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01-11-2020 | Calcineurin Inhibitors | Original Article

Characterizing the frequency of modifiable histological changes observed on surveillance biopsies in pediatric kidney allograft recipients

Authors: James D. Odum, Alexander Kats, Judith Sebestyen VanSickle, Vimal Chadha, Brenda Brewer, Vincent S. Staggs, Bradley A. Warady

Published in: Pediatric Nephrology | Issue 11/2020

Abstract

Background

Rejection is responsible for just under 50% of graft loss in the pediatric kidney transplant population. Early identification and treatment of allograft injury, specifically modifiable pathologies such as subclinical rejection (SCR), calcineurin inhibitor toxicity, and BK virus nephropathy, may improve allograft survival. Protocol surveillance biopsy (SB) currently offers the earliest opportunity for targeted interventions.

Methods

This is a single-center retrospective review of 215 kidney SBs obtained from 2008 to 2016 in 97 pediatric kidney transplant recipients. SBs were obtained at 6, 12, and 24 months post-transplantation. Frequency of abnormal histologic findings, estimated glomerular filtration rate at time of SB, and SB-related complications were recorded. Data were analyzed to investigate possible time trends and the presence of demographic or clinical associations with abnormal histologic findings.

Results

Potentially modifiable histologic findings were seen in 38.1% of all SBs. SCR was found with increasing frequency across all time points with an estimated 49% increase in the odds of a SCR finding per additional 6 months post-transplantation (aOR 1.49, 95% CI 1.06–2.09, p = 0.022). Among follow-up biopsies in patients who underwent treatment for SCR, 50% had no SCR and 18.8% showed histologic improvement. The complication rate associated with SB was 1.9% (4/215 SBs) and consisted of only minor complications.

Conclusions

SBs are safe and offer the opportunity to identify and treat modifiable histologic changes in the pediatric kidney transplant population. The performance of SBs for up to 2 years after transplantation can have meaningful clinical impact.

National Data - OPTN. https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. Accessed 24 Oct 2019

Karcz M, Kusztal M, Boratyńska M, Klinger M (2018) Very long-term survival of the transplanted kidney-characteristics of recipients. Transplant Proc 50:1730–1732. https://doi.org/10.1016/j.transproceed.2018.02.114CrossRefPubMed

Sert I, Yavascan Ö, Tugmen C, Orhan DK, Kilinc S, Dogan SM, Bal A, Kebabci E, Alparslan C, Karaca C, Aksu N (2013) A retrospective analysis of long-term graft survival in 61 pediatric renal transplant recipients: a single-center experience. Ann Transplant 18:497–504. https://doi.org/10.12659/AOT.889117CrossRefPubMed

Naderi G, Latif A, Karimi S, Tabassomi F, Esfahani ST (2017) The long-term outcome of pediatric kidney transplantation in Iran: results of a 25-year single-center cohort study. Int J Organ Transplant Med 8:85–96PubMedPubMedCentral

Hebert SA, Swinford RD, Hall DR, Au JK, Bynon JS (2017) Special considerations in pediatric kidney transplantation. Adv Chronic Kidney Dis 24:398–404. https://doi.org/10.1053/j.ackd.2017.09.009CrossRefPubMed

Graves RC, Fine RN (2016) Kidney retransplantation in children following rejection and recurrent disease. Pediatr Nephrol 31:2235–2247CrossRef

Cihan Y, Kanzelmeyer N, Drube J, Kreuzer M, Lerch C, Hennies I, Froede K, Verboom M, Ahlenstiel-Grunow T, Pape L (2017) Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation. Pediatr Nephrol 32:2133–2142. https://doi.org/10.1007/s00467-017-3725-1CrossRefPubMed

Moreso F, Ibernon M, Gomà M, Carrera M, Fulladosa X, Hueso M, Gil-Vernet S, Cruzado JM, Torras J, Grinyó SD (2006) Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss. Am J Transplant 6:747–752. https://doi.org/10.1111/j.1600-6143.2005.01230.xCrossRefPubMed

Kanzelmeyer NK, Ahlenstiel T, Drube J, Froede K, Kreuzer M, Broecker V, Ehrich JHH, Melk A, Pape L (2010) Protocol biopsy-driven interventions after pediatric renal transplantation. Pediatr Transplant 14:1012–1018. https://doi.org/10.1111/j.1399-3046.2010.01399.xCrossRefPubMed

10.

Seikku P, Krogerus L, Jalanko H, Holmberg C (2005) Better renal function with enhanced immunosuppression and protocol biopsies after kidney transplantation in children. Pediatr Transplant 9:754–762CrossRef

11.

