Hardy P, Morinière P H, Tribout B, Hamdini N, Marié A, Bouffandeau B, Pruna A, Fournier A
Department of Nephrology, Internal Medicine, CHU Amiens, France.
J Nephrol. 1999 Nov-Dec;12(6):398-403.
In 4 of our patients on chronic dialysis, we were intrigued by the association of hypercalcemia +/- hyperphosphatemia and normal intact PTH, with anicteric cholestasis without cytolysis. This picture occurred in 2 patients after they resumed dialysis because of a transplant rejection and in a third one after discontinuation of corticosteroids, prescribed for an idiopathic thrombocytopenia. No patient was under calcitriol, CaCO3 therapy, and their hypercalcemia persisted on a low calcium dialyzate (1.25 mmol/l). Obvious etiologies of hypercalcemia were not found: vitamin D or A intoxication, hyperparathyroidism, aluminum intoxication, hemopathy, HIV infection. The hypothesis of a granulomatous disease was made and a liver biopsy was performed showing granulomas with giant epitheloid cells. In one case foreign material (silicon ?) was present in the macrophages. Extensive investigations for sarcoidosis, tuberculosis and mycosis were negative. In 2 cases the so-called "dialysis" granulomatosis actually occurred in transplanted patients, suggesting the role of a transplantation related factor (toxic or virus). In the last case HCV seroconversion was present. In the 4 cases, corticotherapy led to the disappearance of hypercalcemia and to an increase of PTH. Our patients had the biological pattern of low bone turnover disease (hypercalcemia and normal intact PTH) and bone biopsy performed in 2 showed osteomalacia or ABD without aluminum. The association of this pattern with cholestasis should evoke liver granulomatosis, which should be confirmed by a liver biopsy and lead to a treatment by corticosteroids. The masking effect of previous corticoid therapy for transplantation should be pointed out. In 2 cases serial monitoring of plasma calcitriol showed a relation between decreasing high normal calcitriol with prednisone and normalization of calcemia, suggesting the role of inappropriate synthesis of calcitriol by the granuloma. In conclusion, liver granulomatosis should be looked for in dialysis patients on the association of unexplained hypercalcemia and normal PTH with anicteric cholestasis, and confirmed by a liver biopsy. Although still of unknown etiology, its evolution is favourable under corticotherapy.
在我们的4例长期透析患者中,高钙血症伴或不伴高磷血症以及正常的完整甲状旁腺激素(PTH),与无细胞溶解的无黄疸型胆汁淤积相关,这引起了我们的兴趣。这种情况发生在2例因移植排斥反应恢复透析后的患者以及第3例停用因特发性血小板减少症而开具的皮质类固醇后的患者身上。没有患者接受骨化三醇、碳酸钙治疗,且他们的高钙血症在低钙透析液(1.25 mmol/L)情况下持续存在。未发现高钙血症的明显病因:维生素D或A中毒、甲状旁腺功能亢进、铝中毒、血液病、HIV感染。提出了肉芽肿性疾病的假说,并进行了肝活检,结果显示有含巨大上皮样细胞的肉芽肿。在1例中,巨噬细胞内存在异物(硅?)。对结节病、结核病和霉菌病的广泛检查均为阴性。在2例中,所谓的“透析”性肉芽肿病实际上发生在移植患者中,提示存在与移植相关的因素(毒性或病毒)作用。在最后1例中存在丙型肝炎病毒血清学转换。在这4例中,皮质激素治疗导致高钙血症消失且PTH升高。我们的患者具有低骨转换疾病的生物学特征(高钙血症和正常的完整PTH),对2例进行的骨活检显示为骨软化症或无铝的无动力性骨病。这种特征与胆汁淤积的关联应使人想到肝肉芽肿病,这应由肝活检证实并导致采用皮质类固醇治疗。应指出先前用于移植的皮质激素治疗的掩盖作用。在2例中,对血浆骨化三醇的连续监测显示,随着泼尼松使高于正常的骨化三醇水平降低,血钙恢复正常,提示肉芽肿不适当合成骨化三醇的作用。总之,对于透析患者,若出现无法解释的高钙血症、正常PTH以及无黄疸型胆汁淤积相关情况,应查找肝肉芽肿病,并通过肝活检证实。尽管病因仍不明,但在皮质激素治疗下其病情发展是有利的。