ischemic kidney by means of gadolinium-DOTA enhanced TurboFLASH MR imaging: a preliminary comparison with 99Tc-MAG3 dynamic scintigraphy. Magn Reson Imaging. 1994; 12:413–419. doi:10.1016/0730-725x(94)92534-8
doi: 10.1016/0730-725x(94)92534-8
Lazeyras F, Buhler L, Vallee J-P, et al. Detection of ATP by “in line” 31P magnetic resonance spectroscopy during oxygenated hypothermic pulsatile perfusion of pigs’ kidneys. MAGMA. 2012; 25:391–399. doi:10.1007/s10334-012-0319-6
doi: 10.1007/s10334-012-0319-6
Buchs JB, Lazeyras F, Bühler L, et al. The viability of kidneys tested by gadolinium-perfusion MRI during ex vivo perfusion. Prog Urol. 2009; 19:307–312. doi:10.1016/j.purol.2009.01.004
doi: 10.1016/j.purol.2009.01.004
Meier RPH, Piller V, Hagen ME, et al. Intra-abdominal cooling system limits ischemia-reperfusion injury during robot-assisted renal transplantation. Am J Transplant. 2018; 18:53–62. doi:10.1111/ajt.14399
doi: 10.1111/ajt.14399
Goujon JM, Hauet T, Menet E, et al. Histological evaluation of proximal tubule cell injury in isolated perfused pig kidneys exposed to cold ischemia. J Surg Res. 1999; 82:228–233. doi:10.1006/jsre.1998.5526
doi: 10.1006/jsre.1998.5526
Longchamp A, Meier RPH, Colucci N, et al. Impact of an intra-abdominal cooling device during open kidney transplantation in pigs. Swiss Med Wkly. 2019; 149:w20143. doi:10.4414/smw.2019.20143
doi: 10.4414/smw.2019.20143
Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009; 360:7–19
Kaths JM, Echeverri J, Chun YM, et al. Continuous normothermic ex vivo kidney perfusion improves graft function in donation after circulatory death pig kidney transplantation. Transplantation. 2017; 101:754–763
Kron P, Schlegel A, de Rougemont O, et al. Short, cool, and well oxygenated—HOPE for kidney transplantation in a rodent model. Ann Surg. 2016; 264:815–822
Venema LH, Brat A, Nijkamp DM, et al. Factors that complicated the implementation of a program of donation after unexpected circulatory death of lungs and kidneys. lessons learned from a regional trial in the Netherlands. Transplantation. 2019; 103:e256–e262
Berendsen TA, Izamis ML, Xu H, et al. Hepatocyte viability and adenosine triphosphate content decrease linearly over time during conventional cold storage of rat liver grafts. Transplant Proc. 2011; 43:1484–1488
Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev. 2015; 4:20–27
de Rougemont O, Breitenstein S, Leskosek B, et al. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009; 250:674–683
Longchamp A, Mirabella T, Arduini A, et al. Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H2S production. Cell. 2018; 173:117–129.e14
González FX, Rimola A, Grande L, et al. Predictive factors of early postoperative graft function in human liver transplantation. Hepatology. 1994; 20:565–573
Hamamoto I, Takaya S, Todo S, et al. Can adenine nucleotides predict primary nonfunction of the human liver homograft? Transpl Int. 1994; 7:89–95
Suntharalingam C, Sharples L, Dudley C, et al. Time to cardiac death after withdrawal of life-sustaining treatment in potential organ donors. Am J Transplant. 2009; 9:2157–2165
Vidya Shankar R, Kodibagkar VD. A faster PISTOL for 1 H MR-based quantitative tissue oximetry. NMR Biomed. 2019; 32:e4076
Graveron-Demilly D. Quantification in magnetic resonance spectroscopy based on semi-parametric approaches. MAGMA. 2014; 27:113–130