肾移植术后妊娠九例十次临床分析

doi:10.3877/cma.j.issn.1674-3903.2017.04.003

目的

探讨肾移植受者术后妊娠、分娩的安全性和可行性。

方法

回顾性分析1997年1月至2014年6月在温州医科大学附属第一医院行肾移植术后成功妊娠并分娩的9例受者临床资料。9例受者移植时平均年龄(26±4)岁，8例为尸体肾移植，1例为活体肾移植；原发病均为慢性肾小球肾炎，其中2例为IgA肾病。9例受者共自然受孕12次，成功妊娠并分娩10次，流产2次；成功妊娠时平均年龄(31±6)岁，妊娠距肾移植时间平均(78±46)个月。观察受者妊娠前3个月、妊娠早、中、晚期和分娩后3个月移植肾功能、免疫抑制剂血药浓度、母体和胎儿并发症以及子代生长发育等相关情况。

结果

妊娠前3个月，受者平均血清肌酐和估算肾小球滤过率(eGFR)分别为(68±12)μmol/L和(94±18)mL·min^-1·(1.73 m²)^-1，妊娠早、中期血清肌酐分别为(66±13)、(62±13)μmol/L，妊娠早、中、晚期eGFR分别为(99±19)、(114±24)、(112±26)mL·min^-1·(1.73 m²)^-1，与妊娠前相比，差异均有统计学意义(P均<0.05)。妊娠前环孢素血药浓度谷值为(43±13)ng/mL，妊娠中期下降至(31±14)ng/mL，差异有统计学意义(P<0.05)；他克莫司血药浓度和剂量变化差异均无统计学意义。2例受者妊娠期间出现子痫前期，1例为轻度，1例为重度；6例并发泌尿系统感染，未发生急性排斥反应。10例胎儿平均孕周为(37.4±2.0)周，其中早产2例；出生体重中位数为3 005 g，其中低体重儿1例；1 min Apgar评分除1例为9.5分，其余均为10.0分。截至2017年7月，子代年龄为3个月至17岁，其智力、体格发育和学习能力等方面均无异常，未发生免疫系统缺陷或注意力缺陷多动障碍等。

结论

肾移植术后妊娠对于母体及胎儿均有风险，但是选择合适的受孕时机，适当调整免疫抑制方案，围产期严密监测，能提高肾移植术后妊娠的安全性。

关键词: 肾移植, 妊娠, 妊娠并发症, 钙调磷酸酶抑制剂, 母婴预后

Objective

To discuss the feasibility and safety of pregnancy and delivery after renal transplantation.

Methods

We retrospectively analyzed the clinical data of 9 women who underwent kidney transplantation in the First Affiliated Hospital of Wenzhou Medical University between 1997 and 2014. The average age of the 9 patients at the time of transplantation was (26±4) years old. Eight cases got cadaveric donor transplantation and 1 case got living related donor renal transplantation. The protopathy of recipients were all chronic glomerulonephritis and 2 among them were IgA nephropathy. There were 12 pregnancies in 9 recipients and 2 pregnancies failed. Average age of 9 recipients during pregnancy was (31±6) years old and the average interval between renal transplantation and pregnancy was (78±46) months.The indexes of graft function, immunosuppressant plasma concentration, complication of the mother and the fetus and growth development status of offspring at different time points (3 months before pregnancy, the first, second, third trimesters and 3 months after delivery) were observed.

Results

The mean serum creatinine and estimated glomerular filtration rate (eGFR) of 9 recipients before pregnancy were (68±12) μmol/L and (94±18) mL·min^-1·(1.73 m²)^-1, the serum creatinine of 9 recipients during the first and second trimester were (66±13) and (62±13) μmol/L, the eGFR of 9 recipients during the first, second, third trimesters were (99±19), (114±24) and (112±26) mL·min^-1·(1.73 m²)^-1, there were statistical difference between all the above-mentioned data and the data of 3 months before pregnancy (P all <0.05). The mean lowest cyclosporine plasma concentration during the second trimester declined to (31±14) ng/mL from 3 months before pregnancy [(43±13) ng/mL ], which had statistical difference (P<0.05). No statistical difference was found in plasma concentration and dosage of tacrolimus. Two recipients developed preeclampsia and 6 recipients developed urinary infection. No acute rejection was observed. The median gestation of the 10 babies was (37.4±2.0) weeks (2 cases were preterm ); the median birthweight was 3 005 g with 1 case of low birth weight infant. The 1 min Apgar score of 1 newborn was 9.5 and the rest were all 10. The age of the offspring were 3 months to 17 years old up to July 2017, and no abnormality in intelligence, physical development and learning ability were observed, and there was also no immune system defect or attention deficit hyperactivity disorder.

