Subclinical acute rejections in protocol biopsies at 3 months after kidney transplantation

Česká verzia

Authors: I. Matl ¹; E. Honsová ²; A. Lodererová ²; V. Lánská ³; O. Viklický ¹
Authors place of work: Klinika nefrologie IKEM Praha, přednosta doc. MUDr. Ondřej Viklický, CSc. ¹; Pracoviště klinické a transplantační patologie IKEM Praha, přednostka prim. MUDr. Eva Honsová, Ph. D. ²; Oddělení lékařské statistiky IKEM Praha ³
Published in the journal: Vnitř Lék 2008; 54(11): 1054-1058
Category: Original Contributions

Summary

Aim:
The primary aim of the study was detection of subclinical acute rejection and borderline changes in protocol biopsies at 3 months after transplantation, and assessment of possible clinical and laboratory associations.

Methods:
Biopsy was carried out in 194 patients with stabilized graft function. Patients were treated with immunosuppressive regimen based on cyclosporine A (n = 34), tacrolimus (n = 152), or sirolimus/everolimus (n = 10). Samples were processed by standard paraffine technique, and stained according to laboratory protocol. All samples were tested by immunofluorescence or immunohistochemical procedures for C4d presence as a sign of humoral rejection.

Results:
Of 192 representative samples, subclinical acute rejection and borderline changes were found in 24 samples (12.5%). In patients with this finding, the mean serum creatinine was significantly higher (185.2 ± 2.2 µmol/L), than in patients with normal finding (128.2 ± 28.3 µmol/L) p < 0.001. Using the ROC curve analysis of serum creatinine, the cut‑off point 170 µmol/L was found to discriminate normal findings from subclinical rejection and borderline changes. A significant correlation between acute rejections before protocol biopsy and subclinical acute rejections together with borderline changes in protocol biopsy was found. C4d positivity was found in 6 samples. Immunosuppressive therapy (cyclosporine versus tacrolimus) did not have any impact on subclinical acute rejections and borderline changes prevalence.

Conclusions:
The main conclusion of this study is a finding, that acute rejection early after renal transplantation and serum creatinine ≥ 170 µmol/l at three months after transplantation are risks for development of subclinical acute rejection, even of humoral type, or borderline changes.

Key words:
kidney transplantation – protocol biopsy – subclinical acute rejection – borderline changes – immunosuppressive therapy

Zdroje

1. Burdick JF, Beschorner WE, Smith WJ et al. Characteristics of early routine renal allograft biopsies. Transplantation 1984; 38: 679–684.

2. Choi BS, Shin MJ, Shin SJ et al. Clinical significance of an early protocol biopsy in living-donor renal transplantation: ten-year experience at a single center. Am J Transplant 2005; 5: 1354–1360.

3. Furness PN, Philpott CM, Chorbadjian MT et al. Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates. Transplantation 2003; 76: 969–973.

4. Gloor JM, Cohen AJ, Lager DJ et al. Subclinical rejection in tacrolimus‑treated renal transplant recipients. Transplantation 2002; 73: 1965–1968.

5. Helanterä I, Ortiz F, Helin H et al. Timing and value of protocol biopsies in well‑matched kidney transplant recipients – a clinical and histopathologic analysis. Transplant Int 2007; 20: 982–990.

6. Horčička V Jr, Krejčí K, Zadražil J et al. Arteriovenózní píštěl jako komplikace bio-psie ledvin. Vnitř Lék 2002; 48: 432–437.

7. Kanetsuna Y, Yamaguchi Y, Toma H et al. Histological evaluation of renal allograft protocol biopsies in the early period and 1 year after transplantation. Clin Transplant 2003; 17 (Suppl 10): 25–29.

8. Kee TYS, Chapman JR, Connell PJ et al. Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation 2006; 82: 36–42.

9. Koo DD, Roberts IS, Quiroga I et al. C4d deposition in early allograft protocol biopsies. Transplantation 2004; 78: 398–403.

10. Legendre C, Thervet E, Skhiri H et al. Histologic features of chronic allograft nephropathy revealed by protocol biopsies in kidney transplant recipients. Transplantation 1998; 65: 1506–1509.

11. Matl I, Viklický O, Voska L et al. Naše první zkušenosti s protokolární bio-psií transplantovaných ledvin. Čas Lék Čes 2004; 143: 253–256.

12. Mengel M, Gwinner W, Schwarz A et al. Infiltrates in protocol biopsies from renal allografts. Amer J Transplantation 2007; 7: 356–365.

13. Moreso F, Alperovich G, Fulladosa X et al. Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules. Transplant Proc 2003; 35: 1666–1668.

14. Nankivell BJ, Fenton-Lee CA, Kuypers DRJ et al. Effect of histological damage on long‑term kidney transplant outcome. Transplantation 2001; 71: 515–523.

15. Nankivell BJ, Borrows RJ, Fung CLS et al. Natural history, risk factors, and impact of subclinical rejection in kidney transplantation. Transplantation 2004; 78: 242–249.

16. Nankivell BJ, Chapman JR. The significance of subclinical rejection and the value of protocol biopsies. Amer J Transplantation 2006; 6: 2006–2012.

17. Ponticelli C, Banfi G. The case against protocol kidney biopsies. Transplant Proc 2002; 34: 1716–1718.

18. Racusen LC, Colvin RB, Solez K. An-tibody-mediated rejection criteria – an addition to the Banff ’97 classification of renal allograft rejection. Amer J Transplantation 2003; 3: 708–714.

19. Racusen LC, Solez K, Colvin B et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999; 55: 713–723.

20. Rush D, Jeffery JT, Gough J. Sequential protocol biopsies in renal transplant patients. Transplantation 1995; 59: 511–514.

21. Rush D, Nickerson P, Gough J et al. Beneficial effects of treatment of early sub-clinical rejection: a randomized study. J Am Soc Nephrol 1998; 9: 2129–2134.

22. Scholten EM, Rowshani AT, Cremers S et al. Untreated rejection in 6-month protocol biopsy is not associated with fibrosis or with loss of graft function. J Am Soc Nephrol 2006; 17: 2622–2632.

23. Schück O, Smrčková I, Teplan V et al. Nová metoda stanovení glomerulární filtrace na podkladě sérové koncentrace kreatininu, močoviny a albuminu (MDRD). Vnitř Lék 2004; 50: 507–509.

24. Serón D, Moreso F, Ramón JM et al. Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy. Transplantation 2000; 69: 1849–1855.

25. Sund S, Hovig T, Reisaeter A et al. Complement activation in early protocol kidney graft biopsies after living-donor transplantation. Transplantation 2003; 75: 1204–1213.

26. Tichý T, Tichý M, Zadražil J et al. Histologické nálezy v protokolárních biopsiích transplantovaných ledvin. Čes Slov Patol 2003; 39: 11–16.

27. Veronese FV, Noronha IL, Manfro RC et al. Protocol biopsies in renal transplant patients: three years’ follow‑up. Transplant Proc 2002; 34: 500–501.