X-linked hypophosphatemia (XLH), which results from a loss of phosphate from the kidneys, is known to lead to muscle weakness, muscle pain, and problems with the bones and teeth. But in addition to these common symptoms, patients with XLH also may experience problems directly in their kidneys.
The following is information on the kidney issues that occur with this rare inherited disorder, and how your doctors can diagnose and treat these problems if they affect you.
What is XLH and how does it affect the kidneys?
Mutations in the PHEX gene that resides on the X chromosome cause XLH. The enzyme that this gene encodes plays a role in cutting up other proteins, a process called cleavage.
One such protein may be fibroblast growth factor 23, known as FGF23. FGF23 normally blocks the kidneys’ ability to reabsorb phosphate. The relationship between PHEX and FGF23 or how the PHEX enzyme helps control phosphate reabsorption is not clear. However, researchers know that low levels of phosphate lead to the symptoms of XLH.
Kidney issues in XLH
Kidney issues in XLH include kidney stones, scientifically known as nephrolithiasis, and calcium deposits in the kidneys, called nephrocalcinosis or NC.
Studies have shown that between 22 and 100% of patients with XLH have some level of NC. Researchers think that the primary cause of these calcium deposits, which usually consist of a combination of calcium and phosphate, is the treatment of XLH.
Doctors usually prescribe oral supplements of phosphate and active vitamin D (calcitriol) to treat XLH. These supplements can cause greater absorption of calcium in the intestines and lead to abnormally high levels of calcium, called hypercalcemia. These elevated levels of calcium, in turn, can lead to calcium deposits throughout the body — including the kidneys. Together with a greater amount of phosphate in the urine, these high calcium levels may cause the formation of calcium and phosphate crystals.
High production of calcium channels on the outside of kidney cells also may partially cause NC. These calcium channels, called TRPV5, may make cells of the kidney take in more calcium, which may lead to calcium deposits.
Kidney stones do not appear to be as common as NC. One recent study found that 38.5% of 39 patients had NC but only 10.2% had kidney stones. Both of these percentages were higher than in the general population, however.
How do doctors diagnose and treat kidney problems in XLH?
There are a number of ways that doctors can diagnose and treat kidney problems if you develop them as a result of XLH.
Analyzing a patient’s urine can detect abnormal levels of phosphate and calcium.
Imaging of the kidneys is a non-invasive way for doctors to check to see you may have NC and/or kidney stones. The most common imaging techniques for this purpose are computed tomography, or the use of multiple X-rays, and renal ultrasound, which is the use of high-frequency sound waves to get a picture of the kidneys.
Doctors also can diagnose NC through a renal biopsy, in which they take a small piece of tissue from the kidneys to analyze.
NC does not seem to lead to a loss of kidney function, so treatment may not be necessary. Changes in XLH treatments that may lead to NC, namely phosphate and active vitamin D supplements, also may not be needed.
The standard treatments for kidney stones involve drinking lots of water, taking painkillers, and possibly certain medications to relax the muscles in the urinary tract. This can help patients naturally pass kidney stones that are smaller. For larger ones, doctors may use ultrasound to break up the stone into smaller pieces that patients can pass. Surgery may be necessary in more severe cases.
Last updated: Feb. 12, 2021
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