移植肾局灶性节段性肾小球硬化复发危险因素分析及治疗经验总结

doi:10.3877/cma.j.issn.1674-3903.2017.02.004

目的

探讨肾移植术后移植肾局灶性节段性肾小球硬化(FSGS)复发的危险因素及其治疗效果。

方法

回顾性分析2008年1月至2017年4月浙江大学医学院附属第一医院肾脏病中心16例原发病为FSGS的肾移植受者资料，根据术后移植肾FSGS早期复发情况分为复发组(6例)和未复发组(10例)。两组受者肾移植术前原发病发病年龄、肾移植手术时年龄和供者年龄比较采用t检验；两组受者肾移植术前进展至终末期肾病(ESRD)时间、HLA错配数和透析时间比较采用Mann-Whitney检验；两组受者性别、供肾方式、供者性别、是否进行免疫诱导和是否预防性使用利妥昔单抗比较采用Fisher确切概率法。P<0.05为差异有统计学意义。

结果

复发组和未复发组进展至ESRD的时间分别为1.0年(0.3～5.9年)和9.2年(0.5～14.0年)，差异有统计学意义(U＝7.00，P<0.05)。两组间受者性别、发病年龄、透析时间、供者类型、手术时年龄、HLA错配数、是否进行免疫诱导、是否预防性使用利妥昔单抗、供者年龄和性别等差异均无统计学意义(P均>0.05)。复发组6例受者经血浆置换联合大剂量环孢素治疗后，3例完全缓解，2例短期内部分缓解，1例部分缓解。

结论

早期使用血浆置换联合大剂量环孢素能快速、有效且持续缓解移植肾FSGS复发的病变程度和进程。原发性FSGS快速进展至ESRD时间可能是影响肾移植术后移植肾FSGS早期复发的重要因素。

关键词: 肾移植, 局灶性节段性肾小球硬化, 血浆置换, 环孢素, 利妥昔单抗

Objective

To investigate the risk factors of focal segmental glomerulosclerosis (FSGS) recurrence in renal transplantation and its therapy.

Methods

The clinical data of 16 patients with FSGS underwent transplantation between January 2008 to April 2017 in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, were retrospectively analyzed. The rate of early recurrent FSGS after transplantation was observed in 16 patients. The effect of high-dose cyclosporine combined with plasma exchange was also observed. Including 6 cases in group with recurrence (R group) and 10 cases in group without recurrence (NR group). The age at onset of primary disease, the patients′ age and donors′ age at transplantation were compared by t Test; the progressed to end stage renal disease (ESRD) time, HLA mismatching numbers and duration of dialysis were compared by Mann-Whitney Test; the sex of recipients, donor type, the sex of donors, whether use the immunological induction and whether use the rituximab were compared by Fisher′s Exact Test. P<0.05 was considered statistically significant.

Results

The progressed to ESRD time of R group and NR group was 1.0 year (0.3-5.9 years) and 9.2 years (0.5-14.0 years), it′s statistically significant (U=7.00, P<0.05). The sex of recipients, the age at onset of disease, duration of dialysis, donor type, the age of the patients and the age of donors at transplantation, HLA mismatching numbers, whether use immunological induction, whether use the rituximabthe, age of donors and sex of donors, no differences were observed between two groups (P all>0.05). Of the 6 patients in R group, 3 achieved complete remission, 2 achieved partial remission in a short term, 1 achieved partial remission after the use of high-dose of cyclosporine combined with plasma exchange.

Conclusions

This study confirms that early using of high-dose of cyclosporine combined with plasma exchange can quickly, effectively and continuously relieve the degree and progress of recurrent FSGS in transplanted kidney. It also indicates that a rapid progression to ESRD is a reliable risk factor for the early recurrence of FSGS after renal transplantation.

