Detective Nephron - Jan 2014

By ASN Staff

Detective Nephron:, world-renowned for expert analytical skills, trains budding physician-detectives on the diagnosis and treatment of kidney diseases. L.O. Henle, a budding nephrologist, presents a new case to the master consultant.


Mr. Nice Glom: enters the room along with L.O. Henle to present a case.

Nephron: What do you have for me today, Henle? And we have a new medical student—the word is out that students are not interested in nephrology anymore?

Henle looks at Glom.

Glom: I have a 55-year-old man with a serum potassium level of 6.1 mEq/L.

Nephron: Hyperkalemia! Did you repeat the serum potassium? What did the electrocardiogram (ECG) show?

Glom: I don’t know.

Henle: I did. I actually checked the whole-blood potassium level, and it was 6.2 mEq/L. I personally took the blood sample to the arterial blood gas machine. The ECG was unremarkable: no peak T waves or wide QRS interval.

Nephron: Excellent! You already ruled out pseudohyperkalemia with the measurement of whole-blood potassium. Also, remember to always obtain a 12-lead ECG with any serum potassium level greater than 6 mEq/L. Is the patient using a monitor bed?

Glom: …mmm…

Henle: (interrupting Glom) Of course! The primary team has started the treatment with insulin, dextrose, and albuterol. We will recheck his serum potassium in 1 hour.

Nephron: So, what is your approach to hyperkalemia?

Henle: Generally speaking, hyperkalemia can be caused by translocation or decreased renal K+ excretion.

Glom: (curious) Can you elaborate on translocation?

Henle: Well, translocation refers to shifting of potassium out of the cells. This can result from different mechanisms. The first is from decreased activity of Na-K ATPase that occurs in patients with insulin deficiencies such as diabetes, β-blocker use, or digitalis overdose.

Nephron: (excited) Very good! So, what is the mechanism of hyperkalemia in patients who present with diabetic ketoacidosis?

Henle: Metabolic acidosis, which stimulates exchange of H+ for K+.

Nephron: Actually, that is not true. H+ exchange for K+ is indeed a mechanism for hyperkalemia due to translocation, but it does not explain the hyperkalemia observed in diabetic ketoacidosis. Organic metabolic acidoses such as diabetic ketoacidosis or lactic acidosis do not cause significant hyperkalemia by this mechanism. Only inorganic metabolic acidoses do. There are two reasons why patients with diabetic ketoacidosis experience hyperkalemia: insulin deficiency and solvent drag. You have already talked about insulin deficiency. The second mechanism is solvent drag. Hyperosmolality caused by hyperglycemia pulls water out of the cells, and water carries potassium out. Actually, patients with diabetic ketoacidosis are generally depleted of total body potassium as a result of osmotic diuresis. Only when insulin is used to treat this patient is the total body potassium depletion uncovered.

Nephron: Are there other mechanisms of translocation?

Henle: Tissue destruction.

Glom: Oh, yes! I remember that. Like in rhabdomyolysis?

Nephron: Yes. Also tumor lysis syndrome. Remember: potassium is the most abundant cation in the intracellular compartment, with a concentration of 140 to 150 mEq/L.

Henle: This patient does not have diabetes, nor does he have hyperglycemia. Also, his creatine phosphokinase and uric acid levels are normal.

Nephron: So, it does not seem that he has a translocation, then.

Henle: I don’t believe so.

Nephron: OK, what is the other main pathophysiologic mechanism for hyperkalemia?

Glom: Decreased renal K+ excretion.

Nephron: Correct—but now, could you be more specific?

Henle: Potassium first needs to be filtered. So, any reductions in GFR will cause hyperkalemia.

Nephron: Exactly. Anybody with acute or chronic renal injury who is eating a diet liberal in potassium could experience hyperkalemia.

Henle: His BUN level is 10 mg/dL, and his serum creatinine level is 0.8 mg/dL. So, no decline in GFR.

Nephron: Now, how does the Nephron: handle potassium?

