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UKidney Nephrology News and Insights

FEB
19
0

Renal end-points in the ACCOMPLISH Study: Is it all hype?

imageOver the past 2 years, considerable excitement has been building over the results of the ACCOMPLISH study. This trial suggested that the combination of benazapril plus amlodipine is superior to benazapril plus hydrochlorothiazide for the prevention of a composite cardiovascular outcome. While there are methodological concerns regarding this trial that make me question its generalizability, it is thought-provoking to consider that one medication combination is superior to another even if blood-pressure between the 2 groups is negligible.

In the latest issue of Lancet, a follow-up paper suggests that benzapril-amlodipine prevented renal outcomes more-so than in the benazapril-hydrochlorothiazide arm. However, as the excellent accompanying editorial points out, all is not as it appears. (continued...)

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JAN
16
0

Hyperphosphatemia management - It is time for a randomized trial

Hyperphosphimageatemia has been been linked to poor patient outcomes, including a link to higher mortality. This relationship has been inferred by several retrospective and observational studies. In fact, the relationship between hyperphosphatemia and death is one of the most consistently espoused theories in all of nephrology. There is just problem however; there has never been a randomized trial to confirm this association.

In the latest issue of Nephrology Dialysis and Transplantation, Smith et al cast doubt on this long-held belief. In their retrospective CKD-inception cohort study, there was no association between hyperphosphatemia and death, though there was less risk of renal replacement therapy in patients with better phosphorus control.

This finding is by no means conclusive. I continue to aggressively treat hyperphosphatemia. However, it does lend further support for a large-scale randomized trial to study this seemingly unimpeachable belief.

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DEC
10
0

Removing a failed kidney allograft improves survival?

In a fascinating article from November's Journal of the American Society of Nephrology, researchers present data suggesting that patients returning to dialysis after a transplant fails experience improved survival if the kidney is removed. In this study, despite correction for comorbidities and socioeconomic factors, graft nephrectomy prolonged survival. One explanation of the results might be that nephrectomy removes an inflammatory stimulant and would allow complete withdrawal of immunosuppression and its risks. This finding is somewhat contradictory to current dogma which suggests that immunosuppression should be continued once returning to dialysis in order to preserve residual renal function. This study's finding would need to be reproduced with a prospective randomized trial to reduce bias but in the meantime, is quite compelling.

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NOV
12
0

Dilemma for Dialysis Patients, Skinny is Dangerous

SAN DIEGO—Dialysis patients with low body fat are at increased risk of death—even compared to patients at the highest level of body fat percentage, according to research being presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition in San Diego.

"Our study indicates that body fat may be protective in dialysis patients," said Kamyar Kalantar-Zadeh, PhD, of LABioMed at Harbor-UCLA. "The results add to the increasing number of reports about the 'obesity paradox' or 'reverse epidemiology' in patients with chronic kidney disease and other chronic diseases."

Nephrologists have puzzled over the "obesity paradox" in dialysis patients, Kalantar-Zadeh said. "Counter-intuitively, higher body mass index is associated with greater survival in hemodialysis patients. We hypothesized that very low body fat—less than ten percent—would be a strong predictor of mortality."

Using near-infrared interactance technology, the researchers measured body fat percentage in 671 hemodialysis patients from eight California dialysis centers. They then compared five-year mortality rates for patients at different levels of body fat percentage. The mortality rate was highest for dialysis patients with less than 10 percent body fat—2.5 to 3 times higher than for those with body fat of 20 to 30 percent. The increased risk of death for patients with very low body fat remained after adjustment for age, sex, race, other illnesses, and key laboratory results. Further analyses using continuous values of body fat (rather than categories) confirmed a direct, linear relationship between body fat and mortality risk: "The higher the body fat, the greater the survival," said Kalantar-Zadeh. Although more research is needed, the results suggest that the obesity paradox may be explained by an increased risk of death for patients with very low body fat, compared to those with average—or even very high—body fat percentage.

