This came up on rounds today. I thought I covered this on the blog before but if I did, Google failed me. The answer is 7.7 mEq of Na and 7.7 mEq of HCO3 in every 650 mg tablet of baking soda.

This is just 650 mg divided by the molecular weight of NaHCO3, 84 mg/mmol.

I spend a lot of time talking about how incredible the kidney is but then sometimes you see kidneys that just don’t do anything. I was in the hospital and we had a patient develop acute on chronic kidney disease. Following a few days of anuria they started to make urine so we checked urine creatinine to see how well the kidney was recovering.

Not good, Bob.

The patient had among the lowest urine creatinines I had ever seen. Compare the urine creatinine of 14 to the serum creatinine of 10 and you see the laziest nephron ever. It is barely altering the composition of the urine at all.

The patient also had the highly unusual situation with urine Na greater than serum Na. I think I have only ever seen that in cases of severe hyponatremia due to SIADH.

This patient had a fractional excretion of Na of 70%. Amazing. Normally the kidney reabsorbs 99% of the filtered sodium, here 70% of the filtered sodium just flies by.

This helped our discussions on the patient’s renal prognosis. The urine they were making was a useless gasp of a dying organ.

The first newsletter of 2025 and 30th newsletter for MashUp MD, successfully focuses on various topics while avoiding discussion of the new Trump administration.

Read it here (and subscribe please)

See all of my previous emails here

So I just pushed out the latest episode of Channel Your Enthusiasm. This one was recorded in November of 2022. (Yes, I am a little behind on the editing, but I have a new workflow and its name is Simon Topf. Things are going better.) During the recording Josh mentioned that we had just won the ASN Innovations in Education Award and Melanie pipes in we won the 2022 version of the contest because even then we knew that it was going to be awhile before the episode was published and we all assumed that there would be other, subsequent winners.

Nope

2022 was the last year of the ASN Innovations in Education Award.

The website says that they are skipping 2023 and to check back in 2024

I asked about the contest on ASN Communities and got the following reply:

Hello, Dr. Topf,

Thank you for your post. ASN decided to pause the Innovations in Kidney Content the last couple of years due to declining interest. ASN continues to offer the William and Sandra Bennett Clinical Scholars Program: https://www.asn-online.org/grants/tig/details.aspx?app=BENNETT and the Harold Amos Medical Faculty Development Program Award: https://www.kidneycure.org/grants/faculty-development.aspx 

Sincerely,

Charyl Delaney

The Channelers had a discussion about the award, which you can hear here

The audio is from the podcast recording, most of which ended up being cut from the episode. The images are from our video application for the award. You can see that video with the original audio, here. In the video we discuss how the winners were announced. Edgar took a video which i now on You tube. Take a look:

Awards given by professional societies is one of the ways that an organization can demonstrates its values. And the ASN Innovations in Education Award told the world that nephrology valued education and educators. Unfortunately, we live in a world where promotion and tenure committees undervalue the work that goes into educational initiatives. During my most recent tangle with P&T they expressly said that when outlining what you do for the medical school, to not include teaching, as that is just table stakes and not that important. The ASN education award provided a bit of incentive to pursue big audacious educational projects.

Some of the discussion was about how slipshod the award recognition was in 2022. This was a change from previous years and we couldn’t figure out why. Now it is apparent that the organization had already walked away from Innovation Award.

This is a disappointment. I am sorry to see it go away.

The latest salvo in the hyponatremia wars takes off where Seethapathy left us (NEJM Evidence | NephJC). Last week, Juan Carlos Ayus published his latest study (JAMA Internal Medicine) on hyponatremia, a meta analysis of patient outcomes in the management of hyponatremia.

If you are not aware of Ayus’ prior hits, you should take a look.