Henle: Potassium is freely filtered, and then the proximal tubule reabsorbs about 65 percent of the filtered load. Then the thick ascending limb of the loop of Henle: reabsorbs about 25 percent of the filtered load. The remaining 10 percent is delivered to the distal Nephron:, where—depending on the K+ intake—it could be secreted or reabsorbed. In the case of hyperkalemia, the appropriate response is potassium secretion.

Nephron: Where and how is potassium secreted?

Henle: It is secreted in the cortical collecting duct.

Nephron: Good! There is also some potassium secretion in the connecting tubule and the outer medullary collecting duct.

Glom: I believe there is also some potassium secretion in the thick ascending limb of the loop of Henle, as well.

Nephron: Potassium is technically secreted in the thick ascending limb of the loop of Henle by renal outer medullary potassium (ROMK) channels, but this serves a completely different purpose.

Glom: (surprised) Really?

Nephron: If you remember, we have these Na+/K+/2Cl cotransporters, also known as NKCC2, in the thick ascending limb of the loop of Henle.

Henle: Yes, furosemide inhibits them.

Nephron: Exactly. This NKCC2 needs potassium to function.

Nephron: How much sodium is filtered per day?

Glom: A lot!

Henle: If the normal GFR is 180 L/day, and the normal plasma sodium concentration is 140 mEq/L, then it would be 180 L/day × 140 mEq/day = 25,200 mEq/day.

Nephron: Great! Now, how much of that is reabsorbed in the thick ascending limb?

Henle: About 20 percent.

Nephron: Great again! So that would be 20 percent of 25,200 mEq, or 5040 mEq/day.

Henle: Yes, I guess.

Nephron: What about for potassium?

Henle: If you consider a normal plasma K+ concentration of 4 mEq/L, then it would be 180 L/day × 4 mEq/L, or 720 mEq.

Nephron: You are good at math!

Henle: (smiling) I was an engineering major in college.

Nephron: I knew it! How much of that will reach the thick ascending limb after the proximal tubule reabsorbs most of it?

Glom: 65 percent of 720 mEq is about 468. Then 725 minus 486 is 257 mEq: 257 mEq!

Nephron: Yes, and given that the NKCC2 has to translocate Na+ and K+ in a 1:1 ratio inside the thick ascending limb cells, then you will need about 5000 mEq of potassium for the NKCC2 to work. This of course, does not occur, unless …

Henle: Unless potassium recycles back via the ROMK channels!

Nephron: Exactly. You are very sharp today, my dear apprentice.

Henle: And the K+ recycling also creates an electrical gradient for paracellular transport of calcium and magnesium.

Nephron: That is also true, but let’s go back to my original question. How is potassium secreted in the distal Nephron?

Henle: The basolateral side of the principal cells in the cortical collecting duct have a Na+/K+/ATPase pump that pumps sodium out of the cell in exchange for potassium, which goes inside the cell. This will decrease the intracellular sodium concentration, which will in turn create a chemical gradient for sodium in the tubular lumen to enter the cells. First, sodium has to be delivered to the distal Nephron to be able to enter the principal cells. Sodium enters the cells via the epithelial sodium channel (ENaC). When sodium enters the cell, it brings positive charges inside the cell, and this makes the inside of the cell positively charged and the tubular lumen negatively charged. This electrical gradient is responsible for potassium secretion from the cell into the lumen via the ROMK channels.

Nephron: Are there any other potassium channels in the distal Nephron: besides ROMK that intervene in potassium secretion?

Henle: I don’t know.

Nephron: There are other channels called BK channels or Maxi-K channels, which are flow-mediated channels. They are activated in conditions of high distal flow such as polyuria or use of diuretics.

Henle: Interesting.

Nephron: What is the role of aldosterone in all of this?

Henle: Aldosterone is released in response to hyperkalemia and stimulates the Na+/K+/ATPase, ENaC, and ROMK to secrete potassium.

