Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study
Abstract
:1. Introduction
2. Materials and Methods
Statistical Analysis
3. Results
Summary of Results
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- The incidence of dnDSA was regularly increasing in a prospective group (DSA screening by protocol) with time after transplantation and was 8% at 3 months, 11% at 6, 16% at 14 and finally reached 21% after 2 years of follow-up;
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- The presence of the dnDSA in patients from the prospective group, was associated with a >4.5 higher risk of inferior graft function expressed as a chronic decrease of eGFR by ≥30% from baseline within 2-year follow-up;
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- A median value of all consecutive evaluations (from >1 to 24 months after transplantation) of blood TAC C0 was in the dnDSA- negative patients significantly higher than in the dnDSA- positive patients in a prospective group (7.9 ng/mL vs. 7.1 ng/mL; p = 0.0088);
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- dsDSA- positive and the dnDSA -negative patients did not differ significantly in terms of TAC C0 variability, evaluated during 2-year follow-up;
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- Vasudev score was not significantly different between the dnDSA-seronegative and dnDSA- positive patients at 1, 12 and 24 months after transplantation.
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug | Pediatric Score: Dose per Unit (mg/m2/d) | Immunosuppressive Unit |
---|---|---|
Tacrolimus (TAC) | 1.2 | 1 |
Cyclosporin A (CsA) | 58 | 1 |
Sirolimus (SRL) | 1.2 | 1 |
Mycophenolate mofetil (MMF) | 290 | 1 |
Azathioprine (AZA) | 58 | 1 |
Prednisone (equivalent) | 2.9 | 1 |
Retrospective Group (n = 29) Median (Q1–Q3) # n (%) | Prospective Group (n = 38) Median (Q1–Q3) n (%) | p | |
---|---|---|---|
Age, years | 8.1 (5.0–9.9) | 11.4 (8.0–14.5) | 0.002 |
No. HLA-DR mismatches: 0/1/2 | 5/13/11 (17/45/38) | 8/25/5 (21/66/13) | 0.06 |
No. HLA-B mismatches: 0/1/2 | 1/15/13 (3/52/45) | 2/19/17 (5/50/45) | 1 |
No. HLA-A mismatches: 0/1/2 | 3/14/12 (10/48/41) | 4/19/15 (11/50/39) | 1 |
HLA A+B+DR mismatches | 4 (3–5) | 4 (3–4) | 0.3 |
Maintenance immunosuppression | |||
TAC | 25 (86.2) | 31 (81.6) | 0.75 |
CsA | 7 (24.1) | 7 (18.4) | 0.57 |
MMF | 25 (86.2) | 37 (97.4) | 0.16 |
Pred | 29 (100) | 38 (100) | N/A |
Baseline eGFR (mL/min/1.73 m2), | 72.8 | 76.4 | 0.27 |
No. of patients with kidney biopsies | (53.6–93.1) | (70.3–99.5) | |
23 (79.3) | 10 (26.3) | <0.0001 | |
Follow-up, years | 8 (6–11) | 2 (2–2) | <0.0001 |
Incidence of dnDSA (%) after transplantation overall | 100 | 21 | N/A |
at 3 months | N/A | 8 | N/A |
at 6 months | N/A | 11 | N/A |
at 12 months | N/A | 16 | N/A |
at 2 years | N/A | 21 | N/A |
Variable | Group | p | |
---|---|---|---|
Retro Median (Q1–Q3) n (%) | Pro Median (Q1–Q3) n (%) | ||
Incidence of dnDSA | 29 (100) | 8 (21) | <0.0001 |
eGFR at detection of dnDSA, mL/min/1.73 m2 | 41.0 (28.7–57.2) | 85.0 (55.0–92.5) | 0.004 |
Incidence of biopsy proven rejection | 19 (66) | 7 (18) | <0.0001 |
Incidence of graft loss in cAMR | 12 (41) | 0 | <0.0001 |
Parameter | dnDSA (−) | dnDSA (+) | p |
---|---|---|---|
TAC C0 (ng/mL), median, (Q1–Q3) | 7.9 (6.5–10.3) | 7.1 (5.9–8.5) | 0.0088 ^ |
TAC C0 coefficient of variation (%), median (Q1–Q3) | 31 (23–39) | 29 (17–37) | 0.56 |
Vasudev Score, Median, (Q1–Q3) | dnDSA (−) | ndDSA (+) | p |
---|---|---|---|
1 month after transplantation | 10.6 (8.6–12.5) | 10.5 (8.4–11.0) | NS ^ |
12 months after transplantation | 6.3 (5.5–7.0) | 6.1 (5.4–6.6) | NS ^ |
2 years after transplantation | 5.3 (4.1–6.0) | 4.1 (3.8–5.9) | NS ^ |
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Urzykowska, A.; Piątosa, B.; Grycuk, U.; Kowalewski, G.; Kułaga, Z.; Grenda, R. Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study. Children 2021, 8, 1162. https://doi.org/10.3390/children8121162
Urzykowska A, Piątosa B, Grycuk U, Kowalewski G, Kułaga Z, Grenda R. Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study. Children. 2021; 8(12):1162. https://doi.org/10.3390/children8121162
Chicago/Turabian StyleUrzykowska, Agnieszka, Barbara Piątosa, Urszula Grycuk, Grzegorz Kowalewski, Zbigniew Kułaga, and Ryszard Grenda. 2021. "Evaluation of Cumulative Effect of Standard Triple Immunosuppression on Prevention of De Novo Donor Specific Antibodies (dnDSA) Production in Children after Kidney Transplantation—A Retrospective and Prospective Study" Children 8, no. 12: 1162. https://doi.org/10.3390/children8121162