第一型糖尿病、巨蛋白尿仍是ESRD預測因子


  【24drs.com】根據2月25日線上發表在美國腎臟醫學會期刊的研究結果,儘管最近對腎臟保護措施進步了,第一型糖尿病與巨蛋白尿仍然是末期腎臟病變(end-stage renal disease,ESRD)的高風險因子。
  
  來自麻州波士頓兒童醫院與Joslin糖尿病中心內分泌科的Elizabeth T. Rosolowsky醫師解釋,每3位第一型糖尿病患者中就有1位會發生持續性的巨蛋白尿,這可以視為腎功能惡化與可能導致ESRD的開端。這些病患也處於心臟血管死亡的高風險。在過去30年間,對這些患者的照護歷經許多改變,包括積極控制血壓與腎臟保護性地阻斷腎素血管張力素系統。
  
  其他進展包括改善透析患者的代謝處理策略,以及腎移植患者新的預防排斥方法。部分患者也接受預防性腎臟移植以避免透析。降低心臟血管死亡率的努力則包括治療高膽固醇血症和高血壓,並且鼓勵戒菸。
  
  為了確認這些方法能夠改變進展性糖尿病腎病變的進程,研究人員進行了一項收納423位第一型糖尿病患者的研究,這些患者都有巨蛋白尿(白蛋白排除率≧300微克/分鐘)。病患收納期間是在1991年到2004年間。
  
  到了2008年,後續追蹤率98%,在這段時間,有172位患者發生ESRD(盛行率為每年每100位患者5.8人)。29位患者未發生ESRD即死亡(死亡率每年每100人1人)。這些大部分發生在36到52歲之間的患者,而發生ESRD時的糖尿病罹病時間介於21到37年。
  
  病患發生ESRD的15年累積風險52%(標準差3.5%),發生ESRD前的死亡風險為11.1%(標準差3.5%)。使用腎臟保護策略在這15年間顯著增加,從56%增加到82%(P<0.0001),且患者們血壓顯著改善(收縮壓137-131 mmHg[P<0.0016];舒張壓81-76 mmHg[P=0.0001];血脂肪同樣是改善的)。
  
  但ESRD風險與ESRD前死亡率並沒有改變。在70件罹患ESRD後的死亡事件,1990年代時(每年每100人11.1人;95%信賴區間為每年8.1-15.2人)與2000年後(每年每100人12.8人;95%信賴區間為每年8.6-19.1人)的死亡率僅有些許改變。接受預防性腎臟移植的患者死亡率較低(每年每100人1人),但是這些患者與透析患者在透析前死亡率、估計腎絲球廓清率、性別、ESRD發生年齡、以及糖尿病罹病時間只有些微差異。
  
  這項研究的潛在限制包括糖尿病照護與治療巨蛋白尿的中心(麻州波士頓Joslin糖尿病中心),所提供的可能比一般病患接受的資源要來得好,因此這項研究可能低估在其他中心接受治療的風險。這項研究也收納巨蛋白尿的流行與散發病例,可能讓研究更難偵測ESRD趨勢。
  
  在隨後的主編評論中,亞利桑那州鳳凰城國家衛生研究院國家糖尿病、消化道與腎臟疾病機構的Robert G. Nelson醫師、博士描述該族群的巨蛋白尿治療是有效的,但並沒有奏效。Neslon博士問到:這個族群惡化至ESRD的比例很高是否真的代表沒有效果,或是如果沒有這些新的治療,ESRD的機率是否將會更高?
  
  Rosolowsky博士與同事們寫到,這些研究結果顯示出需要新的、更有效的治療,來降低在Joslin這項研究群眾中所觀察到的巨蛋白尿,或是針對其他與惡化至ESRD有因果關係的途徑下手。
  
  這項研究由青少年糖尿病研究基金會、國家衛生研究院、國家健康兒童健康服務研究機構訓練計畫的研究經費贊助。Nelson博士的工作由國家糖尿病與消化道及腎臟疾病機構院內研究計畫贊助。作者們沒有相關資金上的往來。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6474&x_classno=0&x_chkdelpoint=Y
  

Type 1 Diabetes, Macroalbuminuria Remains Predictor of ESRD

By Jim Kling
Medscape Medical News

March 7, 2011 — Despite recent improvements in renoprotective therapies, patients with type 1 diabetes and macroalbuminuria continue to be at high risk for end-stage renal disease (ESRD), according to research published online February 25 in the Journal of the American Society of Nephrology.

