慢性腎病孩童常見維他命D缺乏

作者：Fran Lowry  
出處：WebMD醫學新聞

　　March 5, 2009 — 根據3月份小兒科期刊的一篇研究報告，慢性腎病孩童的維他命D缺乏常見且日漸增加。
　　
　　芝加哥西北大學Feinberg醫學院的Farah N. Ali醫師等人寫道，小孩缺乏維他命D會因為礦化作用減少而影響骨骼發育。慢性腎病孩童會因為腎性骨病變以及缺乏維他命D而有骨骼發育風險。小兒腎病結果品質初步調查(Kidney Disease Outcomes Quality Initiative[KDOQI] )規範中，如果血清副甲狀腺值高於慢性腎病第二期的目標範圍時，建議測量血清25-羥基維他命D(25[OH]D)值，但慢性腎病孩童的維他命D缺乏問題未被妥善研究。
　　
　　這項研究的目標是確認這些小孩缺乏維他命D的程度，而此一情況的發生率是否會隨著時間改變；研究也檢視25(OH)D值是否有季節性或種族性差異。
　　
　　在1987至1996年間，1,074名非臥床小兒慢腎腎病第一期到第五期患者測量一次25(OH)D值，其中403名病患(38%)在這10年間有進行反覆測量；該研究也在2005至2006年間測量其他88名隨機取樣病患的25(OH)D值。
　　
　　研究作者寫道，我們於進行KDOQI以及常規使用維他命D補充品之前，在過去10年(1987至1996年)密切評估此一世代， 另外也在KDOQI規範出版後，於2005至2006年間，在另一組同齡樣本進行調查。
　　
　　維他命D缺乏定義為，25(OH)D值小於15 ng/mL，在10年研究期間，此類病患有20%到75%；而且，在這10年間，25(OH)D值低於15 ng/mL的情況漸增(P < .001)。
　　
　　同時也發現季節性的25 (OH)D值變化，夏秋之季的值高於冬春之季時(P < .001)；分析只測量一次的病患時，在夏秋之季(從7月至12月)測量25[OH]D值的病患，維他命D值顯著高於冬春之季(從1月至6月)時測量25[OH]D值的病患(P < .05)。
　　
　　分析2005至2006年的同齡樣本時發現，平均25(OH)D值為 21.8 ng/mL，中間值為17.7 ng/mL，研究作者寫道，與10年研究所見相似。
　　
　　同齡樣本群的維他命缺乏發生率為39%，多數病患(72%)之25[OH]D值低於32 ng/mL。
　　
　　根據種族分析此資料發現，13名黑人病患(68%)的25(OH)D 值低於15 ng/mL，26名不同血統之西班牙裔病患(90%)的25[OH]D值低於32 ng/mL；總共有16名白人病患(53%)為維他命D缺乏或不足。黑人和西班牙裔病患的平均25(OH)D 值分別為17和18 ng/mL，顯著低於白人病患的平均值28 ng/mL (P < .05)。
　　
　　黑人和西班牙裔慢性腎病小孩有較多維他命D缺乏的發現，證實了之前有關黑色素增加會導致皮膚減少維他命D生產的知識。研究作者寫道，這是個會影響健康孩童與青少年的問題，特別是皮膚顏色較暗者，但這或許也是慢性腎病且有維他命D代謝問題病患之骨骼健康的另一個威脅。
　　
　　他們也指出，在10年研究中發現維他命D缺乏的發生率增加是值得注意的議題，許多因素與此一發現有關，可能也包括取樣偏差，而醫師可能對疑似維他命D缺乏高風險者增加測量25(OH)D值的醫囑；維他命D缺乏的發生率增加也可能是因為過去10年陽光曝曬程度的改變，這可能是因為小孩防曬用品的使用增加，或者是較少於戶外曬太陽。
　　
　　研究限制之一是缺乏整體的飲食與補充品資訊，也缺乏1987至1996年間有關種族背景與可能診斷的資訊。
　　
　　作者結論表示，我們的資料支持小兒KDOQI 規範測量慢性腎病孩童的12(OH)D值，以減少維他命D缺乏對腎性骨病變的影響，也就是現在所稱的慢性腎病骨質與骨骼異常。
　　
　　作者們宣告沒有相關財務關係。

Vitamin D Deficiency Prevalent in Children With Chronic Kidney Disease

By Fran Lowry
Medscape Medical News

March 5, 2009 — There is a high and growing prevalence of vitamin D deficiency in children with chronic kidney disease, adding to their already high risk for impaired bone development, according to a study reported in the March issue of Pediatrics.

