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Cytopenias in pediatric kidney transplant recipients: preceding factors and clinical consequences

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Abstract

Background

Kidney trans plantation is associated with secondary complications, including the risk of developing posttransplant cytopenias. This study aimed to evaluate the characteristics, identify predictors, and assess the management and consequences of cytopenias in the pediatric kidney transplant population.

Methods

This is a single-center retrospective analysis of 89 pediatric kidney transplant recipients. Possible factors preceding cytopenias were compared with the goal of recognizing predictors for posttransplant cytopenias. Posttransplant neutropenias were analyzed for the total study period and separately for the period beyond 6 months posttransplant (late neutropenias), to rule out confounding influences of induction and initial intensive therapy.

Results

Sixty patients (67%) developed at least one episode of posttransplant cytopenia. All episodes of posttransplant thrombocytopenias were mild or moderate. Posttransplant infections and graft rejection were found to be significant predictors for thrombocytopenia (HR 6.06, 95% CI 1.6–22.9, and HR 5.82, 95% CI 1.27–26.6, respectively). A total of 30% of posttransplant neutropenias were severe (ANC ≤ 500). Pretransplant dialysis and posttransplant infections were significant predictors for late neutropenias (HR 11.2, 95% CI 1.45–86.4, and HR 3.32, 95% CI 1.46–7.57, respectively). Graft rejection occurred in 10% of patients with cytopenia, all following neutropenia, within 3 months from cytopenia appearance. In all such cases, mycophenolate mofetil dosing had been held or reduced prior to rejection.

Conclusions

Posttransplant infections are substantial contributors to developing posttransplant cytopenias. Preemptive transplantation appears to reduce risk of late neutropenia, the accompanying reduction in immunosuppressive therapy, and the ensuing risk of graft rejection. An alternative response to neutropenia, possibly using granulocyte colony stimulating factor, may diminish graft rejection.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Dharnidharka VR, Fiorina P, Harmon WE (2014) Kidney transplantation in children. N Engl J Med 371:549–558. https://doi.org/10.1056/NEJMra1314376

    Article  CAS  PubMed  Google Scholar 

  2. Davidovits M, Reisman L, Cleper R, Bar-Nathan N, Krause I, Dagan A, Zanhendler N, Chodick G, Hocherman O, Mor M, Aisner S, Mor E (2021) Long-term outcomes during 37 years of pediatric kidney transplantation: a cohort study comparing ethnic groups. Pediat Nephrol 36:1881–1888. https://doi.org/10.1007/s00467-020-04908-6

    Article  PubMed  Google Scholar 

  3. Saeed B (2012) Pediatric renal transplantation. Int J Organ Transplant Med 3:62–73

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Sacca E, Hazza I (2003) Pre-emptive pediatric renal transplantation. Saudi J Kidney Dis Transplant 14:442–450

    Google Scholar 

  5. McDonald SP, Craig JC (2004) Long-term survival of children with end-stage renal disease. N Engl J Med 350:2654–2662. https://doi.org/10.1056/NEJMoa031643

    Article  CAS  PubMed  Google Scholar 

  6. Van Arendonk KJ, Boyarsky BJ, Orandi BJ, James NT, Smith JM, Colombani PM, Segev DL (2014) National trends over 25 years in pediatric kidney transplant outcomes. Pediatrics 133:594–601. https://doi.org/10.1542/peds.2013-2775

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zaza G, Tomei P, Granata S, Boschiero L, Lupo A (2014) Monoclonal antibody therapy and renal transplantation: focus on adverse effects. Toxins 6:869–891. https://doi.org/10.3390/toxins6030869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kuypers DRJ, Claes K, Evenepoel P, Maes B, Vanrenterghem Y (2004) Clinical efficacy and toxicity profile of tacrolimus and mycophenolic acid in relation to combined long-term pharmacokinetics in de novo renal allograft recipients. Clin Pharmacol Ther 75:434–447. https://doi.org/10.1016/j.clpt.2003.12.009

