This is my NAGMA lecture. It contains a thorough, but not exhaustive, overview of renal tubular acidosis.
Any feedback would be appreciated.
I need a better technology to make these. Still way too tedious.
The link goes to this article at the Huffington Post Journal of Medicine and this article from 2012:
The story is about a mystery epidemic causing widespread chronic kidney disease and end-stage renal disease in the farmers of Central America. Here is a less sensational view of the epidemic. The best part of the article is the five paragraphs that quote three independent experts that all agree that the most likely etiology is repeated episodes of dehydration:
“I think that everything points away from pesticides,” said Dr. Catharina Wesseling, an occupational and environmental epidemiologist who also is regional director of the Program on Work, Health and Environment in Central America. “It is too multinational; it is too spread out.
“I would place my bet on repeated dehydration, acute attacks everyday. That is my bet, my guess, but nothing is proved.”
Dr. Richard J. Johnson*, a kidney specialist at the University of Colorado, Denver, is working with other researchers investigating the cause of the disease. They too suspect chronic dehydration. “This is a new concept, but there’s some evidence supporting it,” Johnson said. “There are other ways to damage the kidney. Heavy metals, chemicals, toxins have all been considered, but to date there have been no leading candidates to explain what’s going on in Nicaragua… As these possibilities get exhausted, recurrent dehydration is moving up on the list.”
This reasoned diatribe is followed by this:
…scientists have no doubt they are facing something deadly and previously unknown to medicine.
Did the authors even read their own article? Dehydration would hardly be something unknown to medicine. After that, the article really goes off the rails with statements like:
In nations with more developed health systems, the disease that impairs the kidney’s ability to cleanse the blood is diagnosed relatively early and treated with dialysis in medical clinics. In Central America, many of the victims treat themselves at home with a cheaper but less efficient form of dialysis, or go without any dialysis at all.
Newsflash: peritoneal dialysis (the cheaper dialysis that you do at home), is not less efficient than hemodialysis.
The article tips an article that was to be published soon:
Some 30 percent of coastal dwellers had elevated levels of creatinine, strongly suggesting environment rather than agrochemicals was to blame, Brooks, the epidemiologist, said. The study is expected to be published in a peer-reviewed journal in coming weeks.
That article is now available. Here is the primary figure of the article:
|masl is meters above sea level|
It is an interesting story and I am going to keep my ear perked for more information.
Some facts about this CKD epidemic:
Excellent review of renal on-line learning resources in Advances in Chronic Kidney Disease including a complete round-up of the major kidney blogs: NOD, RFN, eAJKD, and Nephron Power. Here is the description of this blog:
Precious Bodily Fluids (www.pbfluids.com) is a kidney blog by Dr. Joel Topf, a Michigan-based nephrologist who has authored many nephrology-related books. He also lectures extensively on kidney topics for medical students, residents, and fellows. The blog is easy to nav- igate and features links to educational handouts, lectures, and books. The handout study guides are creatively termed ‘‘Haggadah’’ and focus on the basics of acid- base, electrolytes, and acute kidney injury. Handouts are also available on hepatitis-B- and C-related kidney disease, glomerular filtration rate/CKD staging, and rhabdomyolysis. There are accompanying question- and-answer sets with detailed explanations for acid- base and electrolytes for self-assessment. The handouts can be downloaded in a PDF format, PDF booklet format, or a Pages format (which needs special software but can be edited and customized for the individual reader). The lectures section contains 21 lectures on kidney basics as well as other points of interest such as cardiorenal syndrome, uric acid, gout, hypertension, and geriatric CKD, among others. The lectures can be accessed in a PDF or PowerPoint format. In the Books portion of the blog, there are links to books that can be downloaded for free, such as The Fluid, Electrolyte, and Acid-Base Companion; Michigan Hypertension Core Curriculum; and Intensive Care Nephrology. The blog has an archive of posts from previous years and mentions other notable kidney blogs. The user-friendly format of the educational material, complete with befitting images and videos, appeals to readers at different stages of learning.