Key words: Renal transplantation, Focal segmental glomerulosclerosis, Plasma exchange, Cyclosporine, Rituximab

表1 肾移植术后FSGS复发危险因素分析结果

组别	例数	受者性别(例，男/女)	受者肾移植术前FSGS发病年龄(岁，±s)	受者肾移植术前进展至ESRD时间[年，M(min，max)]	受者肾移植术前透析时间[年，M(min，max)]	受者肾移植手术时年龄(岁，±s)	供肾方式(例，活体/尸体)
复发组	6	4/2	29±12	1.0 (0.3～ 5.9)	2.0 (0.3～6.0)	34±12	3/3
未复发组	10	7/3	26±11	9.2 (0.5～14.0)	1.15 (0.2～8.7)	37±13	2/8
t/U值	－	－	0.56	7.00	27.00	－0.49	－
P值	－	>0.05	>0.05	<0.05	>0.05	>0.05	>0.05
组别	例数	供受者HLA错配数[个，M(min，max)]	供者年龄(岁，±s)	供者性别(例，男/女)	受者免疫诱导(例，是/否)	受者利妥昔单抗预防(例，是/否)
复发组	6	3.5 (0～4)	40±11	3/3	3/3	1/5
未复发组	10	3.0 (1～4)	33±12	8/2	8/2	1/9
t/U值	－	25.50	1.02	－	－	－
P值	－	>0.05	>0.05	>0.05	>0.05	>0.05

表1 肾移植术后FSGS复发危险因素分析结果

组别	例数	受者性别(例，男/女)	受者肾移植术前FSGS发病年龄(岁，±s)	受者肾移植术前进展至ESRD时间[年，M(min，max)]	受者肾移植术前透析时间[年，M(min，max)]	受者肾移植手术时年龄(岁，±s)	供肾方式(例，活体/尸体)
复发组	6	4/2	29±12	1.0 (0.3～ 5.9)	2.0 (0.3～6.0)	34±12	3/3
未复发组	10	7/3	26±11	9.2 (0.5～14.0)	1.15 (0.2～8.7)	37±13	2/8
t/U值	－	－	0.56	7.00	27.00	－0.49	－
P值	－	>0.05	>0.05	<0.05	>0.05	>0.05	>0.05
组别	例数	供受者HLA错配数[个，M(min，max)]	供者年龄(岁，±s)	供者性别(例，男/女)	受者免疫诱导(例，是/否)	受者利妥昔单抗预防(例，是/否)
复发组	6	3.5 (0～4)	40±11	3/3	3/3	1/5
未复发组	10	3.0 (1～4)	33±12	8/2	8/2	1/9
t/U值	－	25.50	1.02	－	－	－
P值	－	>0.05	>0.05	>0.05	>0.05	>0.05

图1 FSGS复发组1例经血浆置换联合大剂量环孢素治疗后短期部分缓解受者移植肾穿刺活检结果(PAS ×200)

