The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study

Authors

  • Galina Severova-Andreevska University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Ladislava Grcevska University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Gordana Petrushevska Institute of Pathology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Koco Cakalaroski Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Aleksandar Sikole University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Olivera Stojceva–Taneva University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Ilina Danilovska University Clinic of Nephrology, Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje
  • Ninoslav Ivanovski Medical Faculty, Ss Cyril and Methodius University of Skopje, Skopje

DOI:

https://doi.org/10.3889/oamjms.2018.162

Keywords:

Kidney transplantation, protocol biopsy, mixed rejection, ABMR

Abstract

INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR).

AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function.

MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun†were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used.

RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a “mixed†rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR +  IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease.

CONCLUSION: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Opelz G, Dohler B, Ruhenstroth A, et al. The Collaborative Transplant Study Registry. Transplant Rev. 2013; 27: 43-45. https://doi.org/10.1016/j.trre.2013.01.004 PMid:23465693

Matas AJ, Gillingham KJ, Humar A, et al. 2,202 Kidney Transplant Recipients with 10 Years of Graft Function: What Happens Next? Am J Transplant. 2008; 8: 2410- 2419. https://doi.org/10.1111/j.1600-6143.2008.02414.x PMid:18925907 PMCid:PMC2766174

Wang HJ, Skeans MA, Israni AK. Current Status of Kidney Transplant Outcomes: Dying to Survive. Adv Chronic Kidney Dis. 2016; 23: 281-266. https://doi.org/10.1053/j.ackd.2016.07.001 PMid:27742381

Traynor C, Jenkonson A, Williams Y, et al. Twenty-Year Survivors of Kidney Transplantation. Am J Transplant. 2012; 12: 3289-3295. https://doi.org/10.1111/j.1600-6143.2012.04236.x PMid:22947033

McCaughan JA, Courtney AE. The Clinical Cours of Kidney Transplant Recipients After 20 Years of Graft Function. Am J Transplant. 2015; 15: 734-740. https://doi.org/10.1111/ajt.13041 PMid:25683898

Tasaki M, Saito K, Nagawa Y, et al. 20-Year Analysis of Kidney Transplantation: A single Center in Japan. Transplant Proc. 2014; 46: 437-441. https://doi.org/10.1016/j.transproceed.2013.10.052 PMid:24655982

Archdecon P, Chan M, Neuland C, et al. Summary of FDA Antibody-Mediated Rejection Workshop. American Journal of Transplantation. 2011; 11: 896-906. https://doi.org/10.1111/j.1600-6143.2011.03525.x PMid:21521465

Puttarajappa C, Shapiro R, Tan H. Antibody – Mediated Rejection in Kidny Transplantation: A Review. Journal Of Transplantation. 2012; 2012.

Lefaucheur C, Koupya, Vernerey D, et al. Antibody-Mediated Vasular Rejection of Kidney Allografts: A Population-based Study. Lancet. 2013; 381: 313-319. https://doi.org/10.1016/S0140-6736(12)61265-3

Wiebe C, Gibson W, Blydt-Hansen, et al. Evolution and Clinical Pathologic Correlations of De Novo- Specific HLA Antibody Post Kidney Transplant. American Journal of Transplantation. 2012; 12:1157-1167. https://doi.org/10.1111/j.1600-6143.2012.04013.x PMid:22429309

Hill G, Nochy D, Bruneval P, et al. Donor-Specific Antibodies Accelerate Arteriosclerosis After Kiney Transplantation. J Am Soc Nephrol. 2011; 22: 975-983. https://doi.org/10.1681/ASN.2010070777 PMid:21493773 PMCid:PMC3083319

Loupy A, Hill G, Jordan S. The Impact of Donor – Specific anti-HLA Antibodies on Late Kidney Allograft Failure. Nature. 2012; 8: 348-357. https://doi.org/10.1038/nrneph.2012.81

Süsal C, Wettsten BS, Döhler B, et al. Associated of Kidney Graft Loss With De Novo Produced Donor-Specific an Non-Donor-Specific Antibodies Deteted by Single Antigen Testing. Transplantation. 2015; 99: 1976-1980. https://doi.org/10.1097/TP.0000000000000672 PMid:25769065