The observational study had the same limitations as other epidemiological studies, Kalantar-Zadeh points out. "In addition, we estimated body fat by measuring the subcutaneous fat of the upper arm, which may be different from the intra-abdominal fat." 10/31/2009

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NOV
02
1

TREAT Trial with Aranesp in patients with diabetes and chronic kidney disease

The TREAT Trial was presented at the ASN in San Diego. This much publicized trial examined the role of Aranesp in the management of diabetic patients with CKD. One group was randomized to receive Aranesp with a hemoglobin target of 130 g/l while the control group was given placebo and treated with Aranesp only if their hemoglobin fell below 90 g/l.

There was no advantage to the group given Aranesp and a statistically significant increase in strokes observed in the the treatment group. Below is a link to the article from NEJM and the accompanying editorial written by renowned nephrologist, Dr. Phil Marsden of the University of Toronto.

It is worth noting, that the treatment group was targeted to a higher hemoglobin than we now conventionally use. Furthermore, the dose of Aranesp was more than double the typical dosages used by the majority of my predialysis patients. As has been observed in other studies where high hemoglobin seems harmful, the dose of Aranesp required might explain the observation of harm. Perhaps those patients who respond to lower dosages and those whose hemoglobins remain with target would be perfectly safe to continue.

More study is needed to clarify this and perhaps might be forthcoming from further analysis of the TREAT Study.

Click for:

A Trial of Darbepoetin Alfa in Type 2 Diabetes and Chronic Kidney Disease

Treatment of Anemia in Chronic Kidney Disease — Strategies Based on Evidence

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SEP
10
0

Amgen Announces Top-Line Results of Trial to Reduce Cardiovascular Events With Aranesp(R) Therapy (TREAT) in CKD Patients With Type-2 Diabetes

No Statistically Significant Difference in Cardiovascular and Renal Composite Endpoints Between Aranesp and Placebo

THOUSAND OAKS, Calif., Aug. 25 /PRNewswire-FirstCall/ -- Amgen (Nasdaq: AMGN) today announced that in a large, randomized, double-blind, placebo-controlled, Phase 3 study of patients with chronic kidney disease (CKD) (not requiring dialysis), anemia and type-2 diabetes (the Trial to Reduce CardiovascularEndpoints with Aranesp((R)) Therapy, or TREAT), treatment of anemia with Aranesp((R) )(darbepoetin alfa) to a hemoglobin target of 13 g/dL had no statistically significant effect on either of two primary endpoints compared with placebo treatment. The two primary endpoints were a composite of time to all-cause mortality or cardiovascular morbidity (including heart failure, heart attack, stroke, or hospitalization for myocardial ischemia) and a composite of time to all-cause mortality or chronic renal replacement therapy. Among the elements that formed these composite endpoints, an excess of stroke events (a labeled risk of Aranesp therapy) occurred in the Aranesp-treated patients compared to those receiving placebo.

 

These summary results will be followed by full efficacy and safety analyses, which will be shared with global regulatory authorities and presented at an upcoming medical meeting later this year.

"TREAT was designed to answer important questions about the effects of erythropoiesis-stimulating agents (ESAs) on cardiovascular and renal outcomes in patients with renal insufficiency and type-2 diabetes. It is by any measure the most comprehensive analysis that has ever been performed to examine the impact of anemia therapy in patients who do not yet require dialysis. The trial will provide nephrologists with important information as they endeavor to improve renal care," said Roger M. Perlmutter, M.D., Ph.D., executive vice president of Research and Development at Amgen. "In contrast to a recent, smaller study of ESAs in a similar patient population, TREAT did not show a statistically significant adverse effect on all-cause mortality or cardiovascular morbidity when patients were treated to a hemoglobin target of 13 g/dL. We continue to believe that ESAs have a favorable benefit:risk profile when used according to the approved label."

Currently, Aranesp is indicated for the treatment of anemia in patients with chronic renal failure (CRF), including patients on dialysis and patients not on dialysis. The approved label for Aranesp recommends individualizing dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL. TREAT studied uses for Aranesp in which it is not approved.

TREAT Study Design

TREAT was an international, Phase 3, randomized, double-blind, placebo-controlled study of 4,038 chronic kidney disease (CKD) patients with type-2 diabetes and anemia. It is the largest study of ESA use in CKD patients to date. Patients enrolled in the study were randomized in a one-to-one ratio to receive either treatment with Aranesp to a target hemoglobin of 13 g/dL or placebo. Due to the increased risk of negative outcomes associated with low hemoglobin levels, patients in the control arm whose hemoglobin fell below 9 g/dL were given Aranesp until their hemoglobin level was 9 g/dL. Investigators were blinded to this intervention.