One in 3 patients with type 1 diabetes develops persistent macroalbuminuria, which is viewed as the beginning of progressive loss of renal function and potential ESRD, explained lead author Elizabeth T. Rosolowsky, MD, from the Division of Endocrinology, Joslin Diabetes Center and the Children’s Hospital, Boston, Massachusetts, and colleagues in the article. These patients are also at increased risk for cardiovascular death. In the last 30 years, care for these patients has undergone many changes, including aggressive treatment of hypertension and renoprotective blockade of the renin-angiotensin system.

Other advances have included improved metabolic management of patients on dialysis and new methods to prevent graft rejection in renal transplants. Some patients also receive preemptive renal transplants to avoid dialysis. Efforts to reduce cardiovascular mortality have included treatment of hypercholesterolemia and hypertension and encouragement to reduce smoking.

To determine the effects these measures have had on the course of advanced diabetic nephropathy, the researchers conducted a trial of 423 white patients with type 1 diabetes who developed macroalbuminuria (albumin excretion rate ? 300 μg/minute). Patients were enrolled between 1991 and 2004.

The follow-up rate was 98% through 2008, during which time 172 patients developed ESRD (incidence rate, 5.8/100 person-years). Twenty-nine patients died without developing ESRD (mortality rate, 1/100 person-years). These outcomes largely occurred between patient ages 36 and 52 years, and diabetes durations were between 21 and 37 years at time of ESRD.

Patients had 15-year cumulative risks of 52% for ESRD (standard error, 3.5%) and 11.1% for pre-ESRD death (standard error, 3.5%). Use of renoprotective treatments increased during the 15-year follow-up period, from 56% to 82% (P < .0001), and patients had significantly improved blood pressure (systolic, 137 - 131 mmHg [P < .0016]; diastolic, 81 - 76 mmHg [P = .0001]) and lipid levels.

There was no change in risks for ESRD and pre-ESRD death. Among 70 post-ESRD deaths, the mortality rate was little changed between the 1990s (11.1/100 person-years; 95% confidence interval, 8.1 - 15.2 person-years) and the 2000s (12.8/100 person-years; 95% confidence interval, 8.6 - 19.1 person-years). Patients who received a preemptive kidney transplant had low mortality rate (1/100 person-years), but there was little difference between these patients and dialyzed patients in predialysis, estimated glomerular filtration rate, sex, age at onset of ESRD, or duration of diabetes.

Potential limitations of the study include the fact that diabetes care and treatment of macroalbuminuria at the center where the study was conducted (Joslin Diabetes Center, Boston, Massachusetts) may be better than what patients typically receive, in which case the study may underestimate risks at other institutions. The study also includes both prevalent and incident cases of macroalbuminuria, which could make it more difficult to detect an ESRD trend.

In an accompanying editorial, Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, describes the treatment of macroalbuminuria in this population as efficacious but not effective. Dr. Nelson asks: "Do the high rates of progression to ESRD in these cohorts truly reflect a lack of effectiveness, or would the rates of ESRD have been even higher if newer treatments had not been used?"

Dr. Rosolowsky and colleagues write that the results point "to the need for new, more effective therapies to lower the high levels of macroalbuminuria that were observed in the Joslin cohort or to target other causal pathways, which are involved in the progression to ESRD."

The study was supported by research grants from the Juvenile Diabetes Research Foundation, the National Institutes of Health, and the National Institutes of Health Child Health Services Research Training Program. Dr. Nelson's work is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The authors and the editor have disclosed no relevant financial relationships.

J Am Soc Nephrol Published online February 25, 2011

    
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