Table 3.
Metabolomics in kidney preservation for Tx.
| Authors | Model | Metabolomics | Results |
|---|---|---|---|
| Animal studies | |||
| Richer et al., 2000 [45] | SCS in UW vs. EC (48 h); Porcine DBD with autoTx; N = 7/group |
1H NMR spectroscopy; Metabolites from plasma and urine |
SCS in UW vs. EC after reperfusion UW in urine: ↓ trimethylamidoxide/creatinine ratio, ↓ dimethylamine/creatinine ratio; UW in plasma: ↓ trimethylamidoxide |
| Hauet et al., 2000 [20] | SCS in UW vs. EC (48 h); Porcine DBD with autoTx; N = 14/group |
1H NMR spectroscopy; Metabolites from plasma and urine |
SCS in UW vs. EC after reperfusion UW: ↓ dimethylamine/creatinine ratio, ↓ trimethylamidoxide/creatinine ratio, ↑ citrate/creatinine ratio, ↓ acetate/creatinine ratio, ↓ lactate/creatinine ratio |
| Hauet et al., 2000 [46] | SCS in UW vs. EC (24 h) followed by 90 min reperfusion; Porcine DBD, single vs. multiorgan donor without Tx; N = 10/group |
1H NMR spectroscopy; Metabolites from urine |
SCS in UW vs. EC after reperfusion UW in urine: ~N-acetyl-β-D-glucosaminidase, ↓ lactate/creatinine ratio, ↓ acetate/creatinine ratio, ↓ trimethylamineoxide/creatinine ratio; Single vs. multiorgan donor Single organ in urine: ↓ lactate/creatinine ratio, ↓ acetate/creatinine ratio, ↓ trimethylamineoxide/creatinine ratio, ↑ amino acid, ↑ citrate |
| Serkova et al., 2005 [47] | SCS (24 vs. 42 h) ±Tx; Rats DBD with Tx; N = >6–8/group |
1H NMR spectroscopy; Over 50 metabolites from plasma and tissue |
24 vs. 42 h of SCS after reperfusion 24 h in blood: ~creatinine, ↓ allantoin, ↑ polyunsaturated fatty acids; 24 h in tissue: ↓ allantoin, ↓ trimethylamidoxide |
| Buchs et al., 2011 [48] | HOPE vs. SCS (8 and 18 h); Porcine DCD vs. DBD without Tx; N = 7 |
31P NMR spectroscopy; Metabolites from n.d. |
8→18 h of HOPE (DBD): ~phosphomonoester, ~γ-ATP, ~α-ATP, ~β-ATP; 8→18 h of HOPE (DCD): ↑ phosphomonoester, ↓ β-ATP; 8 h of SCS→8 h of HOPE (DBD): ↓ phosphomonoester, ↑ γ-ATP, ↑ α-ATP, ↑ β-ATP; ↑ NADH; 18 h of SCS→8 h of HOPE (DBD): ↓ phosphomonoester, ↑ γ-ATP, ↑ α-ATP, ↓ NADH |
| Bon et al., 2014 [49] | HMP (22 h); Porcine DCD with autoTx; N = 10 |
NMR spectroscopy; Metabolites from perfusate |
Inferior outcomes: ↑ lactate, ↑ choline, ↑ amino acids (valine, glycine and glutamate), ↓ glutathione |
| Nath et al., 2016 [50] | HMP (6 and 24 h); Porcine DBD without Tx; N = 6 |
1H and 13C NMR spectroscopy; Metabolites from perfusate and tissue |
6→24 h of HMP: ↑ lactate, ↑ alanine, ~acetate |
| Nath et al., 2017 [11] | HMP vs. SCS (24 h); Porcine DCD without Tx; N = 20 |
1H NMR spectroscopy; 26 metabolites from storage fluid/perfusate and tissue |
HMP vs. SCS HMP: ↑ glutamate, ↑ myoinositol, ↑ lactate, ↑ formate, ↑ acetate, ↑ inosine, ↑ aspartate, ↑ niacinamide, ↑ fumarate |
| Patel et al., 2019 [51] | HOPE vs. aerated HMP (18 h); Porcine DCD without Tx; N = 16 |
13C NMR spectroscopy and GC-MS; Metabolites from perfusate and tissue |
HOPE vs. aerated HMP HOPE: ↓ lactate, ↑ glutamate, ↑ ATP, ↓ alanine, ~citrate, ↑ succinate, ~malate |
| Darius et al., 2020 [52] | HMP ± 30% vs. 90% oxygen (22 h); Porcine DCD with autoTx; N = 28 |
1H NMR spectroscopy; 16 metabolites from perfusate |
HMP ± 30% vs. 90% oxygen HMP + 90% oxygen: ↓ acetate, ~adenine, ↑ alanine, ↑ aspartate, ↓ formate, ↓ gluconate, ↓ glutamate, ↑ glutathione, ↓ glycine, ↓ hypoxanthine, ~isoleucine, ↓ lactate, ~leucine, ↓ mannitol, ↓ myo-inositol, ↓ succinate |
| Human studies | |||
| Nath et al., 2014 [53] | HMP (45 min and 4 h); Human vs. porcine DBD without Tx; N = 22 |
1H NMR spectroscopy; 30 metabolites from perfusate |
Human vs. porcine grafts Human: ~conc. of 53.3% metabolites, ~change rate of conc. of 96.7% metabolites, ↑ change rate of conc. for 3-hydroxybutyrate |
| Guy et al., 2015 [10] | HMP (45 min and 4 h); DBD and DCD with Tx; N = 26 |
1H NMR spectroscopy; 28 metabolites from perfusate |
DGF vs. IGF DGF: ↓ glucose, ↓ inosine, ↑ leucine, ↓ gluconate; IGF: ↑ glucose, ↑ inosine, ↓ leucine, ↑ gluconate |
ATP, adenosine triphosphate; DBD, donation after brain death; DCD, donation after circulatory death; DGF, delayed graft function; EC, Euro-Collins solution; GC-MS, gas chromatography–mass spectrometry; HMP, hypothermic machine perfusion; HOPE, hypothermic oxygenated machine perfusion; IGF, immediate graft function; NADH, nicotinamide adenine dinucleotide; NMR, nuclear magnetic resonance; SCS, static cold storage; Tx, transplantation.