Retrospective data that looks at speed of correction and uses that to look at outcomes has been a staple in hyponatremia research for decades. It is the basis for the current, decades-old, hyponatremia guidelines from the US and Europe. However, until recently the only outcome of interest was osmotic demyelinating syndrome (ODS, and boy is that a loaded term that probably should be re-litigated, see Seethapathy’s grand rounds in Ottawa, YouTube). When looking at ODS, a pattern emerges that slower correction is associated with fewer cases of hyponatremia, however it is unusual to look at a case series and only care about one outcome. If we pull back a bit and look at all the outcomes that matter, things like length of stay and mortality, the situation changes. In Ayus’ meta-analysis, the primary outcome was mortality and just like in Seethapathy, slower correction was associated with increased mortality. Not a great look. And I think the orders of magnitude are important here.

Patients that experience faster correction of sodium consistently have better clinical outcomes in these sorts of analysis. And the rate of ODS is vanishingly low, expecially with the looming specter of death. The focus on ODS makes us ignore what an ominous sign hyponatremia really is. I can’t think of an electrolyte with such a frightening association with mortality.

The obvious weakness with this type of analysis is they do not provide any insight as to why the correction was slow. While we like to think that the slow correctors are populated by patients with bespeckled nephrologists carefully calculating sodium and water prescriptions according to the Edelman formula, but the reality is that the patients with slow correction is populated by people with liver and heart disease that are not easy to fix. And their prolonged length of stay and poor outcomes are driven by these dismal diagnosis.

And what of the rapid correctors? This cohort gets better quickly, not because cowboy nephrologists are slinging 3% saline to rapidly bring the sodium to heal, no, rather these are patients whose body wants a normal sodium and as soon as it is able to reject the excess water it will return the sodium to normal. And this is often despite the best intention of the treatment team. In Sterns’ study on the DDAVP clamp, 25% of patients in the control group (historic controls for their retrospective case series) made more than 1200 ml of urine an hour.

The slow correctors is populated by patients who are so ill that their bodies have rejected sodium and water homeostasis in the name of perfusion. Not a good place to be, hence the bad outcomes. While the fast correctors is populated by people whose physiology remains committed to sodium and water homeostasis. It is not hard to see why disease so severe that it rewrites the laws of homeostasis would have increased rates of devastating outcomes.

More simply the results are confounded.

Does the confounding explain all of the excess mortality?

Is it that far fetched to believe that the low sodium itself could contribute at least a little to the excess mortality seen with hyponatremia? It seems likely that something the body spends so much energy trying to keep regulated would be important and have an effect on outcomes. And given the rarity of CPM/ODS, even a small residual effect would swamp the concern for CPM/ODS because not only is ODS, rarer than we were lead to believe, the outcomes of ODS are not as bad as we were taught.

In Jason George’s study of nearly 1,500 people with sodiums less than 120, they had 9 patients with ODS on imaging. In terms of neurologic outcomes among these 9, “five patients with documented osmotic demyelination had recovery with no neurologic deficits, two patients died from unrelated causes, and two were lost to follow-up.”

When you look at Ayus’ meta-analysis of hyponatremia are you sure there is no residual signal? Because the people promoting ever slower rates of correction to avoid CPM feel that there is nothing on the other side of the balance pan. That slowing the rates of correction will always be justified. That it is okay to prolong hospitalization by any length of time. That we should adopt interventions like DDAVP clamps without any prospective data because the risk of ODS is so important that concern for this complication should drive the therapeutics in hyponatremia.

And while we are adopting DDAVP, we should restrict and avoid tolvaptan, not because it causes ODS, there were no cases in Schrier’s Phase three SALT1 and SALT2 trials, but because it may correct the sodium faster than guidelines suggest. Now we are not even worried about ODS, but rather the purported risk factor for ODS, speed of correction.

We adopted the risk factor rather than the outcome in the case of hypertension. We want to avoid the stroke and CV death, so we treat the blood pressure to a target BP. But the hypertension guys didn’t just look at retrospective data. They went out and did the work to see if treating blood pressure avoided the outcome, and it did. We should demand similar certainty for the treatment of hyponatremia.

We no longer should accept retrospective observational data. The Hyponatremia Intervention Trial (HIT, Protocol and rational for design publication in PubMed) showed that we could do prospective, randomized trials, in the treatment of hyponatremia. The study was not positive, but it was important. Here are my tweets from the Late Breaking and High Impact Clinical Trial Session at Kidney Week where the results were announced. We are still awaiting publication.

Made it to the LBCT sessionAnd it is a hyponatremia trial!#KidneyWk

— Joel Topf (@kidneyboy.bsky.social) 2024-10-26T17:47:32Z

It is time to demand this. Hyponatremia is too common for us to trust that the mortality signal is entirely a statistical mirage.

Monday night I had my biggest “hit” on Bluesky. I had been tipped about a forthcoming hyponatremia meta-analysis in JAMA Internal Medicine at Kidney Week and so I was primed when it was posted to the JAMA website Monday evening. As soon as I saw it I posted to Bluesky:

Honey, stop what you're doing, new hyponatremia research just dropped!What's it say?It looks like slow correction is associated with worse outcomes, like death and length of stay!Was it just a small study?No, it was a meta-analysis of almost 12,000 patients!jamanetwork.com/journals/jam…

— Joel Topf (@kidneyboy.bsky.social) 2024-11-19T04:51:11.204Z

(OMG, it is so cool to be able to embed a tweet in a blog post again!

So at the time of this blog post it has 290 likes, 105 retweets, and 41 replies.

The next morning, I saw that my post was gaining steam, so I copy-pasted to Twitter at 9:30 AM. Later that day Swap saw that I posted in both places and declared Bluesky the winner.

So @kidneyboy.bsky.social has 15 times more followers on Xitter (along with algorithm boosting blue check) versus a ‘BlueSky Elder’ coveted label here Same post comparison below It’s a #BlueSky blowout #NephSky

— Swapnil Hiremath (@hswapnil.bsky.social) 2024-11-19T19:29:08.277Z

But the Bluesky post had a nine hour head start . How does the twitter post look now compared to Bluesky?

The Twitter post has 27 replies compared to 41 on Bluesky. I find replies to be the best form of engagement, Retweets are similar at 105 on Bluesky versus 129 on Twitter, but Twitter’s 603 hearts and 388 bookmarks swamps Bluesky’s 209 hearts.

But it really doesn’t matter. I’m all in on Bluesky. I like the philosophy. I like the aesthetic. And it is where my people are.

When I first started this blog, it automatically sent a tweet when I had a new post. This continued until Musk disabled a number of APIs, including the one that allowed automatic posting.

Now I am disentangling myself from Twitter and embedding myself in Bluesky. Hopefully, this will post there automatically.

Fingers crossed.

Testing 1…2…3…Testing

I am still in the “amazed by what AI can do” stage

Here is me prompt

i am teaching a class on electrolyte abnormalities for nephrologists. What would be good tricky things to teach

I then ran my prompt through an AI to make my prompt “better” This AI is called PromptPerfect. Here is what it came up with:

As part of my curriculum for a class aimed at nephrologists focusing on electrolyte abnormalities, I am seeking innovative and challenging concepts that can enhance the learning experience. The goal is to identify complex scenarios or case studies that delve into the nuances of electrolyte homeostasis, including mechanisms, clinical implications, and diagnostic challenges. I would appreciate suggestions for specific topics that could provoke critical thinking and discussion among the attendees, such as rare electrolyte disorders, atypical presentations, or the interplay between various electrolytes in different clinical contexts. Additionally, please provide a structured outline of how these concepts can be presented, including key points, potential teaching methods, and examples that could facilitate understanding.

And here is the output that Chat GPT4o came up with:

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Curriculum Outline: Innovative and Challenging Electrolyte Abnormalities for Nephrologists

Module 1: Rare Electrolyte Disorders – Uncommon Mechanisms and Diagnosis

Key Concept: Understanding rare electrolyte disturbances that involve complex mechanisms and atypical presentations.

Key Topics to Discuss:

1. Hyperkalemic Periodic Paralysis (HPP)
   • Mechanism: Mutations in the sodium channel (SCN4A), leading to abnormal potassium shifts during exercise or fasting.
   • Clinical Implication: Presentation with episodic muscle weakness and hyperkalemia.
   • Diagnostic Challenge: Distinguishing HPP from other causes of hyperkalemia, such as renal failure or medications.
   • Teaching Method:
     • Interactive Case Discussion: Present a case of a young athlete with recurrent episodes of weakness and hyperkalemia. Explore diagnostic tests (genetic testing, muscle biopsy).
     • Group Activity: Have the class brainstorm possible causes of episodic hyperkalemia and narrow down to rare causes like HPP.
2. Familial Hyperkalemic Hypertension (FHHt)
   • Mechanism: Mutations in the WNK1 and WNK4 genes leading to excessive sodium retention and secondary hyperkalemia.
   • Clinical Implication: Hypertension with normal or elevated potassium despite low renin and aldosterone.
   • Diagnostic Challenge: Differentiating FHHt from primary hyperaldosteronism or renovascular hypertension.
   • Teaching Method:
     • Case Study: Present a hypertensive patient with hyperkalemia, and have learners differentiate between FHHt and other causes of secondary hypertension.
     • Interactive Q&A: Ask the learners to discuss how genetic testing can be used for diagnosis, and compare the pathophysiology with other causes of secondary hypertension.
3. Tumor Lysis Syndrome (TLS) and Electrolyte Imbalances
   • Mechanism: Rapid release of intracellular electrolytes (potassium, phosphate, and uric acid) due to tumor cell lysis.
   • Clinical Implication: TLS can cause hyperkalemia, hyperphosphatemia, and hypocalcemia, along with acute kidney injury (AKI).
   • Diagnostic Challenge: Early detection of TLS in the absence of clinical symptoms; managing high-risk patients pre-emptively.
   • Teaching Method:
     • Case Study: Present a cancer patient undergoing chemotherapy with electrolyte abnormalities and acute kidney injury. Discuss management strategies, including allopurinol, rasburicase, and hydration.
     • Interactive Poll: Ask learners how they would manage a patient at risk of TLS in the first 48 hours.

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Module 2: Electrolyte Imbalance in Multi-System Disease

Key Concept: The interplay between various electrolytes in patients with complex co-morbidities and multi-system disease.

Key Topics to Discuss:

1. Hyponatremia in Heart Failure and Cirrhosis
   • Mechanism: Discuss hypervolemic hyponatremia in the context of heart failure (low cardiac output, increased ADH release) and cirrhosis (portal hypertension, ascites, altered renal perfusion).
   • Clinical Implication: Both conditions may result in SIADH-like patterns with hypovolemic and euvolemic hyponatremia.
   • Diagnostic Challenge: Distinguishing between cirrhosis with ascites and heart failure with ascites as causes of hyponatremia.
   • Teaching Method:
     • Case Comparison: Present two cases of hyponatremia—one in a patient with heart failure and the other with cirrhosis—and have learners compare and contrast their approaches to diagnosis and management.
     • Group Discussion: Have attendees discuss the pathophysiology of hepatorenal syndromeand cardiorenal syndrome as part of electrolyte disturbances.
2. Potassium Abnormalities in Diabetic Ketoacidosis (DKA)
   • Mechanism: Insulin deficiency, acidosis, and shifts in potassium from the intracellular to extracellular space in DKA.
   • Clinical Implication: Potassium levels can be falsely elevated on presentation due to transcellular shifts, and may drop quickly with insulin therapy.
   • Diagnostic Challenge: Assessing potassium levels and deciding when and how to replete potassium during DKA treatment.
   • Teaching Method:
     • Interactive Case Discussion: Present a case of a diabetic patient with hyperkalemia and acidosis. Discuss the initial approach to potassium monitoring and replacement during DKA management.
     • Problem-Solving Exercise: Have learners calculate the correct amount of potassium to replete in DKA while managing acid-base status and avoiding hypokalemia.

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Module 3: Complex Electrolyte Interactions and Their Clinical Impact

Key Concept: Understanding the dynamic interplay between multiple electrolytes in clinical scenarios, and how changes in one can impact others.

Key Topics to Discuss:

1. The Calcium-Phosphate Paradox in Chronic Kidney Disease
   • Mechanism: In CKD, impaired phosphate excretion leads to elevated phosphate levels, which bind to calcium and precipitate in tissues, contributing to vascular calcification and secondary hyperparathyroidism.
   • Clinical Implication: Elevated calcium-phosphate product is a risk factor for cardiovascular morbidity.
   • Diagnostic Challenge: Monitoring and managing the calcium-phosphate product in the context of dialysis or advanced CKD.
   • Teaching Method:
     • Interactive Discussion: Present a dialysis patient with elevated calcium, phosphate, and secondary hyperparathyroidism. Have learners propose management strategies to reduce the calcium-phosphate product.
     • Case Study: Explore the role of calcimimetics, phosphate binders, and vitamin D analogs in controlling the calcium-phosphate product.
2. Magnesium and Potassium Imbalances: The Subtle Interplay
   • Mechanism: Hypomagnesemia often accompanies hypokalemia, and correcting hypokalemia without addressing magnesium deficiency can lead to refractory hypokalemia.
   • Clinical Implication: Magnesium plays a crucial role in potassium regulation, and untreated magnesium deficiency can hinder recovery of normal potassium levels.
   • Diagnostic Challenge: Identifying hypomagnesemia in patients with unexplained hypokalemia.
   • Teaching Method:
     • Case Presentation: Present a patient with refractory hypokalemia that doesn’t improve despite treatment. Lead a discussion on the potential underlying magnesium deficiency and the rationale for magnesium repletion.
     • Interactive Exercise: Have learners analyze lab results and decide whether magnesium levels should be checked in cases of hypokalemia.
3. Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors and Electrolyte Shifts
   • Mechanism: SGLT2 inhibitors, used in diabetes and CKD, can cause increased sodium excretion, leading to fluid shifts and electrolyte disturbances (e.g., hyponatremia, hypokalemia).
   • Clinical Implication: The risk of electrolyte abnormalities is increased with dehydration,diuretics, or acute kidney injury in patients on SGLT2 inhibitors.
   • Diagnostic Challenge: Early identification of electrolyte imbalances when patients are on SGLT2 inhibitors, especially during periods of acute illness or volume depletion.
   • Teaching Method:
     • Case Study: Present a patient on SGLT2 inhibitors who presents with confusion and low sodium. Discuss the role of SGLT2 inhibitors in electrolyte homeostasis and how to adjust treatment when using these drugs.
     • Interactive Poll: Ask learners to suggest steps for managing a patient on SGLT2 inhibitors who presents with dehydration and electrolyte abnormalities.

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Teaching Methods and Approaches

1. Case-Based Learning: Provide complex, real-world cases where the students can apply their knowledge of electrolyte abnormalities in clinical scenarios. Case discussions should prompt learners to think critically about diagnosis, pathophysiology, and management.
2. Small Group Discussions: Break learners into smaller groups to tackle specific topics or case studies. Afterward, have each group present their findings and management approach to the class.
3. Interactive Polls and Quizzes: Use technology (e.g., Kahoot, Mentimeter) to ask clinical questions and prompt learners to choose the best answer. This can be used to initiate discussions and clarify concepts.
4. Role-Playing and Simulations: Use role-playing to simulate difficult clinical situations (e.g., managing a patient with complex electrolyte imbalances during a crisis). Simulations can help learners practice decision-making under pressure.
5. Expert Panel Discussions: Bring in experts to discuss the nuances of managing rare or complex electrolyte disorders, especially those with genetic or multi-system involvement.

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Conclusion

By focusing on rare disorders, complex interactions, and multi-system involvement, you can stimulate deep clinical reasoning and promote active learning. Encourage learners to approach electrolyte abnormalities not only as isolated issues but also as part of a broader clinical context, where underlying mechanisms, patient history, and comorbidities significantly influence diagnosis and management.

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There are some significant mistakes. Secondary hyperparathyroidism is associated with low a calcium, not a high calcium. And the SGLT2i section in Module 3 would have to be entirely abandoned. But for ten minutes of just fucking around with Chat GHPT it is pretty complete and looks like it would make for a pretty compelling curriculum.