2011年度肾脏病学的十大进展 （MedScape)

以下介绍2011年肾脏病领域的关键性进展

10、慢性肾脏病的矿物质紊乱的风险

    帕尔默和他的同事[1]在JAMA发表的一篇文章，包括系统回顾和荟萃分析研究，针对慢性肾脏病（CKD）血液透析和腹膜透析患者，血清钙，磷，甲状旁腺激素水平和心血管事件和死亡率之间的关系[2]。“这项研究发现，血清磷含量较高情况下，患者死亡率较高，但有甲状旁腺激素水平或钙水平和心血管事件或死亡之间没有任何关系。这项研究和其他以前的基础上，是相当有力的证据。因此在CKD患者中，对于甲状旁腺激素或钙水平不必过份关注，而要维持低血磷水平”

9、早期肾脏病护理是无用的？一个令人担忧的结论

    在内科医学档案（Archives of Internal Medicine ）杂志上，Winkelmayer和他的同事在2011年发表的文章[3]研究1996年和2007年之间透析护理的第一年致死率。主要来自美国肾脏数据系统的数据积累，为2年，使用医疗保险索赔数据回溯。“文章最后的结论还有待充分的探讨，但它建议，透析护理没有显示出任何改善，事实上，研究显示，早期肾脏病的护理（发生透析开始前90天或更长时间），能够减少1年的死亡率的36％。这批队列患者平均年龄约75岁，和有广泛的合并症，2/3患患者有糖尿病，70％患有高血压，心脏衰竭，18％至45％的患者有冠状动脉疾病，脑血管疾病，周围动脉疾病，慢性阻塞性肺疾病和癌症，这是一个具有非常高的死亡率人群。因此，对于这部分人群，透析护理并没有改善死亡率，是不惊奇的。在不同的人口学资料中，可能结果不同。

8、治疗系统性红斑狼疮的新药问世了，它对肾脏功能有何影响？

It has been several decades since a new medication has been approved for the treatment of systemic lupus erythematosus (SLE). In February 2011, The Lancet published results of a phase 3 trial of belimumab, a fully human immunoglobulin G monoclonal antibody that binds to and inhibits the activity of B-lymphocyte stimulator, a survival cytokine for these lymphocytes.^[4] Lynda Szczech wrote in her Medscape Viewpoint, "B-lymphocyte stimulator is overproduced in patients with SLE, and its concentration correlates with disease activity and anti-double-stranded DNA antibody titer. Patients were randomly assigned to either placebo, belimumab 1 mg/kg, or belimumab 10 mg/kg. Both groups receiving belimumab experienced a benefit over those receiving placebo. For each scale, however, the group receiving 10 mg/kg generally experienced a greater benefit than the group receiving 1 mg/kg. It is worth noting, however, that little information is provided in this initial report on how belimumab may have affected the course of those with established renal manifestations of their lupus. The study authors should be encouraged to look at this subgroup to provide those of us in nephrology with insight on the potential use of this drug, with a focus on its effect on the kidney."

7、rt-PA成功击败肝素，但rt-PA就一定要普及使用？

rt-PA在导管故障率、出血率，菌血症率都要优于肝素，但是它的价格高昂，在临床上不考虑价格因素，全部应用rt-PA，还是需要评估的。

A trial reported by Hemmelgarn and colleagues[5] compared lock solutions of rt-PA to standard heparin on the frequency of catheter malfunction and episodes of catheter-related bacteremia. In her Medscape Viewpoint, Lynda Szczech wrote, "Catheter malfunction was the primary outcome. Patients in the heparin group were more likely to experience catheter malfunction than those in the rt-PA group. Similarly, patients in the rt-PA group experienced catheter-related bacteremia at a lesser rate than those in the heparin group. Intuitively, safety (particularly with respect to episodes of bleeding) should be a major consideration on whether to adopt rt-PA and should be balanced against the efficacy of this therapy. Bleeding was examined carefully. Neither the frequency nor the severity of bleeding events differed between groups and, further, all 4 intracranial bleeding episodes (including 1 event that was fatal) were in the heparin group. No subjects in the rt-PA group experienced an intracranial bleed. Much has been written about how the new bundled payment system may affect the provision of dialysis in the United States. Given the constraints of the reimbursement and the inclusion of all medications given in the dialysis unit, concerns have been expressed that the new bundled payment system may stifle innovation, such as this novel use of rt-PA given, that there is no 'room to pay' for anything additional. As we watch the extent to which these and other new expensive therapies become adopted, we must keep in mind that in the absence of a scientific or safety signal that precludes their use, this may be a test of the effect of the payment system on innovation."

