MAY
25
0

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

ADPKD

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
The primary endpoint of the trial was the change in estimated glomerular filtration rate (eGFR) from pre-treatment baseline levels to post-treatment assessment. In patients treated with tolvaptan the reduction in eGFR was significantly less than in patients treated with placebo (p<0.0001). eGFR is an estimate of the sum of the filtration rates of all single functional nephrons (filtering units) in the kidneys, measured through creatinine-based estimation equations. The difference observed in this study represents a 35% reduction in the loss of kidney function compared to placebo in these patients over the course of one year. The key secondary endpoint was a comparison of the efficacy of tolvaptan treatment versus placebo in reducing the decline of annualized eGFR slope across all measured time points in the study. These data also showed significant benefit from tolvaptan vs. placebo (p<0.0001).

These results are preliminary until a peer-reveiwed publication is released, but at face-value, they add to the landmark findings of the TEMPO 3:4 study, reported previously on UKidney.

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JUN
15
0

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

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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2243 Hits
NOV
30
0

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

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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5175 Hits
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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17502 Hits
NOV
07
1

Renal outcomes with Empagliflozin: a game-changer

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)

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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22090 Hits
NOV
26
0

Calcium channel blockers and breast cancer: Update

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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2556 Hits
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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21392 Hits
JAN
11
0

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

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?

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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