Saturday, January 24, 2015

ASN Quiz and Questionnaire 2014: Acid-Base and Electrolyte Disorders

CJASN just published two answers to the Electrolyte quiz from ASN Kidney Week, unfortunately they have the answers right next to the questions, so you can't take the test honestly, Here are the questions, without the answers. Get the article here.


Case 1: Mitchell H. Rosner (Discussant)
A 60 year-old man with a history of a heart transplant and stage 4 CKD was diagnosed with a gout flare 6 days ago and was prescribed prednisone, 30 mg daily; allopuri- nol, 100 mg daily; and colchicine, 0.6 mg three times daily, for the first 2 days and then colchicine, 0.6 mg twice daily thereafter. Before the gout attack, the patient had been feel- ing well and his baseline creatinine was 2.9 mg/dl with an eGFR of 29 ml/min per 1.73 m2. Other medications in- cluded mycophenolate mofetil, cyclosporine, pravastatin, carvedilol, calcitriol, and furosemide.
After 48 hours of taking the allopurinol, colchicine, and prednisone, the patient developed nausea, intermit- tent vomiting, and profuse diarrhea. This continued in- termittently over the next 2 days. However, during the past 2 days, he has developed worsening lethargy; muscle aches; and continued nausea, diarrhea, and abdominal pain. His family brings him to the emergency depart- ment (ED).
In the ED, he was found to be confused, tachycardic, and hypotensive, with a BP of 76/42 mmHg and pulse of 120
beats/min. He then sustained respiratory arrest and was successfully intubated; he was also started on vasopressin, norepinephrine, and intravenous fluids to support his BP. Laboratory results at the time of admission are shown in Table 1.

Question 1a
The acid-base abnormality in this patient is:
     A. Aniongapandnon–aniongapacidosis
     B. Respiratoryacidosisandaniongapacidosis
     C. Respiratoryalkalosisandaniongapacidosis
     D. Respiratory acidosis and anion gap and non–anion gap acidosis
     E. Respiratory alkalosis and anion gap and non–anion gap acidosis 

Question 1b
Which of the following drug interactions were likely responsible for the patients presentation?
     A. Allopurinol,pravastatin,andmycophenolatemofetil 
     B. Allopurinol,pravastatin,andcyclosporine
     C. Colchicine,allopurinol,andmycophenolatemofetil
     D. Colchicine,pravastatin,andcyclosporine 
     E. Colchicine,prednisone,andpravastatin 


Case 2: Mitchell H. Rosner (Discussant)
A 37-year-old woman with a 3-year history of severe sinus disease and headaches is referred to you after several laboratory abnormalities were found. Her medical history is significant for two episodes of nephrolithiasis (no stone analysis was per- formed). On questioning she notes that pain and redness develop in her hands in cold weather. She takes no medications except for occasional antibiotics for her sinus problems. Her BP is 108/50 mmHg and her physical examination is unremarkable except for some fullness over her parotid glands. Her laboratory studies are shown in Table 2. On further questioning, she reports no drug abuse.

Question 2a

Which one of the following laboratory tests would you order next?
     A. Serumandurineproteinelectrophoresis 
     B. Plasmareninandaldosteronelevels
     C. 24-hoururinecortisol
     D. Stool screen for laxative abuse
     E. Anti-SSA,Anti-SSBserologies 

Aggressive intravenous potassium chloride and oral potas- sium citrate supplementation are administered. Laboratory tests repeated 1 week later reveal the following: potassium, 3.5 mEq/L; bicarbonate, 15 mEq/L; and anion gap, 6. The patient is seen by a neurologist for her chronic headaches, and topiramate, 200 mg daily, is started.

Question 2b
Which of the following changes would be expected if lab- oratory work was repeated several weeks after initiation of topiramate?
    A. Potassium,2mEq/L; bicarbonate, 5mEq/L; aniongap,8 
    B. Potassium,4mEq/L; bicarbonate, 20mEq/L; aniongap,8
    C. Potassium, 4 mEq/L; bicarbonate, 5 mEq/L; anion gap, 15 
    D. Potassium, 2 mEq/L; bicarbonate, 5 mEq/L; anion gap, 15
    E. Nochangeinelectrolytesfrompriorvalues 

Tuesday, January 13, 2015

What am I going to do with all of these draft posts?

I have been blogging at PBFluids since 2008 and have 737 posts. What has been slowly growing is the number of unpublished drafts. Mostly this is clever ideas not fully realized like this evocative title:


There are others that if published would be career suicide like my completely overly honest reviews of the ASN Board review with letter grades for each of the speakers. The GPA was 3.7 but there were some clunkers in the mix:


The number of drafts is as of now 70 posts. I am going to try to salvage some of these posts and put them on the blog.