"Vitamin D deficiency in children adversely affects bone development by reducing mineralization. Children with chronic kidney disease are at risk for altered bone development from renal osteodystrophy and concomitant vitamin D deficiency," write Farah N. Ali, MD, from the Feinberg School of Medicine, Northwestern University, Chicago, Illinois, and colleagues. "The pediatric Kidney Disease Outcomes Quality Initiative [KDOQI] guidelines suggest measuring serum 25-hydroxyvitamin D (25[OH]D) levels if serum parathyroid hormone levels are above the target range for chronic kidney disease stages 2 and beyond, but the magnitude of vitamin D deficiency in children with chronic kidney disease is not well studied."

The goals of this study were to determine the extent of vitamin D deficiency in these children and whether the prevalence of this deficiency changed over time. The study also examined seasonal and ethnic differences in 25(OH)D levels.

Levels of 25[OH]D in 1074 ambulatory pediatric patients with chronic kidney disease stages 1 through 5 were measured once during a 10-year period from 1987 to 1996. Of this number, 403 patients (38%) had repeat measures during the decade.

The study also measured 25(OH)D levels in a random sample of 88 additional patients during 2005 to 2006.

"We chose to evaluate a cohort over a past decade (1987 to 1996), before KDOQI and the routine use of vitamin D supplementation, as well as a contemporary population (2005 to 2006) that followed the publication of KDOQI guidelines," the study authors write

The prevalence of vitamin D deficiency, defined as a 25(OH)D level lower than 15 ng/mL, ranged from 20% to 75% in the decade studied. In addition, an increasing prevalence of 25(OH)D levels lower than 15 ng/mL was noted from the beginning to the end of the decade (P < .001).

Seasonal variation in 25 (OH)D levels was also noted, with summer–fall values greater than values in winter–spring (P < .001). Analyzing only 1 measurement per patient, the patients who had their 25[OH]D levels tested in the summer–fall time period (from July through December) had significantly higher levels of vitamin D than those who had their levels of 25(OH)D tested in the winter–spring time period (from January through June; P < .05).

Analysis of the contemporary 2005 to 2006 data found a mean 25(OH)D level of 21.8 ng/mL and a median level of 17.7 ng/mL, "quite similar to those in the decade study," the study authors write.

The prevalence of deficiency in this contemporary study group was 39%, and the majority of the patients (72%) had levels of 25[OH]D lower than 32 ng/mL.

Analysis of the data according to ethnicity found that 13 black patients (68%) had 25(OH)D levels lower than 15 ng/mL, and 26 Hispanic patients of varying ancestry (90%) had 25[OH]D levels lower than 32 ng/mL. A total of 16 white patients (53%) were either vitamin D deficient or insufficient. The mean levels of 25(OH)D in black and Hispanic patients were 17 and 18 ng/mL, respectively, which were significantly lower than the mean level of 28 ng/mL found in white patients (P < .05).

The finding of more vitamin D deficiency in black and Hispanic children with chronic kidney disease validates previous knowledge that increased content of melanin does in fact decrease vitamin D production in the skin. "This is a problem that affects healthy children and adolescents, especially those with darkly pigmented skin, but [it] may be an extra threat to optimal bone health in such patients with underlying [chronic kidney disease] with altered vitamin D metabolism," the study authors write.

They also point out that the finding of increased prevalence of vitamin D deficiency during the decade studied "is noteworthy." Several factors may have contributed to this finding. These include possible referral bias, wherein physicians increasingly ordered 25(OH)D levels to be tested in patients whom they suspected to be at higher risk for vitamin D deficiency. The increasing prevalence of vitamin D deficiency could also be a result of changes in sunlight exposure during the decade, perhaps through increasing use of sunscreen or less time spent outdoors in the sun for this population of children.

A limitation of the study is the lack of dietary and supplement information overall, as well as the lack of data regarding racial background and underlying diagnoses in the population studied between 1987 and 1996.

The authors conclude, "Our data support the pediatric KDOQI guideline for the measurement of 12(OH)D levels in children with [chronic kidney disease], to reduce the effects of vitamin D deficiency as an important component of their renal osteodystrophy, now termed [chronic kidney disease]-mineral and bone disorder."

The authors have disclosed no relevant financial relationships.

Pediatrics. 2009;123:791–796.