Gordillo R, Munshi R, Monroe EJ, Shivaram GM, Smith JM (2019) Benefits and risks of protocol biopsies in pediatric renal transplantation. Pediatr Nephrol 34:593–598. https://doi.org/10.1007/s00467-018-3959-6CrossRefPubMed

12.

Rose EM, Kennedy SE, Mackie FE (2016) Surveillance biopsies after paediatric kidney transplantation: a review. Pediatr Transplant 20:748–755. https://doi.org/10.1111/petr.12733CrossRefPubMed

13.

Zotta F, Guzzo I, Morolli F, Diomedi-Camassei F, Strologo LD (2018) Protocol biopsies in pediatric renal transplantation: a precious tool for clinical management. Pediatr Nephrol 33:2167–2175. https://doi.org/10.1007/s00467-018-4007-2CrossRefPubMed

14.

Rush D, Arlen D, Boucher A, Busque S, Cockfield SM, Girardin C, Knoll G, Lachance JG, Landsberg D, Shapiro J, Shoker A, Yilmaz Y (2007) Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: a randomized study. Am J Transplant 7:2538–2545. https://doi.org/10.1111/j.1600-6143.2007.01979.xCrossRefPubMed

15.

Mehta R, Sood P, Hariharan S (2016) Subclinical rejection in renal transplantation: reappraised. Transplantation 100:1610–1618. https://doi.org/10.1097/TP.0000000000001163CrossRefPubMed

16.

Henderson LK, Nankivell BJ, Chapman JR (2011) Surveillance protocol kidney transplant biopsies: their evolving role in clinical practice. Am J Transplant 11:1570–1575. https://doi.org/10.1111/j.1600-6143.2011.03677.xCrossRefPubMed

17.

Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, Castro MCR, David DSR, David-Neto E, Bagnasco SM, Cendales LC, Cornell LD, Demetris AJ, Drachenberg CB, Farver CF, Farris AB III, Gibson IW, Kraus E, Liapis H, Loupy A, Nickeleit V, Randhawa P, Rodriguez ER, Rush D, Smith RN, Tan CD, Wallace WD, Mengel M (2014) Banff 2013 Meeting report: inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 14:272–283. https://doi.org/10.1111/ajt.12590CrossRefPubMed

18.

Kambham N, Nagarajan S, Shah S, Li L, Salvatierra O, Sarwal MM (2007) A novel, semiquantitative, clinically correlated calcineurin inhibitor toxicity score for renal allograft biopsies. Clin J Am Soc Nephrol 2:135–142. https://doi.org/10.2215/CJN.01320406CrossRefPubMed

19.

Nickeleit V, Singh HK, Randhawa P, Drachenberg CB, Bhatnagar R, Bracamonte E, Chang A, Chon WJ, Dadhania D, Davis VG, Hopfer H, Mihatsch MJ, Papadimitriou JC, Schaub S, Stokes MB, Tungekar MF, Seshan SV (2018) The Banff Working Group Classification of Definitive Polyomavirus Nephropathy: morphologic definitions and clinical correlations. J Am Soc Nephrol 29:680–693. https://doi.org/10.1681/ASN.2017050477CrossRefPubMed

20.

Mian AN, Schwartz GJ (2017) Measurement and estimation of glomerular filtration rate in children. Adv Chronic Kidney Dis 24:348–356. https://doi.org/10.1053/j.ackd.2017.09.011CrossRefPubMedPubMedCentral

21.

de Souza V, Cochat P, Rabilloud M, Selistre L, Wagner M, Hadj-Aissa A, Dolomanova O, Ranchin B, Iwaz J, Dubourg L (2015) Accuracy of different equations in estimating GFR in pediatric kidney transplant recipients. Clin J Am Soc Nephrol 10:463–470. https://doi.org/10.2215/CJN.06300614CrossRefPubMedPubMedCentral

22.

Selistre L, De Souza V, Cochat P, Antonello ICF, Hadj-Aissa A, Ranchin B, Dolomanova O, Varennes A, Beyerle F, Bachetta J, Dubourg L (2012) GFR estimation in adolescents and young adults. J Am Soc Nephrol 23:989–996. https://doi.org/10.1681/ASN.2011070705CrossRefPubMed

23.

Selistre L, Rabilloud M, Cochat P, de Souza V, Iwaz J, Lemoine S, Beyerle F, Poli-de-Figueiredo CE, Dubourg L (2016) Comparison of the Schwartz and CKD-EPI equations for estimating glomerular filtration rate in children, adolescents, and adults: a retrospective cross-sectional study. PLoS Med 13:e1001979. https://doi.org/10.1371/journal.pmed.1001979CrossRefPubMedPubMedCentral

24.

