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甲状旁腺激素和碱性磷酸酶与透析治疗的慢性肾脏病儿童的骨转换和矿化的关系:年龄、性别和种族的影响。

Association of parathormone and alkaline phosphatase with bone turnover and mineralization in children with CKD on dialysis: effect of age, gender, and race.

机构信息

Laboratório de Investigação Médica 16, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Faculdade Pernambucana de Saúde, Recife, Brazil.

出版信息

Pediatr Nephrol. 2020 Jul;35(7):1297-1305. doi: 10.1007/s00467-020-04499-2. Epub 2020 Mar 10.

Abstract

BACKGROUND

Studies investigating bone histology in children with chronic kidney disease (CKD) are scarce.

METHODS

Forty-two patients, mean age 11.3 ± 4.3 years with stage 5 CKD on dialysis, underwent double tetracycline labeling bone biopsy and the relationship between clinical features, biochemical markers, and bone densitometry (DXA) was investigated.

RESULTS

Low bone turnover was present in 59% of patients, abnormal mineralization in 29%, and low bone volume in 7%. Higher bone formation rate was found in non-Caucasian patients, whereas abnormal mineralization occurred in older and shorter children. We found no impact of gender and etiology of renal disease in our population. Parathormone (PTH) and alkaline phosphatase (AP) showed positive associations with bone turnover. ROC curve analysis showed a fair performance of biomarkers to predict TMV status. PTH < 2 times ULN independently associated with low bone turnover (RR 5.62, 95% CI 1.01-31.24; p = 0.049), in a model adjusted for race, calcitriol dosage, and calcium. It was also associated with abnormal mineralization (RR 1.35, 95% CI 1.04-1.75; p = 0.025), in a model adjusted for BMD scores, AP, age, and calcitriol. PTH and AP significantly predicted turnover and mineralization defect, although with low specificity and sensitivity, reaching a maximum value of 64% and 67%, respectively.

CONCLUSIONS

While PTH and AP were associated with turnover and mineralization, we recognize the limitation of their performance to clearly distinguish high from low/normal bone turnover and normal from abnormal mineralization. Our results reinforce the need to expand knowledge about renal osteodystrophy in pediatric population through prospective bone biopsy studies. Graphical abstract.

摘要

背景

目前针对慢性肾脏病(CKD)患儿骨组织学的研究较为匮乏。

方法

42 名平均年龄为 11.3±4.3 岁的处于透析阶段 5 的 CKD 患儿接受了双四环素标记骨活检,我们对其临床特征、生化标志物与骨密度(DXA)之间的关系进行了研究。

结果

59%的患者表现为低转换型骨病,29%的患者表现为骨矿化异常,7%的患者表现为低骨量。非白种人患者的骨形成率较高,而骨矿化异常在年龄较大和身材较矮小的儿童中更为常见。我们的研究人群中,性别和肾脏疾病的病因对结果没有影响。甲状旁腺激素(PTH)和碱性磷酸酶(AP)与骨转换呈正相关。ROC 曲线分析显示,生物标志物对预测 TMV 状态有一定的作用。在校正种族、骨化三醇剂量和钙后,PTH<2 倍 ULN 与低转换型骨病独立相关(RR 5.62,95%CI 1.01-31.24;p=0.049),且与骨矿化异常相关(RR 1.35,95%CI 1.04-1.75;p=0.025)。在校正 BMD 评分、AP、年龄和骨化三醇后,PTH 和 AP 显著预测了骨转换和骨矿化缺陷,尽管特异性和敏感性较低,分别达到 64%和 67%。

结论

虽然 PTH 和 AP 与骨转换和骨矿化相关,但我们认识到它们的性能存在局限性,无法明确区分高转换和低/正常转换以及正常和异常矿化。我们的研究结果强调了通过前瞻性骨活检研究来增加对儿科人群肾性骨营养不良认识的必要性。

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