The first is a post titled "Epic ASN Post" This is from Kidney Week 2011. The post was written 12/1/11.

Landed in Philly and went to the AirBnB room I found. Seventy-five bucks a night and only a mile from the conference center. Awesome!

FourSquare, remember when that was a thing? 
Milagros

Derek


Kenar

Monday, January 12, 2015

ASN #NephWorkForce TwitterChat on Tuesday January 13 at 9pm EST

Mark Parker, the chair of the ASN Workforce Committee, will be on Twitter next Tuesday to discuss the latest report. This report is the second done by Ed Salsberg and his colleagues at GWU. This report is all about the fellow experience in getting a job.

The report is available here.

Dr. Parker answered some questions to stoke the fires of discussion, that interview can be seen on Medium.

ASN Nephrology Workforce Report

The first workforce report stimulated some discussion on Twitter, that discussion is saved here:



A summary of the discussion about the second report so far is available here:

My summary of the report:


  • The survey was distributed to 1,530 ASN Nephrology fellow and trainee members in June and July of 2014.
  • 441 responded. Response rate of 28.8%.
  • There are 930 fellows in ACGME accredited programs and they received 333 responses from this sub-group. 
  • What is up with the 600 trainees not in ACGME spots? DO programs?
Interesting gender differences:
How about this eye opening stat:
USMGs had a median debt of $100,000 to $149,999. IMGs were significantly different with a median debt of $0 and 65% having no debt.

Career plans

Nephrology breaking barriers, has higher starting salaries for women compared to men:
Female respondents had a slightly higher median anticipated base income than male respondents, who had a median anticipated base income of $150,000 to $174,999.
Job hunting troubles were much more common among IMGs with only 22% finding a satisfactory job compared to 56% of USMGs. Visa problems and unappealing locations were leading problems in job hunting. 71% reported no or very few jobs within 50 miles of their training location.

Happily 72% of respondents indicated they would recommend nephrology to medical students and internal medicine residents.

It's an interesting report, take a look and...
Please join Dr. Parker to talk about #NephWorkForce Tuesday, January 13 at 9pm

Saturday, December 27, 2014

Why we needed Kayexalate in the first place

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:


400 mg of spironolactone, daily and this is in a world without loop diuretics!

Tuesday, December 23, 2014

Purple Urine, now that's not something you see everyday

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. 


H/T Life in the Fast Lane

The first Nephrology Social Media Internship

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:

  • Myself
  • 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
The idea behind the internship is to give guidance to doctors or students who want to become experts in social media. There are a number of different techniques and strategies in social media and we will provide the intern an opportunity to work with these techniques first hand. Projects that will be open to the interns include:
  • NephMadness
  • NephJC
  • AJKDblog
  • Renal Fellow Network
  • Research
  • UKidney
  • DreamRCT
Technologies that the intern will be exposed to include:

  • Podcasts
  • Google hangouts
  • Tweet chats
  • Storify for curation
  • Mail Chimp newsletters
  • Twitter analytics
  • Google analytics
  • multiple blogging engines including:
    • Blogger
    • WordPress
    • Medium
    • SquareSpace
But more important than the technology, is that the interns will have access to our collective wisdom and have access to an instant personal learning network to allow them to pursue their personal social media goals. This is the first time we have done this and we are still working out the exact curricula, but if you are in nephrology, residency or medical school and want to learn how to leverage the power of social media consider applying for the position.


Just another day at the PBFluids world headquarters

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. 
Best, 
Julia
My reply
Julia,

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?

Joel
Fingers crossed but with a skeptic's scowl

Thursday, December 18, 2014

Topf gets taken to Dr. Zen's Design Woodshed

I try to design nice posters and one that I was particularly proud of was 2013's Assessment of the Nephrology Blogosphere that I presented at Kidney Week. 

PDF | Powerpoint


A few months ago I submitted it for a design critique at Dr. Zen's Better Posters. Well this tweet surfaced today:


The review isn't pretty:
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 only plotted the 22 with the longest duration of publication. What was the point of graphing KidneyTalk's 6 posts over 2 months? (4 years after the last post, she still owns the URL) 

I also disagree with his critique of the QRcode and bit.ly link. I think QR codes mostly suck and for most people snapping a pic of a URL is quicker and more reliable. I also think every person should have a little home page for their poster where it can be downloaded and supplementary information made available. See the homepage to this year's NephMadness poster.



Overall this was great feedback and I swear my next poster will be better.

Wednesday, December 17, 2014

Over-indexing on medications

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:
She was taking once daily furosemide and we changed it to torsemide, for better pharmacokinetics. She returned a month later and her blood pressure was fixed, systolics equally distributed between the 120s and 130s. So a win for Torsemide, or maybe not...

