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UKidney Nephrology News and Insights

NOV
12
0

Canagliflozin in patients with very low GFR: Protection persists

Excitement for the SGLT2 inhibitor class continued at the 2019 ASN Kidney Week. Evidence continues to accumulate from analyses of the CREDENCE trial which originally showed - for the first time in a randomized controlled study with hard renal outcomes - that patients taking canagliflozin experienced slower decline in their kdiney function and a reduction in the incidence of end-stage renal failure requiring dialysis or kidney transplant. In the CREDENCE study, patients with an estimated eGFR below 30 ml/min were excluded from the trial. However, patients who had a eGFR > 30 ml/min at the time of screening but in whom the eGFR fell below 30 ml/min by the time of randomization were nevertheless included in the study.

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AUG
07
0

Clinical Focus: How can I maximize blood pressure control for my patients and also minimize pill burden?

A 53 M presents for follow-up of his hypertension. He has a history which includes:
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JUN
18
0

The importance of diuretic selection when managing hypertension

Welcome to the Circle of Knowledge Program

Two Canadian experts, Dr. Jordan Weinstein and Dr. Louis Girard, nephrologists, will share how to translate clinical evidence into daily practice for optimal hypertension patient care.

www.CircleofKnowledge.ca

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FEB
20
0

Hypertension Update: Did you know...

Welcome to the Circle of Knowledge Program

Two Canadian experts, Dr. Jordan Weinstein and Dr. Louis Girard, nephrologists, will share how to translate clinical evidence into daily practice for optimal hypertension patient care.

www.CircleofKnowledge.ca

Upon reflection, what percentage of the patients in your practice are on an optimal medication regimen in terms of dosing and medications selected?

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FEB
20
0

Hypertension targets following the SPRINT study

Welcome to the Circle of Knowledge Program

Two Canadian experts, Dr. Jordan Weinstein and Dr. Louis Girard, nephrologists, will share how to translate clinical evidence into daily practice for optimal hypertension patient care.

www.CircleofKnowledge.ca

Hypertension is one of the most important risk factors for adverse health outcomes that we treat either in specialty or primary care. However, controversy has always existed in terms of the target blood pressure that clinicians should aim for when managing patients with different comorbidities. The SPRINT study published in 2015 continues to offer insight and some controversy guiding therapy in patients with hypertension particularly those at high cardiovascular risk.

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SEP
14
0

MR elastography: Revolutionizing the assessment of renal fibrosis

Drs. Anish Kirpalani and Darren Yuen, both of St. Michael's Hospital in Toronto, appear to be on the verge of a major practice-changing advance in the assessment of chronic kidney disease. Their study, appearing in cJASN, describes the new methodology which assesses kidney fibrosis in a novel way using MRI. We caught up with the authors of this exciting study and they shared some further perspective on their exciting findings.

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MAY
25
0

More positive news for Tolvaptan (Jinarc) in ADPKD: Reprise Study topline results

Topline results of the Reprise Study in ADPKD have been announced and the good news continues for ADPKD. According to top-line results released by Otsuka, the maker of Tolvaptan:

- Primary and key secondary endpoints were positive for tolvaptan vs. placebo in an additional Phase 3 clinical trial that examined the efficacy and safety of tolvaptan in autosomal dominant polycystic kidney disease (ADPKD)- The data are intended to address the Complete Response Letter (CRL) issued by the FDA for a New Drug Application (NDA) for tolvaptan in ADPKD in 2013- Trial results will be submitted for presentation at a nephrology medical congress in the second half of 2017
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JUN
15
0

SGLT2 inhibitors and nephroprotection: a perspective on the renal outcome data

A long awaited analysis of the renal outcomes from the EMPA-REG study was published in the New England Journal of Medicine on June 14th [2].  As originally reported on UKidney, compared to patients taking placebo, the use of empagliflozin was associated with significant improvements in important renal end-points, namely doubling of serum creatinine and end-stage renal disease (ESRD). While these results are indeed very promising, some perspective is warranted when considering the potential nephroprotective properties of this drug, and of the SGLT2 inhibitor class in general.

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NOV
30
0

Racing to apply the SPRINT study to your practice? Not so fast

The SPRINT Study was received with great fanfare when it was published on November 26th in the New England Journal of Medicine. The primary results, summarized in the publication’s abstract are these:

"Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group."

The essential word in that abstract’s conclusion - and which prevents the application of these results - is ‘targeting’. The conclusion accepted by many is that aggressive blood pressure reduction, that is the achieved blood pressure, drove the observed results. However, it may well be that the act of targeting a low blood pressure, and using cardioprotective drugs to do so, explained the results rather than the reduction of blood pressure itself. And unravelling this nuance is the key to understanding whether SPRINT’s main message is applicable to the general population. I would argue that in its current form SPRINT suffers from a major methodological short-coming that leaves us in a quagmire.

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NOV
08
2

Empagliflozin and renal outcomes: further insights in to the renal protection of SGLT2 inhibitors

As we continue to process data from the EMPA-REG renal outcomes presentation - which most importantly showed a 46% reduction in the composite of creatinine doubling, end-stage renal disease or renal death - speculation is well underway to explain the mechanism for renal protection. And the emerging story appears to be quite fascinating indeed. 