Naesens M, Lerut E. Calcineurin Inhibitor Nephrotoxicity in the Era of Antibody-Mediated Rejection. Transplantation. 2016; 100:1599-1560. https://doi.org/10.1097/TP.0000000000001244 PMid:27306528

Broecker V, Mengel M. The significance of histological diagnosis in renal allograft biopsies in 2014. Transplant Int. 2015; 28:136-145. https://doi.org/10.1111/tri.12446 PMid:25205033

Devadass WC, Vanikar VA, Nigam KL, et al. Evaluation of Renal Allograft Biopsies for Graft Dysfunction and Relevance of C4d Staining in Antibody Mediated Rejection. Journal of Clinical and Diagnosis Research. 2016; 10:11-15. https://doi.org/10.7860/JCDR/2016/16339.7433

Galichon P, Xu-Dubois YC, Finianos S, et al. Clinical and histological predictors of long-term kidney graft survival. Nephrol Dial Transplant. 2013; 28:1362-1370. https://doi.org/10.1093/ndt/gfs606 PMid:23348884

Garcia-Carro C, Dorje C, Asberg A, et al. Inflammation in Early Kidney Allograft Surveillance Biopsies With and Without Associated Tubulointerstitial Chronic Damage as a Predictor of Fibrosis Progression and Development of De-Novo Donor Specific Antibodies. Transplantation. 2016; 100: 1-6.

Seron D et Moreso F. Protocol Biopsies in Renal Transplantation : Prognostic Value of Structural Monitoring. Kidney Int. 2007; 72: 690-697. https://doi.org/10.1038/sj.ki.5002396 PMid:17597702

Henderson LK, Nankivell BJ, Chapman JR. Suveillance Protocol Kidney Transplant Biopsies: Their Evolving Role in Clinical Practice. Am J Transplant. 2011; 11:1570-1575. https://doi.org/10.1111/j.1600-6143.2011.03677.x PMid:21797971

Bachelet T, Couzi L, Lepreux S, et al. Kidney Intragraft Donor-Specific Antibodies as Determinant of Antibody-Mediated Lesions and Poor Graft Outcome. American Journal of Transplantation. 2013; 13:2855-2864. https://doi.org/10.1111/ajt.12438 PMid:24102857

Arias M, Seron D, Herrero I, et al. Subclinical Antibody mediated rejection. Transplantation. 2017; 101:S1-S18. https://doi.org/10.1097/TP.0000000000001735 PMid:28538291

El Ters M, Grande JL, Keddis MT, et al. Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies. Am J Transplant. 2013; 13:2334-2341. https://doi.org/10.1111/ajt.12370 PMid:23865852

Rush D. Protocol Transplant Biopsies: An Underutilized Tool in Kidney Transplantation. Clin J Am Nephrol. 2006; 1:138-143. https://doi.org/10.2215/CJN.00390705 PMid:17699200

Maluf DG, Mueller TF, Mas VR. Hidden Inflamatory molecular Signatures in Graft Kidney biopsies: Silenт Markers of Graft Rate American Journal of Transplantation. 2016; 16:1947-1948. https://doi.org/10.1111/ajt.13754 PMid:26880183

Eskandary F, Bond G, Kozakowski N, et al. Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection- Results of a Cross-Sectional Screening Study. Transplantation. 2016; 2016.

Masin Spasovska J, Spasovski G, Dzikova S, et al. PROTOCOL BIOPSIES IN Kidney Transplant findings as Prognostic Markers for Graft Function and Outcome. Transplant Proc. 2005; 37: 705-708. https://doi.org/10.1016/j.transproceed.2004.11.032 PMid:15848508

Wehmeier C, Amico P, Hirt-Minkovski P, et al. Acute Rejection Phenotypes in the Current Era of Immunosuppression: A Single-Centre Analysis. Transplantation Direct. 2017; 3.

