本帖最後由 goodcat1111 於 2009-4-12 12:51 編輯
作者：Bob Roehr
出處：WebMD醫學新聞
April 1, 2009 (田那西州那什維爾) —根據發表於國家腎臟基金會2009春季臨床會議中的一篇研究，碳酸鑭減少了第5期慢性腎臟病(CKD)患者的死亡率，且對第3或4期CKD患者的維他命D值沒有負面影響。
碳酸鑭用於第5期CKD病患的前溯研究尚未進行，但是研究者在管理當局的監督下，對初期安全性研究進行事後分析。
兩年期安全性研究中的病患，被隨機指派接受碳酸鑭(n= 682)或者標準治療(n= 677)。碳酸鑭組病患約有20%死亡，標準治療組有23%死亡，不過，差異並無統計上的顯著意義。對65歲以上病患進行的次組分析，顯示兩組之間有統計上的顯著差異(27% vs 39%; P= .04)。
第二篇研究前溯式納入連續兩次測量血清磷值大於4.6 mg/dL的病患(n= 90)，他們被隨機分派接受安慰劑或者碳酸鑭、750 mg/天，在四週期間調整到最多3000 mg/天，接著，進行四週的維持治療。
資深作者、北卡羅來納大學的William Finn醫師向Medscape Nephrology表示，研究設計為測量維他命D值的影響，而非鍵結磷的效果。維他命D是脂溶性，他們並未預期發現碳酸鑭對血清維他命D值有任何效果，而研究證實了。
有趣的事情是，在嚴重維他命D缺乏的人中，可以降低血清副甲狀腺素(PTH)值，只因為我們可以降低血清磷值，這再度強調降低磷值以降低PTH值的重要性。
Finn醫師表示，在短期密集控制試驗中，每一克的鑭可以鍵結多達150 mg的磷；但是在本試驗中，比照腎臟醫學界實際臨床使用狀況的80%順從性 ，每一克藥物的磷鍵結可達110 mg，這顯著優於其他現有藥物。
他承認，碳酸鑭價位相當高，但如果就鍵結磷的平均值看來，費用即可接受；他形容碳酸鑭對於整體是有幫助的。
Finn醫師表示，在診間，我根據病患的磷攝取狀況，從他們攝取的蛋白質進行判斷，進行這種結合治療。一般病患需要每天鍵結450到500mg的磷。鈣無法達到這個目標，sevelaner這個藥也不行，只有碳酸鑭可以，但可能會超出預算。
尚未進行使用較高劑量的研究，但是Finn醫師表示，他發現有些體型較壯碩的病患需要每天6g。如果我這麼治療，他們的磷值下降且可控制。
喬治亞醫學院的Harold M. Szerlip醫師向Medscape Nephrology表示，磷鍵結或許是末期腎臟病中最重要的。越來越多人相信，非鈣鍵結劑在預防心血管死亡上有更多好處，所以我們多數改用非鈣鍵結劑，現在只有兩種：鑭與sevelaner；我認為鑭比sevelaner更好。
Szerlip醫師表示，鑭的磷鍵結力相當強，也減少了你的服藥數。有些關於鑭從腸道吸收、在肝臟與骨骼中也可發現的顧慮，但迄今並未發現負面影響。
Shire Pharmaceuticals資助研究。Finn醫師以及Szerlip 醫師宣告沒有相關財務關係。
國家腎臟基金會2009春季臨床會議：摘要124與31。
NKF 2009: Lanthanum Carbonate Reduces Mortality in Older Patients With Late-Stage CKD
By Bob Roehr
Medscape Medical News
April 1, 2009 (Nashville, Tennessee) — Lanthanum carbonate reduced mortality in patients with stage?5 chronic kidney disease (CKD) and had no negative effect on vitamin?D levels in patients with stage?3 or 4 CKD, according to studies presented here at the National Kidney Foundation 2009 Spring Clinical Meetings.
Prospective-outcomes studies of lanthanum carbonate in stage?5 CKD patients have not yet been conducted, but investigators performed a post hoc analysis of an earlier safety study under guidance from regulatory authorities.
Patients in the 2-year safety study were randomly assigned to lanthanum carbonate (n?= 682) or standard therapy (n?= 677). About 20% of patients in the lanthanum-carbonate group died, as did 23% of patients in the standard-therapy group, but the difference was not statistically significant. Subgroup analysis of patients 65 years and older did show a statistically significant difference between the 2 groups (27% vs 39%; P?= .04).
A second study prospectively enrolled patients (n?= 90) with 2 consecutive measurements of serum phosphorus levels >4.6?mg/dL. They were randomized to either placebo or lanthanum carbonate 750 mg/day titrated up to 3000?mg/day during a 4-week period, followed by 4 weeks of maintenance therapy.
Senior author William Finn, MD, from the University of North Carolina, in Chapel Hill, told Medscape Nephrology that the study was designed to measure the effect on levels of vitamin?D, not efficacy in binding phosphorus. Vitamin?D is fat soluble and they did not expect to see any effect of lanthanum carbonate on serum levels of vitamin?D. The study confirmed that.
"One interesting thing is that in this group of people who were largely vitamin?D deficient, we were able to lower the serum parathyroid hormone (PTH) levels simply because we were able to lower the serum phosphorus levels. It re-emphasizes the importance of lowering phosphorus to lower PTH levels."
Dr. Finn said one can get binding of up to 150?mg of phosphorus per gram of lanthanum in a short, tightly controlled trial. But in this trial, with ~80% compliance for each dose, which he calls "reality nephrology" that better represents clinical use, they still obtained a binding rate of 110?mg of phosphorus per gram of drug. That is a significantly greater binding rate than the other available drugs.
He acknowledged that lanthanum carbonate carries a higher cost but suggested that if one looks at it in terms of units of phosphorus bound, then the cost is roughly comparable with other options. He called lanthanum carbonate "a helpful addition to our armamentarium."
In the clinic, "I dose my binder therapy on the basis of their phosphorus intake, as judged by their protein intake," said Dr. Finn. A typical patient would require binding of 450 to 500 mg of phosphorus per day. "You can't do that with calcium, you can't do that with sevelaner, you can only do that with [lanthanum carbonate], although you would exceed what is in the package insert."
Studies using higher doses have not been done, but Dr. Finn said he finds that "some of my bigger patients require" 6?g per day. "If I do that, their phosphorus levels come down and they are controlled."
"Phosphate binding is probably the most important thing we can do in end-stage renal disease," Harold M. Szerlip, MD, from the Medical College of Georgia, in Augusta, told Medscape Nephrology. "There is a growing belief that noncalcium-containing binders are likely more beneficial in terms of preventing cardiovascular mortality, so most of us are moving toward noncalcium-based binders. There are only 2 of them, lanthanum and sevelaner; I think it is good to have a choice over sevelaner.
"Lanthanum is very potent in its phosphate binding and it decreases your pill burden," Dr. Szerlip added. "There have been concerns about lanthanum absorption from the gut and you can find it in the liver and bone, but as of now we know of no negative effects of that."
Shire Pharmaceuticals funded the studies. Dr. Finn and Dr. Szerlip have disclosed no relevant financial relationships.
National Kidney Foundation 2009 Spring Clinical Meetings: Abstracts 124 and 31. |
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