Mittal S K, Dash S C, Tiwari S C, Agarwal S K, Saxena S, Fishbane S
Division of Nephrology, Winthrop University Hospital, Mineola, New York, USA.
Kidney Int. 1999 May;55(5):1912-9. doi: 10.1046/j.1523-1755.1999.00413.x.
The prevalence of metabolic bone disease in patients with nephrotic syndrome (NS) at normal level of renal function remains uncertain.
To address this issue, we studied 30 patients (20 men and 10 women, mean age 27.3 +/- 11.7 years) with NS who had normal renal function (mean creatinine clearance 103 +/- 4 ml/min). We evaluated their serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), vitamin D metabolites, urinary calcium, and skeletal survey. The extent of bone mineralization was analyzed by histomorphometric analysis of iliac crest bone biopsy specimens in all patients. The findings on bone histology were correlated with biochemical parameters.
The mean duration of NS was 35.5 +/- 26.9 months, with a protein excretion of 7.3 +/- 3.2 g/24 hr and a serum albumin of 2.2 +/- 0.8 g/dl. Total serum calcium was 7.8 +/- 0.8 mg/dl, whereas ionized calcium was 5.7 +/- 0.7 mg/dl, phosphorus 3.2 +/- 1.2 mg/dl, and alkaline phosphatase 149 +/- 48.6 U/liter. Serum iPTH levels were normal in all except two patients. The mean serum 25-hydroxyvitamin D [25(OH)D] level was 3.9 +/- 1.2 ng/ml (normal 15 to 30 ng/ml), whereas 1,25-dihydroxyvitamin D was 24 +/- 4.7 pg/ml (normal 16 to 65). There was an inverse correlation between serum levels of 25(OH)D and the magnitude of proteinuria (r = -0.42, P < 0.05). The mean 24-hour urinary calcium excretion was 82 +/- 21 mg/day. The skeletal survey was normal in all patients. Bone histology was normal in 33.3% of the patients, whereas 56.7% had isolated osteomalacia (OSM), and 10% had an increased bone resorption in association with defective mineralization. The severity of OSM measured by mineralization lag time correlated linearly with the duration (r = 0.94, P < 0.0001) and the amount (r = 0.97, P < 0.0001) of proteinuria. All patients with NS for more than three years had histological changes. Patients with OSM had lower 25(OH)D and serum albumin as compared with those with normal histology (P < 0.005). Bone mineralization had no significant correlation with serum iPTH, divalent ions, or vitamin D levels.
OSM is a frequent finding in adult patients with NS, even at a normal level of renal function. Its severity correlates with the amount and duration of proteinuria.
肾功能正常的肾病综合征（NS）患者中代谢性骨病的患病率仍不确定。
为解决这一问题，我们研究了30例肾功能正常（平均肌酐清除率103±4 ml/分钟）的NS患者（20例男性和10例女性，平均年龄27.3±11.7岁）。我们评估了他们的血清钙、磷、碱性磷酸酶、免疫反应性甲状旁腺激素（iPTH）、维生素D代谢产物、尿钙和骨骼检查。通过对所有患者髂嵴骨活检标本进行组织形态计量学分析来分析骨矿化程度。骨组织学检查结果与生化参数相关。
NS的平均病程为35.5±26.9个月，蛋白排泄量为7.3±3.2 g/24小时，血清白蛋白为2.2±0.8 g/dl。血清总钙为7.8±0.8 mg/dl，而离子钙为5.7±0.7 mg/dl，磷为3.2±1.2 mg/dl，碱性磷酸酶为149±48.6 U/升。除两名患者外，所有患者的血清iPTH水平均正常。血清25-羟基维生素D [25(OH)D]平均水平为3.9±1.2 ng/ml（正常为15至30 ng/ml），而1,25-二羟基维生素D为24±4.7 pg/ml（正常为16至65）。血清25(OH)D水平与蛋白尿程度呈负相关（r = -0.42，P < 0.05）。24小时尿钙排泄平均量为82±21 mg/天。所有患者的骨骼检查均正常。33.3%的患者骨组织学正常，而56.7%有单纯性骨软化（OSM），10%有骨吸收增加伴矿化缺陷。通过矿化延迟时间测量的OSM严重程度与蛋白尿的病程（r = 0.94，P < 0.0001）和量（r = 0.97，P < 0.0001）呈线性相关。所有病程超过三年的NS患者均有组织学改变。与组织学正常的患者相比，OSM患者的25(OH)D和血清白蛋白较低（P < 0.005）。骨矿化与血清iPTH、二价离子或维生素D水平无显著相关性。
即使在肾功能正常的成年NS患者中，OSM也很常见。其严重程度与蛋白尿的量和病程相关。
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