Nephron: I am so glad you understand the physiology so well; I am sure you will be a great nephrologist. So, if anything fails in what you just described, you can expect that hyperkalemia might develop. For instance, if your distal Na+ delivery decreases, as in severe hypovolemia, then hyperkalemia might ensue. If there is decreased activity of ENaC or ROMK caused by mutations, drugs, or lack of aldosterone, then you could expect hyperkalemia to develop. If the electrical gradient for K+ secretion is somehow affected, then hyperkalemia will also develop. Now, let’s go back to our patient. Any other significant findings?

Henle: Well, he does have a mild non–anion gap metabolic acidosis. His total CO2 is 21 mmol/L.

Nephron: Interesting! Did you confirm the metabolic acidosis with an arterial blood gas?

Glom: You don’t have to, right?

Henle: Yes, because a low total CO2 could mean a metabolic acidosis but also a compensatory response to a chronic respiratory alkalosis. His arterial pH was 7.31.

Nephron: What clinical conditions present with hyperkalemia and metabolic acidosis?

Glom: Some renal tubular acidosis (RTA).

Nephron: What is the urine pH?

Henle: His urine pH is 6.0.

Nephron: So he is unable to acidify his urine to a pH less than 5.5 in the presence of metabolic acidosis. How do you call that?

Glom: A renal tubular acidosis?

Nephron: Yes. Now, what renal tubular acidosis goes with hyperkalemia?

Henle: Type 4 RTA.

Nephron: Excellent. What is the problem in type 4 RTA?

Henle: There is no aldosterone, and aldosterone stimulates K+ and H+ secretion.

Nephron: Also, chronic hyperkalemia can inhibit ammoniagenesis and result in metabolic acidosis as well. Type 4 RTA can be due to hypoaldosteronism but also to aldosterone resistance. Let’s start with hypoaldosteronism. What are the causes of hypoaldosteronism?

Henle: Decreased synthesis of aldosterone, as in primary adrenal insufficiency. But his cortisol level is normal.

Nephron: So, probably not that. Good; what else causes decreased synthesis of aldosterone?

Henle: I am not sure.

Nephron: Heparin. Is he getting any heparin?

Henle: No, not even for prophylaxis of deep venous thrombosis.

Nephron: OK, what other mechanisms of hypoaldosteronism you can think of?

Silence.

Nephron: How is aldosterone produced?

Henle: Everything starts with renin. Renin released from the juxtaGlomerular cells transforms angiotensinogen into angiotensin I, and then the angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II, which works in the zona Glomerulosa of the adrenal gland to release aldosterone.

Nephron: Again, I am impressed with your knowledge of physiology. All nephrologists have a good grasp of physiology. From what you just said, is there anything that could interfere with aldosterone release from adrenal gland?

Glom: Angiotensin receptor blockers and ACE inhibitors.

Henle: The patient is not taking any of those drugs. We also now have renin blockers that can do that as well, but he is not taking those either.

Nephron: Certainly. Anything else that could interfere with renin?

Henle: Well, I understand diabetes can cause hyporeninism, but this patient is not diabetic.

Nephron: Yes. Anything else in his medical history?

Henle: Nothing important. He is here for a gout flare. His primary doctors have given him indomethacin for the past 3 days.

Nephron: Interesting! Can nonsteroidal anti-inflammatory drugs cause hyperkalemia?

Henle: I guess. But how?

Nephron: They actually decrease renin synthesis and also can decrease aldosterone release from the adrenal gland.

Glom: So this could be it.

Nephron: Yes. Any other RTA that goes with hyperkalemia?

Glom: Not that I know of.

Nephron: Well, there is a hyperkalemic variant of type 1 RTA, also known as voltage-dependent distal RTA. The problem here is that impaired sodium reabsorption via ENaC decreases the electrical gradient for H+ secretion and K+ secretion via the ROMK channels. But some nephrologists consider this a form of aldosterone resistance and classify it as a type 4 RTA as well.

