本帖最後由 goodcat1111 於 2009-4-5 08:58 編輯
作者：Fran Lowry
出處：WebMD醫學新聞
February 27, 2009 —根據2月份眼科學檔案期刊中的族群基礎世代研究結果，血清cystatin C值以及慢性腎臟病(chronic kidney disease，CKD)，與年齡相關的黃斑部退化(age-related macular degeneration，AMD)發生率有關，與抽菸和其他風險因素無關。
威斯康辛大學醫學與公共衛生學院的Ronald Klein博士等人寫道，血清cystatin C值被用來評估腎絲球過濾速率，以確認有無出現CKD。CystatinC富含於視網膜色素上皮層(RPE)細胞內，假設透過其對於細胞自溶酵素之作用而影響AMD的病理。
研究目標是檢視血清cystatin C值以及慢性腎臟病與AMD病程的關係，研究對象是Beaver Dam Eye Study的4,926名參與者、追蹤15年。
這些參與者居住於威斯康辛州的Beaver Dam，1988年3月1日至1990年9月14日間開始研究時的年紀為43至84歲，以5年間隔進行追蹤檢查。於2003年3月31日至2005年4月30日進行15年的追蹤時，總共有2,119名存活的原始研究世代。
每次檢查時隨機抽取血液樣本以確認白血球數量、血清血液尿素氮、腎絲球過濾速率以及cystatin C。使用「Modification of Diet in Renal Disease (Study) 」預測公式，從血清肌酸酐計算腎絲球過濾速率。輕微慢性腎臟病定義為腎絲球過濾速率超過45 mL/min/1.73 m2 -60 mL/min/1.73 m2以下。中到重度慢性腎臟病定義為腎絲球過濾速率45 mL/min/173 m2 以下。以隨機尿液樣本進行浸液試片檢驗測量總體蛋白尿濃度。以黃斑體照片確認AMD。
早期AMD的15年累積發生率為14.3%；純地圖狀萎縮為1.3%；滲出性AMD為2.0%；漸進式AMD為12.2%。男性和女性隨年紀增加的AMD流行率以及15年累積發生率相似。
控制年紀與其他風險因素，開始時的血清cystatin C值與早期AMD發生率有關(絕對數標準差之勝算比[OR]為1.16; 95%信心區間[CI]為1.01 –1.35)，滲出性AMD (OR, 1.42; 95% CI, 1.03 – 1.96)。不過，開始時cystatin C與地圖狀萎縮 (OR, 0.89; 95% CI, 0.56 – 1.41) 或者漸進式AMD無關。
輕微慢性腎臟病與早期AMD的15年累積發生率有關(絕對數標準差之勝算比為1.36; 95% CI, 1.00 – 1.86)。不過，與其他AMD終點的發生率無關。
作者指出，輕微慢性腎臟病與早期AMD有統計上的顯著關係，但是與滲出性AMD、地圖狀萎縮、漸進式AMD則無關，Beaver Dam Eye Study的發現與稍早的研究資料一致。
研究作者寫道，Blue Mountains Eye Study顯示，校正年紀、性別與其他風險因素之後，相較於輕微或者無CKD者，中度CKD病患發生早期AMD的風險是3倍(OR [95% CI], 3.2 [1.8 – 5.7]; P<.001)。當使用和Blue Mountains Eye Study同樣的CKD定義 (根據Cockcroft-Gault公式)，控制多變項模式的其他因素時，我們發現CKD與偶發早期AMD之間的關係(OR [95% CI], 1.53 [1.10 – 2.11]; P = .01) ，但是與滲出性AMD無關(1.38 [0.68 – 2.66]; P = .37)。
作者指出，慢性腎臟病以及純地圖狀萎縮之低發生率，限制了我們偵測(或反駁)有意義之關聯的能力，有些有潛在生物顯著意義的發現也可能因為檢視的關聯數量而完全是因為機率。最後，他們指出，有些風險因素和AMD之間沒有顯著關係，可能是因為有這些因素而發生AMD的人在進行追蹤檢查前已經過世。
他們結論表示，需要以其他研究確認他們的發現，以更清楚瞭解這些發現的生物過程。
國家眼科研究中心、國家糖尿病與消化道和腎臟病研究中心、國家健康研究中心、以及防盲研究資深科學獎支持本研究。作者宣稱沒有相關財務關係。
High Levels of Serum Cystatin C and Chronic Kidney Disease Linked to Age-Related Macular Degeneration
By Fran Lowry
Medscape Medical News
February 27, 2009 — Serum cystatin C level and chronic kidney disease may have a link to incidence of age-related macular degeneration (AMD) that is independent of smoking and other risk factors, according to a population-based cohort study reported in the February issue of the Archives of Ophthalmology.
