Clinical Significance of Protocol Biopsy Soon after Renal Transplantation

Seung-Young Oh; Il Min Sang; Sanghyun Ahn; Min Kim Suh; Daedo Park; Taejin Park; Chul Moon Kyung; Jongwon Ha; Joon Kim Sang

doi:10.4285/jkstn.2011.25.4.264

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Oh, Sang, Ahn, Suh, Park, Park, Kyung, Ha, and Sang: Clinical Significance of Protocol Biopsy Soon after Renal Transplantation

Original Article

J Korean Soc Transplant 2011;25(4):264-269.

Published online: 10 January 2011

DOI: https://doi.org/10.4285/jkstn.2011.25.4.264

Clinical Significance of Protocol Biopsy Soon after Renal Transplantation

Seung-Young Oh, M.D.¹, Il Min Sang, M.D.¹, Sanghyun Ahn, M.D.¹, Min Kim Suh, M.D.¹, Daedo Park, M.D.¹, Taejin Park, M.D.¹, Chul Moon Kyung, M.D.², Jongwon Ha, M.D.^1,³, Joon Kim Sang, M.D.^1,³

Departments of Surgery and Pathology, Seoul National University College of Medicine Korea

Departments of Transplantation Research Institute, Seoul National University Medical Research Center, Seoul Korea

Correspondence：Sang Joon Kim, Department of Surgery, Seoul National University Hospital, Yeongeon-dong, Jongno-gu, Seoul 110-719, Korea Tel: +82-2-2072-3088, Fax: +82-2-766-3975 E-mail: sjkimgs@plaza.snu.ac.kr

Received 18 October 2011 Revised 30 November 2011 Accepted 8 December 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Several studies reported that sub-clinical rejection (SCR) detected by a protocol biopsy soon after renal transplantation does permanent damage to a renal allograft, contributing to chronic allograft nephropathy (CAN). This article investigated the risk factors involved in SCR and the effects of treating SCR, and evaluated the clinical significance of a protocol biopsy soon after renal transplantation.

Methods

From January 2007 to June 2010, 253 patients received renal transplantation. Patients were divided into two groups according to whether or not they had undergone a protocol biopsy. To analyze the effect of SCR treatments, patients who were diagnosed with SCR were divided into two groups according to whether or not they had been treated with SCR. The patients who did not undertake a protocol biopsy were included in the untreated groups.

Results

Among 138 patients who undertook protocol biopsies, 65 patients (47.1%) showed SCR. In univariate analysis, both the number of HLA-DR mismatches (P=0.003) and not using Simulect (P=0.01) were identified as risk factors of SCR. In multivariate analysis, not using Simulect (P=0.006) was identified as an risk factor independent of SCR. δ GFR, subtracting GFR at 1 week from GFR at that point, showed significant differences between SCR-treated patients and untreated patients at 1, 3, 6, 9, 12, 24, and 36 months with a P value of less than 0.05.

Conclusions

A protocol biopsy can detect SCR, especially in patients with risk factors such as a high number of HLA mismatches or not using Simulect. Treatment of SCR detected by protocol biopsy will help to improve long-term renal function.

Keywords: Protocol biopsy, Subclinical rejection (SCR), Renal transplantation

References

1). Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. Natural history, risk factors, and impact of subclinical rejection in kidney transplantation. Transplantation. 2004; 78:242–9.

2). Morath C, Ritz E, Zeier M. Protocol biopsy: what is the rationale and what is the evidence? Nephrol Dial Transplant. 2003; 18:644–7.

3). Moreso F, Ibernon M, Goma M, Carrera M, Fulladosa X, Hueso M, et al. Subclinical rejection associated with chronic allograft nephropathy in protocol biopsies as a risk factor for late graft loss. Am J Transplant. 2006; 6:747–52.

4). Nankivell BJ, Borrows RJ, Fung CL, O'Connell PJ, Allen RD, Chapman JR. The natural history of chronic allograft nephropathy. N Engl J Med. 2003; 349:2326–33.

5). Min SI, Yun IJ, Kang JM, Park YJ, Min SK, Ahn C, et al. Moderate-to-severe early-onset hyperuricaemia: a prognostic marker of longterm kidney transplant outcome. Nephrol Dial Transplant. 2009; 24:2584–90.

6). Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int. 1999; 55:713–23.

7). hoi BS, Shin MJ, Shin SJ, Kim YS, Choi YJ, Kim YS, 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; 5:1354–60.

8). Furness PN, Philpott CM, Chorbadjian MT, Nicholson ML, Bosmans JL, Corthouts BL, et al. Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates. Transplantation. 2003; 76:969–73.

9). Wilczek HE. Percutaneous needle biopsy of the renal allograft. A clinical safety evaluation of 1129 biopsies. Transplantation. 1990; 50:790–7.

10). Masin-Spasovska J, Spasovski G, Dzikova S, Petrusevska G, Lekovski Lj, Ivanovski N, et al. Do we have to treat subclinical rejections in early protocol renal allograft bi-opsies? Transplant Proc. 2007; 39:2550–3.

11). Rush D, Nickerson P, Gough J, McKenna R, Grimm P, Cheang M, et al. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol. 1998; 9:2129–34.

12). Rush D. Protocol biopsies for renal transplantation. Saudi J Kidney Dis Transpl. 2010; 21:1–9.