Henle: He is not taking any ENaC blockers, or any aldosterone antagonist drugs, either.

Nephron: What ENaC blockers do you know?

Henle: Amiloride, triamterene, and trimethoprim.

Nephron: Good; also pentamidine. So, what do we need to do next?

Henle: We can calculate the transtubular potassium concentration gradient (TTKG)?

Nephron: Well, that would have been the right thing to do in the past. However, the Halperin group, which developed this tool, has recently discouraged its use because one of the main assumptions for the use of TTKG is that there is no significant reabsorption of osmoles downstream from the cortical collecting duct, and apparently there is a large amount of urea recycling in the inner medullary collecting duct, which aids in potassium secretion. This makes the calculation of TTKG invalid. As my good friend Dr Joel Topf posted in his pbfluids blog, “Discovered by Halperin and killed by Halperin.”

Henle: Can we measure renin and aldosterone levels?

Nephron: That seems more appropriate. We also need to give him a low potassium diet and discontinue indomethacin.

Henle: Will do.

Two days later:

Nephron: (sipping his coffee) OK, so what happened with the patient?

Henle: His renin and aldosterone levels were reduced, and his hyperkalemia has improved with the discontinuation of indomethacin. His latest serum potassium level is 4.9 mEq/L.

Nephron: Great job, my apprentice. You have a great future ahead of you. Remember, besides laboratory data and clinical acumen, you need a good history and physical examination because they will never be replaced. No online tool or laboratory test is going to give you the most information as well as the patient can.

The concept of Detective Nephron: was developed by Kenar D. Jhaveri, MD, associate professor of medicine at Hofstra North Shore LIJ School of Medicine and an attending nephrologist at North Shore University and Long Island Jewish Medical Center in Great Neck, NY. Special thanks to Dr. Helbert Rondon, assistant professor of medicine in the renal and electrolyte division at the University of Pittsburgh School of Medicine, writer and submitter for this case. Send correspondence regarding this section to kjhaveri@nshs.edu or kdj200@gmail.com

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Detective Nephron:, world-renowned for expert analytical skills, trains budding physician-detectives on the diagnosis and treatment of kidney diseases. L.O. Henle, a budding nephrologist, presents a new case to the master consultant.


Mr. Nice Glom: enters the room along with L.O. Henle to present a case.

Nephron: What do you have for me today, Henle? And we have a new medical student—the word is out that students are not interested in nephrology anymore?

Henle looks at Glom.

Glom: I have a 55-year-old man with a serum potassium level of 6.1 mEq/L.

Nephron: Hyperkalemia! Did you repeat the serum potassium? What did the electrocardiogram (ECG) show?

Glom: I don’t know.

Henle: I did. I actually checked the whole-blood potassium level, and it was 6.2 mEq/L. I personally took the blood sample to the arterial blood gas machine. The ECG was unremarkable: no peak T waves or wide QRS interval.

Nephron: Excellent! You already ruled out pseudohyperkalemia with the measurement of whole-blood potassium. Also, remember to always obtain a 12-lead ECG with any serum potassium level greater than 6 mEq/L. Is the patient using a monitor bed?

Glom: …mmm…

Henle: (interrupting Glom) Of course! The primary team has started the treatment with insulin, dextrose, and albuterol. We will recheck his serum potassium in 1 hour.

Nephron: So, what is your approach to hyperkalemia?

Henle: Generally speaking, hyperkalemia can be caused by translocation or decreased renal K+ excretion.

Glom: (curious) Can you elaborate on translocation?

Henle: Well, translocation refers to shifting of potassium out of the cells. This can result from different mechanisms. The first is from decreased activity of Na-K ATPase that occurs in patients with insulin deficiencies such as diabetes, β-blocker use, or digitalis overdose.

Nephron: (excited) Very good! So, what is the mechanism of hyperkalemia in patients who present with diabetic ketoacidosis?

Henle: Metabolic acidosis, which stimulates exchange of H+ for K+.

