LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Molecular Analyses
2.2.1. PCR-Based Deletion Confirmation
- CNV915.1-F: 5’-AAAGACCTCAAATCAATAGCCTG-3’
- CNVR915.1-R: 5’-GGACATTTAGGCTGCTTCTG-3’
2.2.2. HLA Genotyping
2.2.3. Anti-HLA Antibody Screening
2.2.4. Biochemical Tests
2.3. Follow-Up Principles
2.4. Histopathological Evaluation for Classifying Rejection
2.5. RNA Extraction and Real-Time PCR Analysis
2.6. Immunohistochemistry
2.7. Statistical Analyses
3. Results
3.1. Study Population
3.2. Clinical, Histopathologic, and Therapeutic Features
3.3. Allograft Biopsies
3.4. Banff Classification Scores
3.5. LIMS1 and GCC2 Expression in Non-Utilized Ischemic Kidneys
3.6. LIMS1 and GCC2 Immunohistochemical Staining of Non-Utilized Kidneys
3.7. Follow-Up and Outcomes
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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GG Genotype (n = 24) | AA/AG Genotype (n = 86) | p Value | |
---|---|---|---|
Age (years), mean ± SD | 30 ± 12 | 32 ± 12 | 0.41 |
Sex (M/F), n (%) | 18 (75%)/6 (25%) | 49 (57%)/37 (43%) | 0.11 |
Pretransplant dialysis, n (%) | |||
Preemptive | 2 (8.3%) | 12 (14%) | |
HD | 17 (70.8%) | 61 (70.9%) | |
PD | 4 (16.7%) | 6 (7%) | 0.42 |
HD + PD | 1 (4.2%) | 7 (8.1%) | |
Previous kidney transplant, n (%) | 1 (4.2%) | 2 (2.3%) | 0.62 |
Pretransplant last PRA level, n (%) | |||
<10% | 24 (100%) | 83 (96.5%) | |
10% to 79% | - | 3 (3.5%) | 0.35 |
≥80% | - | - | |
Donor age (years), mean ± SD | 43 ± 12 | 42 ± 13 | 0.83 |
Donor sex (M/F), n (%) | 16 (67%)/8 (33%) | 47 (55%)/39 (45%) | 0.29 |
Donor type (living/deceased), n (%) | 17 (71%)/7 (29%) | 70 (81%)/16 (19%) | 0.26 |
HLA mismatches, mean ± SD | 3.4 ± 1.1 | 3.0 ± 1.2 | 0.07 |
Induction treatment, n (%) | |||
ATG | 7 (29%) | 4 (16%) | 0.51 |
IL2rAb | 4 (17%) | 16 (19%) | |
No induction | 13 (54%) | 56 (65%) | |
Maintenance immunosuppression, n (%) | |||
Tac + MMF/AZA + Pred | 8 (33.3%) | 28 (32.6%) | |
CsA + MMF/AZA + Pred | 12 (50%) | 39 (45.3%) | |
mTORi-based | 2 (8.3%) | 8 (9.3%) | 0.97 |
AZA/MMF + Pred | 2 (8.3%) | 8 (9.3%) | |
CNI + MMF/AZA | - | 2 (2.3%) | |
CNI + Pred | - | 1 (1.2%) |
GG Genotype (n = 24) | AA/AG Genotype (n = 86) | p Value | |
---|---|---|---|
Allograft biopsy time after KTx (years), median (IQR) | 7.6 (4.0–12.8) | 5.4 (1.9–12.8) | 0.35 |
Serum creatinine (mg/dL), median (IQR) | 2.2 (1.5–2.5) | 2.2 (1.68–2.8) | 0.84 |
Proteinuria (g/day), median (IQR) | 0.25 (0.03–1.43) | 1 (0–2.5) | 0.33 |
DSA, n (%) | 11 (45.8%) | 30 (34.9%) | 0.33 |
Baseline biopsy results | |||
Morphologic TCMR lesions and scores | |||
Tubulitis score ≥ 1, n (%) | 24 (100%) | 77 (89.5%) | 0.09 |
Tubulitis score, mean ± SD | 1.42 ± 0.65 | 1.12 ± 0.66 | 0.03 |
Interstitial inflammation ≥ 1, n (%) | 21 (87.5%) | 70 (91.9%) | 0.51 |
Interstitial inflammation, mean ± SD | 1.33 ± 0.76 | 1.27 ± 0.68 | 0.57 |
