I’m not surprised that Secrets is the best selling new release in Nephrology. The series is very popular and the last edition is 10 years old. I suspect there is significant pent up demand.
What shocked me is where the Fluid Electrolyte Acid Base Companion is on the Nephrology Best Seller List:
Fluids came out in 2000. I think we printed 1,200 copies and never did a second printing. We sold out the last of our inventory over a decade ago. If Amazon is telling the truth about their sales either someone has counterfeited the book, these are used books that are being sold over and over again, or this is new old stock that someone found at the back of a warehouse.
My daughter suggested another possibility, that all nephrology books sell like crap. (I’m beginning to come around to this theory as I see how much the sales rank jumps around.
Here are the current sales ranks for some nephrology books of note:
The rankings look funky because I wrote this post in two sessions, separated by a number of hours. Apparently at these sales volumes the the ranking are pretty erratic.
I am a primary investigator of the Regulus RG012 study using RNA inhibition to treat Alport Syndrome.
Here are some good resources that I used to brush up my Alport and RNA inhibition skills.
First a video review of Alport
The best part of the video is the detailed description of collagen IV at 4 minutes. This finally allowed me to understand the multiple mutations that cause Alport.
This video is grand-rounds length description of Alport with a focus on how it affects women by my friend Michelle Rheault.
RG-012 uses a drug that is a oligonucleotide that inhibits the activity of miR-21. miR-21 is a micro RNA which affects the translation of mRNA to protein. In high school biology I learned about messenger RNA, transfer RNA, and ribosomal RNA and that was enough RNA for anyone. But then the Nobel Prize guys had to go and give a prize for the discovery of RNA interference in 2006. Here is a basic explainer about RNA interference.
Here is Regulus’ presentation on RG-012
If you are a physician in Michigan with a patient with Alport Syndrome (needs to be pre-dialysis and per-transplant) or a patient with Alport Syndrome please get in touch, we want to hear from you.
Every intern knows that the evaluation of hyponatremia includes a TSH and a cortisol level to rule out hypothyroidism and adrenal insufficiency as occult causes of euvolemic hyponatremia.
The mechanism of adrenal insufficiency is a bit confusing with some sources stating that these patients are volume depleted while others are euvolemic.
@askrenal in regards to hypoNa ep w/@kidney_boy a listener wants to know if adrenal insufficiency causes euvolemic or hypovolemic hyponatremia. Apparently various sources disagree. pic.twitter.com/PKsVqq5LVq
In some patients without aldosterone, the patients develop severe salt wasting, become hypotensive and get a non-osmotic release of ADH resulting in hyponatremia. These patients will respond to saline. Treat the hypovolemia and the sodium will go up.
Hyponatremia is a common manifestation of adrenal insufficiency even in cases without adrenal crisis. Giving saline to these patients is not effective at correcting the hyponatremia. Giving cortisol, however, results in a brisk water diuresis and rapid correction of the serum sodium (Oelkers, NEJM, 1989).
This means cortisol corrects an abnormality that is due to excess ADH.
Here is the explanation from the late 90’s from The Fluid, Electrolyte and Acid-Base Companion.
Bartter and Schwartz original definition of SIADH required a normal cortisol specifically to exclude patients with hypopituitism and primary adrenal insufficiency. In primary adrenal insufficiency, in addition to loss of cortisol there is an aldosterone deficiency which can result in sodium wasting, volume depletion and a non-osmotic (decreased perfusion in this case) stimulates for the release of ADH. In this scenario, the patient should appear salt/volume depleted and would not be considered euvolemic.
A nice review of secondary adrenal insufficiency and hyponatremia was done by Sven Diederich.
Remember:
Primary adrenal insufficiency: destruction of the adrenal glands leads to loss of endogenous cortisol. These patients typically also have aldosterone deficiency, so they will be salt wasters, resulting in hypovolemia. They will also have hyperkalemia.
Secondary adrenal insufficiency: decreased ACTH (from pituitary or hypothalamic disease, or from pharmacologic steroids) prevents secretion of cortisol
In Diederich’s review they pulled 139 cases of hyponatremia that were referred to endocrinology. (Clearly this study suffers from profound selection bias. Here is a a cleaner study on the epidemiology of hyponatremia by Schrier, from back in the day.) They found 28 cases of hypopituitism leading to hyponatremia. Patients tended to be older (average age 68) and more female (75%). In 25 cases the hypopituitism had not previous been diagnosed and 12 patients had previously been admitted (between 1 and 4 times) for severe hyponatremia without an adequate diagnosis.