Nephron: Actually, that is not true. H+ exchange for K+ is indeed a mechanism for hyperkalemia due to translocation, but it does not explain the hyperkalemia observed in diabetic ketoacidosis. Organic metabolic acidoses such as diabetic ketoacidosis or lactic acidosis do not cause significant hyperkalemia by this mechanism. Only inorganic metabolic acidoses do. There are two reasons why patients with diabetic ketoacidosis experience hyperkalemia: insulin deficiency and solvent drag. You have already talked about insulin deficiency. The second mechanism is solvent drag. Hyperosmolality caused by hyperglycemia pulls water out of the cells, and water carries potassium out. Actually, patients with diabetic ketoacidosis are generally depleted of total body potassium as a result of osmotic diuresis. Only when insulin is used to treat this patient is the total body potassium depletion uncovered.

Nephron: Are there other mechanisms of translocation?

Henle: Tissue destruction.

Glom: Oh, yes! I remember that. Like in rhabdomyolysis?

Nephron: Yes. Also tumor lysis syndrome. Remember: potassium is the most abundant cation in the intracellular compartment, with a concentration of 140 to 150 mEq/L.

Henle: This patient does not have diabetes, nor does he have hyperglycemia. Also, his creatine phosphokinase and uric acid levels are normal.

Nephron: So, it does not seem that he has a translocation, then.

Henle: I don’t believe so.

Nephron: OK, what is the other main pathophysiologic mechanism for hyperkalemia?

Glom: Decreased renal K+ excretion.

Nephron: Correct—but now, could you be more specific?

Henle: Potassium first needs to be filtered. So, any reductions in GFR will cause hyperkalemia.

Nephron: Exactly. Anybody with acute or chronic renal injury who is eating a diet liberal in potassium could experience hyperkalemia.

Henle: His BUN level is 10 mg/dL, and his serum creatinine level is 0.8 mg/dL. So, no decline in GFR.

Nephron: Now, how does the Nephron: handle potassium?

Henle: Potassium is freely filtered, and then the proximal tubule reabsorbs about 65 percent of the filtered load. Then the thick ascending limb of the loop of Henle: reabsorbs about 25 percent of the filtered load. The remaining 10 percent is delivered to the distal Nephron:, where—depending on the K+ intake—it could be secreted or reabsorbed. In the case of hyperkalemia, the appropriate response is potassium secretion.

Nephron: Where and how is potassium secreted?

Henle: It is secreted in the cortical collecting duct.

Nephron: Good! There is also some potassium secretion in the connecting tubule and the outer medullary collecting duct.

Glom: I believe there is also some potassium secretion in the thick ascending limb of the loop of Henle, as well.

Nephron: Potassium is technically secreted in the thick ascending limb of the loop of Henle by renal outer medullary potassium (ROMK) channels, but this serves a completely different purpose.

Glom: (surprised) Really?

Nephron: If you remember, we have these Na+/K+/2Cl cotransporters, also known as NKCC2, in the thick ascending limb of the loop of Henle.

Henle: Yes, furosemide inhibits them.

Nephron: Exactly. This NKCC2 needs potassium to function.

Nephron: How much sodium is filtered per day?

Glom: A lot!

Henle: If the normal GFR is 180 L/day, and the normal plasma sodium concentration is 140 mEq/L, then it would be 180 L/day × 140 mEq/day = 25,200 mEq/day.

Nephron: Great! Now, how much of that is reabsorbed in the thick ascending limb?

Henle: About 20 percent.

Nephron: Great again! So that would be 20 percent of 25,200 mEq, or 5040 mEq/day.

Henle: Yes, I guess.

Nephron: What about for potassium?

Henle: If you consider a normal plasma K+ concentration of 4 mEq/L, then it would be 180 L/day × 4 mEq/L, or 720 mEq.

Nephron: You are good at math!

Henle: (smiling) I was an engineering major in college.

Nephron: I knew it! How much of that will reach the thick ascending limb after the proximal tubule reabsorbs most of it?