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NOV
07
1

Renal outcomes with Empagliflozin: a game-changer

Data from the EMPA-REG study were unveiled in Stockholm 6 weeks ago. In more than 7,000 adults with type 2 diabetes (T2D) at high risk for CV events, EMPA-REG OUTCOME met its primary endpoint and demonstrated superiority of JARDIANCE, when added to standard of care, in CV risk reduction. The primary endpoint was defined as time to first occurrence of either CV death, or non-fatal myocardial infarction or non-fatal stroke[1].

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FEB
26
0

Jinarc (Tolvaptan) approved in Canada for the management of autosomal dominant polycystic kidney disease (ADPKD)

Canada becomes the first country outside Japan to approve JinarcTM (Tolvaptan) for the treatment of ADPKD. This medication, dosed twice daily, is the first of its kind to show a slowing in renal function decline as well as a slowing in kidney enlargement among patients with ADPKD.

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NOV
26
0

Calcium channel blockers and breast cancer: Update

Previously, UKidney News reported a possible link between calcium channel blockers and the development of breast cancer. Data from the Intermountain Medical Center Heart Institute study were presented at the 2014 American Heart Association Scientific Sessions in Chicago, dispelling some of this concern:

"We found no robust data that calcium channel blocker medications increase a person's risk of breast cancer," said Jeffery L. Anderson, MD, a cardiologist and researcher at the Intermountain Medical Center Heart Institute. "Given the important role calcium channel blocker medications play in treating heart conditions, we think it's premature to discontinue their use. At this point we recommend that patients continue taking these medications to treat their hypertension."

While it is very difficult to ever prove a negative association, these data do provide some reassurance to a large number of patients using this important antihypertensive.

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JAN
28
1

Dream RCT: A placebo-controlled trial of hyperphosphatemia management

Dream RCT logoImagining the Dream RCT in nephrology is an important exercise, but not for the reasons you might think. For many, there might be the temptation to devise trials that will pave the way for future enhancements to patient care or to some other exciting, forward thinking outcome. For me however, the Dream RCT in nephrology is about shattering or affirming nephrology dogma - and in nephrology we seem to have more dogma influencing core tenets of our specialty than in other medical disciplines. There is a popular saying among those in the clinical epidemiology world - that you don’t need to conduct an RCT to prove that parachutes are required when jumping out of a plane. Unfortunately in nephrology, thought leaders have bestowed parachute status on too many interventions. I can think of no better example for this analogy than treating hyperphosphatemia in CKD/ESRD. And it is this topic that would underlie my Dream RCT.

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JAN
11
0

Renal denervation safe, but fails to meet primary end-points in Symplicity 3

Top-line results of the Symplicity 3 trial were revealed this week, showing that despite being safe, renal denervation was no better than a sham procedure at controlling blood pressure at 6 months. As reported on Medscape:

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AUG
06
0

Calcium channel blockers and breast cancer: an important risk factor discovered?

A report in JAMA - Internal Medicine[1] raises important safety concerns about calcium channel blockers, one of the most widely prescribed classes of antihypertensives used world-wide.

In the population-based case-control study by Li et al, participants in the 3-county Seattle–Puget Sound metropolitan area were women aged 55 to 74 years, 880 of them with invasive ductal breast cancer, 1027 with invasive lobular breast cancer, and 856 with no cancer serving as controls. The exposures studied were recency and use of antihypertensive medications while the main outcome measures were risks of invasive ductal and invasive lobular breast cancers.

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JUL
29
2

Are calcium-based phosphate binders obsolete?

As reported on UKidney, earlier in July 2013, Jamal et al published a systematic review comparing calcium-based phosphate binders with non-calcium-based phosphate binders in terms of their impact on cardiovascular outcomes. This pivotal work shows a small but statistically significant advantage of non-calcium-based binders over calcium vis-à-vis mortality outcomes in patients with chronic kidney disease and hyperphosphatemia.

Calcium dose has been implicated in the development of vascular calcification and in the excess cardiovascular morbidity common in patients with CKD, especially those on dialysis. The hope for non-calcium-based phosphate binders has always been that by limiting calcium intake, patients taking non-calcium-based binders would benefit from phosphate reduction without the exposure to potentially harmful dosages of calcium. While individual clinical trials have failed to show any clear advantage of non-calcium-based phosphate binders in terms of reducing cardiovascular morbidity and mortality, this latest systematic review now shows a statistically significant advantage of non-calcium-based phosphate binders over calcium in terms of limiting mortality in patients with CKD.

So where do we go from here? There will likely be discussion as to whether the finding in this systematic review is valid. Furthermore, even if the effect is indeed real, the cost of non-calcium-based binders over calcium-based binders is substantial. Nevertheless, it is likely time to consider whether calcium-based phosphate binders should be made obsolete. There are now substantial data supporting at least a modest effect of calcium dose on mortality and the rationale for using phosphate binders that are not calcium-based. An important question remains as to whether hyperphosphatemia should be treated at all – that is, with binders of any sort. It is entirely possible that non-calcium-based phosphate binders are superior to calcium simply because they limit calcium intake and that the drugs themselves do not offer any other outcome advantage - even if they lower phopshate.

