Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Population
2.2. Protocol Kidney Biopsies and Histological Analyses
2.3. PRO-C6 Detection
2.4. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. PRO-C6 and Biopsy-Proven Histological Changes over Follow-Up
3.3. Association between PRO-C6 and Biopsy Changes
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristics at Enrollment | Overall | Randomized Group | p Value | |
---|---|---|---|---|
CsA | EVL | |||
Number of patients, n | 94 | 51 | 43 | |
Age, years (SD) | 52 (13) | 51 (13) | 54 (12) | 0.30 |
Sex (male), n (%) | 64 (68) | 33 (65) | 31 (72) | 0.44 |
Race (Caucasian), n (%) | 83 (88) | 47 (92) | 36 (84) | 0.21 |
Primary kidney disease, n (%) | 0.81 | |||
Polycystic kidney disease | 24 (26) | 13 (26) | 11 (26) | |
Glomerulonephritis | 16 (17) | 9 (18) | 7 (16) | |
Hypertension | 15 (16) | 7 (14) | 8 (19) | |
Urologic | 8 (9) | 3 (6) | 5 (12) | |
Vascular | 5 (5) | 2 (4) | 3 (7) | |
Focal segmental glomerulosclerosis | 3 (3) | 1 (2) | 2 (5) | |
Diabetes mellitus | 3 (3) | 2 (4) | 1 (2) | |
Unknown cause | 16 (17) | 11 (22) | 5 (12) | |
Donor type, n (%) | 0.81 | |||
Living unrelated | 29 (31) | 15 (29) | 14 (33) | |
Deceased after brain death | 28 (30) | 15 (29) | 13 (30) | |
Living related | 22 (23) | 14 (28) | 8 (19) | |
Deceased after cardiac death | 14 (15) | 7 (14) | 7 (16) | |
Donor age, years (SD) a | 50 (13) | 51 (13) | 49 (12) | 0.55 |
Antigen mismatch, n (IQR) | 3 (2–4) | 3 (2–3) | 3 (2–4) | 0.52 |
TTKRT, months (IQR) | 24 (5–46) | 18 (6–46) | 24 (5–48) | 0.53 |
Characteristics at Randomization | Overall | Randomized Group | p value | |
---|---|---|---|---|
CsA | EVL | |||
eGFR, mL/min/1.73 m2 | 49 (42–62) | 49 (43–57) | 49 (40–67) | 0.89 |
Weight, kg (SD) a | 79 (14) | 81 (15) | 78 (13) | 0.24 |
BMI, kg/m2 (SD) a | 26.7 (3.5) | 26.0 (3.9) | 25.4 (3.1) | 0.44 |
SBP, mmHg (SD) b | 144 (20) | 144 (20) | 145 (21) | 0.82 |
DBP, mmHg (SD) b | 84 (12) | 84 (11) | 83 (12) | 0.68 |
LDL, mmol/L (SD) b | 3.19 (2.39–3.75) | 3.19 (2.37–3.95) | 3.15 (2.40–3.70) | 0.84 |
HDL, mmol/L (SD) b | 1.39 (1.20–1.73) | 1.30 (1.17–1.71) | 1.49 (1.20–1.76) | 0.49 |
Cholesterol, mmol/L (SD) b | 5.13 (4.34–6.10) | 5.16 (4.26–6.23) | 5.08 (4.40–6.07) | 0.92 |
Statins use, n (%) | 55 (59) | 32 (63) | 23 (54) | 0.36 |
Glucose, mmol/L c | 5.10 (4.50–5.80) | 5.10 (4.70–5.80) | 4.90 (4.50–5.90) | 0.35 |
HbA1c, % (SD) c | 6.08 (1.10) | 6.14 (1.25) | 6.01 (0.88) | 0.60 |
Diabetes mellitus, n (%) | 2 (2) | 0 (0) | 2 (5) | 0.12 |
Smoking current, n (%) | 15 (16) | 10 (20) | 5 (12) | 0.29 |
Biomarkers and Histological Characteristics | Overall | Randomized Group | p | |
---|---|---|---|---|
CsA | EVL | |||
Biomarkers | ||||
6 Months | ||||
Plasma | ||||
PRO-C6 (ng/mL) a | 9.5 (3.4) | 9.5 (3.1) | 9.4 (3.9) | 0.93 |
Creatinine, µmol/L (SD) | 130 (33) | 130 (31) | 130 (35) | 0.96 |
Urine | ||||
PRO-C6 (ng/mg creat) b | 6.7 (4.8–12.4) | 6.6 (4.9–12.9) | 6.8 (3.8–12.8) | 0.70 |
24 Months | ||||
Plasma | ||||
PRO-C6 (ng/mL) c | 9.4 (4.3) | 9.6 (4.5) | 9.1(4.3) | 0.72 |
Creatinine, µmol/L (SD) | 143 (49) | 149 (46) | 136 (53) | 0.22 |
Urine | ||||
PRO-C6 (ng/mg creat) b | 5.9 (3.4–21.5) | 4.5 (3.2–10.2) | 7.5 (4.6–40.7) | 0.02 |
Delta24-6 | ||||
Plasma | ||||
PRO-C6 (ng/mL) c | 0.3 (3.9) | 0.6 (3.1) | 0.01 (4.6) | 0.67 |
Urine | ||||
