Ramachandran R, Jairam A, Bhansali A, Jha V, Gupta K L, Sakhuja V, Kohli H S
Department of Nephrology, PGIMER, Chandigarh, India.
Department of Endocrinology, PGIMER, Chandigarh, India.
Indian J Nephrol. 2015 Jan-Feb;25(1):12-5. doi: 10.4103/0971-4065.136884.
Pulse methyl prednisolone followed by oral prednisolone and abrupt switch to chlorambucil/cyclophosphamide (Ponticelli/modified Ponticelli regimen) is used in patients with idiopathic membranous nephropathy. This therapy where steroids are stopped abruptly is unphysiologic and expected to have hypothalamic pituitary adrenal (HPA) axis suppression; however, this has not been evaluated. A total of 13 consecutive adult patients with idiopathic membranous nephropathy who had completed modified Ponticelli regimen were studied. The regimen included administration of pulse methylprednisolone 1 g for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days followed by oral cyclophosphamide at a dose of 2 mg/kg/day for the next month. This was repeated for three courses. Patients who had received corticosteroids prior to therapy were excluded. The HPA axis was evaluated after 1 month of completing the last course of steroid therapy. The evaluation was done using a low-dose adrenocorticotropic hormone stimulation test. A single intravenous bolus dose of synacthen (1 μg) was given at 9.00 am and the serum cortisol levels were estimated by radioimmunoassay at 0, 30, and 60 min. A peak cortisol level of 550 nmol/L or higher was considered as normal. Mean baseline cortisol levels was 662.3 ± 294.6 nmol/L and peak cortisol level was 767 ± 304.4 nmol/L. A total of 6 patients (46.2%) had low basal cortisol levels, only 3 (23%) had both basal and peak cortisol levels < 550 nmol/L suggestive of HPA axis suppression. To conclude, 23% of patients had suppression of HPA axis after modified Ponticelli regimen.
对于特发性膜性肾病患者,采用静脉注射甲泼尼龙后口服泼尼松龙,然后突然换用苯丁酸氮芥/环磷酰胺(Ponticelli/改良Ponticelli方案)进行治疗。这种突然停用类固醇的治疗方法不符合生理规律,预计会导致下丘脑-垂体-肾上腺(HPA)轴抑制;然而,尚未对此进行评估。本研究共纳入了13例连续的成年特发性膜性肾病患者,他们均已完成改良Ponticelli方案治疗。该方案包括静脉注射甲泼尼龙1g,持续3天,随后口服泼尼松龙0.5mg/kg/天,持续27天,接下来的一个月口服环磷酰胺,剂量为2mg/kg/天。此过程重复三个疗程。排除治疗前接受过皮质类固醇治疗的患者。在完成最后一个疗程的类固醇治疗1个月后评估HPA轴。评估采用低剂量促肾上腺皮质激素刺激试验。上午9点静脉推注一次西那肽(1μg),并在0、30和60分钟通过放射免疫分析法测定血清皮质醇水平。皮质醇峰值水平达到550nmol/L或更高被认为是正常的。平均基础皮质醇水平为662.3±294.6nmol/L,峰值皮质醇水平为767±304.4nmol/L。共有6例患者(46.2%)基础皮质醇水平较低,只有3例(23%)基础和峰值皮质醇水平均<550nmol/L,提示HPA轴抑制。综上所述,23%的患者在改良Ponticelli方案治疗后出现HPA轴抑制。