Detective Nephron: A 56-year-old female with hyperkalemia of 6.5 mEq/L


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, readies himself to present another case to the master consultant.

Henle enters Detective Nephron’s brightly lit office, fidgeting nervously.
Henle, with excitement Dr. Nephron, we have a case!
Nephron Fantastic! I hope it proves challenging this time.
Detective Nephon places ASN Kidney News on the table and readies himself to take notes.
Nephron What do you have for me, Henle?
Henle A 56-year-old female with hyperkalemia of 6.5 mEq/L who presents with…
Nephron, interrupting impatiently Stop right there! You have a lot to learn, Henle. A potassium value alone can be quite enlightening.
After a pause for deep contemplation, Nephron continues…
Nephron Hyperkalemia would not produce consternation in a patient with abnormal kidney function. High potassium is exciting when the GFR is normal. Since my expertise is requested, I conclude the renal function is normal.
Henle Correct again, Dr. Nephron! She has human immunodeficiency virus (HIV) as well…
Nephron, with some anger Remember: no more information until I ask for it!
After a pause…
Nephron Let us begin with hyperkalemia. Most of the potassium in our body is intracellular. The Na-K ATPase pump tightly regulates the ratio of intracellular and extracellular potassium. Minute changes in intracellular potassium can cause profound changes in cardiac and neurological status. Was she symptomatic?
Henle She described no cardiac or neurologic symptoms. Her electrocardiogram showed peaked T waves in lateral and inferior leads.
Nephron, patting Henle’s back You are giving me more information than requested! Nevertheless, she has no known renal injury and hyperkalemia with ECG changes. You checked her urine potassium?
Henle It is 44 mEq/L. The urine sodium is 102 mEq/L, and urine osmolarity is 551 mOsm/kg. The serum osmolarity is 288 mOsm/kg. I even calculated a transtubular potassium gradient (TTKG); it is 4.
Henle looks a bit scared, realizing he has provided more information than requested…
Nephron Good work, Henle! The kidney should be dumping potassium with a TTKG of at least 10, especially with high urine sodium. Urine osmolarity is not low enough to affect tubular flow and potassium excretion. Is she orthostatic?
Henle, with a curious look A tad; no change in heart rate, but a 10 mm Hg drop in systolic blood pressure.
Nephron, confidently You shall see! Is the patient on HIV retroviral medications?
Henle She has been stable for 10 years on lamivudine, stavudine, and nevirapin. She also takes…
The detective listens carefully as his assistant reads out a long list of medications…
Henle …besides those, she takes multivitamins once a day. She is not on digoxin or nonsteroidal anti-inflammatory medications (NSAIDs), sulfamethoxazole-trimethoprim, an angiotensin converting enzyme inhibitor (ACEI), or angiotensin receptor blocker (ARB).
Nephron Great work, my protégé. At this time, you can rule out acute kidney injury, medications, and hyperosmolarity. Did you consider pseudohyperkalemia?
Henle, smirking Yes, Detective. Her platelet count is less than 500,000/µL. Hemolysis, leukocytosis, and severe thrombocytosis have been associated with hyperkalemia. Her complete blood counts were all within the normal ranges.
Nephron What is her urine pH?
Henle 5.5
Nephron Let me complete your laboratory data for you. She also has hyponatremia, a normal gap metabolic acidosis, mild hypercalcemia, and hypoglycemia.
Henle You are correct! What…how…why…?
Nephron, very excited You mentioned she was orthostatic. Is she craving salt?
Henle As a matter of fact, she mentioned that!
Nephron Is she having night sweats, weight loss, or fatigue? Any abdominal pain?
Henle, astounded Yes! All of those!
Nephron, calm My dear apprentice, she has a systemic disorder that needs your attention as soon as possible. Before I elucidate, please admit her to the hospital for intravenous hydration.
Henle exits and Detective Nephron resumes his readings.
A few hour pass, and Henle returns to the office for discussion. The detective sets his work aside and looks into the eyes of his junior colleague before speaking…
Nephron You worked well, but you missed a major diagnosis that will make the patient critically ill in a few hours. She has Addison’s disease.
Henle, frightened How did you conclude this?