Glom: 65 percent of 720 mEq is about 468. Then 725 minus 486 is 257 mEq: 257 mEq!

Nephron: Yes, and given that the NKCC2 has to translocate Na+ and K+ in a 1:1 ratio inside the thick ascending limb cells, then you will need about 5000 mEq of potassium for the NKCC2 to work. This of course, does not occur, unless …

Henle: Unless potassium recycles back via the ROMK channels!

Nephron: Exactly. You are very sharp today, my dear apprentice.

Henle: And the K+ recycling also creates an electrical gradient for paracellular transport of calcium and magnesium.

Nephron: That is also true, but let’s go back to my original question. How is potassium secreted in the distal Nephron?

Henle: The basolateral side of the principal cells in the cortical collecting duct have a Na+/K+/ATPase pump that pumps sodium out of the cell in exchange for potassium, which goes inside the cell. This will decrease the intracellular sodium concentration, which will in turn create a chemical gradient for sodium in the tubular lumen to enter the cells. First, sodium has to be delivered to the distal Nephron to be able to enter the principal cells. Sodium enters the cells via the epithelial sodium channel (ENaC). When sodium enters the cell, it brings positive charges inside the cell, and this makes the inside of the cell positively charged and the tubular lumen negatively charged. This electrical gradient is responsible for potassium secretion from the cell into the lumen via the ROMK channels.

Nephron: Are there any other potassium channels in the distal Nephron: besides ROMK that intervene in potassium secretion?

Henle: I don’t know.

Nephron: There are other channels called BK channels or Maxi-K channels, which are flow-mediated channels. They are activated in conditions of high distal flow such as polyuria or use of diuretics.

Henle: Interesting.

Nephron: What is the role of aldosterone in all of this?

Henle: Aldosterone is released in response to hyperkalemia and stimulates the Na+/K+/ATPase, ENaC, and ROMK to secrete potassium.

Nephron: I am so glad you understand the physiology so well; I am sure you will be a great nephrologist. So, if anything fails in what you just described, you can expect that hyperkalemia might develop. For instance, if your distal Na+ delivery decreases, as in severe hypovolemia, then hyperkalemia might ensue. If there is decreased activity of ENaC or ROMK caused by mutations, drugs, or lack of aldosterone, then you could expect hyperkalemia to develop. If the electrical gradient for K+ secretion is somehow affected, then hyperkalemia will also develop. Now, let’s go back to our patient. Any other significant findings?

Henle: Well, he does have a mild non–anion gap metabolic acidosis. His total CO2 is 21 mmol/L.

Nephron: Interesting! Did you confirm the metabolic acidosis with an arterial blood gas?

Glom: You don’t have to, right?

Henle: Yes, because a low total CO2 could mean a metabolic acidosis but also a compensatory response to a chronic respiratory alkalosis. His arterial pH was 7.31.

Nephron: What clinical conditions present with hyperkalemia and metabolic acidosis?

Glom: Some renal tubular acidosis (RTA).

Nephron: What is the urine pH?

Henle: His urine pH is 6.0.

Nephron: So he is unable to acidify his urine to a pH less than 5.5 in the presence of metabolic acidosis. How do you call that?

Glom: A renal tubular acidosis?

Nephron: Yes. Now, what renal tubular acidosis goes with hyperkalemia?

Henle: Type 4 RTA.

Nephron: Excellent. What is the problem in type 4 RTA?

Henle: There is no aldosterone, and aldosterone stimulates K+ and H+ secretion.

Nephron: Also, chronic hyperkalemia can inhibit ammoniagenesis and result in metabolic acidosis as well. Type 4 RTA can be due to hypoaldosteronism but also to aldosterone resistance. Let’s start with hypoaldosteronism. What are the causes of hypoaldosteronism?

Henle: Decreased synthesis of aldosterone, as in primary adrenal insufficiency. But his cortisol level is normal.