It’s a nice article, but looking at online education and not even mentioning twitter seems to be skating where the puck is…
Primo was published a year ago in JAMA. I’m trying to think of another randomized controlled trial done in pre-dialysis patients looking at metabolic bone disease. I think PRIMO is the only one that looks at an end-point besides PTH. Could that be right?
I must be forgetting one (or a dozen)…
Ooops. Forgot about the proteinuria trials:
Yesterday’s post has stimulated a lot of interesting discussion on Twitter. I have updated the post with some of the tweets. Here are two more that have stimulated some additional thoughts:
When I was discussing the case with my dad, a surgeon, he kept asking if I would have given a diuretic. I wouldn’t. In fact I wouldn’t have managed the case like the doctors in the case report did.
Now before I express my criticism, it must be noted that the doctors took on a lethal poisoning and undoubtedly saved his life. Criticizing their management may appear to be deducting style points from a walk off home run, who cares if they swung at a bad pitch, they won the game. I want to recognize the bravery, intelligence and success of the medical team but I don’t think it was ideal care and I feel they were just as lucky as they were good.
The crux of their treatment was a massive infusion of D5W. Dextrose infusions are the bedrock of treatment of hypernatremia. The reason is that most routine cases of hypernatremia are due to water deficits:
Outside of treating the side effects of too much sodium bicarbonate (remember the sodium concentration in an amp of sodium bicarbonate is 1,000 mmol/L) we don’t routinely see hypernatremia from salt overdoses.
This patient did not suffer a water deficit, he had salt overdose, a month worth of sodium in a single quart. I think the infusion of 6 liters of D5W in 30 minutes had a high chance of causing serious problems, especially since the patient in question was not volume or water depleted. Not only was he not volume depleted, the high serum sodium was pulling water from the intracellular compartment and shifting it to the interstitial and vascular space, so not only was he not volume depleted, he likely was volume expanded. The treating doctors took a patient with a lethal sodium ingestion and treated it with a lethal water ingestion (Jennifer Strange who died in the tragic Wee for a Wii incident ingested 7.5 liters over 2 hours).
While in most cases of hypernatremia we give water because that is what is missing, in this case we need to remove the sodium. The treating doctors decided to depend on the kidneys to clear the excess sodium. The kidneys did an admirable job with extremely high urine sodium levels and concentrated urine, however they made that decision while his creatinine was going up. That seems a bit questionable.
The fluid also raised his glucose and lowered his potassium (the D5W infusion dropped the potassium from 5.1 to 2.5 in 30 minutes, I suspect this was an insulin effect). The increased glucose actually blunted the decrease in osmolality that occurred during treatment. In fact if you calculate the osmolality, the infusion of D5W had a surprisingly modest effect on serum osmolality, especially compared to it’s effect on the sodium concentration.
|If you do any math on your Mac you stop using the calculator and buy Soulver.|
|Large change in sodium with 6 liter D5W infusion|
|Much more modest change in osmolality due to D5W induced hyperglycemia|
Again, the treatment worked and perhaps the hyperglycemia helped protect the brain or ameliorated the cerebral desiccation of hypernatremia. I don’t know.
My work-shop on sodium includes a bit on all the cases of hyponatremia due to fraternity hazing.
I also include the crazy case of Jennifer Strange.
But I had never heard of idiot induced hypernatremia until this case report:
A nineteen year old male drank a quart sized bottle of soy sauce on a bet.
Two hours later he was brought to the ER comatose and seizing. His sodium was 177. They initiated hypotonic fluids and arranged transfer to a tertiary care center. At the tertiary care center the sodium was still higher at 191. The doctors then changed the fluids to D5W at 12,000 mL per hour. They gave 6 liters of D5W in 30 minutes.
After the infusion he opened his eyes and regained spontaneous movement. He was discharged on hospital day four neurologically intact with only some minor abnormalities on the head MRI, all attributed to postictal changes.