 

TREAT had two primary endpoints. The first evaluated time to all-cause mortality or cardiovascular morbidity including heart attack (myocardial infarction), congestive heart failure, hospitalization for angina (myocardial ischemia), or stroke (cerebrovascular accident). The second primary endpoint evaluated time to all-cause mortality or chronic dialysis. TREAT was not designed to determine the appropriate hemoglobin target in this patient population.

 

For patients randomized to the Aranesp group, the starting dose was 0.75 mcg/kg administered subcutaneously every two weeks; subsequent doses were titrated to achieve hemoglobin target of 13.0 g/dL. Once the target hemoglobin was reached, the frequency of administration was extended to once-monthly.

 

Chronic Kidney Disease: Impact and Prevalence

CKD affects more than 26 million Americans and millions more worldwide. The disease is characterized by progressive kidney damage and impaired kidney function and is most often caused by type-2 diabetes or high blood pressure. When CKD progresses to kidney failure, chronic dialysis or a kidney transplant are required to sustain life. Approximately 350,000 people in the United States are on dialysis today. Anemia is a common complication of CKD that may begin in the early stages of the disease and becomes more common and severe as kidney function declines. Studies have shown that anemia is associated with an increased risk of mortality and cardiovascular morbidity in CKD patients.

 

About Aranesp

Aranesp was approved by the U.S. Food and Drug Administration in 2001 for the treatment of anemia associated with CRF for patients on dialysis and patients not on dialysis. The European Commissiongranted marketing authorization for the same indication in 2001 and subsequently updated it for CRF patients with symptomatic anemia in 2008.

 

In 2002, the FDA approved the treatment of anemia caused by concomitantly administered chemotherapy in patients with nonmyeloid malignancies. The European Commission authorized the treatment of anemia caused by concomitantly administered chemotherapy in patients with non-haemological malignancies in 2002 and extended it to include non-myeloid malignancies in patients receiving chemotherapy in 2003.

 

Important Aranesp Safety Information

WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR and THROMBOEMBOLIC EVENTS, and TUMOR PROGRESSION

 

Renal failure: Patients experienced greater risks for death and serious cardiovascular events when administered erythropoiesis-stimulating agents (ESAs) to target higher versus lower hemoglobin levels (13.5 vs. 11.3 g/dL; 14 vs. 10 g/dL) in two clinical studies. Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL.

 

Cancer:

 

-- ESAs shortened overall survival and/or time-to-tumor progression in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers when dosed to target a hemoglobin of greater than or equal to 12 g/dL.

 

-- To minimize these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusions.

 

-- Use only for treatment of anemia due to concomitant myelosuppressive chemotherapy.

 

-- ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. (This information is specific to the U.S. prescribing information)

 

-- Discontinue following the completion of a chemotherapy course.

 

Aranesp is contraindicated in patients with uncontrolled hypertension.

 

All patients, including patients with cancer or chronic kidney failure:

 

-- You may get serious heart problems such as heart attack, stroke, heart failure, and may die sooner if you are treated with Aranesp to a hemoglobin level above 12 g/dL.

 

-- You may get blood clots at any time while taking Aranesp. If you are receiving Aranesp and you are going to have surgery, talk to your healthcare provider about whether or not you need to take a blood thinner to lessen the chance of blood clots during or following surgery. Clots can form in blood vessels (veins), especially in your leg (deep venous thrombosis or DVT). Pieces of a blood clot may travel to the lungs and block the blood circulation in the lungs (pulmonary embolus).

 

 

About Amgen

Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. To learn more about our pioneering science and our vital medicines, visit www.amgen.com.

 

Forward-Looking Statements

This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in theSecurities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and most recent periodic reports on Form 10-Q and Form 8-K. Please refer toAmgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Aug. 25, 2009 and expressly disclaims any duty to update information contained in this news release.

 

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.

 

In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.

 

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration(FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Only the FDA can determine whether the product candidates are safe and effective for the use(s) being investigated. Further, the scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by theU.S. Food and Drug Administration (FDA) for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.