Nephron: So, probably not that. Good; what else causes decreased synthesis of aldosterone?

Henle: I am not sure.

Nephron: Heparin. Is he getting any heparin?

Henle: No, not even for prophylaxis of deep venous thrombosis.

Nephron: OK, what other mechanisms of hypoaldosteronism you can think of?

Silence.

Nephron: How is aldosterone produced?

Henle: Everything starts with renin. Renin released from the juxtaGlomerular cells transforms angiotensinogen into angiotensin I, and then the angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II, which works in the zona Glomerulosa of the adrenal gland to release aldosterone.

Nephron: Again, I am impressed with your knowledge of physiology. All nephrologists have a good grasp of physiology. From what you just said, is there anything that could interfere with aldosterone release from adrenal gland?

Glom: Angiotensin receptor blockers and ACE inhibitors.

Henle: The patient is not taking any of those drugs. We also now have renin blockers that can do that as well, but he is not taking those either.

Nephron: Certainly. Anything else that could interfere with renin?

Henle: Well, I understand diabetes can cause hyporeninism, but this patient is not diabetic.

Nephron: Yes. Anything else in his medical history?

Henle: Nothing important. He is here for a gout flare. His primary doctors have given him indomethacin for the past 3 days.

Nephron: Interesting! Can nonsteroidal anti-inflammatory drugs cause hyperkalemia?

Henle: I guess. But how?

Nephron: They actually decrease renin synthesis and also can decrease aldosterone release from the adrenal gland.

Glom: So this could be it.

Nephron: Yes. Any other RTA that goes with hyperkalemia?

Glom: Not that I know of.

Nephron: Well, there is a hyperkalemic variant of type 1 RTA, also known as voltage-dependent distal RTA. The problem here is that impaired sodium reabsorption via ENaC decreases the electrical gradient for H+ secretion and K+ secretion via the ROMK channels. But some nephrologists consider this a form of aldosterone resistance and classify it as a type 4 RTA as well.

Henle: He is not taking any ENaC blockers, or any aldosterone antagonist drugs, either.

Nephron: What ENaC blockers do you know?

Henle: Amiloride, triamterene, and trimethoprim.

Nephron: Good; also pentamidine. So, what do we need to do next?

Henle: We can calculate the transtubular potassium concentration gradient (TTKG)?

Nephron: Well, that would have been the right thing to do in the past. However, the Halperin group, which developed this tool, has recently discouraged its use because one of the main assumptions for the use of TTKG is that there is no significant reabsorption of osmoles downstream from the cortical collecting duct, and apparently there is a large amount of urea recycling in the inner medullary collecting duct, which aids in potassium secretion. This makes the calculation of TTKG invalid. As my good friend Dr Joel Topf posted in his pbfluids blog, “Discovered by Halperin and killed by Halperin.”

Henle: Can we measure renin and aldosterone levels?

Nephron: That seems more appropriate. We also need to give him a low potassium diet and discontinue indomethacin.

Henle: Will do.

Two days later:

Nephron: (sipping his coffee) OK, so what happened with the patient?

Henle: His renin and aldosterone levels were reduced, and his hyperkalemia has improved with the discontinuation of indomethacin. His latest serum potassium level is 4.9 mEq/L.

Nephron: Great job, my apprentice. You have a great future ahead of you. Remember, besides laboratory data and clinical acumen, you need a good history and physical examination because they will never be replaced. No online tool or laboratory test is going to give you the most information as well as the patient can.

The concept of Detective Nephron: was developed by Kenar D. Jhaveri, MD, associate professor of medicine at Hofstra North Shore LIJ School of Medicine and an attending nephrologist at North Shore University and Long Island Jewish Medical Center in Great Neck, NY. Special thanks to Dr. Helbert Rondon, assistant professor of medicine in the renal and electrolyte division at the University of Pittsburgh School of Medicine, writer and submitter for this case. Send correspondence regarding this section to kjhaveri@nshs.edu or kdj200@gmail.com