Morphologic ABMR lesions and scores | |||
Glomerulitis score ≥ 1, n (%) | 14 (58.3%) | 41 (47.7%) | 0.36 |
Glomerulitis score, mean ± SD | 0.96 ± 1.04 | 0.78 ± 0.96 | 0.41 |
Peritubular capillaritis score ≥ 1, n (%) | 17 (70.8%) | 50 (58.1%) | 0.26 |
Peritubular capillaritis score, mean ± SD | 1.21 ± 1.06 | 0.93 ± 0.96 | 0.25 |
Microvascular inflammation (glomerulitis + peritubular capillaritis) score, mean ± SD | 2.17 ± 1.86 | 1.71 ± 1.70 | 0.26 |
Transplant glomerulopathy score ≥ 1, n (%) | 9 (37.5%) | 33 (38.4%) | 0.94 |
Transplant glomerulopathy score, mean ± SD | 0.54 ± 0.83 | 0.64 ± 0.93 | 0.77 |
C4d in peritubular capillaritis (≥1), n (%) | 12 (50%) | 29 (34%) | 0.15 |
C4d score, mean ± SD | 1.04 ± 1.23 | 0.86 ± 1.28 | 0.33 |
Interstitial fibrosis score ≥ 1, n (%) | 22 (91.7%) | 74 (86%) | 0.58 |
Interstitial fibrosis score, mean ± SD | 1.25 ± 0.61 | 1.16 ± 0.65 | 0.58 |
Tubular atrophy score ≥ 1, n (%) | 23 (94%) | 78 (91%) | 0.42 |
Tubular atrophy score, mean ± SD | 1.21 ± 0.51 | 1.29 ± 0.63 | 0.45 |
Banff 2013 rejection types and categories | |||
Acute/active TCMR, n (%) | 10 (42%) | 22 (26%) | 0.13 |
Acute/active ABMR, n (%) | 10 (42%) | 33 (38%) | 0.77 |
Chronic/active ABMR, n (%) | 4 (17%) | 11 (14%) | 0.79 |
C4d-positive ABMR, n (%) | 11 (46%) | 24 (28%) | 0.09 |
Banff borderline lesion, n (%) | 3 (13%) | 16 (19%) | 0.48 |
TCMR + ABMR, n (%) | 4 (17%) | 7 (8%) | 0.22 |
Recurrent/de novo GN, n (%) | 1 (4%) | 5 (6%) | 0.75 |
CNI toxicity, n (%) | - | 3 (4%) | 0.35 |
BKV nephropathy, n (%) | - | 1 (1%) | 0.60 |
Diabetic nephropathy, n (%) | - | 1 (1%) | 0.60 |
Amyloidosis, n (%) | - | 1 (1%) | 0.60 |
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Caliskan, Y.; Ozluk, Y.; Kurashima, K.; Mirioglu, S.; Dirim, A.B.; Hurdogan, O.; Oto, O.A.; Syn, M.; Nazzal, M.; Jain, A.; et al. LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation. Genes 2024, 15, 773. https://doi.org/10.3390/genes15060773
Caliskan Y, Ozluk Y, Kurashima K, Mirioglu S, Dirim AB, Hurdogan O, Oto OA, Syn M, Nazzal M, Jain A, et al. LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation. Genes. 2024; 15(6):773. https://doi.org/10.3390/genes15060773
Chicago/Turabian StyleCaliskan, Yasar, Yasemin Ozluk, Kento Kurashima, Safak Mirioglu, Ahmet Burak Dirim, Ozge Hurdogan, Ozgur Akin Oto, Marzena Syn, Mustafa Nazzal, Ajay Jain, and et al. 2024. "LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation" Genes 15, no. 6: 773. https://doi.org/10.3390/genes15060773
APA StyleCaliskan, Y., Ozluk, Y., Kurashima, K., Mirioglu, S., Dirim, A. B., Hurdogan, O., Oto, O. A., Syn, M., Nazzal, M., Jain, A., Edwards, J., Yazici, H., & Lentine, K. L. (2024). LIM Zinc Finger Domain Containing 1 Risk Genotype of Recipient Is Associated with Renal Tubular Inflammation in Kidney Transplantation. Genes, 15(6), 773. https://doi.org/10.3390/genes15060773