13). Beimler J, Zeier M. Borderline rejection after renal transplantation – to treat or not to treat. Clin Transplant. 2009; 23(Suppl 21):19–25.

14). Kee TY, Chapman JR, O'Connell PJ, Fung CL, Allen RD, Kable K, et al. Treatment of subclinical rejection diagnosed by protocol biopsy of kidney transplants. Transplantation. 2006; 82:36–42.

15). Rush D, Arlen D, Boucher A, Busque S, Cockfield SM, Girardin C, et al. Lack of benefit of early protocol biopsies in renal transplant patients receiving TAC and MMF: a randomized study. Am J Transplant. 2007; 7:2538–45.

16). Mao Y, Yu J, Chen J, Yang H, He Q, Shou Z, et al. Diagnosis of renal allograft subclinical rejection by urine protein fingerprint analysis. Transpl Immunol. 2008; 18:255–9.

Fig. 1.

Changes in mean MDRD GFR of each group. There were no significant differences between two groups in GFR after 3 months. *P＜0.05.

Fig. 2.

δ GFR defines as a result of subtraction MDRD GFR at 1 wk from MDRD GFR at the point. There were significant differences between two groups in δ GFR at 1, 3, 6, 9, 12, 24 and 36 months. *P＜0.05.

Table 1.

Demographics

	Protocol Bx (＋) (n=138)	Protocol Bx (－) (n=115)	P value
Recipient sex,	75：63	65：50	0.413
M： F (n)
Recipient age (yr)	45.15±13.30	41.87±11.82	0.041
Donor age (yr)	43.02±14.18	37.62±10.40	0.001
Dialysis duration	55.50±45.86	27.78±34.34	＜0.001
Number of HLA	3.59±1.60	3.05±1.50	0.007
mismatches (n)
HLA-A (n)	1.04±0.61	0.93±0.59	0.164
HLA-B (n)	1.36±0.72	1.16±0.67	0.021
HLA-DR (n)	1.20±0.655	0.97±0.66	0.004
Donor type,	43：94	102：11	＜0.001
L： D (n)
Tac use (n, %)	120 (87.0)	88 (76.5)	0.02
CsA use (n, %)	12 (8.7)	21 (18.3)	0.027
Simulect use (n, %)	108 (78.3)	70 (60.9)	0.011

Mean±SD.

Abbreviations: HLA, human leukocyte antigen; Tac, taclolimus; CsA, cyclosporine A.

Table 2.

SCR prevalence in early protocol biopsy

		No. of patients	Prevalence (%)	Accumulative prevalence (%)
SCR	AMR	2	1.4	1.4
	Borderline change	46	33.3	34.8
	TCR – IA or IB	11	7.9	42.8
	TCR – IIA or IIB	6	4.3	47.1
NR		73	52.9	100
Total		138	100	100

Abbreviations: SCR, subclinical rejection; AMR, antibody mediated rejection; TCR, T-cell mediated rejection.

Table 3.

Univariate analysis of risk factors for SCR

	NR (n=73)	SCR (n=65)	P value
Recipient sex, M： F (n)	36：37	39：26	0.208
Recipient age (yr)	44±13.29	45.52±13.26	0.915
Donor age (yr)	42.21±13.06	43.58±15.97	0.333
Dialysis duration	51.38±54.84	63.17±34.85	0.331
HTN (n, %)	13 (17.8)	9 (13.8)	0.526
DM (n, %)	3 (4.1)	5 (7.7)	0.369
ABO mismatch (n, %)	8 (11.0)	6 (9.2)	0.717
Number of HLA	3.26±1.68	3.97±1.44	0.127
mismatches (n)
HLA-A (n)	1.03±0.67	1.05±0.54	0.101
HLA-B (n)	1.22±0.75	1.52±0.66	0.354
HLA-DR (n)	1.01±0.61	1.42±0.64	0.003
PRA＞20% (n, %)	9 (12.3)	8 (12.3)	0.997
Donor type, L： D (n)	24：49	19：45	0.688
Immunosuppression			0.074
Tac/CsA+MMF+Pred (n, %)	67 (91.8)	64 (98.5)
Others (n, %)	6 (8.2)	1 (1.5)
Simulect use (n, %)	61 (83.6)	47 (72.3)	0.01

Abbreviations: NR, normal; SCR, subclinical reaction; HTN, hypertension; DM, diabetes mellitus; HLA, human leukocyte antigen; PRA, panel reactive antigen; Tac, tacloimus; CsA, cyclosporine A; MMF, mycophnolatemofetil; Pred, prednisolon.

Table 4.

Multivariate analysis of risk factors for SCR: multiple logistic regression

	Odds ratio	95% CI	P value
Number of HLA	1.195	0.292∼4.890	0.805
mismatches (≤3 or ＞3)
HLA-A	0.498	0.220∼1.128	0.095
HLA-B HLA-DR	2.062 2.162	0.851∼4.995 0.994∼4.705	0.109 0.052
PRA＞20%	1.445	0.437∼4.778	0.546
Simulect use	0.219	0.074∼0.650	0.006

Number of HLA mismatches and PRA already known as risk factors for SCR were included in analysis.

Abbreviations: HLA, human leukocyte antigen; PRA, panel reactive antigen.

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