    Article  CAS  PubMed  Google Scholar 

  9. Smith A, Couvillion R, Zhang R, Killackey M, Buell J, Lee B, Saggi BH, Paramesh AS (2014) Incidence and management of leukopenia/neutropenia in 233 kidney transplant patients following single dose alemtuzumab induction. Transplant Proc 46:3400–3404. https://doi.org/10.1016/j.transproceed.2014.07.070

    Article  CAS  PubMed  Google Scholar 

  10. Brum S, Nolasco F, Sousa J, Ferreira A, Possante M, Pinto JR, Barroso E, Santos JR (2008) Leukopenia in kidney transplant patients with the association of valganciclovir and mycophenolate mofetil. Transplant Proc 40:752–754. https://doi.org/10.1016/j.transproceed.2008.02.048

    Article  CAS  PubMed  Google Scholar 

  11. Vinson A, Teixeira A, Kiberd B, Tennankore K (2021) Predictors and complications of post kidney transplant leukopenia. Prog Transplant 31:249–256. https://doi.org/10.1177/15269248211024614

    Article  PubMed  Google Scholar 

  12. Luan FL, Kommareddi M, Ojo AO (2011) Impact of cytomegalovirus disease in D+/R– kidney transplant patients receiving 6 months low-dose valganciclovir prophylaxis. Am J Transplant 11:1936–1942. https://doi.org/10.1111/j.1600-6143.2011.03611.x

    Article  CAS  PubMed  Google Scholar 

  13. Keisu M, Wiholm B, Palmblad J (1999) Trimethoprim-sulphamethoxazole-associated blood dyscrasias. ten years’experience of the Swedish spontaneous reporting system. J Intern Med 228:353–360. https://doi.org/10.1111/j.1365-2796.1990.tb00245.x

    Article  Google Scholar 

  14. Golde DW, Bersch N, Quan SG (1978) Trimethoprim and sulphamethoxazole inhibition of haematopoiesis in vitro. Br J Haematol 40:363–367. https://doi.org/10.1111/j.1365-2141.1978.tb05807.x

    Article  CAS  PubMed  Google Scholar 

  15. Smith EP (2010) Hematologic disorders after solid organ transplantation. Hematol 1:281–286. https://doi.org/10.1182/asheducation-2010.1.281

    Article  Google Scholar 

  16. Zafrani L, Truffaut L, Kreis H, Etienne D, Rafat C, Lechaton S, Anglicheau D, Zuber J, Ciroldi M, Thervet E, Snanoudj R, Mamzer MF, Martinez F, Timsit MO, Bergougnoux L, Legendre C (2009) Incidence, risk factors and clinical consequences of neutropenia following kidney transplantation: a retrospective study. Am J Transplant 9:1816–1825. https://doi.org/10.1111/j.1600-6143.2009.02699.x

    Article  CAS  PubMed  Google Scholar 

  17. Yang Y, Yu B, Chen Y (2015) Blood disorders typically associated with renal transplantation. Front Cell Dev Biol 3:18. https://doi.org/10.3389/fcell.2015.00018

    Article  PubMed  PubMed Central  Google Scholar 

  18. Khalil MAM, Khalil MAU, Khan TFT, Tan J (2018) Drug-induced hematological cytopenia in kidney transplantation and the challenges it poses for kidney transplant physicians. J Transplant 2018:9429265. https://doi.org/10.1155/2018/9429265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xie L, He S, Fu L, Ashok K, Huang Z, Wang L, Lin T (2013) The prevalence and risk factors of thrombocytopenia after living-related renal transplantation in Chinese adult recipients. Transplant Proc 45:197–199. https://doi.org/10.1016/j.transproceed.2012.09.113

    Article  CAS  PubMed  Google Scholar 

  20. Jafari A, Najivash P, Khatami M-R, Dashti-Khavidaki S (2017) Cytopenia occurrence in kidney transplant recipients within early post-transplant period. J Res Pharm Pract 6:31–39. https://doi.org/10.4103/2279-042X.200983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jarasvaraparn C, Choudhury S, Rusch C, Nadler M, Liss KHH, Stoll J, Hmiel S, Khan A, Doyle M, Kulkarni S (2022) Characteristics, risk factors, and outcomes of neutropenia after liver or kidney transplantation in children. Pediatr Transplant 26:14131. https://doi.org/10.1111/petr.14131

    Article  CAS  Google Scholar 

  22. Mavrakanas TA, Fournier MA, Clairoux S, Amiel JA, Tremblay ME, Vinh DC, Coursol C, Thirion DJG, Cantarovich M (2017) Neutropenia in kidney and liver transplant recipients: risk factors and outcomes. Clin Transplant 31:(10). https://doi.org/10.1111/ctr.13058

  23. Solez K, Axelsen RA, Benediktsson H, Burdick JF, Cohen AH, Colvin RB, Croker BP, Droz D, Dunnill MS, Halloran PF (1993) International standardization of criteria for the histologic diagnosis of renal allograft rejection: the Banff working classification of kidney transplant pathology. Kidney Int 44:411–422. https://doi.org/10.1038/ki.1993.259

    Article  CAS  PubMed  Google Scholar 

  24. Mitsnefes MM, Subat-Dezulovic M, Khoury PR, Goebel J, Strife CF (2005) Increasing incidence of post-kidney transplant anemia in children. Am J Transplant 5:1713–1718. https://doi.org/10.1111/j.1600-6143.2005.00919.x

    Article  PubMed  Google Scholar 

  25. Krause I, Davidovits M, Tamary H, Yutcis M, Dagan A (2016) Anemia and markers of erythropoiesis in pediatric kidney transplant recipients compared to children with chronic renal failure. Pediatr Transplant 20:958–962. https://doi.org/10.1111/petr.12792

    Article  CAS  PubMed  Google Scholar 

  26. Chen G, Gu J, Qiu J, Wang C, Fei J, Deng S, Li J, Huang G, Fu Q, Chen L (2013) Efficacy and safety of thymoglobulin and basiliximab in kidney transplant patients at high risk for acute rejection and delayed graft function. Exp Clin Transplant 11:310–314. https://doi.org/10.6002/ect.2012.0103

    Article  PubMed  Google Scholar 

  27. Becker-Cohen R, Ben-Shalom E, Rinat C, Feinstein S, Geylis M, Frishberg Y (2015) Severe neutropenia in children after renal transplantation: incidence, course, and treatment with granulocyte colon-stimulating factor. Pediatr Nephrol 30:2029–2036. https://doi.org/10.1007/s00467-015-3113-7

    Article  PubMed  Google Scholar 

  28. Hurst FP, Belur P, Nee R, Agodoa LY, Patel P, Abbott KC, Jindal RM (2011) Poor outcomes associated with neutropenia after kidney transplantation: analysis of United States Renal Data System. Transplantation 92:36–40. https://doi.org/10.1097/TP.0b013e31821c1e70

    Article  PubMed  Google Scholar 

  29. Gupta N, Lawrence RM, Nguyen C, Modica RF (2015) Increased prevalence of polyomavirus BK viruria that correlates with thrombocytopenia in patients with systemic lupus erythematosus on intensive immunosuppressive therapy. Autoimmunity 42:216–223. https://doi.org/10.1080/08916930802709125

    Article  CAS  Google Scholar 

  30. Wang W, Yin H, Li XB, Hu XP, Yang XY, Liu H, Ren L, Wang Y, Zhang XD (2012) A retrospective comparison of the efficacy and safety in kidney transplant recipients with basiliximab and anti-thymocyte globulin. Chin Med J (Engl) 125:1135–1140

    CAS  PubMed  Google Scholar 

  31. Garcia CD, Bittencourt VB, Rohde RW, Dickel S, Pires I, Tumba K, Vitola SP, de Souza V, Wagner M, Garcia VD (2015) Pre-emptive pediatric kidney transplantation or not? Transplant Proc 47:954–957. https://doi.org/10.1016/j.transproceed.2015.03.019

    Article  CAS  PubMed  Google Scholar 

  32. Bock ME, Cohn RA (2010) Editorial: pre-emptive kidney transplantation - just do it!! Pediatr Transplant 14:561–564. https://doi.org/10.1111/j.1399-3046.2010.01347.x