6、血压控制目标：140mmHg，对每个人都适用吗？

尤其针对伴有肾脏病或蛋白尿患者， 140/90 mm 这个控制目标是否需要修正？130/80 mm Hg的目标应该更倾向一些。

According to a review from Katrin Uhlig and colleagues,^[6] published in April 2011 in the Annals of Internal Medicine, CKD patients had no improvements in measured outcomes -- including kidney failure, cardiovascular events, and death -- when managed with a blood pressure target of < 130/80 mm Hg, rather than the normal target of < 140/90 mm Hg. The only significant exception was in the Modification of Diet in Renal Disease (MDRD) study, in which patients in a low target arm had a 23% reduction in hazard for kidney failure at a follow-up of about 6 years. The review included 3 trials and a total of 2272 patients with CKD. The studies also included subgroups of patients with proteinuria, but all excluded patients with actively managed diabetes. George Bakris, in a Skype discussion with Rajiv Agarwal, said, "There's been a groundswell of evidence that less than 140 mm Hg is perfectly appropriate. We do not need to go to less than 130 mm Hg, even in diabetes. Certainly the National Institute for Health and Clinical Excellence (NICE) guidelines have this information in their recent update and JNC 8 is certainly going to talk about this as well."^[7] He continued, " There's one exception to the < 140/90 mm Hg, and that is people with proteinuria, usually with chronic kidney disease and, specifically, proteinuria at levels well above 300 mg/L a day and certainly up to 500 mg/L and higher. In that circumstance the data are pretty clear that less than 130 mm Hg still is the goal and still should be there."

5、Dipstick：一种简单测试肾功能的主要指标测试方法问世

The Dipstick: A Simple Test With Major Implications for Kidney Function

A prospective observational study from Clark and colleagues[8] followed 3371 participants longitudinally with yearly blood and urine samples addressing these key questions:

    What is the difference between microalbuminuria, albuminuria, and proteinuria?
    When do you use a urine dipstick to screen vs an albumin-to-creatinine ratio (ACR) vs a protein-to-creatinine ratio?
    What exactly are we screening for?

In her monthly Medscape Viewpoint, Lynda Szczech wrote, "Among the entire cohort, the likelihood of developing rapid kidney function decline (RKFD) was 3.2 times greater among those with albuminuria as compared with those without. When persons with at least trace proteinuria were compared with those without proteinuria on dipstick, the likelihood of RKFD was 3.7 times greater in those with trace proteinuria, which was comparable to using albuminuria as the screening test. While the Chronic Kidney Disease Prognosis Consortium suggests that albuminuria is an important tool in identifying individuals at risk for renal outcomes, the study presented here by Clark and colleagues is the first to compare ACR with dipstick in a head-to-head manner. These results suggest that the use of the urine dipstick to identify people with at least trace proteinuria is more effective in screening for individuals who will go on to lose significant amounts of kidney function in the short term."

4、周末休息：会不会损害透析患者健康？

Never on Sunday -- Except for Dialysis?

A recent study in The New England Journal of Medicine by Robert Foley and colleagues[9] suggests that weekends may be bad for dialysis patients. Jeffrey Berns commented, "In this interesting study of more than 36,000 patients who had participated in the End-Stage Renal Disease (ESRD) Clinical Performance Measures Project, these investigators found that on the day after the long weekend, interdialytic interval, all-cause mortality, cardiac mortality, vascular mortality, admissions for cardiovascular disease, as well as infection-related mortality were significantly increased. There has already been discussion of whether dialysis schedules should be changed to be every other day or more frequently, or whether an extra dialysis treatment should be inserted somewhere up along the way. Whether patients need an extra treatment, whether they need a longer treatment on Friday and Monday or Tuesday and Saturday, or whether they need an adjustment in the ultrafiltration rate or even in the dialysate composition all remain unknown. Before we jump in and make changes in our dialysis therapies on the basis of this study (which was fascinating and elegant but, nonetheless, still retrospective) we need to think about prospective studies that might be done to answer some of the questions and hypotheses that are raised by this study."

