|
|
The role of nutritional vitamin D in chronic kidney disease–mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation—a European consensus statement
营养性维生素D在儿童和成人慢性肾脏病、透析和肾移植后的矿物质和骨代谢异常中的作用——欧洲共识声明
Nephrology Dialysis Transplantation, Volume 40, Issue 4, April 2025, Pages 797–822,
Published: 28 January 2025
https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfae293/7985766
https://doi.org/10.1093/ndt/gfae293
维生素D缺乏在慢性肾脏病（CKD）患者中十分常见，且与不良预后相关。然而，对于CKD患者维生素D缺乏的评估与管理仍存在争议。虽然活性维生素D制剂治疗未能改善CKD患者结局，且已知可能引发高钙血症风险，但现行临床实践指南仍建议：对于晚期CKD合并严重进展性甲状旁腺功能亢进的患者，可考虑使用骨化三醇等活性维生素D类似物；而对普通CKD患者则推荐与一般人群相同的营养性维生素D补充方案。
最近，大规模随机对照试验（RCT）如维生素D与omega-3试验（VITAL）表明，即使在基线25-羟维生素D[25(OH)D]水平低下的人群中，营养性维生素D补充也未能带来健康获益。这些试验结果公布后，部分权威专家建议医疗机构停止维生素D缺乏的筛查，并呼吁大众停用维生素D补充剂，而另一些学者则主张更审慎地解读数据。这些试验的结果传播至肾脏病学界，引发了对CKD患者是否也应停止营养性维生素D补充的讨论，另外，关于CKD患者最佳监测[定量检测与维生素D代谢物比值、总25(OH)D和游离25(OH)D]与治疗策略[目标25(OH)D水平、营养性维生素D与活性维生素D制剂的联合治疗]的问题也需予以关注。
针对这些问题，欧洲肾脏病协会（ERA）和欧洲儿科肾脏病学会（ESPN）制定了《营养性维生素D在儿童和成人慢性肾脏病、透析和肾移植后的矿物质及骨代谢异常中的作用——欧洲共识声明》，2025年1月在 Nephrology Dialysis Transplantation 发布。共识声明旨在为儿童及成人CKD、透析患者和肾移植受者维生素D缺乏提供基于营养性维生素D的监测与纠正方案。
这个共识声明的关键临床实践要点包括：
·监测与纠正维生素D缺乏：建议对CKD患者及肾移植后患者监测并纠正维生素D缺乏，目标是将25-羟维生素D水平维持在＞75nmol/L（＞30ng/mL）。
·安全性建议：尽管维生素D补充总体耐受性良好且安全，但应避免超大剂量（≥100000IU）和25-羟维生素D水平过高（＞150-200nmol/L或60-80ng/mL），以降低中毒风险。
·未来研究方向：需通过临床试验进一步探究维生素D补充对不同阶段CKD合并维生素D缺乏患者临床相关结局的益处。
现摘录共识声明的“关键循证要点”（Key evidence points）和“临床实践要点”（Clinical practice points）相关内容以供学习参考，“背景与依据”（Background and rationale）部分可到原文网址查阅。
Q1：目前对一般人群补充维生素D的建议是什么？
1.1 健康状态下的维生素D代谢
关键循证要点：
·人体内维生素D最重要的来源是皮肤在紫外线B（UVB）照射下的合成，因为大多数食物中天然维生素D的含量较低。
·肝脏25-羟化酶活性是受代谢调控的，而非由组成性因素决定。
·肾脏对1,25-二羟维生素D[1,25(OH)2D]的合成与降解过程受到矿物质代谢相关激素[甲状旁腺激素(PTH)、成纤维细胞生长因子23(FGF23)及维生素D代谢物]的精密调控。
·肾外组织1,25(OH)2D的生成主要依赖底物浓度，这种生成机制可能有助于维持循环中1,25(OH)2D的水平，至少在肾脏合成不足的情况下如此。
·Dermal production upon ultraviolet-B light exposure is the most important source of vitamin D in humans as most foods have a low natural content of vitamin D.
·Liver 25-hydroxylase activity is metabolically controlled, rather than constitutively determined.
·Renal 1,25 dihydroxy vitamin D (1,25(OH)2D) production and degradation is tightly controlled by the hormones that govern mineral metabolism (PTH, FGF23, vitamin D metabolites).
·Extrarenal 1,25(OH)2D production is largely substrate-dependent and may assist in maintaining circulating 1,25(OH)2D levels, at least in conditions of insufficient renal production.
1.2 一般人群营养维生素D目标和补充指南
关键循证要点：
·婴幼儿应补充维生素D（400-600国际单位/天），至少在出生后的最初几年内需要持续补充。
·成人（尤其是老年人与孕妇）应适当补充维生素D，但推荐剂量差异较大（每日200-2000IU不等），这反映出学界对25(OH)D理想血清最低浓度尚未达成共识。
·Infants and small children should be supplemented with vitamin D (400–600 IU/day), at least during their first years of life.
