Detective Nephron: Hyperphosphatemia

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

Nephron I am craving a good case today. Wonder what Henle has in store for me.
L. O. Henle enters the room.
Nephron What do you want?
Henle I… have a case for us.
Nephron Is it another electrolyte disorder?
Henle Hyperphosphatemia.
Nephron Hmm…well, let’s take that one, then.
Henle (prepared) A 67-year-old man with multiple myeloma presents with acute kidney injury secondary to obstruction. They placed a Foley catheter in the emergency room, and his renal function is improving. Initially he had a creatinine level of 4.0 mg/dL, and over the past 2 days it is down to 1.3 mg/dL. Interestingly, the phosphorus level is rising. It was 6 mg/dL on presentation and now it is up to 15 mg/dL.
Nephron (chuckling) Near-normal renal function and elevated phosphorus…always an interesting combination.
Henle The medical team wants to start binders as soon as possible.
Nephron (confused) Ahah! This is going be exciting.
Henle (with caution) Just some more information, if you will allow, sir.
Nephron (chuckling) Sure—I hope it is the information I am looking for.
Henle The calcium and magnesium levels are normal. The patient doesn’t have any signs of tumor lysis syndrome, or acidosis of any kind. Lactate was normal. Also, he has not been getting any vitamin D supplementation or any phosphate enemas.
Nephron Wow, you really are taking the fun out of this by giving me a laundry list of differential diagnoses that can cause elevated phosphorus. It seems that you have already ruled out the major common causes. What bothers me is that this is rising in the setting of improving renal function.
Henle We repeated the tests multiple times.
Nephron (laughing) I believe you!
Henle To me this is very confusing. What could be causing such high levels of phosphorus?
Nephron Is it the kidney?
Henle The kidneys, I know, are highly efficient in maintaining phosphate balance even when the dietary intake of phosphorus is increased severalfold. If, however, there is an acute phosphate load (i.e., an increase in phosphate concentration over a few hours rather than days), then the entry of phosphate into the extracellular compartment exceeds the rate at which it is excreted, and hyperphosphatemia results.
Nephron Exactly! So, think of the causes of hyperphosphatemia in three ways. (1) You gave him too much (we caused it) (i.e., a phosphate load sufficient enough to overwhelm the ability of the kidney to excrete it). (2) His kidneys stopped working (acute renal or chronic renal injury). (3) The kidney is deciding to enhance proximal tubular phosphate reabsorption (very rare).
Henle Seems like we had ruled out causes of acute phosphate load.
Nephron Well. the phosphate load can be endogenous or exogenous. No exogenous causes (i.e., ingestion of phosphate-containing laxatives) were found in your case. Endogenous causes can be from cell breakdown—so tumor lysis, rhabdomyolysis, and marked hemolysis can do it. In your particular case, the myeloma history does concern me a bit. Hmmm!
Henle (astounded) But with normal calcium, potassium, creatine kinase, and uric acid, less likely any of the above.
Nephron (calm) Fascinating!
Henle The other causes of mobilization of intracellular phosphate into the extracellular fluid are lactic acidosis and diabetic ketoacidosis. Severe metabolic acidosis can cause cellular phosphate utilization because of inhibition of glycolysis. There is no tissue hypoxia in this case, to our knowledge.
Nephron And it’s not renal failure; this man’s GFR is actually improving and most likely will be normal soon. Now, let’s look at the third set of causes and perhaps come up with a diagnosis. What in this patient’s history might have warranted a medication that can have direct effects on phosphorus absorption?
Henle (chuckling) You mean bisphosphonates? No, he didn’t get that one. I know—they can cause mild hyperphosphatemia because they stimulate phosphate transport directly. His parathyroid hormone (PTH) is around 50 pg/mL, so hypoparathyroidism is less likely, and he has no signs of clinical acromegaly. Thought you might like that one, given your prior cases.
Nephron Good work, my apprentice. Either deficient PTH secretion or renal resistance to PTH (pseudohypoparathyroidism) results in increased phosphate reabsorption and leads to hyperphosphatemia. Usually in this case the calcium is low, too. Tumoral calcinosis might be rare in this case because that is more of a genetic disease. Hmm… tough case, but I think I might have just thought of the answer. Like I said, the myeloma history bothers me.
Henle (puzzled) What could this possibly be, given that the renal function is getting better and the phosphorus level is getting worse?
Nephron How controlled is his myeloma? And what light chain is it?
Henle Hmm… Not so well controlled. A multiple regimen is failing, and it’s IgM kappa type.
Nephron (confident) All right, then, go ahead and reassure the team to do nothing, and make sure they don’t start any binders because that might be harmful.
Henle exits without questioning.
Nephron (to himself) Wonder why he just left without asking me “why”?
Before Detective Nephron can go down to get coffee, Henle returns to the office.
Nephron You’re back.
Henle I am puzzled. I think you are getting at pseudohyperphosphatemia from paraproteins? Is that right? Should I ask the lab to de-proteinate?
Nephron Good work!
Henle So this is all a factitious result.
Nephron Spurious hyperphosphatemia due to interference with analytic methods may occur in patients with hyperglobulinemia, hyperlipidemia, hemolysis, and hyperbilirubinemia. Phosphate can be determined accurately by reanalysis of the specimen after removal of protein by ultrafiltration. Classically this can be seen with IgM-related diseases rather than IgG, but even in IgG-related paraprotein diseases, this has been recorded. Paraproteins can cause Na, creatinine, CO2, and Ca values to be spurious. When dealing with large molecules like IgM, one has to be extremely careful about these spurious results.
Henle Yes, you are correct.
Nephron Now, go and get the real result. (with confidence)
Henle exits, and Detective Nephron starts reading ASN Kidney News. A few days later, the detective is sipping away at his coffee when Henle enters the office.
Nephron Nothing is better than a cup of warm coffee. And a great case.
Henle After removal of the proteins, a phosphorus level came back 4.0 mg/dL, and the regular blood work still reads 13–14 mg/dL. This is fascinating.
Nephron Great work, Henle (with a smirk). Again, my dear apprentice, never underestimate the power of the nephrologist. Not every electrolyte disorder is real, and not every number should be treated. By not treating here, you prevented harm. Pseudoelectrolyte disorders are a common finding in paraproteinemias.
Detective Nephron was developed by Kenar Jhaveri, MD, assistant professor of medicine at Hofstra North Shore LI School of Medicine. Thanks to Dr. Rimda Wanchoo, clinical instructor, division of nephrology, Weill Cornell Medical Center, New York, for her editorial assistance. Send correspondence regarding this section to kjhaveri@nshs.edu or kdj200@gmail.com.
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