Loupy A, Haas M, Solez K, et al. The BANFF 2015 Kidney Meeting Report: Current challenges in Rejection Classification and Prospects fro Adopting Molecular Pathology. Am J Transplant. 2017; 17:28-41. https://doi.org/10.1111/ajt.14107 PMid:27862883 PMCid:PMC5363228

Haas M, Sis B, Racusen L, et al. BANFF 2013 Meeting Report: Inclusion of C4d – negative Antibody-Mediated Rejection and Antibody-Associated Arterial Lesions. Am J Transplant. 2014; 14: 272-283. https://doi.org/10.1111/ajt.12590 PMid:24472190

Katsuma Ai, Yamakawa T, Yasuyuki N, et al. Histopathological findings in transplanted kidneys. Renal Replacement Therapy. 2017; 3:6. https://doi.org/10.1186/s41100-016-0089-0

Halloran FP, Lopez M, Baretto Pereira A. Identifying Subphenotypes of Antibody-Medaited Rejection in Kidney Transplants. A J Transplant. 2016; 16:908-920. https://doi.org/10.1111/ajt.13551 PMid:26743766

Haas M, Mirocha J, Reinsmoen N, et al. Differences in pathologic features and graft outcomes in antibody-mediated rejection of renal allografts due to persistent /recurrent versus de novo donor specific antibodies. Kidney Int. 2017; 91:729-737. https://doi.org/10.1016/j.kint.2016.10.040 PMid:28104301

Loupy A, Vernerey D, Tinel C, et al. Subclinical Rejection Phenotypes at 1 year Post-Transplant and Outcome of Kidney Allografts. J Am Soc Nephrol. 2015; 26:1-11. https://doi.org/10.1681/ASN.2014040399 PMid:25556173 PMCid:PMC4483584

Mehta R, Sood P and Hariharan S. Subclinical Rejection in Renal Transplantation: Reappraised. Transplantation. 2016; 100:1610-1618. https://doi.org/10.1097/TP.0000000000001163 PMid:26985747

Farris AB, Chan S, Climenhaga B, et al. BANFF Fibrosis Study: Multicenter Visual Assessment and Computerized Analysis of Interstitial Fibrosis in Kidney Biopsies. American Journal of Transplantation. 2014; 14:897-907. https://doi.org/10.1111/ajt.12641 PMid:24712330

Mengel M, Gwinner W, Schwarz A, et al. Infiltrates in Protocol Biopsies from Renal Allografts. Am J Transplant. 2007; 7:356-365. https://doi.org/10.1111/j.1600-6143.2006.01635.x PMid:17283485

Halloran FP, Chang J, Famulski K, et al. Disappearance of T Cell-Mediated Rejection Despiote Continued Antibody-Mediated Rejection in Late Kidney Transplant Recipients. J Am Soc Nephrol. 2015; 26:1711-1720. https://doi.org/10.1681/ASN.2014060588 PMid:25377077 PMCid:PMC4483591

O'Connell P, Zhang W, Menon M, et al. Biopsy transcriptome expression profiling to identify kidney transplants risk of chronic injury: a multicerntre, prospective study. Lancet. 2016; 388: 983-989. https://doi.org/10.1016/S0140-6736(16)30826-1

Lefaucheur C, Koupy a, Vernerey D et al. Antibody-Mediated Vasular Rejection of Kidney Allografts: A Population-based Study. Lncet. 2013; 381:313-319. https://doi.org/10.1016/S0140-6736(12)61265-3

Ishihara H, Ishida H, Unagami K, et al. Evaluation of Microvascular Inflammation in ABO- Incompatible Kidney Transplantation. Transplantation. 2017; 101:1423-1432. https://doi.org/10.1097/TP.0000000000001403 PMid:27495756

Published

2018-03-30

How to Cite

1.
Severova-Andreevska G, Grcevska L, Petrushevska G, Cakalaroski K, Sikole A, Stojceva–Taneva O, Danilovska I, Ivanovski N. The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study. Open Access Maced J Med Sci [Internet]. 2018 Mar. 30 [cited 2021 Jun. 25];6(4):606-12. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.162

Issue

Section

B - Clinical Sciences

Most read articles by the same author(s)

1 2 > >>