1/n a case of hypomagnesemia: pt sent to clinic 2/2 incidental finding: serum Mg 1.0 mg/dL. Not on diuretics, no diarrhea. Yep, common suspect is present: omeprazole, PPI-induced hypoMg is well-reported. First in 2006, this is an early case series pubmed.ncbi.nlm.nih.gov
2/why do PPIs cause hypoMg?
3/n turns out that the same Mg channel TRPM6 that is expressed in the DCT is also expressed in the gut. Top 2 panels are colon & duodenum. Bottom right is DCT.
pubmed.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
4/n apical TRPM6 in DCT is regulated by the EGFR. Thatโs why chemoagents that inhibit EGFR, like cetuximab, can lead to profound urine Mg wasting and hypoMg pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
5/n back to the gut, how does proton pump inhibition lead to โฌ๏ธMg gut absorption? First, itโs known that acidic pH enhances TRPM6 channel activity pubmed.ncbi.nlm.nih.gov
6/n it is also known that PPIs not only increase gastric pH but also that of the duodenum & jejunum. Not much effect beyond that pubmed.ncbi.nlm.nih.gov
7/n therefore, duodenal/jejunal TRPM6 activity is impaired. Compensatory TRPM6 expression follows, which may explain why itโs not a common side effect pubmed.ncbi.nlm.nih.gov
8/n back to the case: pt states that has โbad refluxโ. So, next step is to manage and to establish the diagnosis. Pt asymptomatic Mg-wise. Thus, a 24-hr urine collection for Mg and Cr is ordered, once specimen dropped, pt starts Mg Oxide 400 mg BID. Not letโs waitโฆ
9/n results arrive: urine Mg below the lower limit of detection. No need to calculate fractional excretion of Mg here, the kidneys are doing what they should. There r many things that the kidneys are really good at, one of them is holding on Mg when needed
10/n at this point PPI-hypoMg is the likely diagnosis. Rec 2 stop PPI. Pepcid started. Repeat Mg 1.8 mg/dL. We r getting there. Mg Oxide stopped. Week later, Mg 2.2 mg/dL. Success! Wait, 2 wks later, Mg down to 1.2. Huh? Called pt, back on PPI. โPepcid ainโt no good docโ
11/n to treat over. Keep PPI, Mg Oxide 400mg BID back on. 3 wks later, Mg 1.6. Not quite there. Concern here is that Mg supplements often cause diarrhea and perpetuate GI Mg losses. Dose was โฌ๏ธ to 800mg BID. I was prepping plan B with other formulations. pubmed.ncbi.nlm.nih.gov
12/n Iโve had inconsistent success with other formulations. Was getting read to try to Mg citrate gummies. But no need, pt tolerated higher dose Mg Oxide and serum Mg is now 2.0 mg/dL, on PPI.
13/n shortly after, another (elderly) pt is seen with milder hypoMg, 1.5 mg/dL. HTN, type 2 diabetes, GERD. Not on diuretics, no diarrhea. Yep, also on a PPI. No symptoms. So time to diagnose before managing. A 24 hr urine Mg is obtained.
14/n in this case, the FE Mg was estimated at 8%, clearly higher than 2-3% or less expected w/normal kidneys. Thus, this is a case of urine Mg wasting. Intrinsic tubular disorder? Unlikely to present late in life. Normal K, Ca, Phos. Notably, pt has type 2 diabetes. DM-hypoMg?
15/n first letโs establish the fact that prevalence of hypoMg is higher in diabetics compared to non-diabetics. Eg, One study found hypoMg in 37% vs 11% in control pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
16/n urine Mg wasting has also been established in diabetics. One study reported that low level of serum Mg inversely correlated with urinary Mg excretion rate pubmed.ncbi.nlm.nih.gov
17/n whatโs the link between for urine Mg wasting and insulin resistance?
17/n the mechanism for hypoMg in diabetes isnโt fully elucidated. But, it has been observed that insulin regulates TRPM6 in the DCT. Thus, it is conceivable that insulin deficiency or resistance could be linked to urine Mg wasting pubmed.ncbi.nlm.nih.gov
18/n osmotic diuresis and hyperfiltration may enhance urine Mg loss, but pt had normal Gluc and only w/eGFR 74 ml/min. So, in this case stopping the PPI may not be the most effective intervention. Mg supplementation was started. A Flozin may b an option pubmed.ncbi.nlm.nih.gov
19/19 will finish reminding good dietary sources of magnesium. Spinach on top of the list. Maybe the creator of Popeyeโs was well versed on hypoMg-induced muscle weakness / end.
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