Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Dynamics of mtDNA in Different Vascular Compartments
2.2.1. Systemic Venous mtDNA
2.2.2. Systemic Arterial mtDNA
2.2.3. Renal Venous mtDNA
2.3. Plasma mtDNA Variability between Subjects
2.3.1. D-Loop
2.3.2. ND1
2.3.3. ND6
2.4. Prediction of eGFR Using mtDNA Variables
2.5. Prediction of Acute Rejection Episodes Using mtDNA Variables
3. Discussion
4. Materials and Methods
4.1. Study Design
4.2. Sample Size Calculation
4.3. Outcome Measures
4.4. Timepoints
4.5. mtDNA Analysis
4.6. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Donor | n = 56 |
---|---|
Age (y) | 52.5 (±10.9) |
Male (n (%)) | 26 (46.4%) |
BMI (kg/m2) | 27 (±3.2) |
Active smokers (n (%)) | 16 (28.6%) |
Cardiovascular comorbidity (n (%)) | 17 (30.4%) |
Medication use (n (%)) | |
Antihypertensive therapy | 15 (26.8%) |
Statins | 7 (12.5%) |
PPI’s | 9 (16.1%) |
Pre-donation mGFR (mL/min) | 111 (97–135) |
Recipient | n = 56 |
Age (y) | 53.5 (45.3–58.8) |
Male (n (%)) | 26 (46.4%) |
BMI (kg/m2) | 24.8 (22.4–27.7) |
Cardiovascular comorbidity (n (%)) | 38 (67.9%) |
Medication use (n (%)) | |
Antihypertensive therapy | 51 (91.1%) |
Phosphate binders | 31 (55.4%) |
Statins | 27 (48.2%) |
Unrelated donor (n (%)) | 28 (50%) |
Pre-emptive transplantation (n (%)) | 27 (48.2%) |
Re-transplantation (n (%)) | 7 (12.5%) |
≥3 HLA mismatches (n (%)) | 34 (60.7%) |
Positive PRA (n (%)) | 7 (12.5%) |
Ischemia times (min) | |
WIT 1 | 4 (3–4) |
CIT | 172.5 (155.5–187.5) |
WIT 2 | 42.9 (±7.4) |
Kidney and patient outcomes | n = 56 |
DGF (n (%)) | 3 (5.4%) |
eGFR 1 month post transplantation (mL/min/1.73 m2) | 51.0 (±14.9) |
eGFR 3 months post transplantation (mL/min/1.73 m2) | 46.2 (38.8–58.6) |
eGFR 6 months post transplantation (mL/min/1.73 m2) | 47.6 (38.6–61.1) |
eGFR 12 month post transplantation (mL/min/1.73 m2) | 50.2 (±14.4) |
eGFR 24 month post transplantation (mL/min/1.73 m2) | 51.8 (±17.6) |
Acute rejection 2 years (n (%)) | 9 (16.1%) |
Graft loss (n (%)) | 2 (3.6%) |
Mortality (n (%)) | 1 (1.8%) |
Systemic Venous | Systemic Arterial | Renal Venous | |||||||
---|---|---|---|---|---|---|---|---|---|
Variables | B | SE | p | B | SE | p | B | SE | p |
D-loop | |||||||||
Recipient sex (I) Male = 0, female =1 | 0.95 | 0.32 | 0.0039 | 0.79 | 0.38 | 0.043 | |||
Pre-emptive tx (S) No = 0, yes = 1 | 0.057 | 0.029 | 0.0492 | ||||||
CIT (S) In minutes | −0.001 | 0.00050 | 0.0450 | ||||||
ND1 | |||||||||
Unrelated donor (I) No = 0, yes = 1 | −0.60 | 0.29 | 0.0419 | ||||||
Recipient sex (S) Male = 0, female =1 | 0.10 | 0.045 | 0.0265 | ||||||
Anesthetic regimen (S) * SEVO vs. PROP | 0.12 | 0.057 | 0.0389 | ||||||
CIT (S) In minutes | −0.000098 | 0.000045 | 0.0313 | ||||||
ND6 | |||||||||
WIT2 (S) In minutes | −0.0041 | 0.002 | 0.0435 | ||||||
CIT (S) In minutes | −0.000088 | 0.000031 | 0.0046 |
eGFR | Acute Rejections Episodes | ||||
---|---|---|---|---|---|
Single Timepoints of mtDNA | |||||
Variable | p-value | Estimate with SE | Variable | p-value | Exp(B) with 95% CI |
SA D-loop (logSQ) 2 h after reperfusion | 0.0392 | 3.34 (1.57) | SV D-loop (logSQ) Donor pre-transplantation | 0.042 | 0.52 (0.28–0.98) |
SV ND1 (logSQ) Day 9 post transplantation | 0.022 | 2.92 (1.23) | SA ND1 (logSQ) 5 min after reperfusion | 0.047 | 1539 (1.01–2.36) |
SA ND6 (logSQ) 5 min after reperfusion | 0.020 | 2.61 (1.16–5.84) | |||
Slopes of mtDNA (categorical) | |||||
Variable | p-value | Estimate with SE | Variable | p-value | Exp(B) with 95% CI |
SV ND6 Negative slope = 0 Positive slope =1 | 0.0076 | 10.26 (3.69) | SA ND6 Negative slope = 0 Positive slope =1 | 0.036 | 0.14 (0.02–0.88) |
Slopes of mtDNA (absolute) | |||||
Variable | p-value | Estimate with SE | Variable | p-value | Exp(B) with 95% CI |
SA ND6 (logSQ) | 0.022 | 0.30 (0.11–0.84) |
eGFR | |||
---|---|---|---|
Variable | p-Value | Estimate with SE | |
Crude model | Donor age (y) | <0.001 | −0.66 (0.14) |
Addition of single time-points mtDNA | SA D-loop (logSQ) 2 h after reperfusion | 0.0817 | 2.46 (1.38) |
SV ND1 (logSQ) Day 9 post transplantation | 0.0131 | 2.63 (1.02) | |
Addition of slope of mtDNA | SV ND6 Negative slope = 0 Positive slope =1 | 0.0204 | 7.81 (3.26) |
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Kroneisl, M.; Spraakman, N.A.; Koomen, J.V.; Hijazi, Z.; Hoogstra-Berends, F.H.; Leuvenink, H.G.D.; Struys, M.M.R.F.; Henning, R.H.; Nieuwenhuijs-Moeke, G.J. Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation. Int. J. Mol. Sci. 2023, 24, 13579. https://doi.org/10.3390/ijms241713579
Kroneisl M, Spraakman NA, Koomen JV, Hijazi Z, Hoogstra-Berends FH, Leuvenink HGD, Struys MMRF, Henning RH, Nieuwenhuijs-Moeke GJ. Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation. International Journal of Molecular Sciences. 2023; 24(17):13579. https://doi.org/10.3390/ijms241713579
Chicago/Turabian StyleKroneisl, Marie, Nora A. Spraakman, Jeroen V. Koomen, Zeinab Hijazi, Femke H. Hoogstra-Berends, Henri G. D. Leuvenink, Michel M. R. F. Struys, Rob H. Henning, and Gertrude J. Nieuwenhuijs-Moeke. 2023. "Peri-Operative Kinetics of Plasma Mitochondrial DNA Levels during Living Donor Kidney Transplantation" International Journal of Molecular Sciences 24, no. 17: 13579. https://doi.org/10.3390/ijms241713579