本帖最後由 lsc0019 於 2009-4-4 13:44 編輯
作者：Laurie Barclay, MD
出處：WebMD醫學新聞
March 19, 2009 — 根據線上發表在3月18日美國腎臟醫學會臨床期刊的兒童慢性腎臟疾病（CKiD）世代研究結果顯示，罹患慢性腎臟疾病（CKD）兒童的蛋白尿與腎臟受損的程度有關（以一種顯影劑iohexal清除來評量腎絲球廓清率[GFR]）。
阿布奎基新墨西哥大學的Craig S. Wong博士與其CKiD研究者的同事們寫到，蛋白尿與CKD有關，且嚴重蛋白尿可以預測腎臟功能的快速下降。然而，並未在兒童CKD族群有該重要生物標記很好的流行病學分布研究。
研究者們評估419位CKiD研究受試者，蛋白尿程度與試驗前臨床變項之間的關係，這是一項北美兒童CKD斷面研究。平均iohexal為基礎的GFR為每分鐘每1.73 m2體表面積42 ml，CKD患病時間平均為6年。腎絲球相關疾病佔了CKD所有診斷的22%。
腎病症候群範圍的蛋白尿，以尿液蛋白質與肌酐酸比值（Up/c）超過2.0定義，出現在14%兒童身上；62%病童有顯著的蛋白尿；24%病童的Up/c比值正常。以iohexol評量的GFR下降與Up/c增加有關。在任何GFR下，與腎絲球疾病相關的CKD及非高加索裔可以預測Up/c比值較高。
在腎絲球疾病相關CKD中，使用腎素－血管張力素系統（RAS）拮抗劑病童的Up/c（平均Up/c為0.93）比未接受這些藥物的病童低（平均Up/c為3.78）。
研究作者寫到，來自CKiD研究的數據顯示，腎臟受損的程度、種族、CKD病因、以及據報使用RAS拮抗劑與蛋白尿（Up/c）有關。CKiD世代研究的縱向實驗設計，與所檢驗的大量受試者，已經為定義蛋白尿與CKD惡化之間關聯開創了一個很好的機會。
這項研究的限制包括斷面性研究設計、妨礙了Up/c與iohexol量測GFR之間的時序與因果關係定義；以及觀察性設計可能會有的未量測誤差、納入誤差等等。
研究作者們的結論是，儘管有這些限制，這項研究為之後前瞻性標準化量測、中央化實驗室研究、以及整個北美不同兒童腎臟科中心這麼大數量的受試者帶來了很大的支持。腎絲球與非腎絲球原因的CKD，之間蛋白尿嚴重度的差異代表了自然史與對治療反應以減緩或逆轉CKD惡化。縱向評估這個世代將可以提供有關於蛋白尿與CKD惡化之間因果關係途徑的資訊。
CkiD前瞻性世代研究由國家糖尿病與消化及腎臟疾病機構贊助，國家神經疾病與中風機構提供額外贊助；國家兒童健康與人類發展機構、國家心臟、肺臟與血液機構贊助。參與機構性一般臨床研究中心與臨床轉化研究中心也贊助這項研究。研究作者們表示沒有資金上的往來。
Factors Predicting Proteinuria Identified in Children With Chronic Kidney Disease
By Laurie Barclay, MD
Medscape Medical News
March 19, 2009 — Proteinuria in children with chronic kidney disease (CKD) is associated with level of kidney impairment (glomerular filtration rate [GFR] as measured by iohexol disappearance), cause of CKD, and race, according to the results of the Chronic Kidney Disease in Children (CKiD) cohort study reported in the March 18 Online First issue of the Clinical Journal of the American Society of Nephrology.
"Proteinuria is associated with...CKD, and heavy proteinuria predicts a rapid decline in kidney function," write Dr. Craig S. Wong, from University of New Mexico, Albuquerque, and colleagues from the CKiD investigators. "However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population."
The investigators evaluated the association of level of proteinuria with baseline clinical variables among 419 participants in CKiD, a cross-sectional study of North American children with CKD. Median iohexol-based GFR was 42 mL/minute/1.73 m2, and median duration of CKD was 6?years. Glomerular diseases comprised 22% of the CKD diagnoses.
Nephrotic-range proteinuria, defined as urinary protein-to-creatinine ratios (Up/c) of more than 2.0, was present in 14% of children; significant proteinuria was present in 62%; and normal-range Up/c (< 0.2) in 24%. Decrease in iohexol-based GFR was associated with an increase in Up/c. At any level of GFR, a glomerular cause of CKD and non-Caucasian race predicted a higher Up/c.
Among participants with a glomerular cause of CKD, Up/c was lower in those treated with renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) vs those not receiving these drugs (median Up/c = 3.78).
"Data from the CKiD study demonstrate that the level of kidney impairment, race, cause of CKD, and reported use of a RAS antagonist are associated with proteinuria (Up/c)," the study authors write. "The longitudinal study design of...CKiD cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression."
Limitations of this study include cross-sectional design, preventing the definition of temporal and causal relationships between Up/c and iohexol-based GFR; and observational design withpossible unmeasured factors, introducing bias.
"Despite these limitations, this study draws tremendous strength from the prospective standardized measurements, the centralized laboratory studies, and the large number of participants across multiple pediatric nephrology centers across North America," the study authors conclude. "The significant differences in levels of proteinuria between glomerular and nonglomerular causes of CKD indicate potential differences in the natural histories and response to therapies to slow or reverse of CKD progression. The longitudinal assessment of the cohort will be able to provide further insights regarding the causal pathways for the factors associated with proteinuria and CKD progression."
The CKiD prospective cohort study is funded by the National Institute of Diabetes and Digestive and Kidney Disease, with additional funding from the National Institute of Neurologic Disorders and Stroke; National Institute of Child Health and Human Development; and the National Heart, Lung, and Blood Institute. Participating institutional General Clinical Research Centers and Clinical Translational Research Centers also supported this study. The study authors have disclosed no relevant financial relationships.
Clin J Am Soc Nephrol. Published online March 18, 2009. |
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