Alkandari O, Hebert D, Langlois V, Robinson LA, Parekh RS (2017) Validation of serum creatinine-based formulae in pediatric renal transplant recipients. Pediatr Res 82:1000–1006. https://doi.org/10.1038/pr.2017.209CrossRefPubMed

25.

Birk PE (2012) Surveillance biopsies in children post-kidney transplant. Pediatr Nephrol 27:753–760. https://doi.org/10.1007/s00467-011-1969-8CrossRefPubMed

26.

Dharnidharka VR, Vyas N, Gaut JP, Walther L, Hmiel SP (2018) The utility of surveillance biopsies in pediatric kidney transplantation. Pediatr Nephrol 33:889–895. https://doi.org/10.1007/s00467-017-3864-4CrossRefPubMed

27.

Birk PE, Blydt-Hansen TD, Dart AB, Kaita LM, Proulx C, Taylor G (2007) Low incidence of adverse events in outpatient pediatric renal allograft biopsies. Pediatr Transplant 11:196–200CrossRef

28.

Nazario M, Nicoara O, Becton L, Self S, Hill J, Mack E, Evans M, Twombley K (2018) Safety and utility of surveillance biopsies in pediatric kidney transplant patients. Pediatr Transplant 22:e13178. https://doi.org/10.1111/petr.13178CrossRefPubMed

29.

Rush DN, Henry SF, Jeffery JR, Schroeder TJ, Gough J (1994) Histological findings in early routine biopsies of stable renal allograft recipients. Transplantation 57:208–211CrossRef

30.

Rush D (2006) Protocol transplant biopsies: an underutilized tool in kidney transplantation. Clin J Am Soc Nephrol 1:138–143. https://doi.org/10.2215/CJN.00390705CrossRefPubMed

31.

Foster BJ, Dahhou M, Zhang X, Platt RW, Samuel SM, Hanley JA (2011) Association between age and graft failure rates in young kidney transplant recipients. Transplantation 92:1237. https://doi.org/10.1097/TP.0b013e31823411d7CrossRefPubMed

32.

Tanabe T (2014) The value of long-term protocol biopsies after kidney transplantation. Nephrology (Carlton) 19(Suppl 3):2–5. https://doi.org/10.1111/nep.12253CrossRef

33.

Cosio FG, Grande JP, Wadei H, Larson TS, Griffin MD, Stegall MD (2005) Predicting subsequent decline in kidney allograft function from early surveillance biopsies. Am J Transplant 5:2464–2472. https://doi.org/10.1111/j.1600-6143.2005.01050.xCrossRefPubMed

34.

Stegall MD, Park WD, Larson TS, Gloor JM, Cornell LD, Sethi S, Dean PG, Prieto M, Amer H, Textor S, Schwab T, Cosio FG (2011) The histology of solitary renal allografts at 1 and 5 years after transplantation. Am J Transplant 11:698–707. https://doi.org/10.1111/j.1600-6143.2010.03312.xCrossRefPubMed

35.

Hergesell O, Felten H, Andrassy K, Kühn K, Ritz E (1998) Safety of ultrasound-guided percutaneous renal biopsy-retrospective analysis of 1090 consecutive cases. Nephrol Dial Transplant 13:975–977. https://doi.org/10.1093/ndt/13.4.975CrossRefPubMed

36.

Hassler J, Tanriover B, Ariyamutu V, Burguete D, Hendricks AR, Torrealba JR (2019) 2013 Banff criteria for acute antibody-mediated rejection are superior to 2007 Banff criteria in the diagnosis and assessment of renal allograft outcomes. Transplant Proc 51:1791–1795. https://doi.org/10.1016/j.transproceed.2019.04.060CrossRefPubMed

37.

Chua A, Cramer C, Moudgil A, Martz K, Smith J, Blydt-Hansen T, Neu A, Dharnidharka VR (2019) Kidney transplant practice patterns and outcome benchmarks over 30 years: the 2018 report of the NAPRTCS. Pediatr Transplant 23:e13597. https://doi.org/10.1111/petr.13597CrossRefPubMed

Title: Characterizing the frequency of modifiable histological changes observed on surveillance biopsies in pediatric kidney allograft recipients
Authors: James D. Odum
Alexander Kats
Judith Sebestyen VanSickle
Vimal Chadha
Brenda Brewer
Vincent S. Staggs
Bradley A. Warady
Publication date: 01-11-2020
Publisher: Springer Berlin Heidelberg
Keyword: Calcineurin Inhibitors
Published in: Pediatric Nephrology / Issue 11/2020
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-020-04624-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Characterizing the frequency of modifiable histological changes observed on surveillance biopsies in pediatric kidney allograft recipients

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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