In February I’m giving grand rounds on the Potassium Wars (what, you didn’t realize we are in the opening stages of the potassium wars?). I was looking at the original research on Kayexalate from 1961 and came across this ad. Check out the doses of spironolactone they were slinging:
From the NEJM 2007.
Purple discoloration can occur in alkaline urine as a result of the degradation of indoxyl sulfate (indican), a metabolite of dietary tryptophan, into indigo (which is blue) and indirubin (which is red) by bacteria such as Providencia stuartii, Klebsiella pneumoniae, P. aeruginosa, Escherichia coli, and enterococcus species. The clinical course is benign, and the urine typically clears with resolution of the bacteriuria and acidification of the urine.
A few pioneers at the intersection of social media and nephrology have banded together to create an internship in social media. The founding members of the loosely coordinated Nephrology Social Media Collective (logo pending, but it should be pretty cool) are:
- Swapnil Hiremath, co-founder and brain child of NephJC
- Matt Sparks, savior of Renal Fellow Network and co-creator of NephMadness
- Kenar Jhaveri, blogger at NephronPower and editor of AJKDblog
- Paul Phelan, contributor to NephJC, Renal Fellow Network and AJKDblog
- Jordan Weinstein, creator of UKidney
- Edgar Lerma, creator of #NephPearls hashtag and serial author
- Renal Fellow Network
- Google hangouts
- Tweet chats
- Storify for curation
- Mail Chimp newsletters
- Twitter analytics
- Google analytics
- multiple blogging engines including:
Waiting for me in my inbox today:
Hello Dr. Topf,
My name is Julia XXXXX, and on behalf of Keryx Biopharmaceuticals, I’d like to introduce Keryx as a resource for you as you develop content for your blog, Precious Bodily Fluids, given your commitment to advancing understanding of renal diseases. I’d like to periodically share updates from the company to keep you informed regarding its lead therapeutic product and commitment to patients on dialysis.
In fact, Keryx just announced it has begun shipping AURYXIA™ (ferric citrate) tablets to wholesalers in the U.S. Auryxia is approved for the control of serum phosphorus levels in patients with chronic kidney disease (CKD) on dialysis. Auryxia is the first and only absorbable-iron-based phosphate binder that is clinically proven to effectively control phosphate levels within the KDOQI guidelines range of 3.5 mg/dL to 5.5 mg/dL. The U.S. Food and Drug Administration approved Auryxia in September 2014. In addition, Keryx has created the “Keryx Patient Plus” program to assist with patient accessibility to Auryxia.
For more information, please visit http://www.auryxia.com/. The full press release is below and includes additional information.
If you are amendable, we will continue to reach out to share updates from Keryx and AURYXIA in the coming year that we hope will be useful for your readers and followers.
Please feel free to reach out with any questions.
Thanks for reaching out. I’m glad there is a new phosphate binder available for dialysis patients. I was wondering if you have any data that shows Auryxia reduces any patient oriented outcomes (e.g. hospitalization, mortality, fractures, morbidity)? And if not, is Karyx planning on doing such a study? And if not, why not?
Fingers crossed but with a skeptic’s scowl
|PDF | Powerpoint|
The colours in the table are not explained anywhere. I am guessing “green”means statistically significant, and “orange” means… a decline in posts over time? Maybe that could be mentioned in the main text at the left.
The table is big and dense. Again, I wonder if it could be simplified, either graphically (first step: remove the vertical gridline!) or even removed. If I’m reading it right, some of the information in the table is repeated in the graphs to the right of the table.
The last line of the table – “Totals” – appears to be incorrect. It looks like most of those entries are means, not totals.
Also, the text mentions 30 blogs, but only 22 are plotted.
I have a patient with CKD stage four, diabetes and hypertension. In fact, I have a hundred patients with CKD stage four, diabetes and hypertension. However, this patient had uncontrolled blood pressures. Here is the nomogram from her home blood pressures:
- More fruits and vegetables
- Decreased processed and restaurant food
- Decreased fructose intake
- Improved compliance
She denied non-compliance on her previous visit, but her new focus on her health should certainly increase her medication compliance. All of this was in play.
I remember a time when I thought the treatment of chronic SIADH was going to be revolutionized by the vaptans. These small molecular ADH antagonists would interrupt the disease the precise mechanism of disease. I expected a Banting and Best like revolution. (If you have not seen the story of the discovery of insulin take a moment to watch the movie, Glory Enough for All, especially if you thought the greatest thing to come out of Canada was Tim Horton’s)
The initial data was promising with convincing studies on conivaptan and tolvaptan, but something happened on the way to SIADH nirvana.
First the EVEREST trial went sideways. In heart failure:
- Angiotensin 2 is elevated and blocking it prolongs life
- The sympathetic nervous system is up-regulated and blocking it prolongs life
- Aldosterone is elevated and blocking it prolongs life
- ADH is elevated and blocking it doesn’t do a damn thing
With no hope for a heart failure indication the drug was marketed solely as a treatment for hyponatremia where it was shown to be effective. The pitch was that doctors should not discharge people with hyponatremia and tolvaptan was faster and more effective than the previous standard of care. The drug was priced for short-term inpatient use at $300 a pill tolvaptan was a non-starter for chronic outpatient SIADH.
The side effects reported for demeclocycline and lithium were such that we recommend not using them for any degree of hyponatraemia.