3、促红素治疗肾脏疾病，真的安全吗？

In July 2011, the US Food and Drug Administration (FDA) changed the package inserts for erythropoietin-stimulating agent (ESA) therapy.[10] The new black box warnings pointed out that hemoglobin levels above 11 g/dL in CKD and dialysis patients have been associated with death, cardiovascular risk, and stroke. No safe level of hemoglobin or safe dose of ESA has been established in these patients. The new FDA recommendations in the package insert initiate ESA therapy in patients with CKD when the hemoglobin is below 10 g/dL and stop or reduce ESA therapy dosing when the hemoglobin level is above 10 g/dL. In dialysis patients, a 10- to 11-g/dL hemoglobin range has been recommended, with initiation of therapy when the hemoglobin falls below 10 g/dL. Most of this information is extrapolated from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).[11] In his Medscape commentary, Jeffrey Berns expressed some concern about what is going to be happening to patients, particularly those who don't closely reflect the patient populations that participated in the most recent clinical trials, and especially the young patients and relatively healthy patients without extensive comorbidity.

2、SHARP: 依泽替米贝/辛伐他汀组合减少肾脏疾病患者的动脉粥样硬化和血管事件
Ezetimibe/Simvastatin Combo Cuts Atherosclerotic and Vascular Events in Kidney-Disease Patients

Final results of the Study of Heart and Renal Protection (SHARP), published in June 2011, showed that, compared with placebo, cholesterol lowering with a combination of simvastatin and ezetimibe (Vytorin®; Merck) in patients with advanced CKD significantly reduced the risk for "major atherosclerotic events" by 17% and of major vascular events -- the primary endpoint for the study -- by almost the same degree.[12] According to trial investigator Adeera Levin (University of British Columbia, Vancouver), the results should change practice by providing a clear answer to physicians, who have "been all over the map. Variability in practice was huge, and there was a lot of misunderstanding. Everyone worried that these drugs might be unsafe [in chronic kidney disease patients] and that they didn't work. Now what SHARP says is, these drugs are safe and they work." In November 2011, the Endocrinologic and Metabolic Drugs FDA Advisory Committee, chaired by Abraham Thomas (Henry Ford Hospital; Detroit, Michigan), voted 16 to 0 in favor of an expanded indication for Vytorin to reduce the risk for cardiovascular events in CKD patients not on dialysis. On the other hand, they voted 10 to 6 against the same expanded indication in end-stage renal-disease patients on dialysis.

1、何时是最佳透析时间？GFR在5-10 mL/min可能最佳

When Is the Best Time to Start Dialysis?

A 2011 paper in the Archives of Internal Medicine by Rosansky and colleagues[13] and a follow-up commentary[14] addressed the issue of the appropriate time to start dialysis. Jeffrey Berns, in a Medscape commentary, said that this "particular study looked at United States RDS [Renal Data System] data from 1996 to 2006 in a large cohort of healthy dialysis patients. They had no substantial comorbidities other than hypertension, and the top age was 64 years. Patients who started dialysis with GFRs in the 5-10 mL/min range had substantially lower mortality than those who started dialysis at each successively higher level of GFR, including 10-15 mL/min and over 15 mL/min. This was a relatively healthy group. When the investigators looked at patients who were the most healthy -- that is, those who had normal albumin levels and hemoglobin levels and so forth -- the data were equally striking. This study is very important, very well done, observational, and retrospective. What would be useful here is a comparative-effectiveness study, because we really do need to balance not only this mortality difference that we are seeing but quality of life at the start of dialysis vs remaining off dialysis; an examination of those tradeoffs is sorely needed. We start dialysis sometimes at the earlier sign of symptoms, but maybe that is not appropriate either, and maybe the tradeoff is increasing mortality for dialytic management of relatively minor symptoms, something that probably needs to be more individualized."