Rostaing L, Boisseau M, Huyn A, Durand D
Service de Néphrologie, CHU Rangueil, Toulouse-France.
Scand J Urol Nephrol. 1995 Dec;29(4):399-406. doi: 10.3109/00365599509180020.
We studied whether post-renal transplant erythrocytosis (PRTE) could be corrected by enalapril with minimal side-effects, thus avoiding iterative phlebotomies or bilateral nephrectomy of native kidneys. From our renal transplant patients, 12 presented a true PRTE as defined by a 51-Cr red blood cell mass (RBCM) above 32 ml/kg for women and above 36 ml/kg for men. Secondary polycythemia was ruled out: all the patients had a normal renal artery pulsed ultrasonography; in all cases the blood arterial 02 saturation was above 96%. Bone marrow aspiration and histology were performed for each patient: none of them showed evidence of Vaquez disease. All of them had stable renal function i.e. the mean serum creatinine was 112.8 +/- 26.3 mumol/l. They all received the same immunosuppression: azathioprine; ciclosporine A; methylprednisolone. PRTE occurred within the first year post transplant (median 7.5 months; range: 2-34). Their mean RBCM was 37.38 +/- 2.7 ml/kg. Their mean serum value of Epo was 17.41 +/- 13.5 mU/ml (range: 9.1-54). After informed consent, all patients received enalapril starting with 5 mg/day, progressively increased to 20 mg/day, if necessary, in order to maintain the hematocrit below 45%. The mean daily dosage of enalapril was 13.75 +/- 6.1 mg (range: 5-20). The mean follow-up was 14.8 months (range: 3.5-29.5). There was no change in renal function (mean serum creatinine: 126.3 +/- 35 mumol/l). A successful response to enalapril was obtained with a median of 40 days (range: 20-120). 11 patients out of 12 responded to enalapril with a decrease of Hb (14 +/- 2 g/dl vs 16.8 +/- 1.04 g/dl; p = 0.0006) and Ht (41.9 +/- 6.17% vs 51.14 +/- 2%; p = 0.0002) without a significant decrease of Epo (8.1 +/- 3.87; p = 0.1). One patient did not respond to enalapril nor to captopril, but did respond to a combined treatment of enalapril and theophilline. Moreover, all PRTE patients but two did not have Epo levels, before enalapril, above the normal range, suggesting mechanisms other than Epo overproduction by native kidneys i.e. erythropoiesis dysregulation. In conclusion, all patients but one were successfully treated by enalapril without side effects. The treatment was effective as early as 3 weeks from the start and avoided the need for iterative phlebotomies and nephrectomy of native kidneys.
我们研究了依那普利能否纠正肾移植后红细胞增多症(PRTE)且副作用最小,从而避免反复进行静脉放血或切除自体肾脏的双侧肾切除术。在我们的肾移植患者中,12例出现了真正的PRTE,其定义为女性51-铬红细胞容量(RBCM)高于32 ml/kg,男性高于36 ml/kg。排除了继发性红细胞增多症:所有患者肾动脉脉冲超声检查均正常;所有病例的动脉血氧饱和度均高于96%。对每位患者进行了骨髓穿刺和组织学检查:均未显示出真性红细胞增多症的证据。他们的肾功能均稳定,即平均血清肌酐为112.8±26.3 μmol/l。他们均接受相同的免疫抑制治疗:硫唑嘌呤;环孢素A;甲泼尼龙。PRTE发生在移植后的第一年内(中位数7.5个月;范围:2-34个月)。他们的平均RBCM为37.38±2.7 ml/kg。他们的促红细胞生成素(Epo)平均血清值为17.41±13.5 mU/ml(范围:9.1-54)。在获得知情同意后,所有患者开始服用依那普利,起始剂量为5 mg/天,必要时逐渐增加至20 mg/天,以将血细胞比容维持在45%以下。依那普利的平均日剂量为13.75±6.1 mg(范围:5-20)。平均随访时间为14.8个月(范围:3.5-29.5个月)。肾功能无变化(平均血清肌酐:126.3±35 μmol/l)。依那普利治疗的中位起效时间为40天(范围:20-120天)。12例患者中有11例对依那普利有反应,血红蛋白(Hb)下降(14±2 g/dl对16.8±1.04 g/dl;p = 0.0006),血细胞比容(Ht)下降(41.9±6.17%对51.14±2%;p = 0.0002),而Epo无显著下降(8.1±3.87;p = 0.1)。1例患者对依那普利和卡托普利均无反应,但对依那普利与茶碱的联合治疗有反应。此外,除2例患者外,所有PRTE患者在服用依那普利前Epo水平均未高于正常范围,提示除自体肾脏Epo产生过多外的其他机制,即红细胞生成失调。总之,除1例患者外,所有患者均成功接受依那普利治疗且无副作用。治疗从开始后3周就有效,避免了反复静脉放血和切除自体肾脏的需要。