Actual 10-year Outcomes of Tacrolimus/MMF Compared with Cyclosporin/MMF in Kidney Transplantation

Yaerim Kim; Sungbae Park; Hyoungtae Kim; Seungyeup Han

doi:10.4285/jkstn.2014.28.2.69

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Kim, Park, Kim, and Han: Actual 10-year Outcomes of Tacrolimus/MMF Compared with Cyclosporin/MMF in Kidney Transplantation

Original Article

J Korean Soc Transplant 2014;28(2):69-77.

Published online: 10 June 2014

DOI: https://doi.org/10.4285/jkstn.2014.28.2.69

Actual 10-year Outcomes of Tacrolimus/MMF Compared with Cyclosporin/MMF in Kidney Transplantation

Yaerim Kim, M.D.¹, Sungbae Park, M.D.^1,², Hyoungtae Kim, M.D.^2,³, Seungyeup Han, M.D.^1,²

¹Department of Internal Medicine, Keimyung University School of Medicine, DaeguKorea

²Department of Keimyung University Kidney Institute, Keimyung University School of Medicine, DaeguKorea

³Department of General Surgery, Keimyung University School of Medicine, Daegu, Korea Korea

책임저자：한승엽, 대구시 중구 달성로 56계명대학교 의과대학 내과학교실, 700-712 Tel: 053-250-7399, Fax: 053-253-7976 E-mail: hansy@dsmc.or.kr

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

Kidney transplantation is the most effective treatment in patients with chronic kidney disease. Recently, the survival rate of kidney allografts has been markedly increased by the development of immunosuppressants. According to research reports published in Symphony in 2007 and 2009, low dose tacrolimus/mycophenolate mofetil (MMF) showed better results than cyclosporin/MMF in renal function and rejection.

Methods

We compared patient survival rate, graft survival rate, incidence of rejection, and metabolic complications in two groups of patients who received immunosuppressants with either tacrolimus/MMF/steroid or cyclosporin/MMF/steroid. All patients underwent kidney transplants at Keimyung University Dongsan Medical Center between January 1997 and December 2003 with follow-up over 10 years.

Results

A total of 180 patients were included in the research (117 patients were treated with tacrolimus/MMF/steroid and 63 patients with cyclosporin/MMF/steroid). The incidence rate of acute rejection was higher in the cyclosporin/MMF/steroid group; however, the difference was not statistically significant. In the case of metabolic complications, new onset diabetes after transplantation was more frequent in the tacrolimus/MMF/steroid group. The cyclosporin/MMF/steroid group appeared to have a higher rate of hypertension and hyperlipidemia.

Conclusions

Overall, no significant differences in patient and graft survival rate were observed between the two groups.

Keywords: Kidney transplantation, Cyclosporin, Tacrolimus

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Fig. 1.

The flow diagram shows patient selection process, with inclusion and exclusion criteria. Abbreviations: Tac, tacrolimus; MMF, mycophenolate mofetil; Cyc, cyclosporine; f/u, follow-up; KT, kidney transplantation.

Fig. 2.

The annual changes of donor type (A) and immunosuppressive agent (B) in kidney transplantation from 1997 to 2003. Abbreviation: MMF, mycophenolate mofetil.

Fig. 3.

Patient (A) and graft (B) survival of kidney transplantation according to maintenance immunosuppressant. Abbreviations: MMF, mycophenolate mofetil; NS, not significant.

Table 1.

The baseline characteristics of the study population

Characteristic	Tacrolimus/ MMF/Steroid	Cyclosporin/ MMF/Steroid	P-value
No. of patient	117	63
Male:Female	66:51	31:32	NS
Recipient age	40.2±9.9	39.3±11.4	NS
	(19∼61)	(20∼63)
Donor age	38.2±10.8	36.1±14.8	NS
	(7∼59)	(12∼67)
Deceased donor	33 (28.4)	25 (40.9)	NS
HLA mismatch			NS
AB 0	16 (13.7)	9 (14.3)
1∼4	101 (86.3)	54 (85.7)
DR 0	23 (19.7)	14 (22.2)
1∼2	94 (80.3)	49 (77.8)
Total 0	13 (11.1)	9 (14.3)
1∼6	104 (88.9)	54 (85.7)
RRT before KT			NS
HD	75 (63.6)	44 (69.8)
PD	23 (19.7)	11 (17.5)
None	19 (16.2)	8 (12.7)
Etiology (%)			NS
CGN	98 (83.8)	55 (87.3)
Hypertension	7 (6.0)	5 (7.9)
DM	8 (6.8)	2 (3.2)
Others	4 (3.4)	1 (1.6)
Follow-up (mo)	115.0±40.3	133.7±53.0	＜0.05
	(0.3∼169.6)	(3.4∼195.2)

Data are presented as mean±SD (range) or number (%).

Abbreviations: MMF, mycophenolate mofetil; NS, not significant; HLA, human leucocyte antigen; RRT, renal replacement therapy; KT, kidney transplantation; HD, hemodialysis; PD, peritoneal dialysis; CGN, chronic glomerular nephritis; DM, diabetes mellitus.