 

 

SOURCE Amgen

 

 

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SEP
02
0

KDIGO Bone and Mineral Guidelines now available

The KDIGO guideline group has released its bone and mineral guidelines.

  • These can be seen online at this link.
  • Alternatively, you may download the .PDF of these guidelines using this link

Dr. Jeff Berns, editor in chief of Medscape Nephrology, had this to say on this development:

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JUL
22
0

Sodium bicarbonate replacement delays progression of chronic kidney disease

In the latest edition of the Journal American Association of Nephrology, investigators report that sodium bicarbonate administration delays the progression of kidney disease to end-stage renal failure. 134 adult patients with CKD (creatinine clearance [CrCl] 15 to 30 ml/min per 1.73 m2) and serum bicarbonate 16 to 20 mmol/L to either supplementation with oral sodium bicarbonate or standard care for 2 yr. With this simple intervention, patients receiving sodium bicarbonate were significantly less likely to experience rapid progression (9 versus 45%; relative risk 0.15; 95% confidence interval 0.06 to 0.40; P < 0.0001). Compared with the control group, decline in CrCl was slower with bicarbonate supplementation (5.93 versus 1.88 ml/min 1.73 m2; P < 0.0001). Nutritional parameters were improved as well. This very simple intervention, practiced variably by nephrologists, shows great promise in the management of patients with chronic kidney disease.

Click here to download the PDF

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JUN
05
0

INSPRA approved as adjunct to standard therapy to reduce risk of death

KIRKLAND, QC, June 3 /CNW/ - A new treatment option for heart failure is now available in Canada (from CNW Group)

Canada as an adjunct to standard therapy, to reduce the risk of deathfollowing a heart attack in clinically stable patients who have evidence of heart failure and left ventricular systolic dysfunction: INSPRA (eplerenonetablets) is the first aldosterone receptor blocker to be approved for thisindication in Canada. In the landmark Eplerenone Post-acute myocardial infarction Heart failureEfficacy and SUrvival Study (EPHESUS),(1) INSPRA provided significant earlyand sustained all-cause mortality benefits above and beyond standardtherapies, including angiotensin converting enzyme (ACE) inhibitors,angiotensin receptor blockers (ARBs) and beta blockers in patients with acutemyocardial infarction (AMI) complicated by heart failure. "Pfizer Canada is pleased to introduce INSPRA as part of our establishedportfolio of cardiovascular treatment options. This innovative medication willprovide Canadians afflicted by congestive heart failure after a myocardialinfarcation, with a proven and effective treatment," said Dr. Bernard Prigent,Vice President and Medical Director, Pfizer Canada Inc. "We are confident thatINSPRA will become an essential, life-saving component of standardpost-myocardial infarction care in Canada, based on the 2009 American Collegeof Cardiology and American Heart Association guidelines that recommendshort-term and long-term use of aldosterone blockade."

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JUN
02
0

ASH: Calcium Channel Blocker Benefits in ACCOMPLISH Not Explained by Ambulatory BP

By Crystal Phend, Staff Writer, MedPage Today
Published: May 12, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

SAN FRANCISCO, May 12 -- Ambulatory blood pressure monitoring didn't explain the cardiovascular advantage of calcium channel blockade found in the ACCOMPLISH trial, researchers said.

The primary findings of that trial revealed a 20% reduction in cardiovascular mortality and morbidity with the calcium channel blocker amlodipine (Norvasc) versus the diuretic hydrochlorothiazide (Microzide) as the initial antihypertensive in combination with the ACE inhibitor benazepril (Lotensin).

But in a secondary analysis of ACCOMPLISH results, 24-hour blood pressure monitoring revealed no difference in blood pressure control between the regimens, Kenneth Jamerson, M.D., of the University of Michigan in Ann Arbor, and colleagues found.

These results affirm that the calcium channel blocker combination has some "pleiotropic" benefits beyond blood pressure lowering alone, Dr. Jamerson reported at the American Society of Hypertension meeting.
Action Points  

    * Note that guidelines from the National Heart, Lung, and Blood Institute (JNC 7) recommend thiazide-type diuretics as initial therapy for most hypertensive patients, whether alone or in combination with an agent from another class.


    * Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

"It really does matter what agent you use," he said.

