Todd Alexander, MD: Claudins and the Kidneys

A relatively new research field could produce big results in nephrology.

Claudins, discovered in 1998, are tight junction membrane proteins expressed in epithelia and endothelia that function both as pores and barriers in the paracellular pathway. In the kidney, this family of proteins determine the permeability and selectivity of different nephron segments along the renal tubule.

During the American Society of Nephrology (ASN) Kidney Week in Washington, D.C., Todd Alexander, MD, PhD, staff nephrologist, Stollery Children’s Hospital, explained in an interview with MD Magazine® how this field has grown over the past 2 decades and what the future has in store.

MD Magazine: Are there any gaps in research in the field of claudins and kidneys?

Alexander: This field is a very new field, claudins were identified in 1998 by the late Tsukita as opposed to transperitoneal transport, which we've been studying and working on for probably more than 50 years.

Really, this is a field in its infancy and there's huge questions we're only beginning to understand in the proximal tubule what controls paracellular divalent cation transport such as calcium magnesium.

We still open questions around what's controlling chloride reabsorption and therefore regulating GFR. There's a lot to be done in this field, it's a very new field.

MD Magazine: How do you think this field of research will evolve in the next few years?

Alexander: So, I think this field is going to identify molecular pathways both in the nephron, but also in the intestine.

That will be targetable because this is regulating the majority of calcium reabsorption in the kidney, magnesium reabsorption in the kidney, sodium reabsorption, but in the intestine phosphate and potassium.

I think that these pathways will be druggable for the treatment hyperphosphatemia and hyperkalemia.

MD Magazine: Is this research applicable to any certain demographic?

Alexander: I wouldn't say so. I think it's very applicable to chronic kidney disease and end-stage renal disease understanding these pathways.

Very applicable to understanding normal physiology, but also pathophysiology of hypercalcemia and kidney stone formation. These pathways, they've been known to be dysregulated in single gene defects causing disorders of magnesium and calcium homeostasis.

So, I think it's very broad and there's probably ways that I can't even imagine that these pathways are going to be important for kidney disease and kidney health.