1	Ponticelli C. Recurrence of focal segmental glomerular sclerosis(FSGS) after renal transplantation[J]. Nephrol Dial Transplant, 2010, 25(1): 25-31.
2	Hubsch H,Montane B,Abitbol C, et al. Recurrent focal glomerulosclerosis in pediatric renal allografts: the Miami experience[J]. Pediatr Nephrol (Berlin), 2005, 20(2): 210-216.
3	Fornoni A,Sageshima J,Wei C, et al. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis[J]. Sci Transl Med, 2011, 3(85): 85ra46.
4	Newstead CG. Recurrent disease in renal transplants[J]. Nephrol Dial Transplant, 2003, 18(Suppl 6): vi68-vi74.
5	Belson A,Yorgin PD,Al-Uzri AY, et al. Long-term plasmapheresis and protein A column treatment of recurrent FSGS[J]. Pediatr Nephrol (Berlin), 2001, 16(12): 985-989.
6	Ponticelli C,Glassock RJ. Posttransplant recurrence of primary glomerulonephritis[J]. Clin J Am Soc Nephrol, 2010, 5(12): 2363-2372.
7	Messina M,Gallo E,Mella A, et al. Update on the treatment of focal segmental glomerulosclerosis in renal transplantation[J]. World J Transplant, 2016, 6(1): 54-68.
8	Hoyer JR,Vernier RL,Najarian JS, et al. Recurrence of idiopathic nephrotic syndrome after renal transplantation[J]. Lancet, 1972, 2(7773): 343-348.
9	Briganti EM,Russ GR,McNeil JJ, et al. Risk of renal allograft loss from recurrent glomerulonephritis[J]. N Engl J Med, 2002, 347(2): 103-109.
10	Vinai M,Waber P,Seikaly MG. Recurrence of focal segmental glomerulosclerosis in renal allograft: an in-depth review[J]. Pediatr Transplant, 2010, 14(3): 314-325.
11	Francis A,Trnka P,McTaggart SJ. Long-term outcome of kidney transplantation in recipients with focal segmental glomerulosclerosis[J]. Clin J Am Soc Nephrol, 2016, 11(11): 2041-2046.
12	Tejani A,Stablein DH. Recurrence of focal segmental glomerulosclerosis posttransplantation: a special report of the North American Pediatric Renal Transplant Cooperative Study[J]. J Am Soc Nephrol, 1992, 2(12 Suppl): S258-S263.
13	Vincenti F,Biava C,Tomlanovitch S, et al. Inability of cyclosporine to completely prevent the recurrence of focal glomerulosclerosis after kidney transplantation[J]. Transplantation, 1989, 47(4): 595-598.
14	Banfi G,Colturi C,Montagnino G, et al. The recurrence of focal segmental glomerulosclerosis in kidney transplant patients treated with cyclosporine[J]. Transplantation, 1990, 50(4): 594-596.
15	Cravedi P,Kopp JB,Remuzzi G. Recent progress in the pathophysiology and treatment of FSGS recurrence[J]. Am J Transplant, 2013, 13(2): 266-274.
16	Myers BD,Sibley R,Newton L, et al. The long-term course of cyclosporine-associated chronic nephropathy[J]. Kidney Int, 1988, 33(2): 590-600.
17	Salomon R,Gagnadoux MF,Niaudet P. Intravenous cyclosporine therapy in recurrent nephrotic syndrome after renal transplantation in children[J]. Transplantation, 2003, 75(6): 810-814.
18	Raafat RH,Kalia A,Travis LB, et al. High-dose oral cyclosporin therapy for recurrent focal segmental glomerulosclerosis in children[J]. Am J Kidney Dis, 2004, 44(1): 50-56.
19	Canaud G,Zuber J,Sberro R, et al. Intensive and prolonged treatment of focal and segmental glomerulosclerosis recurrence in adult kidney transplant recipients: a pilot study[J]. Am J Transplant, 2009, 9(5): 1081-1086.
20	Ohta T,Kawaguchi H,Hattori M, et al. Effect of pre-and postoperative plasmapheresis on posttransplant recurrence of focal segmental glomerulosclerosis in children[J]. Transplantation, 2001, 71(5): 628-633.
21	Kashgary A,Sontrop JM,Li L, et al. The role of plasma exchange in treating post-transplant focal segmental glomerulosclerosis: A systematic review and meta-analysis of 77 case-reports and case-series[J]. BMC Nephrol, 2016, 17(1): 104.
22	Zimmerman SW. Plasmapheresis and dipyridamole for recurrent focal glomerular sclerosis[J]. Nephron, 1985, 40(2): 241-245.
23	Gohh RY,Yango AF,Morrissey PE, et al. Preemptive plasmapheresis and recurrence of FSGS in high-risk renal transplant recipients[J]. Am J Transplant, 2005, 5(12): 2907-2912.
24	Chikamoto H,Hattori M,Kuroda N, et al. Pretransplantation combined therapy with plasmapheresis and rituximab in a second living-related kidney transplant pediatric recipient with a very high risk for focal segmental glomerulosclerosis recurrence[J]. Pediatr Transplant, 2012, 16(7): E286-E290.
25	Pescovitz MD,Book BK,Sidner RA. Resolution of recurrent focal segmental glomerulosclerosis proteinuria after rituximab treatment[J]. N Engl J Med, 2006, 354(18): 1961-1963.
26	Hristea D,Hadaya K,Marangon N, et al. Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab[J]. Transplant Int, 2007, 20(1): 102-105.
27	Gossmann J,Scheuermann EH,Porubsky S, et al. Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant patient with relapsed focal segmental glomerulosclerosis[J]. Transplant Int, 2007, 20(6): 558-562.
28	Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action[J]. Am J Transplant, 2006, 6(5 Pt 1): 859-866.
29	Trachtman H. Busy Bs[J]. J Am Soc Nephrol, 2016, 27(6): 1584-1586.

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Risk factors and treatment of focal segmental glomerulosclerosis recurrence in renal transplantation

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