After the primary report of the data, concerns had arisen that lower blood pressure in the calcium channel blocker group biased the results, commented co-author George Bakris, M.D., of the University of Chicago, who moderated a press conference at which the findings were presented. (See ACC: Calcium Channel Blocker Beats Diuretic for Initial BP Combo Therapy)

Also, the trial used hydrochlorothiazide rather than the longer-acting diuretic chlorthalidone, which could have meant less blood pressure control over the full 24 hours compared with the other combination regimen.

But the ambulatory blood pressure results lay these questions to rest, Dr. Jamerson said.

"This type of data has the potential to change the paradigm to treat blood pressure from mostly being diuretic-based combination therapy to being amlodipine with benazipril type regimens," he said.

In the analysis of 573 patients in ACCOMPLISH, the in-clinic systolic blood pressure after two years of treatment averaged 0.6 mm Hg lower with amlodipine plus benazipril compared with hydrochlorothiazide plus benazipril (129.7 versus 130.3 mm Hg, P=0.621).

But the 24-hour blood pressure average actually favored the diuretic-ACE combination (122.3 versus 123.9 mm Hg, P=0.128), as did daytime and nighttime averages (P=0.097 and P=0.332).

For diastolic pressure, the diuretic combination also had a small, 0.3-mm Hg advantage over 24 hours (P=0.7).

None of these were significant differences, and both groups attained greater than 80% blood pressure control rates (81.3% with the calcium channel blocker and 84.9% with the diuretic combination, P=0.243).

Dr. Bakris said that a calcium channel blocker may have "pleiotropic" benefits for endothelial function and the atherosclerotic process that may have lowered cardiovascular risk despite similar blood pressure.

However, some at the late-breaking clinical trials session where the research was presented were skeptical.

Marvin Moser, M.D., of Yale University, who moderated the session, cautioned that the conclusions of the trial may have been overstated.

"The weight of data suggests it's the blood pressure level and not the specific drug," he said.

Guidelines from the National Heart, Lung, and Blood Institute (JNC 7) recommend thiazide-type diuretics as initial therapy for most hypertensive patients, whether alone or in combination with an agent from another class.

"Diuretics have held up as well as anything else," Dr. Moser said. "Before we abandon them we need further confirmation."

Another study presented at the same session, on which Dr. Bakris was also a co-author, suggested there was no difference between agents for left ventricular hypertrophy regression. (See ASH: Lower Blood Pressure Trumps Regimen in LV Remodeling)

Dr. Bakris noted that this surrogate endpoint may be important, but doesn't capture broader cardiovascular effects or the more important mortality endpoint.
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APR
20
0

RecycleMe: An innovative website promoting organ donation

The Trillium Gift of Life Program has launched a very innovative website promoting organ donation. The website is very slick and provides excellent and entertaining information on organ donation. Have a look.

 

 

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APR
18
0

High cut-off hemodialysis for the treatment of multiple myeloma

Myeloma cast nephropathy has a very high morbidity and mortality, largely due to many of these patients' dependence on hemodialysis. Several attempts have been made to improve these outcomes with extracorporeal strategies that remove toxic light chains characteristic of this disease. In the latest issue of the Clinical Journal of the American Society of Nephrology, investigators report on an uncontrolled pilot study of high cut off hemodialysis (HCO-HD), a strategy that removes light chains in addition to traditional solutes. Although uncontrolled, 75% of patients studied became independent of dialysis compared to traditional studies where fewer than 25% come off dialysis. This promising result will be studied further in a multicenter randomized control trial, known as EuLITE (European Trial of Free Light Chain Removal by Extended Hemodialysis in Cast Nephropathy).

 

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APR
16
0

More evidence for mycophenolate mofetil in lupus nephritis

Many nephrologists, myself included, are eager to find alternatives to cyclophosphamide in the management of lupus nephritis. As many of these patients are young men and women of child-bearing age, the effects of cyclophosphamide on fertility, along with bone marrow and other adverse effects make alternative medications more attractive. Several studies have suggested that mycophenolate mofetil (MMF) may be superior and less toxic than cyclophosphamide in the management of lupus nephritis. In the May issue of the Journal of the American Society of Nephrology, investigators report the result of a study comparing IV cyclophsphamide with oral MMF. While a reprint is not yet available for review, preliminary reports suggest that MMF is slightly more effective and less toxic in this trial. In a 24-week open-label induction study of 370 patients with class III-V lupus, there were no differences in the primary end-point (a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine) or the secondary end-point (complete renal remission, systemic disease activity and damage, and safety).  As well, there were no differences in the rate of adverse events between the 2 groups. For the studied patients, IV cyclophosphamide and oral MMF share similar efficacy and harm. This study adds to the growing evidence base showing no difference between these 2 treatment strategies.