·Adults, especially elderly and pregnant individuals, should have access to vitamin D supplementation, but recommended doses vary widely (from 200 IU to 2000 IU/day), in line with the uncertainty regarding the minimal desirable serum concentration of 25(OH)D.
1.3 慢性肾脏病（CKD）的维生素D代谢
关键循证要点：
·CKD会导致维生素D代谢紊乱并引发维生素D反应低下。
·CKD很可能是一种伴随肾外CYP27B1酶激活及1,25(OH)2D肾外合成的病理状态。
·CKD is a state of dysregulated vitamin D metabolism and vitamin D hyporesponsiveness.
·CKD is likely a state of extrarenal CYP27B1 activation with extrarenal production of 1,25-dihydroxyvitamin D.
1.4 肾移植受者的维生素D代谢特征
关键循证要点：
·肾移植术后早期患者25(OH)D水平会出现短暂性下降。
·随着移植肾功能恢复，肾脏1,25(OH)2D的合成能力也逐步回升。
·25(OH)D levels show a transient decline early after kidney transplantation.
·Renal production of 1,25(OH)2D recovers after kidney transplantation paralleling kidney graft function.
Q2：维生素D检测与监测中存在哪些（前）分析阶段的技术问题？
2.1 分析阶段考虑事项
关键循证要点：
·液相色谱-串联质谱法（LC-MS/MS）是检测维生素D代谢物的首选方法，尤其适用于CKD患者。
·游离维生素D或代谢比率的临床评估价值尚不明确。
·LC-MS/MS is the method of choice for measuring vitamin D metabolites, particularly in patients with CKD.
·The added value of the assessment of free vitamin D or metabolic ratios is uncertain.
2.2 监测策略
关键循证要点：
·针对CKD G2-5D期患者，我们建议在首次就诊时检测25(OH)D水平，并在调整维生素D补充方案后3个月复查，此后至少每年监测一次。
·不推荐常规监测1,25(OH)2D水平、游离维生素D水平及维生素D代谢物比值。
·In patients with CKD G2-5D, we suggest measuring 25(OH)D concentrations at first presentation, with repeated analysis 3 months after any changes to vitamin D supplementation, and at least annually thereafter.
·Routine monitoring of 1,25(OH)2D levels, free vitamin D levels, and ratios between vitamin D metabolites are not recommended.
Q3：慢性肾脏病（CKD）患者补充维生素D对骨骼及矿物质代谢是否具有临床获益证据？
3.1 CKD患者的维生素D补充与甲状旁腺激素（PTH）调控
关键循证要点：
·维生素D补充治疗可改善CKD成人与患儿继发性甲状旁腺功能亢进症的病情控制。
临床实践要点：
·针对CKD G2-5D期成人和患儿，我们建议将维生素D补充至＞75nmol/L（＞30ng/mL）水平，以延缓继发性甲状旁腺功能亢进症的发生或改善其控制效果，但需注意该措施对CKD G5-5D期患者的疗效尚不明确。
·对于CKD G2-3期患者，我们建议在使用活性维生素D制剂前先补充维生素D；而对于CKD G4-5D期患者，则建议在开始活性维生素D治疗前或同时进行维生素D补充。
·Vitamin D supplementation improves control of secondary hyperparathyroidism in adults and children with CKD.
·Clinical practice points
We recommend supplementing vitamin D to >75 nmol/l (>30 ng/ml) in adults and children with CKD G2-5D to delay the onset, or improve the control, of secondary hyperparathyroidism, recognizing that the effect in CKD G5–5D is uncertain.
·We suggest replenishing vitamin D before using an active vitamin D compound in CKD G2-3 and before or concomitantly with an active vitamin D compound in CKD G4-5D.
3.2 维生素D补充对CKD患者骨骼结局的影响
关键循证要点：
·现有证据表明，单纯补充维生素D并不能降低CKD成人和儿童患者的骨质流失及骨折风险，对CKD患儿的生长发育也无显著改善作用。
·There is no evidence for a benefit of vitamin D supplementation alone on the risk of bone loss and fractures in adults or children with CKD, or for improved growth in children with CKD.
3.3 肾移植受者维生素D代谢、甲状旁腺激素调控与骨骼结局
关键循证要点：
·补充维生素D可改善肾移植术后继发性甲状旁腺功能亢进的控制。
·补充维生素D或可降低肾移植术后骨质流失及骨折风险。
临床实践要点：
·我们建议为肾移植受者补充维生素D，使其血清水平维持在＞75nmol/L（＞30ng/mL）以上，以降低骨质流失及骨折风险。
·Vitamin D supplementation improves the control of hyperparathyroidism after kidney transplantation.