And so, while this systematic review comes closer to answering a long-standing question in nephrology related to optimal phosphate binder class, it underscores an important lingering question as to whether hyperphosphatemia requires treatment at all. To answer this critical question, we require a long overdue placebo-controlled trial of hyperphosphatemia treatment. Objections to a placebo-controlled trial in this area have often centered around the ethics of withholding treatment for hyperphohsphatemia in the form of phosphate binders. However, there appears to be equipoise in this area; there is real uncertainty as to the saftey of calcium-based phosphate binders and whether hyperphosphatemia truly mediates cardiovascular illness in patients with CKD, or if it is only a disease association and nothing more.

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JUL
22
0

Calcium-based phosphate binders likely harmful in CKD

Researchers from the University of Toronto and the University of Alberta add to existing data that calcium-based phosphate binders are harmful compared to binders that do not contain calcium. An updated systematic review on this topic that appears in the July 19th online version of the Lancet shows that patients with CKD across 8 studies (5 randomized) treated with non-calcium based binders had a 22% reduction in all-cause mortality compared to those taking calcium based binders.

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JUN
21
0

SAVOR Trial Negative: No CVD advantage for Saxagliptin

Top-line results for the SAVOR trial were announced this week in which Saxagliptin (Onglyza, Bristol-Myers Squibb/AstraZeneca) failed to demonstrate superiority over placebo in reducing a composite end point of cardiovascular death, nonfatal MI, or nonfatal ischemic stroke when added to usual care in patients with type 2 diabetes with either a history of established CVD or multiple CVD risk factors.  While the trial did demonstrate non-inferiority from a cardiovascular safety perspective, it failed to show any efficacy advantage. As reported originally on theheart.org:

Princeton, NJ and Wilmington, DE - The SAVOR-TIMI 53 trial has failed to demonstrate the superiority ofsaxagliptin (Onglyza, Bristol-Myers Squibb/AstraZeneca) over placebo in reducing a composite end point of cardiovascular death, nonfatal MI, or nonfatal ischemic stroke when added to usual care in patients with type 2 diabetes with either a history of established CVD or multiple CVD risk factors [1].

The trial sponsors, Bristol-Myers Squibb and AstraZeneca, announced the top-line results from the trial early this morning. The full findings will be presented September 2, 2013 at the European Society of Cardiology(ESC) 2013 Congress. The trial did meet its "primary safety objective of noninferiority" vs placebo, a joint statement from the companies reads. SAVOR-TIMI-53 is part of an ESC hot-line session dedicated to risk factors and diabetes. The full schedule of ESC 2013 hot lines was published on the ESC website earlier this week.

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor approved in the US, Canada, Europe, and elsewhere as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Other, nonrandomized analyses had raised hopes that this class of drugs might have a protective effect on the vasculature of diabetes patients.

Saxagliptin was the first new diabetes drug to receive FDA approval after the issuance of new agency guidelines in July 2009, requiring companies to perform CV-outcomes studies with new diabetes drugs. The drug's clinical development program had been completed before the guidance, but because of the new rule, the company launched SAVOR-TIMI 53. The four-year-long trial had a target enrollment of 16 500 patients, and principal investigators for the trial are Dr Itamar Raz (Hadassah Medical Organization, Jerusalem, Israel) and Dr Deepak Bhatt (Brigham and Women's Hospital, Boston, MA).

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NOV
03
3

Tolvaptan in Polycystic Kidney Disease (ADPKD): the most exciting nephrology development in years

The High Impact Clinical Trials Session at this year's American Society of Nephrology Renal Week was the site of one of the most important and exciting nephrology developments to materialize in years. Researchers presented the results of a Phase 3 study using Tolvaptan (a vasopressin receptor antagonist) for the treatment of autosomal dominant polycystic kidney disease (ADPKD). Previously a disease with no medical treatment, ADPKD accounts for 10% of the dialysis population and is associated with pain, hematuria, hypertension and a number of extra-renal manifestations.

The Tempo 3:4 Study randomized 1445 patients to receive a mean dose of 95 mg of Tolvaptan versus placebo over a 3 year period of observation. Patients receiving active drug experienced a slowing of kidney volume by 50% and also a slower deterioration in GFR,  the primary and secondary outcomes of the study respectively. While there was a greater number of adverse effects related to the medication (polyuria, thirst, hyperuricemia, gout, hepatitis, hypernatremia), there were less ADPKD-related effects (pain, hemturia, urinary tract infection).

While the primary invstigator V. E Torrres was quick to temper enthusiasm until regulatory bodies such as the FDA weigh in on these findings, this study is a major breakthrough in the management of ADPKD and represents a shining example of bench to bedside research that will provide hope for a large group of patients who previously had no medical option for delaying the onset of end-stage renal disease in ADPKD. This will truly be a fascinating story to watch unfold as more study in this area continues.

Please see the New England Journal of Medicine publication here.

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