Basal cortisol levels were as follows:
Below 100 nmol/L (3.6 mcg/dL) in 7
Below 200 nmol/L (7.2 mcg/dL) in 21
The mean level was 157 nmol/L (5.7 mcg/dL)
The highest basal level was 439 nmol/L (16 mcg/dL)
Imaging results:
Twelve patients had an ‘empty sella’
Six patients had pituitary tumors
One had secondary adrenal insufficiency due to chronic treatment with prednisolone because of ankylosing spondylitis
Don’t be the doctor that corrects the hyponatremia but fils to diagnose adrenal insufficiency and discharges and sends the patient home only to redevelop hyponatremia another day. Turn over every stone, especially in patients with SIADH of undetermined etiology.
John Arthur asked Matt to talk about his career and how he navigated medicine to become an accomplished scientist, clinician, and educator. Matt organized his talk around the mentors that guided him. The theme was that the way he made his way forward was by finding the best mentors available and learning as much as he could from them. It started with Wynton Marsalis
.@Nephro_Sparks telling his story – started in college with the goal to play trumpet in the symphony as a performance major. Ended up in microbiology because it was next to music in the course catalogue. #KIDNEYconpic.twitter.com/gtTCtsGueB
Though he went to the University of Arkansas to play trumpet he transitioned to biomedical science and found Dr Jeannine Durdik, an inspiring basic science professor, who taught him the scientific method.
After flirting with a career in basic science he went medical school at the University of Arkansas and matched at Arkansas where also did a chief resident year. The chair of medicine was Dr. Andreoli. I never knew Andreoli, but he sounds like the type of physician they don’t make any more…and you are simultaneously saddened and relieved by that fact. Andreoli was a giant in nephrology and Sparks worked close with him as a resident and closer during his chief year.
Then Matt talked about going to Mount Desert Island and meeting Nate Hellman. Matt was already an avid reader of the Renal Fellow Network, and Nate invited Matt to contribute. Matt really didn’t get involved until after Nate passed away and this ignited his desire to contribute to the Renal Fellow Network. This is how Matt got involved in and ultimately helped forge what would eventually become our online tribe of nephrologists.
Matt seems to know every nephrology fellow in the country and he takes an interest in promoting them and getting them involved. He is a strong advocate for fellows, both in and outside of Duke.
Even though Matt is younger than me, he is one of my important mentors. He has a wisdom that I don’t have and I often go to him with questions. I also trace my success with social media to his reaching out to me back in 2010. He guided me and really transformed my efforts from a solo project to one that recognizes that we can go further and do better by working together. Its a simple lesson but it has been critical to all of the successes we have found in social media.
Matt,
Congratulations on the Keynote.
Congratulations on putting together an amazing conference.
Dr. Berger responded to my post with another TweetStorm.
It starts here:
Dr. Topf's argument is summarized very well by his concluding paragraph. In short, there is nothing wrong in modeling estimated GFR based on "physiologic differences between the races."/2 pic.twitter.com/dvBSk77JYu
The Effluent Eight for #NephMadness are out and The Swami is not looking so hot.
Let’s break it down by region
Women’s Health Region
Swami’s Pick: Menopause and CKD
Blue Ribbon Panel’s Pick: Reproductive Planning
I still like my pick. Menopause in CKD is so poorly understood and it affects so many more people with CKD. I think this is a #BlueRibbonFail
Animal House
Swami’s Pick: Shark Maintenance of Osmolality
Blue Ribbon Panel’s Pick: Camel Water Storage
I went with what I thought was the crowd favorite, shark. This is a case where the blue ribbon panel dug in to the science and I just waved with the crowd. #SwamiSucks
Peritoneal Dialysis Region
Swami’s Pick: Volume Control in PD
Blue Ribbon Panel’s Pick: Volume Control in PD
A win.
Trial Outcomes Region
Swami’s Pick: 40% Reduction in eGFR
Blue Ribbon Panel’s Pick: Patient Related Outcomes
Interesting pick by the BRP. I can see the logic. Fair choice.
Hyponatremia Region
Swami’s Pick: US Guidelines
Blue Ribbon Panel’s Pick: US Guidelines
Another win. Two for five would get me in the Hall of Fame if I was up against major league pitching. I’m not.