·Vitamin D supplementation may reduce the risk of bone loss and fractures after kidney transplantation.
·We suggest supplementing vitamin D to >75nmol/l (>30ng/ml) in kidney transplant recipients to reduce the risk of bone loss and fractures.
Q4：目前是否有证据表明补充维生素D对慢性肾脏病（CKD）患者的心血管结局及全因死亡率具有改善作用？
4.1 维生素D补充对慢性肾脏病（CKD）患者心血管结局及死亡率的影响
关键循证要点：
·现有证据表明，补充维生素D并不能改善CKD患者的心血管结局或降低全因死亡率。
·目前研究未发现维生素D补充治疗存在具有临床意义的心血管安全性风险。
·There is no evidence for a benefit of vitamin D supplementation on cardiovascular outcomes or all-cause mortality in CKD.
·No studies revealed clinically relevant cardiovascular safety concerns of vitamin D supplementation.
Q5：慢性肾脏病（CKD）患者维生素D缺乏的管理与预防策略是什么？
5.1 药物应用考量
临床实践要点：
·我们建议使用口服胆钙化醇（维生素D3）来提升并维持血清25(OH)D浓度在目标范围内。如无法获得胆钙化醇，可使用等效剂量的口服麦角钙化醇（维生素D2）。
·应优先选择胆钙化醇口服给药途径，仅对存在胃肠道吸收障碍的患者考虑肌肉注射给药。
·维生素D制剂均应经口服用，禁止通过饲管给药。
·We suggest using oral cholecalciferol to increase and maintain serum 25(OH)D concentration in the target range. If cholecalciferol is unavailable, oral ergocalciferol may be used in an equivalent dose.
·Oral administration of cholecalciferol should be preferred, with intramuscular administration reserved for patients with gastrointestinal malabsorption disorders.
·Vitamin D compounds should be administered by mouth and not through feeding tubes.
5.2 CKD患者推荐给药方案
临床实践要点：
·我们建议采用口服胆钙化醇（维生素D3）治疗，可选用每日一次、每周一次、每两周一次或每月一次的给药方案，并根据基线25(OH)D水平和体型调整剂量。
·针对CKD G2-5D期或肾移植术后血清25(OH)D浓度＜75nmol/L（＜30ng/mL）的成人患者，建议等效日剂量为5000-7000IU的胆钙化醇，持续12周以达到目标范围。为维持血清25(OH)D在目标浓度，建议持续给予等效日剂量2000IU的治疗。
·对于CKD G2-5D期或肾移植术后血清25(OH)D浓度＜75nmol/L（＜30ng/mL）的儿童患者，建议等效日剂量3000-7000IU的胆钙化醇，持续12周以达到目标范围。为维持血清25(OH)D在目标浓度，建议持续给予等效日剂量1000-2000IU的治疗，并需根据体型调整剂量。
·我们建议避免单次给药剂量超过100000IU。
·We suggest using oral cholecalciferol with once-daily, weekly, fortnightly, or monthly dosing schedules, adjusting the dose for baseline 25(OH)D levels and body size.
·In adults with CKD G2-5D or after kidney transplantation with serum 25(OH)D concentration <75nmol/l (<30ng/ml), we suggest an equivalent daily dose of 5000-7000 IU/day of cholecalciferol for a duration of 12 weeks to achieve the optimal target range. To maintain serum 25(OH)D concentration in the target range, we suggest continuous dosing with an equivalent daily dose of 2000IU/day.
·In children with CKD G2-5D or after kidney transplantation with serum 25(OH)D concentration <75nmol/l (<30ng/ml), we suggest an equivalent daily dose of 3000-7000 IU/day of cholecalciferol for a duration of 12 weeks to achieve the optimal target range. To maintain serum 25(OH)D concentration in the target range, we suggest continuous dosing with an equivalent daily dose of 1000-2000IU/day, adjusting for body size.
·We suggest avoiding exceeding doses of 100000IU given as a single dose.
5.3 CKD患者（缓释型）骨化二醇的应用
临床实践要点：
·对于合并肝功能衰竭的CKD患者，可考虑使用骨化二醇替代胆钙化醇或麦角钙化醇。
·对于CKD G3-4期合并继发性甲状旁腺功能亢进的成人患者，可考虑使用缓释型骨化二醇。
·Calcifediol may be considered instead of cholecalciferol or ergocalciferol in patients with CKD and liver failure.
·Extended release calcifediol may be considered in adults with CKD G3-4 and secondary hyperparathyroidism.
