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UKidney Nephrology News and Insights

JUL
22
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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.

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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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