Conclusions

Pregnancy after renal transplantation is risky for mother and fetus, but choosing the right time to be pregnant, taking appropriate immunosuppressive drugs, closely monitoring during perinatal period may improve the safety of pregnancy after renal transplantation

Key words: Kidney transplantation, Pregnancy, Pregnancy complication, Calcineurin inhibitor, Maternal and neonatal outcomes

表1 9例肾移植受者妊娠前至分娩后实验室检查指标变化(±s)

时间	血清肌酐(μmol/L)	eGFR[mL·min^-1·(1.73 m²)^-1]	空腹血糖(mmol/L)	血白蛋白(g/L)	尿酸(μmol/L)	总胆固醇(mmol/L)	三酰甘油(mmol/L)
妊娠前	68±12	94±18	4.8±0.6	45.2±2.4	283±46	5.0±0.9	1.2±0.5
妊娠早期	66±13^a	99±19^a	4.6±0.5	43.7±2.2^a	278±50	4.4±0.7^a	1.3±0.6
妊娠中期	62±13^a	114±24^a	4.2±0.4^a	39.6±3.5^a	288±49	5.8±0.8^a	2.4±1.1^a
妊娠晚期	69±17	112±26^a	4.0±0.4^a	35.2±2.3^a	375±112^a	6.9±0.9^a	3.5±0.8^a
分娩后	71±13	96±18	5.0±0.6	43.3±4.0^a	337±71^a	6.1±1.4^a	1.9±0.8^a
时间	HDL(mmol/L)	LDL(mmol/L)	总胆红素(μmol/L)	直接胆红素(μmol/L)	血红蛋白(g/L)	血白细胞(×10⁹/L)	血小板(×10⁹/L)
妊娠前	1.7±0.3	2.7±0.9	12.8±5.8	3.8±1.6	124±15	7.5±2.5	236±100
妊娠早期	1.5±0.3	2.2±0.7^a	12.4±6.4	4.6±2.3	117±12^a	8.8±2.9^a	218±　81
妊娠中期	1.9±0.4	2.9±0.7	8.6±3.2^a	2.5±1.0^a	109±14^a	9.4±3.5^a	195±　55
妊娠晚期	1.7±0.3	3.6±0.8^a	8.9±2.9^a	2.6±1.3	112±15	9.5±3.4^a	191±　76
分娩后	1.5±0.3	3.5±1.2^a	11.9±3.0	3.5±1.1	121±14	8.4±3.2	225±　82

表1 9例肾移植受者妊娠前至分娩后实验室检查指标变化(±s)

时间	血清肌酐(μmol/L)	eGFR[mL·min^-1·(1.73 m²)^-1]	空腹血糖(mmol/L)	血白蛋白(g/L)	尿酸(μmol/L)	总胆固醇(mmol/L)	三酰甘油(mmol/L)
妊娠前	68±12	94±18	4.8±0.6	45.2±2.4	283±46	5.0±0.9	1.2±0.5
妊娠早期	66±13^a	99±19^a	4.6±0.5	43.7±2.2^a	278±50	4.4±0.7^a	1.3±0.6
妊娠中期	62±13^a	114±24^a	4.2±0.4^a	39.6±3.5^a	288±49	5.8±0.8^a	2.4±1.1^a
妊娠晚期	69±17	112±26^a	4.0±0.4^a	35.2±2.3^a	375±112^a	6.9±0.9^a	3.5±0.8^a
分娩后	71±13	96±18	5.0±0.6	43.3±4.0^a	337±71^a	6.1±1.4^a	1.9±0.8^a
时间	HDL(mmol/L)	LDL(mmol/L)	总胆红素(μmol/L)	直接胆红素(μmol/L)	血红蛋白(g/L)	血白细胞(×10⁹/L)	血小板(×10⁹/L)
妊娠前	1.7±0.3	2.7±0.9	12.8±5.8	3.8±1.6	124±15	7.5±2.5	236±100
妊娠早期	1.5±0.3	2.2±0.7^a	12.4±6.4	4.6±2.3	117±12^a	8.8±2.9^a	218±　81
妊娠中期	1.9±0.4	2.9±0.7	8.6±3.2^a	2.5±1.0^a	109±14^a	9.4±3.5^a	195±　55
妊娠晚期	1.7±0.3	3.6±0.8^a	8.9±2.9^a	2.6±1.3	112±15	9.5±3.4^a	191±　76
分娩后	1.5±0.3	3.5±1.2^a	11.9±3.0	3.5±1.1	121±14	8.4±3.2	225±　82

图1 9例肾移植受者妊娠前至分娩后CNI剂量及血药浓度谷值变化

表2 9例肾移植受者妊娠前至分娩后CNI剂量及血药浓度谷值变化(±s)

时间	环孢素剂量(mg)	环孢素血药浓度谷值(ng/mL)	他克莫司剂量(mg)	他克莫司血药浓度谷值(ng/mL)
妊娠前	113±33	42±13	2.4±1.4	2.7±0.7
妊娠早期	112±32	34±14	2.5±1.5	2.2±0.5
妊娠中期	108±36	31±14^a	2.9±1.5	1.7±0.6
妊娠晚期	104±40	39±24	3.2±0.9	2.6±0.7
分娩后	95±37	46±25	2.7±1.2	2.9±0.7

表2 9例肾移植受者妊娠前至分娩后CNI剂量及血药浓度谷值变化(±s)

时间	环孢素剂量(mg)	环孢素血药浓度谷值(ng/mL)	他克莫司剂量(mg)	他克莫司血药浓度谷值(ng/mL)
妊娠前	113±33	42±13	2.4±1.4	2.7±0.7
妊娠早期	112±32	34±14	2.5±1.5	2.2±0.5
妊娠中期	108±36	31±14^a	2.9±1.5	1.7±0.6
妊娠晚期	104±40	39±24	3.2±0.9	2.6±0.7
分娩后	95±37	46±25	2.7±1.2	2.9±0.7

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Clinical analysis of 10 pregnancies in 9 recipients after kidney transplantation

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Clinical analysis of 10 pregnancies in 9 recipients after kidney transplantation