Doctors use blood tests to check how well kidneys work, but these tests may not be accurate for people with X-linked hypophosphatemia (XLH), a rare genetic condition affecting bone health. Researchers studied 20 adults with XLH and found that standard kidney function tests overestimated how well their kidneys were working. This matters because doctors might miss early kidney problems in these patients. The study suggests using a different type of blood test (cystatin C) instead, which gave more accurate results. Understanding these testing challenges could help doctors better monitor and protect kidney health in people with XLH.

The Quick Take

  • What they studied: Whether standard kidney function blood tests accurately measure how well kidneys work in people with X-linked hypophosphatemia, a rare genetic bone disease.
  • Who participated: 20 adults with XLH (mostly women, average age 35 years) from a single medical center, plus 14 children with a similar condition for comparison.
  • Key finding: The standard kidney test (based on creatinine) made kidneys appear to work 35% better than they actually did. A different test using cystatin C was much more accurate, overestimating by only 14%.
  • What it means for you: If you have XLH, ask your doctor to use cystatin C blood tests instead of standard creatinine tests to check your kidney health. This may help catch kidney problems earlier. However, this study is small and focused on one medical center, so more research is needed.

The Research Details

Researchers looked back at medical records of 20 adults with XLH and compared three different ways of measuring kidney function. They used two common blood test formulas (CKD-EPIcreat and CKD-EPIcyst) and compared the results to a more accurate measurement called measured GFR, which involves injecting a special substance and tracking how quickly the kidneys filter it out. In five patients, they also measured kidney function before and after starting a new treatment called burosumab. Finally, they studied 14 children with a different condition (fibrous dysplasia) that also causes high levels of a hormone called FGF23, to understand how this hormone might affect kidney filtering.

This research approach is important because it compares what the simple blood tests predict against what actually happens in real kidneys. This helps doctors understand which tests are trustworthy. The study also looks at what happens when patients start new treatments, which shows how kidney function changes over time in real life.

This study has some important limitations: it only included 20 patients from one hospital, so results may not apply everywhere. The study looked backward at existing medical records rather than following patients forward over time. However, the researchers used the most accurate kidney function measurement available (measured GFR), which strengthens their findings. The comparison with another disease (fibrous dysplasia) helps support their theory about why the tests don’t work well.

What the Results Show

The standard creatinine-based kidney test dramatically overestimated kidney function. When the test said kidneys were filtering at 125 mL/min/1.73m², the actual measurement showed only 90 mL/min/1.73m². This is a huge difference—the test made kidneys look 35% healthier than they really were. The cystatin C test was much better, showing 103 mL/min/1.73m² compared to the actual 90, an overestimate of only 14%. When doctors used the standard test, they correctly classified kidney health only 25% of the time. With the cystatin C test, they got it right 93% of the time. This means many XLH patients might be told their kidneys are fine when they actually need monitoring.

In five patients who started the new treatment burosumab, kidney function actually decreased from 98 to 84 mL/min/1.73m² after treatment began. This suggests the treatment might affect kidney filtering, which doctors should watch for. The study also found that FGF23 (a hormone that’s abnormally high in XLH) moderately correlated with kidney function in children with fibrous dysplasia, supporting the idea that this hormone might make kidneys filter too much, which could eventually harm them.

Previous research suggested that standard kidney tests might not work well in people with low muscle mass, and XLH patients often have reduced muscle. This study confirms that problem and shows it’s even worse than expected in XLH. The finding that FGF23 might affect kidney filtering is newer and suggests doctors need to think about this hormone when assessing kidney health in XLH patients.

The study only included 20 patients from one hospital, so results might be different in other places or larger groups. Eight patients had secondary hyperparathyroidism, which could affect results. None had advanced kidney disease, so we don’t know if these findings apply to XLH patients with more serious kidney problems. The study didn’t follow patients over many years, so we can’t say how kidney function changes long-term. The comparison with fibrous dysplasia patients was small (14 people) and indirect.

The Bottom Line

If you have XLH, ask your doctor to measure kidney function using cystatin C blood tests annually, especially if kidney disease is suspected (moderate confidence). If you’re starting burosumab treatment, get baseline kidney function measured and recheck it regularly (moderate confidence). Discuss with your doctor whether you need more frequent monitoring based on your individual situation (moderate confidence).

This research is most important for adults and children with X-linked hypophosphatemia, especially those taking phosphate supplements or vitamin D analogs, or considering burosumab treatment. Doctors who treat XLH patients should be aware of these testing limitations. People with other conditions causing high FGF23 levels might also benefit from this information. This research is less relevant for people without XLH or similar rare bone diseases.

Kidney damage from inaccurate testing happens slowly. Using better tests now could help catch problems in months to years, before serious damage occurs. If you start burosumab, kidney function changes might appear within weeks to months, so early monitoring is important.

Want to Apply This Research?

  • Track your annual cystatin C test results and kidney function estimates. Record the date, cystatin C value, and calculated kidney function percentage. Note any changes in urination patterns, swelling, or fatigue.
  • Set a yearly reminder to schedule your cystatin C kidney function test. When discussing test results with your doctor, specifically ask for cystatin C-based estimates rather than creatinine-based ones. Keep a record of all kidney function tests to show trends over time.
  • Create a simple spreadsheet or use your app to track cystatin C results, kidney function estimates, and any symptoms yearly. If you start or change XLH treatment, increase monitoring to every 3-6 months for the first year. Share this tracking data with your doctor at each visit to catch any declining kidney function early.

This research describes kidney function testing challenges in X-linked hypophosphatemia and should not replace professional medical advice. If you have XLH or suspect you do, consult with your doctor or endocrinologist before making any changes to your testing or treatment. This study involved only 20 patients from one center, so results may not apply to all XLH patients. Always discuss kidney function testing options and monitoring schedules with your healthcare provider based on your individual situation. Do not stop or change any medications without medical supervision.