Ingulli E, Tejani A, Markell M
Department of Pediatrics, SUNY Health Science Center, Brooklyn 11203.
Transplantation. 1993 May;55(5):1029-33. doi: 10.1097/00007890-199305000-00015.
Steroid therapy posttransplantation has been correlated with hyperlipidemia and hypertension. With improved graft survivals in the cyclosporine (CsA) era, post-tx hyperlipidemia and hypertension may place children at high risk for early atherosclerosis. Presently there are no large studies assessing the metabolic effects of steroid withdrawal in tx children. Thus, we report on the effect of prednisone withdrawal on blood pressure, weight, and serum lipid levels in children post-tx maintained on CsA alone. Pred taper is attempted in patients on CsA (6-7 mg/kg/day) with stable graft function and is extended over a 6-month period. Once a rejection is diagnosed pred is restarted and no future attempts to withdraw are made. BP, weight, and overnight fasting serum cholesterol (Schol) levels were measured 1 month prior to complete withdrawal (A), and after 6 months without pred (B). In patients requiring the restart of pred, subsequent measurements were obtained 6 months later (C). Of 74 tx children, 7 had primary nonfunction. Pred was successfully withdrawn in 49% (33) of the remaining 67. Of these patients, 42% (14/33) are still maintained off pred with stable renal function for a mean duration of 58.5 months (range 8-99 months). Nineteen patients had to be restarted on pred secondary to rejection between 7-36 months after withdrawal. Three of the patients subsequently lost their grafts to further rejection episodes. Univariate and multivariate analysis failed to identify clinical predictors of successful steroid withdrawal. The Schol at B, 171 +/- 5.4 mg/dl (mean +/- SEM) was lower (P < .001) than at A (249 +/- 10 mg/dl) or C (257 +/- 20 mg/dl). The systolic BP at B (108 +/- 2.8 mmHg) and diastolic BP at B (68 +/- 2.6 mmHg) were also lower (P < .001) than at A (122 +/- 3.2, 76 +/- 2.7 mmHg) or C (130 +/- 5, 80 +/- 3.2 mmHg), respectively. No difference in weight was noted. Lipid profile (total chol, triglyceride, HDL, VLDL, LDL) was measured in 10/14 patients off pred (mean age at sample 16.25 years) and was compared with 13 patients on pred (mean 15.5 years). Both the total chol (176 +/- 9.2, 265 +/- 8.3 mg/dl) and LDL (109 +/- 10, 167 +/- 9.2 mg/dl) were higher (P < .001) in the group on pred. Based on our findings of increased LDL and total chol, children on long-term pred therapy post-tx may be at increased risk for atherosclerotic disease.
移植后使用类固醇疗法与高脂血症和高血压相关。在环孢素(CsA)时代,随着移植物存活率的提高,移植后高脂血症和高血压可能使儿童面临早期动脉粥样硬化的高风险。目前尚无大型研究评估撤减类固醇对移植儿童代谢的影响。因此,我们报告了单独使用CsA维持治疗的移植后儿童停用泼尼松对血压、体重和血脂水平的影响。对于移植肾功能稳定且使用CsA(6 - 7mg/kg/天)的患者尝试逐渐减少泼尼松用量,并在6个月内完成。一旦诊断出排斥反应,就重新使用泼尼松,且不再尝试撤减。在完全撤减前1个月(A)以及停用泼尼松6个月后(B)测量血压、体重和空腹过夜血清胆固醇(Schol)水平。对于需要重新使用泼尼松的患者,在6个月后进行后续测量(C)。74例移植儿童中,7例出现原发性无功能。其余67例中,49%(33例)成功撤减了泼尼松。在这些患者中,42%(14/33)仍未使用泼尼松且肾功能稳定,平均持续时间为58.5个月(范围8 - 99个月)。19例患者在撤减后7 - 36个月因排斥反应不得不重新使用泼尼松。其中3例患者随后因进一步的排斥反应失去了移植物。单因素和多因素分析均未能确定成功撤减类固醇的临床预测因素。B时的Schol为171±5.4mg/dl(均值±标准误),低于A时(249±10mg/dl)或C时(257±20mg/dl)(P <.001)。B时的收缩压(108±2.8mmHg)和舒张压(68±2.6mmHg)也分别低于A时(122±3.2,76±2.7mmHg)或C时(130±5,80±3.2mmHg)(P <.001)。体重未发现差异。对10/14例停用泼尼松的患者(采样时平均年龄16.25岁)进行了血脂谱(总胆固醇、甘油三酯、高密度脂蛋白、极低密度脂蛋白、低密度脂蛋白)检测,并与13例使用泼尼松的患者(平均15.5岁)进行比较。使用泼尼松的组中总胆固醇(176±9.2,265±8.3mg/dl)和低密度脂蛋白(109±10,167±9.2mg/dl)均较高(P <.001)。基于我们发现低密度脂蛋白和总胆固醇升高,移植后长期接受泼尼松治疗的儿童可能患动脉粥样硬化疾病的风险增加。