    Article  PubMed  Google Scholar 

  33. Vats AN, Donaldson L, Fine RN, Chavers BM (2000) Pretransplant dialysis status and outcome of renal transplantation in north american children : a NAPRTCS study North American Pediatric Renal Transplant Cooperative Study. Transplantation 69:1414–1419. https://doi.org/10.1097/00007890-200004150-00035

    Article  CAS  PubMed  Google Scholar 

  34. Cendoroglo M, Jaber BL, Balakrishnan VS, Perianayagam M, King AJ, Pereira BJG (1999) Neutrophil apoptosis and dysfunction in uremia. J Am Soc Nephrol 10:93–100. https://doi.org/10.1681/ASN.V10193

    Article  CAS  PubMed  Google Scholar 

  35. Lemesch S, Ribitsch W, Schilcher G, Spindelböck W, Hafner-Gießauf H, Marsche G, Pasterk L, Payerl D, Schmerböck B, Tawdrous M, Rosenkranz AR, Stiegler P, Kager G, Hallström S, Oettl K, Eberhard K, Horvath A, Leber B, Stadlbauer V (2016) Mode of renal replacement therapy determines endotoxemia and neutrophil dysfunction in chronic kidney disease. Sci Rep 6:34534. https://doi.org/10.1038/srep34534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Woods GN, Ewing SK, Sigurdsson S, Kado DM, Ix JH, Hue TF, Eiriksdottir G, Xu K, Gudnason V, Lang TF, Vittinghoff E, Harris TB, Rosen CJ, Li X, Schwartz AV (2018) Chronic kidney disease is associated with greater bone marrow adiposity. J Bone Miner 33:2158–2164. https://doi.org/10.1002/jbmr.3562

    Article  CAS  Google Scholar 

  37. Clayton PA, McDonald SP, Russ GR, Chadban SJ (2019) Long-term outcomes after acute rejection in kidney transplant recipients: an ANZDATA analysis. J Am Soc Nephrol 30:1697–1707. https://doi.org/10.1681/ASN.2018111101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Jamil B, Nicholls K, Becker GJ, Walker RG (1999) Impact of acute rejection therapy on infections and malignancies in renal transplant recipients. Transplantation 68:1597–1603. https://doi.org/10.1097/00007890-199911270-00027

    Article  CAS  PubMed  Google Scholar 

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Author information

Author notes

  1. Shira Regev-Sadeh and Yael Borovitz equally contributed in the study.

Authors and Affiliations

  1. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shira Regev-Sadeh, Yael Borovitz, Orna Steinberg-Shemer, Oded Gilad & Joanne Yacobovich

  2. Nephrology Institute, Schneider Children’s Medical Center, Petach Tikva, Israel

    Yael Borovitz

  3. Department of Pediatric Hematology and Oncology, Schneider Children’s Medical Center, Petach Tikva, Israel

    Orna Steinberg-Shemer, Oded Gilad & Joanne Yacobovich

  4. Research Authority, Schneider Children’s Medical Center, Petach Tikva, Israel

    Shoval Shoham

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  1. Shira Regev-Sadeh
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Contributions

Ms. Regev-Sadeh and Dr. Borovitz designed the data collection instruments, collected data, wrote the main manuscript text, and reviewed and revised the manuscript. Dr. Steinberg-Shemer and Dr. Oded Gilad participated in data interpretation and reviewed the manuscript. Ms. Shoham carried out the statistical analyses. Dr. Yacobovich conceptualized and designed the study, advised on the statistical analysis, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Yael Borovitz.

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Ethical approval

The study was approved by the local ethics committee in accordance with GCP guidelines. Due to the retrospective nature, patient/guardian consent was not required.

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The authors declare no competing interests.

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Regev-Sadeh, S., Borovitz, Y., Steinberg-Shemer, O. et al. Cytopenias in pediatric kidney transplant recipients: preceding factors and clinical consequences. Pediatr Nephrol 38, 3445–3454 (2023). https://doi.org/10.1007/s00467-023-05905-1

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