"Serum cystatin C has been used to estimate glomerular filtration rate to define the presence of CKD," write Ronald Klein, MD, MPH, from the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues. "It is abundant in retinal pigment epithelium (RPE) cells and has been hypothesized through its effects on cathepsins to have a role in the pathogenesis of AMD."
The goal of this study was to examine the associations of the serum cystatin C level and chronic kidney disease with the incidence and progression of AMD during 15 years of follow-up in 4926 participants of the Beaver Dam Eye Study.
The participants were residents of Beaver Dam, Wisconsin, and were 43 to 84 years old at the time of their baseline examination, which took place between March 1, 1988, and September 14, 1990. Follow-up examinations were done at 5-year intervals. The 15-year follow-up examination was performed from March 31, 2003, through April 30, 2005, and included 2119 survivors of the original study cohort.
Casual blood specimens were obtained at each examination to determine white blood cell count, serum blood urea nitrogen, glomerular filtration rate, and cystatin C. The glomerular filtration rate from serum creatinine was estimated using the Modification of Diet in Renal Disease (Study) prediction equation. Mild chronic kidney disease was defined as a glomerular filtration rate of more than 45 mL/min/1.73 m2 to 60 mL/min/1.73 m2 or less. Moderate to severe chronic kidney disease was defined as a glomerular filtration rate of 45 mL/min/173 m2 or more. Gross proteinuria concentration was determined using a dipstick test on a casual urine sample. AMD was determined by grading photographs of the macula.
The 15-year cumulative incidence of early AMD was 14.3%; pure geographic atrophy, 1.3%; exudative AMD, 2.0%; and progression of AMD, 12.2%. The prevalence and 15-year cumulative incidence and progression of AMD were similar in men and women and increased with age.
After controlling for age and other risk factors, the level of serum cystatin C at baseline was associated with the incidence of early AMD (odds ratio [OR] per log standard deviation, 1.16; 95% confidence interval [CI], 1.01 – 1.35) and exudative AMD (OR, 1.42; 95% CI, 1.03 – 1.96). However, baseline cystatin C was not associated with geographic atrophy (OR, 0.89; 95% CI, 0.56 – 1.41) or progression of AMD.
Mild chronic kidney disease was associated with the 15-year cumulative incidence of early AMD (OR per log standard deviation, 1.36; 95% CI, 1.00 – 1.86). However, it was not associated with the incidence of other AMD endpoints.
The statistically significant relationship of mild chronic kidney disease with early AMD but not with exudative AMD, geographic atrophy, or progression of AMD that was found in the Beaver Dam Eye Study is consistent with data from earlier studies, the authors comment.
"The Blue Mountains Eye Study showed that after adjusting for age, sex, and other risk factors, individuals with moderate CKD are 3 times as likely to develop early AMD compared with individuals with no or mild CKD (OR [95% CI], 3.2 [1.8 – 5.7]; P<.001)," the study authors write. "When using the same definition of CKD (based on the Cockcroft-Gault equation) as used in the Blue Mountains Eye Study, while controlling for other factors in a multivariable model, we found a relationship of CKD to incident early AMD (OR [95% CI], 1.53 [1.10 – 2.11]; P = .01) but not to incident exudative AMD (1.38 [0.68 – 2.66]; P = .37)."
The authors warn that the low frequency of chronic kidney disease and pure geographic atrophy "limit our ability to detect (or reject) meaningful relations" and that some findings that appear to be of potential biological significance may be entirely owing to chance, given the number of associations examined. Finally, they point out the possibility that no significant relationships between some risk factors and AMD were found because individuals with these factors who developed AMD did not live to participate in the follow-up examination.
They conclude that confirmation of their findings in other studies and a better understanding of the biological processes underlying these findings are needed.
This study was supported by the National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institutes of Health, and Senior Scientific Investigator Awards from Research to Prevent Blindness. The authors have disclosed no relevant financial relationships.
Arch Ophthalmol. 2009;127:146–152. |
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