5.4 安全性考量
关键循证要点：
·当25(OH)D水平低于250nmol/L（＜100ng/mL）时，营养性维生素D补充剂罕见导致高钙血症。
·目前尚未明确CKD患者25(OH)D的安全上限值及长期使用营养性维生素D的安全性。
临床实践要点：
·针对CKD或肾移植后的成人及儿童患者，我们建议当血清25(OH)D水平高于150-200nmol/L（60-80ng/mL）且未出现高钙血症时，暂停营养性维生素D补充剂的使用。
·对于合并高钙血症的CKD患者，在停用维生素D前，需排查并处理其他可能导致血钙升高的因素，包括：医源性因素（使用活性维生素D制剂、高钙透析液、含钙口服药物）、CKD相关因素（存在三发性甲状旁腺功能亢进）以及非CKD相关疾病（恶性肿瘤、血液系统疾病、结节病、维生素A缺乏症等）。
·Hypercalcemia is rarely seen with nutritional vitamin D supplements when 25(OH)D levels are below 250nmol/l (<100ng/ml).
·The upper safe limit of 25(OH)D and the safety of long-term use of nutritional vitamin D in patients with CKD are unknown.
·In adults and children with CKD or after kidney transplantation, we suggest withholding nutritional vitamin D supplements when serum 25(OH)D levels are above 150-200nmol/l (60-80ng/ml) in the absence of hypercalcemia.
·In patients with CKD and hypercalcemia, check for and manage other causes of high calcium including iatrogenic (the use of active vitamin D compounds, high dialysate calcium, oral calcium-containing medications), CKD-related (presence of tertiary hyperparathyroidism), and non-CKD-related conditions (malignancy, haematological conditions, sarcoidosis, hypovitaminosis A, etc.) before stopping vitamin D supplementation.
小结评述：
尽管在普通人群和慢性肾脏病（CKD）患者中，维生素D缺乏与发病率及死亡率之间存在明确关联，但目前尚无确凿证据表明补充维生素D能改善患者相关的骨骼或非骨骼临床结局。然而，CKD患者存在严重的维生素D代谢障碍，这会加剧CKD矿物质和骨代谢异常（CKD-MBD）的复杂代谢紊乱，而补充维生素D已被证实可改善继发性甲状旁腺功能亢进的控制。因此，基于现有证据，我们推荐对各期CKD患者及肾移植术后成人和儿童进行维生素D缺乏的监测与治疗。
维生素D补充在CKD患者中耐受性良好，未出现显著安全性信号，但参照普通人群的研究警示，我们建议避免使用超大剂量维生素D及维持过高的血清25-羟维生素D[25(OH)D]水平。未来研究应聚焦于开展（实用性）临床试验，探究在不同阶段CKD合并维生素D缺乏患者中，维生素D补充对患者相关临床结局的获益。
Despite consistent associations between vitamin D deficiency and morbidity and mortality both in the general population and in patients with CKD, there is no conclusive evidence for a benefit of vitamin D supplementation on patient-relevant skeletal or non-skeletal outcomes. However, CKD is a setting of severely affected vitamin D metabolism, which contributes to the complex mineral metabolism disturbances of CKD-MBD, and vitamin D supplementation has been shown to improve the control of secondary hyperparathyroidism. Therefore, based on available evidence, we recommend monitoring for, and treating, vitamin D deficiency in adults and children with CKD across stages of disease and after kidney transplantation.
Vitamin D supplementation is well-tolerated without prominent safety signals in CKD, but based on concerns raised in the background population, we suggest avoiding mega-doses of vitamin D and very high serum levels of 25(OH)D. Future research should focus on (pragmatic) clinical trials investigating the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency, across the spectrum of CKD.
本文根据机器翻译整理，仅供参考，完整准确内容请查阅原始文献：On behalf of the European Renal Osteodystrophy (EUROD) initiative under the Chronic Kidney Disease–Mineral and Bone Disorder working group of the European Renal Association (ERA) and the Dialysis and Chronic Kidney Disease–Mineral and Bone disorder working groups of the European Society of Paediatric Nephrology (ESPN). The role of nutritional vitamin D in chronic kidney disease–mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation－a European consensus statement, Nephrology Dialysis Transplantation, 2025; DOI：https://doi.org/10.1093/ndt/gfae293
【链接】
综述：维生素D在肾移植结局中的作用
http://yizhiwang.org.cn/forum.php?mod=viewthread&tid=89027
肾脏病和肾移植患者能否补充普通维生素D？
http://yizhiwang.org.cn/forum.php?mod=viewthread&tid=89911
肾移植受者营养治疗2020美国指南摘读
http://yizhiwang.org.cn/forum.php?mod=viewthread&tid=87440
2021，肾移植受者营养治疗官方指南
https://bbs.yizhiwang.org.cn/forum.php?mod=viewthread&tid=87419
|
|
发表于