Ralston S H, Gardner M D, Jenkins A S, McKillop J H, Boyle I T
University Department of Medicine, Glasgow Royal Infirmary, Scotland.
Bone Miner. 1987 May;2(3):227-42.
The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.
对50例已补液的癌症相关性高钙血症患者的高钙血症病理生理机制进行了评估。令人惊讶的是，随着血清钙升高，肾小管钙重吸收似乎逐渐增加，这表明用于计算的列线图可能在绝对值上不准确，可能是因为它没有考虑尿钠排泄水平。然而，不同患者亚组的高钙血症机制存在显著差异，与尿钠排泄差异无关。在骨转移很少或没有骨转移的患者中，肾小管钙重吸收增加是高钙血症的主要原因，通常与骨吸收增加有关。这些异常被认为反映了肿瘤相关体液介质对肾脏和骨骼的作用。广泛转移性骨病患者高钙血症的主要原因是骨吸收增加，同时伴有肾小球滤过率受损，以及在较小程度上肾小管钙重吸收增加。这些异常被认为反映了高钙血症主要的局部溶骨机制以及肾小球滤过率的继发性损害。在所有治疗前评估的生化变量中，高钙血症的肾小管成分与治疗后血清钙值的相关性最强（r = 0.61，P < 0.001）。由于广泛骨骼转移患者的肾小管钙重吸收水平普遍较低，他们治疗后的钙值也显著低于骨转移很少或没有骨转移的患者（P < 0.05）。这些数据表明，高钙血症的病理生理机制是抗高钙血症治疗后钙降低反应的主要决定因素。在对恶性肿瘤患者抗高钙血症治疗的比较研究中应考虑到这一点。