How high is a sodium of 191? MedCalc will not even accept it as a possible sodium concentration:
A couple items of note:
Some nerdery about the sodium exposure: He drank a quart of soy sauce. A quart is 946 mL. The article states that soy sauce is 17-18% sodium chloride. Here are some meta calculations, in case you are interested:
Update from Twitter:
I wrote a post for the Pediatric Career blog. It is about July first, the most significant date in the academic medicine calendar. I did not discuss patient risk or medical mistakes. I have blogged about those before. I discussed how to leverage this new beginning to develop a fulfilling and productive career in medicine. Read it.
Highest CPK I have ever seen:
That is the first CPK over one million I have seen. I love how the CPK of 4,000 on day one, you know the CPK that is 20x the upper limit of normal, is not high enough to even be rendered on the graph. For the scientific-minded here is the same data on a log rhythmic scale:
We were able to successfully alkalinize the urine (EBM purists can bite me, I believe the bench data here) and she never became oliguric, however on day three her potassium was 7 and we initiated dialysis. Surprisingly, phosphorous never got out of control.
She also had the highest CRP I have ever seen, 147.
The etiology you ask? She presented three days after a sore throat. We initially discounted viral rhabdo because the CPKs were so high but the Coxsackie B type 3 and 4 antibodies were off the scale and the literature is sprinkled with similar case reports (here and here). Muscle biopsy results are pending.
Muddy brown cast (day one, unspun specimen):
Urine sample (day two with urine pH of 8.5), no red cell on U/A
If you want to start a fight among nephrologists, start talking about paying donors for their kidneys. This may be the most contentious issue in nephrology. I personally am a believer in the concept but trying to imagine a free market for organs makes me nauseous.
|Mitra Mahdavi-Mazdeh. Kidney International, 2012|
The current system of paired exchanges and campaigns for kidney donors has noble intentions, but it’s not working. People are needlessly dying as a result.
I was never a big fan of the trans-tubular potassium gradient. I taught it because it was expected core knowledge for medicine residents. While I thought it was a poor test to assist in clinical management I delighted in using it to teach physiology. Understanding how the TTKG works, why it works and the thinking behind the exclusion criteria required sophisticated understanding of potassium and solute handling in the distal nephron.
My primary complaint of the TTKG was how useless it was in the assessment of hyperkalemia. In persistent hyperkalemia the TTKG is always inappropriately low (except in cases of rhabdomyolysis or tumor lysis syndrome where it is possible to get persistent hyperkalemia despite normal renal potassium handling, woe to the patient, whose doctor is relying on the TTKG to diagnose rhabdo). The TTKG was not useful for differentiating the various elements of renal potassium handling that can go off the rails to cause hyperkalemia.
The TTKG could do a neat job of differentiating renal from extra-renal potassium losses in hypokalemia.
Then in 2011 this article came out which showed urea cycling to occur in the late cortical collecting duct. The authors believed that urea delivery to the cortical collecting duct was an important driver of potassium secretion. This broke one of the central assumptions of the TTKG: that no appreciable solute resorption occurs in the medullary collecting duct, the only reason the osmolality increases is the absorption of water.
It looks like the editors of UpToDate have voted the TTKG off the island, here is what UpToDate has to say about the TTKG. In Evaluation of the patient with hypokalemia:
Trans-tubular potassium concentration gradient — The transtubular potassium concentration gradient (TTKG) has been primarily used in the evaluation of patients with hyperkalemia. However, we do not recommend using the TTKG. Details pertaining to the TTKG and the reasons for our recommendation not to use it in hyperkalemia are discussed in detail elsewhere. (See “Causes and evaluation of hyperkalemia in adults”, section on ‘Transtubular potassium gradient’.)
Trans-tubular potassium gradient — It would be desirable to assess the degree of aldosterone activity in patients with hyperkalemia by estimating the tubular fluid potassium concentration at the most distal site of potassium secretion in the cortical collecting tubule. Although this measurement cannot be made in humans, it was proposed that the potassium concentration at this site could be estimated clinically from calculation of the transtubular potassium gradient (TTKG) [91-93].
However, in a later publication, the authors of the original studies found that the assumptions underlying the TTKG were not valid . It was concluded that the TTKG was not a reliable test for the diagnosis of hyperkalemia. We recommend not using the TTKG to evaluate patients with hyperkalemia.