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APR
11
0

Major breakthrough in transplantation immunity

Professor Jonathan Sprent and Dr Kylie Webster from Sydney's Garvan Institute of Medical Research, in collaboration with colleagues, Dr Shane Grey and Stacey Walters reported a major breakthrough in the area of transplantation tolerance in this month's issue of the Journal of Experimental Medicine. This fascinating report describes a method of inducing tolerance of islet cell grafts transplanted into mice. The technique involves combining an antibody with IL2 in a complex that upregulated T-regulatory cells, suppressing T-Killer cells that lead to acute rejection. No immunosuppression was required by the animals and 80% enjoyed tolerance of the graft. While these results are preliminary and in an animal model, it does offer a glimpse at a potential strategy that might obviate  or significantly reduce the need for toxic medications in human transplant recipients of all kinds.

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APR
10
0

eGFR and microalbuminuria: a powerful duo

Estimates of glomerular filtration rate (GFR) have been the mainstay of kidney functional assessment for some time and have been the most widely relied upon test to predict progression to end-stage renal disease (ESRD). Urinary microalbuminuria (MAU) has more recently been added to the assessment of chronic kidney disease. In this month's issue of the Journal of the American Society of Nephrology, researches confirm that the use of these two tests in conjunction improves the accuracy of predicting which patients will go on to develop ESRD. According to their analysis, if one uses eGFR and MAU together, the number of patients referred to a nephrologist that ultimately develop ESRD would fall from 38.4 to 11.4. This dramatic reduction implies that these 2 tests when used in conjunction greatly increases the diagnostic and prognostic accuracy of primary care physicians assessing for chronic kidney disease.

For  a presentation on this topic, please see these links on UKidney:

  1. Microalbuminuria testing
  2. eGFR and MAU in primary care

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APR
09
0

ACE and ARB in combination: Still a viable option?

In the wake of the ONTARGET study, there is a movement away from using ACE and ARBs in combination for hypertension or general vascular protection. However, the combination is still an option for patients with heart failure where the it has been shown to reduce hospitalization. There remains a question whether the combination can reduce the rate of progression in diabetic nephropathy and other kidney diseases. While the ONTARGET study did include a relatetively small number of patients with nephropathy, it was not designed or powered to show a difference in renal outcomes. A new study, the VA-NEPHRON D, is currently underway to examine the effect of lisinopril plus losartan versus lisinopril plus placebo on the progression of chronic kidney disease. A copy of this study design can be found here. This study should shed light on the role of this medication combination in a disease state with a large unmet therapeutic need.

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APR
08
0

In-center nocturnal hemodialysis: a novel therapy

Nocturnal hemodialysis in the home has emerged as a very impressive modality when managing patients with end-stage renal failure. The added dialysis time, combined with gentle solute and water removal has led to the improvement in several important parameters in patients who undergo it. However, not all patients can manage the complexities or some of the practicalities of having dialysis in the home. In this month's issue of Clinical Journal of the ASN, Dr. Goldstein et al report on their experience with nocturnal dialysis in hospital. Several parameters were positively effected by this novel therapy where patients sleep three nights per week at St. Michael's Hospital in Toronto. The study suggests that this modality is a viable option when caring for patients with end-stage renal failure.

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APR
05
0

Statins in end-stage renal failure: failure revisted

After disappointing findings in the 4D Study, a subsequent trial reported in a recent issue of the New England Journal of Medicine once again demonstrated disappointing results with statin therapy in patients with end-stage renal failure. In the AURORA study, 2776 patients aged 50-80 were randomized to 10 mg of Crestor or placebo. Despite an average of 43% reduction in LDL, there was no change in the primary end-point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke after 3.8 years of follow-up.

This study is an unfortunate reminder of the difficulty creating measurable impact on hard clinical end-points in patients with end-stage renal failure.

 

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