Hsiao R J, Mezger M S, O'Connor D T
Department of Medicine, University of California, San Diego.
Kidney Int. 1990 Mar;37(3):955-64. doi: 10.1038/ki.1990.71.
Chromogranin A is a soluble protein that is stored and released with catecholamines from their secretory vesicles. Its measurement is a probe of exocytotic sympathoadrenal activity, and in plasma it may also be a useful tool in the diagnosis of peptide producing endocrine neoplasms. Because we have found that chromogranin A is elevated in secondary (uremic) hyperparathyroidism, we systematically investigated the influence of renal dysfunction and its attendant hyperparathyroidism on chromogranin A in several subject groups: normal controls (serum creatinine less than or equal to 1.2 mg/dl), nonazotemic renal transplant recipients, nonazotemic subjects with glomerular disease (serum creatinine between 1.2 and 2 mg/dl), mid-range renal disease subjects (serum creatinine between 2 and 7.5 mg/dl), and end-stage renal disease subjects (serum creatinine greater than 7.5 mg/dl). Plasma chromogranin A rose with deterioration of renal function, and the rise was independent of etiologic diagnosis, blood pressure, or indices of sympathoadrenal activity or hyperparathyroidism. Size fractionation of uremic plasma by gel filtration, and immunoextraction by region-specific anti-chromogranin A (anti-N-terminal, anti-C-terminal, and anti-mid-molecule) antibodies suggested that chromogranin A immunoreactivity circulates in uremia as lower molecular weight fragments of the parent chromogranin A molecule, with mid-molecule fragments the major constituent. This immunoreactivity is only minimally removed by peritoneal dialysis and is not at all hemodialyzable. The uremia-dose-dependent accumulation of chromogranin A immunoreactive fragments in renal failure suggests that the kidney is a major site of disposition or removal of the immunoreactivity. Furthermore, lack of detectable chromogranin A immunoreactivity in normal subjects' urine suggests that the immunoreactivity is destroyed as it is removed by the kidney. We conclude that plasma chromogranin A increases in proportion to degree of renal insufficiency and that renal function must therefore be controlled when using plasma chromogranin A in the investigation of amine or peptide hormone storage and release.
嗜铬粒蛋白A是一种可溶性蛋白质，它与儿茶酚胺一起储存于分泌囊泡并从中释放。其检测是对胞吐性交感肾上腺活动的一种探查，并且在血浆中它也可能是诊断产生肽的内分泌肿瘤的一种有用工具。因为我们发现嗜铬粒蛋白A在继发性（尿毒症性）甲状旁腺功能亢进中升高，所以我们系统地研究了肾功能不全及其伴随的甲状旁腺功能亢进对几个受试者组中嗜铬粒蛋白A的影响：正常对照组（血清肌酐小于或等于1.2mg/dl）、非氮质血症肾移植受者、患有肾小球疾病的非氮质血症受试者（血清肌酐在1.2至2mg/dl之间）、中度肾病受试者（血清肌酐在2至7.5mg/dl之间）以及终末期肾病受试者（血清肌酐大于7.5mg/dl）。血浆嗜铬粒蛋白A随着肾功能恶化而升高，并且这种升高与病因诊断、血压、交感肾上腺活动指标或甲状旁腺功能亢进无关。通过凝胶过滤对尿毒症血浆进行大小分级分离，以及使用区域特异性抗嗜铬粒蛋白A（抗N端、抗C端和抗中分子）抗体进行免疫提取表明，嗜铬粒蛋白A免疫反应性在尿毒症中以亲本嗜铬粒蛋白A分子的较低分子量片段形式循环，其中中分子片段是主要成分。这种免疫反应性仅通过腹膜透析有少量清除，并且完全不能通过血液透析清除。肾衰竭中嗜铬粒蛋白A免疫反应性片段的尿毒症剂量依赖性积累表明肾脏是免疫反应性处置或清除的主要部位。此外，正常受试者尿液中未检测到嗜铬粒蛋白A免疫反应性表明该免疫反应性在被肾脏清除时被破坏。我们得出结论，血浆嗜铬粒蛋白A与肾功能不全程度成比例增加，因此在使用血浆嗜铬粒蛋白A研究胺或肽激素的储存和释放时必须控制肾功能。