Nephron Patients with Addison’s disease can present with profound electrolyte findings. Ninety percent have hyponatremia, reflecting both sodium loss and volume depletion caused by mineralocorticoid deficiency, plus increased vasopressin secretion caused by cortisol deficiency. Recall the diagram in every textbook that shows the breakdown of euvolemic hypoosmolar hyponatremia. Remember, we always rule out adrenal insufficiency and hypothyroidism before we label someone with syndrome of inappropriate antidiuretic hormone (SIADH). Here we are, now rule it out.
Henle listens intently and takes notes.
Nephron Hyperkalemia, often associated with a mild hyperchloremic acidosis, occurs in 60–65 percent of patients due to mineralocorticoid deficiency. Hypercalcemia occurs rarely; increased calcium input into the extracelluar space and reduced renal clearance may account for this phenomenon. Slightly reduced GFR or increased tubular calcium reabsorption are candidate mechanisms. Measurement of blood or urine aldosterone levels will indicate whether the adrenal gland is producing aldosterone. Low levels support the diagnosis of primary adrenal insufficiency.
Henle I see!
Nephron, with confidence Loss of mineralocorticoid activity in this woman led to salt dumping, which explains her elevated urine sodium and decreased aldosterone activity that produced her hyperkalemia. Her peripheral hypoglycemia can also be explained by this disorder. I deduce her urine glucose was negative.
Henle Correct.
Nephron Good. I like it when you hide information from me.
They both chuckle…
Nephron Did you obtain a plasma renin activity and a serum aldosterone level? What results do you predict for these assays?
Henle, confidently I ordered those tests. I expect the aldosterone to be low and the renin high as a secondary response.
Nephron Correct again, Henle!
They pause…
Henle Detective Nephron, is this a type IV renal tubular acidosis?
Nephron, with a smirk Almost all states of primary hypoaldosteronism generate a chronic normal-gap metabolic acidosis. Inhibition of any step from the production of renin to angiotensin II formation, from aldosterone production to cortical collecting duct response, will promote hyperkalemia. No matter what the cause of hypoaldosteronism, distal tubule sodium reabsorption and proton secretion will be slowed. Hyperkalemia can also inhibit ammonia production which will reduce acid secretion. You can give this patient a diagnosis of renal tubular acidosis, but it is meaningless until you identify the cause. In this case, adrenal insufficiency is the cause. In other cases, it could occur from drugs such as NSAIDs, ACEIs or ARBs, chronic heparin, spironolactone, amiloride, or trimethoprim. Anything that affects any step in this endocrine pathway can result in hyperkalemia and a normal-gap metabolic acidosis.
The detective pauses to sip his coffee…
Nephron I would ask the primary physician to perform a morning cortisol level, corticotrophin stimulation test, and radiological examination of the adrenal glands. She could be suffering from adrenal tuberculosis or a lymphoma and might need urgent attention. Endocrine abnormalities are common in asymptomatic patients with HIV infection and those with acquired immunodeficiency syndrome. The adrenal glands may show a necrotizing adrenalitis caused by cytomegalovirus infection, but infection with Mycobacterium avium-intracellulare or cryptococci and infiltration by metastatic Kaposi’s sarcoma are also possible.
One week later, Henle returns to present results.
Henle Her serum aldosterone level was less than 4.1 ng/dL, and her plasma renin was 5 ng/mL. Aldosterone was low and renin elevated appropriately. Cortisol level was also low, and she failed the corticotrophin stimulation test. These results confirm your diagnosis of primary adrenal insufficiency.
Her CD4 count was decreased to 300/µL. Her doctors eventually diagnosed adrenal tuberculosis, and therapy was begun. Mineralocorticoid replacement was begun, but corticosteroids were not, in fear of worsening her tuberculosis.
Nephron, pleased Excellent!
Henle She is doing relatively well now, and her electrolyte abnormalities are correcting.
Nephron I just want to point out to you that from a single electrolyte disturbance we diagnosed a life-threatening systemic disorder. Always be a good detective. Observe, think, read, and apply! If it doesn’t cross your mind, you will never diagnosis it.
Great case, Henle! Now let’s go get some real coffee.
Detective Nephron was developed by Kenar Jhaveri, MD, an assistant attending in nephrology at North Shore University and Long Island Jewish Medical Center in Great Neck, N.Y. Detective Nephron was inspired by Mitch Halperin, MD, and Muthukumar Thangamani, MD, both of the University of Toronto, and Alan Weinstein, MD, of Cornell University.