NephJC is a Twitter Journal Club that discusses the latest developments in nephrology in an open public forum, everyone is welcome and we have had excellent input from attendings, professors, med students and patients.
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Speaking of the twitter chat we meet every other week to open the discussion on a new topic and then conclude the discussion a week later with a Google Hangout where we summarize the discussion and if we are lucky dig a little deeper. This week we are looking at the positive trial, POSEIDON from the Lancet
Joining me today we have
Dr. Somjot Brar Lead author of POSEIDON
Dr. Peter McCullough the rare cardiologist who has made the kidney his area of expertise
And before we go any further, I want to establish any do any of you have any conflicts of interest?
I have none?
Dr. Brar, can you tell me about the funding for the project?
Dr. McCullough, any COIs?
To get everybody up to speed, allow me to quickly summarize the paper.
Contrast nephropathy is a signifigant cause of AKI, causing 10% of hospital acquired AKI in some series
Standard of care is prophylactic sodium loading. Numerous protocols are used varying doses, solutions and prescriptions are used but the data guiding these choices has not been thoroughly vetted.
The authors claim that this trial the POSEIDON trial was the first to investigate various rates of infusion to determine their relative efficacy.
The cohort of roughly 400 patients all received 0.9% Saline at 3mL/kg for 1 hour and then
The control group 1.5 mL/kg/hr
the experimental group had their LVEDP measurede and the subsequent fluid was given based on that measurement
LVEDP < 13 mmHg: 5 mL/kg/hr
LVEDP 13-18 mmHg: 3 mL/kg/hr
LVEDP >18 mmHg: 1.5 mL/kg/h
over half the cohort had LVEDP <13 and subsequently the experimental group received nearly twice as much NS as the control group.
the results of this intervention were impressive:
...as compared with standard treatment resulted in a significant 68% relative reduction in the primary endpoint of contrast-induced acute kidney injury, and a significant 59% relative reduction in major adverse clinical events.
Dr. Brar is that a fair summary of the paper?
Dr McCollough what was your initial reaction to the paper?
What do you think about the rate of CIN in the control group, was it too high? are we seeing significance more to do with poor outcomes in the control group or better outcomes in the intervention group
The tweetchat brought up an important point that there was no evidence in this paper that the measurement of LVEDP was helpful. Some suggested that having a second control group receiving the high dose without regard to LVEDP would have been interesting.
CHF is a powerful risk factor for CIN and presumably blindly increasing fluids would have caused some people to get CIN, thus proving the utility of LVEDP.
Dr. Brar any thoughts on an additional study to prove the importance of LVEDP?
Another issue people brought up was we would have liked to see the rate of CIN in the control group based on LVEDP. Is LVEDP an independent risk factor for CIN?
One thing I thought was interesting that I did not see commented on in the discussion was that this trial design was not so much about prophylaxis because the change in the treatment really happened concurrent with the toxin, but a trial of an antidote. Is this the first tim we have seen an intervention that was given with the contrast that made a difference in outcomes?
Persistent renal failure after AKI is a hot issue that was called into question with the recent CORONARY trial, do either of you have some color on what the results of this trial have to say about that?
do you think that two weeks is too short to define persistent AKI?
Dr. Brar I was delighted to see that you guys included long term outcomes in the secondary outcomes.
one thing of note was the increase in MIs in the control group that continued to occur even more than 90 days after the cath, what possible mechanism could explain that?
Any thoughts Dr. McCullough?
Next week’s NephJC will be on the Perspective by Richard Johnson et al on the central american CKD epidemic. Thius was published as the first story in Nature Reviews Nephrology May. They have graciously agreed to make the arricle open access. We are appreciative of that especially on this story which I think is the story of the decade in nephrology. I recently saw a map of the world that showed the leading cause of death around the world and was suprised to see in that CKD popped up in Central America. This should make for an interesting article and discussion next Tuesday.