Table 2.

The incidence of acute rejection and graft loss

Variable	Tacrolimus/ MMF/Steroid (n=117)	Cyclosporin/ MMF/Steroid (n=63)	P-value
Acute rejection	27 (23.1)	18 (29.0)	NS
Graft loss	28 (23.9)	23 (35.5)	NS
Death with functioning	9 (32.2)	5 (21.7)
graft
Return to RRT	17 (60.7)	12 (52.2)
Retransplantation	2 (7.1)	6 (26.1)
Death cause
Infection	4 (44.5)	0
Cerebrovascular	2 (22.2)	0
Cardiovascular	1 (11.1)	0
Malignancy	1 (11.1)	1 (20)
Others	1 (11.1)	4 (80)

Data are presented as number (%).

Abbreviations: MMF, mycophenolate mofetil; NS, not significant; RRT, renal replacement therapy.

Table 3.

The incidence of complications

Variable	Tacrolimus/ MMF/Steroid (n=117)	Cyclosporin/ MMF/Steroid (n=63)	P-value
HTN	93 (79.5)	58 (92.1)	＜0.05
NODAT	26 (22.2)	8 (12.7)	NS
Hypercholesterolemia	19 (16.2)	39 (61.9)	＜0.05
Malignancy	9 (7.7)	5 (7.9)	NS
Infection	74 (63.2)	34 (54.0)	NS
Viral infection	53 (45.3)	21 (33.3)	NS
Bacterial infection	23 (19.7)	17 (27.0)	NS
Tb infecion	8 (6.8)	4 (6.3)	NS
Fungal infection	1 (0.9)	0 (0)	NS
Data are presented as n	number (%).

Abbreviations: MMF, mycophenolate mofetil; HTN, hypertension; NODAT, new onset diabetes after transplantation; NS, not significant; Tb, turberculosis.

Table 4.

The incidence of infection events

Variable	Tacrolimus/ MMF/Steroid (n=117)	Cyclosporin/ MMF/Steroid (n=63)	P-value
Total (graft loss)	74 (18)	34 (14)	NS
Viral	28 (15)	20 (11)	NS
Bacterial	23 (4)	16 (3)	NS
Tb	8 (1)	4 (2)	NS
Fungal	1	0	NS

Data are presented as number (%).

Abbreviations: MMF, mycophenolate mofetil; NS, not significant; Tb, tuberculosis.

Table 5.

The comparison of characteristics between graft loss and survival group

Characteristic	Graft loss (n=51)	Graft survival (n=129)	P-value
Recipient age			NS
＜30	10 (19.6)	22 (17.1)
30∼49	31 (60.8)	79 (61.2)
≥50	10 (19.6)	28 (21.7)
Male： Female	25：26	72：57	NS
Donor age			NS
＜50	40 (78.4)	105 (81.4)
≥50	11 (21.6)	24 (18.6)
HLA mismatch			NS
AB 0	4 (7.8)	21 (16.3)
1∼4	47 (92.2)	108 (83.7)
DR 0	7 (13.7)	30 (23.3)
1∼2	44 (86.3)	99 (76.7)
Total 0	4 (7.8)	18 (14.0)
1∼6	47 (92.2)	111 (86.0)
RRT before KT			NS
None	6 (11.8)	21 (16.3)
HD	34 (66.6)	85 (65.9)
PD	11 (21.6)	23 (17.8)
Acute rejection	26 (51.0)	19 (14.7)	＜0.05
Immunosuppressant			NS
Tacrolimus	28 (54.9)	89 (69.0)
Cyclosporin	23 (45.1)	40 (31.0)

Data are presented as number (%).

Abbreviations: NS, not significant; HLA, human leucocyte antigen; RRT, renal replacement therapy; KT, kidney transplantation; HD, hemodialysis; PD, peritoneal dialysis.

Table 6.

Univariated and multivariated analysis for risk factors of graft loss

	Univariated analysis		Multivariated analysis
	Unadjusted OR (95% CI)	P-value	Adjusted OR (95% CI)	P-value
Male	0.761 (0.397∼1.458)	0.507	−	−
Recipient (age ≥50)	0.880 (0.392∼1.974)	0.841	−	−
Donor (age ≥50)	1.203 (0.540∼2.681)	0.678	−	−
HLA AB mismatch	2.285 (0.743∼7.022)	0.160	2.500 (0.498∼12.557)	0.266
HLA DR mismatch	1.905 (0.777∼4.667)	0.219	1.107 (0.310∼3.953)	0.876
Acute rejection	6.021 (2.890∼12.542)	0.000	6.016 (2.815∼12.859)	0.000
Immunosuppressant (tacrolimus)	0.547 (0.281∼1.065)	0.084	0.871 (0.493∼1.541)	0.109

Abbreviations: OR, odds ratio; CI, confidence interval; HLA, human leucocyte antigen.

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