Thread by @iheartkidneys

1/ Hi #medtwitter! Let’s talk about the 2nd most abundant intracellular cation, magnesium (Mg), by discussing a patient with hypomagnesemia. #tweetorial #nephtwitter #FOAMED @TheSkeletonKG @NSMCinternship
Read our post @RenalFellowNtwk here: renalfellow.org/2020/03/12/ske…

2/ You are asked to see an elderly man, who was recently diagnosed with rectal adenocarcinoma, with a [Mg] of 0.6mg/dL and baseline Cr of 0.9mg/dL. He had loose bowel movements and abdominal pain 2 months ago. Here are his labs from today:

3/ Patient is receiving FOLFOX (folinic acid, fluorouracil and oxaliplatin) for metastatic rectal adenocarcinoma over the past 3 months, and cetuximab was added last month. His other medications include chlorthalidone, atenolol, nifedipine and sitagliptin.

4/ What do you think is the cause of hypomagnesemia in this patient?

5/ How can you distinguish gastrointestinal vs kidney etiologies of hypomagnesemia? By calculating the fractional excretion of Mg (FEMg). Here is the equation to calculate FEMg:

6/ Plasma [Mg] in the denominator is multiplied by 0.7 to calculate the amount of plasma Mg that is actually filtered. This is because roughly 70% of Mg is in its free, ionized form. Check out: pubmed.ncbi.nlm.nih.gov/12766548 and image source: ncbi.nlm.nih.gov/pubmed/26069819

7/ FEMg of >15% suggests improper handling of Mg by the tubules leading to urinary Mg wasting, as most of the filtered Mg should be reabsorbed in the setting of hypomagnesemia. A normal FEMg should be less than 3% in response to hypomagnesemia. pubmed.ncbi.nlm.nih.gov/9513927/

8/ Before we can calculate FEMg, let’s get some urine studies.

9/ Now that we have the numbers we need, let’s calculate FEMg for our patient:

10/ Great - now that we have established that our patient has Mg wasting nephropathy, with FEMg of 21%, what is the most likely cause of this improper Mg handling in this patient?⬇️

11/ TRPM6 is an important transporter of Mg in the DCT. Drugs that interfere with its expression will lead to decreased Mg reabsorption and increased urinary excretion of Mg.

12/ Looking at our patient’s medications - most likely culprits are cetuximab and chlorthalidone. But how do they cause hypomagnesemia???

13/ Cetuximab, an epidermal growth factor (EGFR) inhibitor, leads to impaired translocation of TRPM6, which is an important transporter of Mg in the distal convoluted tubule. Image source: cjasn.asnjournals.org/content/7/10/1…

14/ Chronic use of thiazides leads to decreased expression of TRPM6, independent of the EGFR. This is similar to the cause of hypomagnesemia as in Gitelman syndrome.
ncbi.nlm.nih.gov/pmc/articles/P…

15/ Here is a list of other medications that are associated with hypomagnesemia:

16/ We discontinued cetuximab and chlorthalidone in our patient and started Mg oxide 800mg twice a day. Here is his trend of plasma Mg:

17/ Check out our post on @RenalFellowNtwk to learn more about tubular transport of Mg along the nephron and also about additional electrolyte abnormalities associated with hypomagnesemia (hypokalemia and hypocalcemia). VA by @kkalra_22 renalfellow.org/2020/03/12/ske…