She was excited because she had been reworking her diet and was no longer drinking pop. She was eating more home-cooked meals and really focusing on eating more vegetables and fruits. She was also being more conscious of her sodium intake.

When I walked into the room I was focused on the medication change, because that was my intervention. But the more I spoke with her, the more I began to lean to the lifestyle interventions. She was adopting spontaneous DASH diet:
  • 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. 

In the end, medicine is a giant, uncontrolled experiment and correlation does not equal causation. Just because you changed medicine doesn't mean that is was what fixed the blood pressure.

Saturday, December 13, 2014

SIADH and lasix

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.
So generous of Otsuka to make the 30 mg dose the same price as the 15 mg

But I held out hope, I felt that as soon as the FDA licensed tolvaptan for ADPKD, the drug would be re-priced for chronic use and the price would come down. In fact during a TEMPO investigator meeting, an Otsuka executive hinted they would lower the price on approval (personal communication). However, despite being the only known treatment that slows the loss of renal function in autosomal dominant polycystic kidney disease, the FDA told Otsuka and the ADPKD community to pound sand.



Somewhere in there, Otsuka changed the labelling and limited tolvaptan to 30 days or less for hyponatremia, so the dream...is officially dead.

But my patients are still alive and they still have sodiums of 125. Demeclocycline, despite being a generic, is very expensive and not a good option. From the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association guidelines on hyponatremia:
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.

I also have data on the urine sodium, to get an idea of the electrolyte free water clearance. The change is not nearly as dramatic or convincing.

I have some of the data to calculate electrolyte free water clearance, but I'm missing urine volumes. We can determine the character of the urine from the following formula:

The following percentages represent the fraction of the urine volume which is electrolyte free water. The first three columns are negative, indicating that the urine the patient is producing has less than no free water. Urinating is more like drinking water as urination actually causes the sodium to fall, rather than rise. For a more in-depth explanation of the electrolyte free water calculation, check out this video.

It will be interesting to see if this improvement continues. I now believe that the reason I was underwhelmed when I used loop diuretics in the hospital is that I was working in the compressed time scale of inpatient medicine and only when you stretch the time horizon to months does the drug become effective. I think the reason it takes so long is that loop diuretics need to wash out the concentrated medullary interstitium, thus preventing the ADH from reabsorbing much water. A drug induced partial nephrogenic diabetes insipidus.


Friday, December 12, 2014

Yes, it's a little pocket of insanity but does it have something to teach us?

A few months ago there was a screen shot of a clinic note floating around the internet. It was, in the words of another nephrologist the most passive-aggressive nephrology consult note I have read in a long time:
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:
Before 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.

So, if the problem is an inadequate amount of urine the logical next step would be to increase the volume of urine with a diuretic:
With diuretics
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 next sentence of the rant: 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. I have a problem with this sentence and do not think it is well thought out. The nephrologists clearly believes this patient is over diuresed, we see this situations all the time and they respond briskly to additional fluids. Don't complain that the patient has been overdosed with diuretics and then refuse to provide the antidote for this overdose. I am skeptical of his theory that the patient has SIADH and it is a bit unreasonable to even give a trial of 0.9% saline. In regards to 3% saline, our good doctor might want to take a look at some of the data on the use of 3% saline in heart failure: SMAC-HF (PDF) or Seminars in Nephrology summary. While it is not standard of care the data are certainly intriguing and when the traditional approach is not helping the patient, as apparently is occurring in this patient, it may be worth a look.

The next sentence is regarding conivaptan: If he is volume depleted, and we use conivaptan, he could develop hypotension which would be difficult to fix. Conivaptan is a non-selective vasopressin antagonist, as opposed to tolvaptan which is a selective V2 receptor antagonist. Blocking V1 could cause hypotension as has been reported in multiple case reports. See this open access review.

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. This complaint that tolvaptan fixes a number seems a bit obtuse for a nephrologists who was presumably consulted to fix a number. It also implies that tolvaptan is unique in that it has only been shown to fix a number. Well unfortunately, all the therapies of hyponatremia, outside of acute symptomatic hyponatremia have only been shown to fix a number. However given the profound morbidity associated with low sodium, it seems judicious to correct hyponatremia until data proves it is unhelpful. Additionally, to claim in one sentence that you refuse to allow the sodium to fall below 120 and in the next sentence to rail against a therapy that has only has been shown to fix a number seems to belie a profound lack of self awareness.

But keep fighting the good fight against the cardiologists, somebody needs to keep their egos in check. #PracticallySurgeons


Thursday, December 11, 2014

Last chance to vote

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.

Go vote

Polls close tomorrow. 


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.
Related Posts Plugin for WordPress, Blogger...