Contrast Region
Swami’s Pick: Contrast is nephrotoxic
Blue Ribbon Panel’s Pick: Contrast in CKD 4
Not sure I understand the logic here. If you really think contrast is nephrotoxic, don’t you need to double down and take it over Contrast in CKD 4? If you giving contrast to a patient with a GFR of 16 ml/min, you really don’t think it’s nephrotoxic, now do you?
Update from January 2021: This is an old post and I have evolved my thoughts on this issue. I leave this here mainly as bread crumb on the trail of my evolving thoughts about this topic.
Zachery Berger published this epic tweet storm last week about estimated GFR. It starts here:
What a great question. Why do estimates of kidney function include different normal ranges for African Americans than non African Americans? Therein hangs a tale. (A thread to be intermittently updated between patients & work)/1 https://t.co/MKsU08oCfj
The conclusion is that using race in the MDRD formula (and by extension the CKD-epi formula) is inherently racist.
What have we learned up to now (well, I think many of us knew this stuff, but anyway): 1. Race is applied a priori without justification 2. Its definition is not specified 3. The definition can vary 4. It is ported into modern lab values/analyses without thinking/25
I do not think this is the case. Trying to estimate GFR from a serum creatinine and a few demographic variables is impossible, the best we can hope for is a reasonable guess. To see how bad we are take a look at the wide variability at high GFRs with the current CKD-Epi formula:
So that GFR of 60 has a 95% CI of being between 35 ml/min and 92 ml/min. Not so reassuring.
One of the primary reasons for this imprecision is that creatinine production varies from body to body. When one person produces more creatinine than another, for a set rate of creatinine excretion his serum creatinine concentration (what we measure on a blood test) will be higher. Who produces more creatinine? People with more muscle mass.
Larger people produce more creatinine than smaller people
More muscular people produce more creatinine than less muscular people
People with four limbs produce more creatinine than people with 3 limbs
Men produce more creatinine than women, on average
Young people produce more creatinine than older people, on average
Even though Dr. Berger did not draw the conclusion that estimated GFR is inherently sexist, let’s look at gender first. I have recolored the two graphs and superimposed them on one another. Men are in red and women are in blue:
It is clear that for any given GFR the men tend to have a higher creatinine than the women. This is not perfect and it is not hard to pick out individuals where this generalization fails, but in general this is a fair generalization. Levey comments and quantifies this gender difference:
At any given GFR, the serum creatinine concentration is significantly higher in men than in women (P 0.001).
The figure, without any recoloring, provides the curves for black (solid line) compared to non-black (dotted line) patients. Again it is clear that the average GFR is higher for black patients at any set creatinine. Levey comments and quantifies the racial difference:
At any given GFR, the serum creatinine concentration is significantly higher in men than in women and in black persons than in white persons (P=0.001).
Dr. Berger misses this fact:
Interesting: how do we know *that* to be true? Three references are given: Cohn 1977, Harsha 1978, and Worrall 1990. Let's go down the memory hole (for a scientist, 1977 is OLD)./17 pic.twitter.com/8Fn77B3j6G
How do we know *that* to be true? BECAUSE THEY MEASURED IT!
The refernces are just there to show that this is not a new and novel finding. This was an expected finding. The study does not rest on these references. The investigators in the MDRD study measured the serum creatinine, GFR, and asked patents if they were white, black or hispanic. The data shows that black people had, on average, 18% higher GFR for any measured creatinine. The fact that the prior work on this subject was deplorable does not alter the findings.
Berger is so upset that the estimated GFR differentiates black and white people that he misses the real problem with the MDRD study, the embarrassing lack of black people in the original data set. Only 12% of that cohort was African American, less than 200 people. A group that has the greatest incidence of end-stage kidney disease should be over-represented in a study about reducing the progression of CKD, not under-represented. Remember, Levey was using the data already collected for the Modification of Diet on Renal Disease study. This was not de novo data collected for the purpose of generating this equation. This weakness was corrected in the CKD-Epi equation where there were nearly 3,000 African Americans representing 30% of the cohort. The adjustment for race went from an 18% bump in GFR for a given creatinine down to 15.9%. Not much difference.
We use race, gender, and age not because we are racists, sexists, and agists, but rather because there are physiologic differnces between the races, the genders, and the aged. We exploit those differences to improve the accuracy of our estimate. All of these adjustment are just attempts to use demographic variables to squeeze a better correlation of GFR from a serum creatinine.