Fluid restriction, the cornerstone of therapy, is difficult to maintain and in severe cases is insufficient to correct hyponatremia (I’m thinking of patients with negative free water clearance). Urea has a good track record but I have not heard of it being used in the United States. Salt tablets can help, but often are inadequate to correct the hyponatremia.
On the list of possible treatments are loop diuretics. I have tried loops in hyponatremia on a number of occasions and though the math works, in my hands I have not found them to be effective. In the past, I have used loops in hospitalized patients with hyponatremia. The results have been underwhelming. But I know have a loop diuretic success story in a patient with significant but stable outpatient hyponatremia.
I met the patient when he was admitted to the ICU with mental status changes due to a sodium south of 120. This was not his first episode of hyponatremia. We corrected the sodium and restored normal mentation. We did a thorough work-up, looking for the etiology of the SIADH and despite some promising leads that turned into blind alleys, I am quite confident, now, that this is idiopathic SIADH.
During subsequent outpatient follow-up he had persistent hyponatremia with sodiums running in the high 120’s. During this time, treatment consisted of salt tablets and fluid restriction. A couple of visits ago I added torsemide, and boom the two sodiums since have been 138 and 134.
Here is the sodium and urine osmolality over time. It plummets after the torsemide is started. This increases the free water clearance.
Patient’s sodium dropped further to 120 in the evening. He has had a precipitous drop that I suspect is due to over-diuresis, which does not seem to be a diagnosis within the lexicon of heart failure cardiologists. It is possible that he could have developed SIADH, through a drug side effect. In any case, we have reached the usual place where attempts to fix the heart have blithely interfered with renal physiology, and I am not willing to let his serum sodium decline into the 110s. If we give NS, and he has SIADH, we will worsen his serum sodium. We could use 3% NS, but he is not having mental status changes, yet, and this is bad form for a patient in heart failure. If he is volume depleted, and we use conivaptan, he could develop hypotension which would be difficult to fix. So I seem to have been finagled into ordering tolvaptan, which will hopefully prevent any further decrease tonight. Tolvaptan fixes a number and has not been shown to improve clinical outcomes with chronic use.
Clearly there is a large dose of crazy in the assessment and plan, but it highlights a number of real issues in hyponatremia. Let’s dissect the note a bit and tease out the best parts.
The first clam that over-diuresis does not seem to be a diagnosis within the lexicon of heart failure cardiologists seems to be true. A brief survey of google finds a paucity of relevant hits for the phrase and most of those are from nephrologists or family practitioners. Given the frequency that I see patients suffering from this I was a bit shocked at these results.
The next sentence seems a bit preposterous, It is possible that she could have developed SIADH, through a drug side effect. Presuming that a patient with heart failure induced hyponatremia now has a second denovo disease seems a bit of a stretch, but we don’t have access to the clinical data and so it is hard to determine if this is true. However the definition of SIADH requires that patients be euvolemic and judging from as much of the story as we know it seems like this patient is clinically hypervolemic. This rules out a clinical diagnosis of ADH, because the release of ADH in heart failure is due to physiological trigger for ADH, a decrease in perfusion. The disease of SIADH is specifically reserved for patients in which there is no physiologic stimuli for ADH release. The presence of heart failure and volume overload, definitionally rule out SIADH.
The next sentence is interesting: In any case, we have reached the usual place where attempts to fix the heart have blithely interfered with renal physiology, and I am not willing to let his serum sodium decline into the 110s. Diuretics increase water and sodium loss, but the cation content of the urine is almost always significantly lower than the plasma cation content, urinary sodium with loop diuretics is typically around 70 mmol/L. So use of loop diuretics cause loss of relatively more water than sodium and result in hypernatremia, except in heart failure. To understand why, one needs to understand electrolyte free water clearance (and an example of using it in the treatment in hypernaatremia is here). The higher the free water clearance, the less prone patients are to hyponatremia. Here are the calculations for electrolyte free water clearance for a patient with hyponatremia due to CHF before and after the addition of loop diuretics:
In CHF, the patient is actually doing a pretty good job clearing free water. More than half of the urine output is electrolyte free water, the character of the urine is appropriate for correcting the hyponatremia. The problem is not the character of the urine but the amount. The patient just doesn’t make enough urine to generate adequate electrolyte free water to account for the water the patient is drinking. Water restriction will be effective for these patients.
Unfortunately, though the diuretic increases the volume of urine, it also changes the character of the urine. In this case, it dramatically increases the urine sodium content. This makes the urine almost completely ineffective at removing electrolyte free water and the net result is that the electrolyte free water clearances actually falls with the addition of the diuretic. This is the trap our poor nephrologist is raging against.
The longest tradition in the nephrology blogosphere, the Renal Fellow Network’s Nephrology Story of the Year! For five years RFN has been posting the top stories of the year and for the last few years they have been off loading the work to the crowd. So do your duty and vote.
And to the losers stuffing the ballot box for “Perivascular Gli1+ progenitors contribute to myofibroblast pool leading to fibrosis in multiple organs including kidney Cell Stem Cell” I will not stand for that!
I’m pulling for Dendritic cell isoketals activate T cells and promote hypertension as covered in NephJC.
Run by master tweeter Nikhil Shah, Nephrology Fellow at the University of Alberta, Nephrology Tweetbook is primarily a collection of educational tweets with, as far as I can tell, a single long form post on the use of What’s App as an educational tool. Very interesting use of the app.
I’m not sure what he is using to post the tweets to blogger, but he would get better, most useful posts if he used the embed code from twitter.
This is what his posts look like:
No active links.
If he were to use the embed tool in twitter it would look like this: