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.

The ASN Kidney Week podcast day three has low volume levels and a lot of background noise. This is easy to correct. I ran the podcast through Auphonic, which is free and got a huge improvement.

You can listen to the improved podcast here:

and here is the original for comparison

My attitude toward the supplement has been a journey.

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I was a supplement hater for a long time. I was a supplement hater even after I begrudgingly realized how critical it was to truly understand a study.

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I am now converted and I pray at the Alter of the Supplement. However, as a private practice nephrologist, working on the edge of the academy, getting access to manuscripts means that I have always depended on the kindness of strangers (actually usually less strangers and more friends, but one never pass up an opportunity to drop a Blanche DuBois quote). Using this beg-borrow-steal system means I almost always end up with the the manuscript sans supplement. Why do journals have separate downloads for the manuscript and supplement? Contemporary manuscripts regularly reference a table or figure from the supplement so you can’t even understand the manuscript without the supplement. I can get behind requiring a separate download for super specialized information like a protocol, or raw data tables, but most of the content of a typical supplement should ride with the core manuscript and not be a separate download.

A casualty of the tyranny of the page and figure count is the consort diagram. The consort diagram used to be the traditional figure 1, but it is now regularly banished to the supplement. We should not allow rules designed to minimize shipping costs determine the length and completeness of our scientific manuscripts. We need to embrace the reality of frictionless distribution and throw away print-inspired word and figure limits and provide all of the relevant information and data in the manuscript itself (or in a supplement that is part of the download package.

Here was my most recent tweet of this idea:

I guess this has bubbling in my head for a few years now

Josh Farkas is also steadfast in his conspiracy explanation

two years ago:

and here is his reply to my latest tweet on the topic

Nephrologists and calculators go together like Captain Kirk and his communicator.

We all have our favorites and work flows get cemented around these favorites. My favorite calculator for eGFR and the Kidney Failure Risk Equation is Stephen Fadem’s MDRD.com. It isn’t pretty but it is amazingly functional. It reminds me of how Neal Stephenson describes the power of Unix by telling a story of a drill in the essay In the Beginning was the Command Line (which amazingly enough is available, in its entirety, on a single web page at Stanford.edu). I am including it here

THE HOLE HAWG OF OPERATING SYSTEMS

Unix has always lurked provocatively in the background of the operating system wars, like the Russian Army. Most people know it only by reputation, and its reputation, as the Dilbert cartoon suggests, is mixed. But everyone seems to agree that if it could only get its act together and stop surrendering vast tracts of rich agricultural land and hundreds of thousands of prisoners of war to the onrushing invaders, it could stomp them (and all other opposition) flat.

It is difficult to explain how Unix has earned this respect without going into mind-smashing technical detail. Perhaps the gist of it can be explained by telling a story about drills.

The Hole Hawg is a drill made by the Milwaukee Tool Company. If you look in a typical hardware store you may find smaller Milwaukee drills but not the Hole Hawg, which is too powerful and too expensive for homeowners. The Hole Hawg does not have the pistol-like design of a cheap homeowner's drill. It is a cube of solid metal with a handle sticking out of one face and a chuck mounted in another. The cube contains a disconcertingly potent electric motor. You can hold the handle and operate the trigger with your index finger, but unless you are exceptionally strong you cannot control the weight of the Hole Hawg with one hand; it is a two-hander all the way. In order to fight off the counter-torque of the Hole Hawg you use a separate handle (provided), which you screw into one side of the iron cube or the other depending on whether you are using your left or right hand to operate the trigger. This handle is not a sleek, ergonomically designed item as it would be in a homeowner's drill. It is simply a foot-long chunk of regular galvanized pipe, threaded on one end, with a black rubber handle on the other. If you lose it, you just go to the local plumbing supply store and buy another chunk of pipe.

During the Eighties I did some construction work. One day, another worker leaned a ladder against the outside of the building that we were putting up, climbed up to the second-story level, and used the Hole Hawg to drill a hole through the exterior wall. At some point, the drill bit caught in the wall. The Hole Hawg, following its one and only imperative, kept going. It spun the worker's body around like a rag doll, causing him to knock his own ladder down. Fortunately he kept his grip on the Hole Hawg, which remained lodged in the wall, and he simply dangled from it and shouted for help until someone came along and reinstated the ladder.

I myself used a Hole Hawg to drill many holes through studs, which it did as a blender chops cabbage. I also used it to cut a few six-inch-diameter holes through an old lath-and-plaster ceiling. I chucked in a new hole saw, went up to the second story, reached down between the newly installed floor joists, and began to cut through the first-floor ceiling below. Where my homeowner's drill had labored and whined to spin the huge bit around, and had stalled at the slightest obstruction, the Hole Hawg rotated with the stupid consistency of a spinning planet. When the hole saw seized up, the Hole Hawg spun itself and me around, and crushed one of my hands between the steel pipe handle and a joist, producing a few lacerations, each surrounded by a wide corona of deeply bruised flesh. It also bent the hole saw itself, though not so badly that I couldn't use it. After a few such run-ins, when I got ready to use the Hole Hawg my heart actually began to pound with atavistic terror.

But I never blamed the Hole Hawg; I blamed myself. The Hole Hawg is dangerous because it does exactly what you tell it to. It is not bound by the physical limitations that are inherent in a cheap drill, and neither is it limited by safety interlocks that might be built into a homeowner's product by a liability-conscious manufacturer. The danger lies not in the machine itself but in the user's failure to envision the full consequences of the instructions he gives to it.

A smaller tool is dangerous too, but for a completely different reason: it tries to do what you tell it to, and fails in some way that is unpredictable and almost always undesirable. But the Hole Hawg is like the genie of the ancient fairy tales, who carries out his master's instructions literally and precisely and with unlimited power, often with disastrous, unforeseen consequences.

Pre-Hole Hawg, I used to examine the drill selection in hardware stores with what I thought was a judicious eye, scorning the smaller low-end models and hefting the big expensive ones appreciatively, wishing I could afford one of them babies. Now I view them all with such contempt that I do not even consider them to be real drills--merely scaled-up toys designed to exploit the self-delusional tendencies of soft-handed homeowners who want to believe that they have purchased an actual tool. Their plastic casings, carefully designed and focus-group-tested to convey a feeling of solidity and power, seem disgustingly flimsy and cheap to me, and I am ashamed that I was ever bamboozled into buying such knicknacks.

It is not hard to imagine what the world would look like to someone who had been raised by contractors and who had never used any drill other than a Hole Hawg. Such a person, presented with the best and most expensive hardware-store drill, would not even recognize it as such. He might instead misidentify it as a child's toy, or some kind of motorized screwdriver. If a salesperson or a deluded homeowner referred to it as a drill, he would laugh and tell them that they were mistaken--they simply had their terminology wrong. His interlocutor would go away irritated, and probably feeling rather defensive about his basement full of cheap, dangerous, flashy, colorful tools.

Unix is the Hole Hawg of operating systems, and Unix hackers, like Doug Barnes and the guy in the Dilbert cartoon and many of the other people who populate Silicon Valley, are like contractor's sons who grew up using only Hole Hawgs. They might use Apple/Microsoft OSes to write letters, play video games, or balance their checkbooks, but they cannot really bring themselves to take these operating systems seriously.

I never realized how irreplaceable MDRD.com was until it went offline for a couple of weeks.

People were quick to offer suggested work arounds.

KidneyFailureRisk.com was a frequent suggestion. I love KidneyFailureRisk.com, but it is not a serious tool for my workflow. It is designed for patients and provides a clean, patient-friendly interface and provides the results in a way that encourages intervention while providing reliable, actionable information with links for further education from vetted sources. All good. But it fails me as a serious tool:

1. When you arrive at the website you need to click calculate to get to the calculator. Then after entering the four-variables it requires another click to bypass entering information for the 8-variable version of the KFRE. I never want to so that, another wasted screen and button press.
2. It does not remember units. My albuminuria is always measured in mg/g. All of my patients are from North America. Why won’t this tool remember this?
3. Once you have a result there is no way to navigate back to the calculation page except to reload the home page kidneyfailurerisk.com. The URL for the result page is just kidneyfailurerisk.com, so the forward and back arrows are useless because as far as the browser is concerned you have not left the main page.

And the most important reason this page fails as a serious tool is it requires me to know the eGFR. MDRD, starts with creatinine, age, gender, and cystatin C, so it first calculates the eGFR and then the Tangri KFRE. This small innovation makes it so powerful. Love this insight into how professionals work.

The other alternative recommended was Calculate by QxMD from Medscape which is actually pretty good, the only problem is that it again requires that you know the eGFR to run the calculation.

And honestly, I don’t love that the calculator is supported by pharmaceutical advertising.

But MDRD.com is back and I am happy with my ugly, but highly efficient tool.

This week I discussed last week’s examination of the Calcifediol story.

You can see all of my newsletters here.

I’m enjoying this. It is forcing me to develop some isolated tweets into longer, hopefully, more thoughtful blog posts that then turn into newsletters.

Please subscribe.

We all are drowning in e-mail. Today I got one from Akhtar Ashfaq, Senior Vice President, Clinical R&D, and Medical Affairs Renal Division at OPKO Pharmaceuticals.

The e-mail promises that new research shows that using calcifediol to correct PTH slows the progression of chronic kidney disease. Big if true. It is not true, and this publication actually lays bare how cynical some pharma-sponsored publishing can be.

The Tweet (actually in this case a Tweetorial)

Hours after writing this I was thinking about the tweet and it hit me. If the data OPKO used to see that the drop in PTH was associated with decreased progression of CKD was from the pivotal trial they used for approval then it was a randomized, placebo-controlled, trial and that OPKO had the data that would actually answer the question. So I pulled up the methods of the manuscript to see where the data came from.

Yep, they were randomized, placebo controlled trials. The two trials were combined and published in this manuscript (Sprague, S Am J Nephrol 2016).

And the authors looked at the most important question regarding the treatment of secondary hyperparathyroidism in CKD, “Does it slow the loss of GFR?”

No. Despite a powerful effect on PTH, there was no signal that use of calcifediol made a bit difference in the loss of eGFR.

Now this study only had patients on placebo controlled medications for 26 weeks, so perhaps there was not enough time to see a difference. But this is not the only attempt to use vitamin D to preserve kidney function. The large (1300 people randomized) and long (5 years) VITAL Study included an analysis of CKD progression and found no effect on eGFR or albuminuria. (H/T Gunnar Henrik Heine)

And last year Yeung, et al did a meta analysis of vitamin D therapy in CKD and likewise found no effect on all-cause mortality (relative risk [RR], 1.04; 95% CI: 0.84, 1.24), cardiovascular death (RR, 0.73; 95% CI: 0.31, 1.71), or fractures (RR, 0.68; 95% CI: 0.37, 1.23).

Every hyponatremia consult recommends increasing protein intake to increase the solute load and increase urine output. But how much protein do you need to move the needle?

Here is another way to do the calculation

Protein is about 16% nitrogen

And urea is just under 50% nitrogen by weight

So if you are using 2 packets of urea (30 grams) a day for SIADH, you should get an equivalent amount of urinary solute (and increased urine output) with three scoops of protein powder.

For this calculation I used this protein powder which has 18 scoops for $22.

Published literature

The TREASURE Study (H/T Pablo Garcia) tested 17 patients with SIADH. They were given 90 grams of protein (three scoops!) for seven days then after a washout they were given 30 grams of urea. for seven days

The results were modest, but there was little material difference between the two therapies.

Patients quality of life improved during the protein phase and fell during the urea phase

The rating for overall well-being slightly improved from 7 VAS points (6-8) to 8 VAS points (7-8) (P = .24) upon protein intake, whereas it slightly worsened from 7 VAS points (6-7) to 6 VAS points (6-7) (P = .40) upon urea intake.

Update

David Goldfarb asked about changes in bicarb with the protein supplement

So I went digging into the supplement to see if they reported it. (They did not) and I came across this humdinger

It shows patient level data on the change in Na. Strange that they didn’t mention that almost a third of patients in the in protein supplement group had their sodium fail. No failures among the urea patients (except one person with inadequate protein intake. That is the asterisk).

Animated gif to make this more clear

I’m glad this is reported. But it should not be in the supplement, it should be in the main paper.

Hot Dog Therapy

In a related note, Roger Rodby suggests hot dog therapy.

I took Roger’s hotdog therapy and made it into an animated gif

Here are the two key slides in the build

and

Cardiology developed one the most fantastic medical technologies of the late twentieth century, the percutaneous coronary intervention. The problem that PCI tackled was obvious, patients with coronary artery disease had demonstrable arterial narrowing and we had a technique that could treat this narrowing. How could we not treat it? How could patients not benefit from this? And following these interventions patients had remarkable improvements in angina, the primary symptom of coronary disease. In addition to improving chest pain, this intervention had to prevent heart attacks and save lives. This assumption was accepted fact at the beginning of my career, however some cardiologists were unsatisfied with using intuition to guide therapy and PCI came under the sharp blade of the randomized controlled trial. COURAGE shot down the idea that providing cardiac (bare metal) stents in patients with stable coronary disease provided any survival benefit. This was repeated with ISCHEMIA (now with drug eluting stents). And then ORBITA used sham procedures to question whether PCI even reduced angina, a finding that was at least partly reversed by ORIBITA-2 which removed the use of anti-anginal medications.

This post is not intended to provide a comprehensive review of the use of PCI in coronary disease but to use it as a demonstration how an intuitive therapy that seems to have obvious and unquestioned use, can be questioned and through those qquestions we can reposition the procedure to use it where it is helpful and not waste resources and treat patients with science and not vibes.

This takes us to dialysis. Dialysis unquestionably helps some patients but I don’t think it helps all patients. Nephrology has rarely subjected dialysis to the rigors of a randomized controlled trial and this is to our patients detriment. We have little evidence to guide us as to when to offer dialysis and when not to. One area that has been extensively explored with RCTs is when to initiate dialysis in AKI, and honestly, it wasn’t pretty for dialysis.

Last week Dr. Manjula Tamura published a Target Trial Emulation of an RCT to see how survival differs between elderly patients (age over 65) with a GFR of 12 and immediately starting dialysis (average was 8 days after trial inclusion) versus delaying dialysis at least 30 days (average was 3 years after trial inclusion). The author tracked two outcomes:

1. Survival
2. Cumulative time at home

The results showed that starting dialysis at 12 ml/min resulted in survival for 770 days. For the cohort who delayed dialysis survival was 761 days. The difference was non-significant.

This image is powerful

The trial was covered in the New York Times!

I am confused by Target Trial Emulation. I am suspicious that people started on dialysis at a GFR of 12 and people that go for 3 years before starting dialysis (in the delayed group) are really interchangeable. I am confused how the late start group can start dialysis an average of 3 years after inclusion in the study while only surviving an average of 761 days (2.1 years) But it is clear to me that nephrology has failed at doing studies to determine who benefits from dialysis. And I believe that old frail people do not get the benefit from dialysis that we dream of. This was shown in an earlier study by Dr. Manjula Tamura which showed dialysis to be a blood bath for nursing home patients. (Tamura, NEJM 2009). I have used this study to guide me in the advice I give patients. It is just an observational study but it showed the folly in believing that the frail patient in the nursing home will turn around as soon you clear the uremia. That’s just a fairy tale we tell ourselves. It almost never happens and the reality is that almost all of these patients are either dead or further debilitated a year later.

As Dr Tamura says in her Tweetorial about the study, it is time for randomized trials to see where dialysis helps and where it falls down. We need to have the COURAGE to test whether what is intuitively helpful actually delivers benefits. The cardiologists have used clinical trials to define the role of PCI in coronary disease, we should do the same for our patients.

Good question about a confusing topic:

In Lecture 19, it is mentioned that hypokalemia leads to decreased NaCl reabsorption in the distal convoluted tubule. I do not understand why this occurs. Dr. Topf said that when you have hypokalemia, you will have decreased Na/Cl/K activity in the TAL, which will lead to increased Na and Cl delivery distally, so shouldn’t that increase NaCl reabsorption in the DCT?

It is also mentioned in this lecture that hypokalemia stimulates H+ secretion in the PCT. I am confused why this occurs as well.

Okay, let’s take this one question at a time, and let’s do it in anatomic order starting in the proximal tubule.

Hypokalemia and the the proximal tubule

In hypokalemia potassium leaks out of the cell to restore extracellular potassium. In order to maintain electroneutrality, Hydrogen ions (protons) move into the cell.

This causes intracellular acidosis. In the proximal tubule this intracellular acidosis “fools” the proximal tubule cells into thinking there is systemic acidosis and their natural response to this “acidosis” is to accelerate the movement of intracellular hydrogen into the tubule, there by increasing proximal tubule bicarbonate resorption.

Here are the relevant slides from the presentation:

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Anatomically the next relevant tissue is the thick ascending limb of the loop of Henle (TAL)

Here the question is how hypokalemia affects the TAL, the TAL is powered by the Na-K-2Cl pump, decreased potassium means decreased NaK2Cl activity, so less sodium is reabsorbed and more sodium moves distally. Here is the relevant slide from the deck.

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And finally to the crux of your question, “Shouldn’t that increase NaCl reabsorption in the DCT?”

YES it does!

The increased sodium reabsorption in the distal cortical collecting tubule is what drives further H and K secretion which perpetuates the metabolic alkalosis and hypokalemia!

Here is a text slide describing it followed by an animated gif of the relevant slides

I hope that helps clarify the question.