PRO-C6 (ng/mg creat) b | −0.5 (−2.6–4.8) | −1.4 (−3.6–0.27) | 0.9 (−2.2–23.9) | 0.01 |
Histological analyses | ||||
6 Months | ||||
IF/TA-score | 1 (0–1) | 1 (0–1) | 1 (1–2) | 0.56 |
PSR, % | 13.3 (6.0) | 13.0 (6.1) | 13.6 (6.0) | 0.65 |
ti-score, % | 10.0 (5.0–15.8) | 10.0 (5.0–10.0) | 10.0 (5.0–20.0) | 0.38 |
24 Months | ||||
IF/TA-score | 1 (1–2) | 1 (0–1) | 1 (1–2) | 0.36 |
PSR, % | 17.3 (10.6) | 19.7 (11.7) | 14.5 (8.5) | 0.02 |
ti-score, % | 20.0 (10.0–41.3) | 20.0 (10.0–50.0) | 15.0 (10.0–30.0) | 0.16 |
Delta24-6 | ||||
IF/TA-score | 0.5 (0–1) | 1 (0–1) | 0 (0–1) | 0.23 |
PSR, % | 4.0 (11.4) | 6.7 (13.1) | 0.9 (7.9) | 0.01 |
ti-score, % | 10 (0–30) | 10 (0–45) | 5 (0–20) | 0.09 |
Histological Analyses | 6-Months PRO-C6 | 24-Months PRO-C6 | Delta24-6 PRO-C6 | |||
---|---|---|---|---|---|---|
Plasma, ng/mL | Urine, ng/mg | Plasma, ng/mL | Urine, ng/mg | Plasma, ng/mL | Urine, ng/mg | |
Std. β | Std. β | Std. β | Std. β | Std. β | Std. β | |
6 Months | ||||||
IF/TA | 0.34 ** | 0.20 | ||||
PSR | 0.11 | −0.18 | ||||
ti-score | 0.04 | 0.08 | ||||
24 Months | ||||||
IF/TA | 0.24 * | 0.06 | 0.08 | 0.13 | −0.04 | 0.02 |
PSR | 0.01 | −0.30 * | 0.06 | −0.24 | −0.01 | 0.04 |
ti-score | 0.23 * | 0.23 | 0.16 | 0.09 | 0.05 | −0.03 |
Delta24-6 | ||||||
IF/TA | −0.03 | −0.08 | −0.20 | −0.07 | −0.16 | 0.01 |
PSR | −0.06 | −0.17 | −0.009 | −0.19 | 0.04 | −0.04 |
ti-score | 0.22 * | 0.20 | 0.11 | −0.02 | 0.01 | −0.02 |
Histological Analyses | 24 Months | Delta24-6 | ||||||
---|---|---|---|---|---|---|---|---|
Plasma PRO-C6, ng/mL | Urine PRO-C6, ng/mg | Plasma PRO-C6, ng/mL | Urine PRO-C6, ng/mg | |||||
CsA | EVL | CsA | EVL | CsA | EVL | CsA | EVL | |
Std. β | Std. β | Std. β | Std. β | Std. β | Std. β | Std. β | Std. β | |
24 Months | ||||||||
IF/TA | −0.11 | 0.32 | −0.25 | 0.30 | −0.31 | 0.16 | 0.13 | −0.11 |
PSR | −0.07 | 0.18 | −0.09 | −0.31 | −0.47 | 0.25 | 0.12 | −0.11 |
ti-score | −0.07 | 0.40 | 0.18 | 0.14 | −0.37 | 0.32 | 0.08 | −0.07 |
Delta24-6 | ||||||||
IF/TA | −0.30 | −0.07 | −0.43 * | 0.07 | −0.40 | −0.01 | 0.12 | −0.003 |
PSR | 0.001 | −0.06 | −0.10 | −0.27 | −0.28 | 0.25 | 0.03 | −0.18 |
ti-score | −0.08 | 0.33 | 0.07 | 0.05 | −0.35 | 0.25 | 0.09 | 0.04 |
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Yepes-Calderón, M.; Sotomayor, C.G.; Rasmussen, D.G.K.; Hijmans, R.S.; te Velde-Keyzer, C.A.; van Londen, M.; van Dijk, M.; Diepstra, A.; Berger, S.P.; Karsdal, M.A.; et al. Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial. J. Clin. Med. 2020, 9, 3216. https://doi.org/10.3390/jcm9103216
Yepes-Calderón M, Sotomayor CG, Rasmussen DGK, Hijmans RS, te Velde-Keyzer CA, van Londen M, van Dijk M, Diepstra A, Berger SP, Karsdal MA, et al. Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial. Journal of Clinical Medicine. 2020; 9(10):3216. https://doi.org/10.3390/jcm9103216
Chicago/Turabian StyleYepes-Calderón, Manuela, Camilo G. Sotomayor, Daniel Guldager Kring Rasmussen, Ryanne S. Hijmans, Charlotte A. te Velde-Keyzer, Marco van Londen, Marja van Dijk, Arjan Diepstra, Stefan P. Berger, Morten Asser Karsdal, and et al. 2020. "Biopsy-Controlled Non-Invasive Quantification of Collagen Type VI in Kidney Transplant Recipients: A Post-Hoc Analysis of the MECANO Trial" Journal of Clinical Medicine 9, no. 10: 3216. https://doi.org/10.3390/jcm9103216