Comparing protein levels in urine, blood may help diagnose renal sarcoidosis
New study suggests ACE also may be used to assess severity of kidney damage
Written by |
Comparing levels of a protein known as ACE, fully, angiotensin-converting enzyme, in urine and blood may help diagnose renal sarcoidosis and assess how severely the kidneys are affected, according to a retrospective analysis of data from a single center in Japan.
The findings suggest that measuring ACE levels in urine and blood could offer a simple, minimally invasive way to detect kidney involvement in sarcoidosis.
Further studies are needed to confirm these findings, but the researchers noted that the data show these ACE ratios “could be useful biomarkers for diagnosing [renal sarcoidosis].”
The study, “Novel clinical application of urinary angiotensin-converting enzyme assay in renal sarcoidosis: a retrospective observational study,” was published in the journal Clinical and Experimental Nephrology by a team of researchers in Japan.
Sarcoidosis is an inflammatory disease marked by clumps of immune cells called granulomas that can form in different organs, most often the lungs, eyes, and skin.
Kidney involvement seen in up to 5% of sarcoidosis patients
However, the condition can also involve the kidneys. This form, called renal sarcoidosis, is uncommon, affecting about 1% to 5% of people with sarcoidosis.
It commonly manifests as tubulointerstitial nephritis (TIN), or inflammation of the kidneys’ tiny filtering tubes and surrounding tissue. Renal sarcoidosis can lead to lasting kidney damage if not diagnosed and treated early.
Blood levels of ACE, a protein produced in the kidneys and lungs and by cells within sarcoidosis granulomas, can serve as an add-on diagnostic method for renal sarcoidosis. However, it is associated with high rates of false negatives, meaning it misses many cases of the disease.
“Therefore, we hypothesized that urinary ACE (uACE) could indicate kidney granulomas and serve as a disease-specific marker for RS [renal sarcoidosis],” the researchers wrote.
To test this, the team retrospectively analyzed data from 60 people with and without sarcoidosis who were followed at their center and who had their blood and urine samples collected.
A total of 18 people had renal sarcoidosis, 18 had sarcoidosis without poor kidney function, 14 had sarcoidosis and chronic kidney disease, and 10 had TIN unrelated to sarcoidosis.
Urine-to-blood ACE ratio was strongest measure in testing
The data showed that the renal sarcoidosis group had significantly higher blood ACE levels than the group of sarcoidosis patients without poor kidney function and the group with non-sarcoidosis TIN.
A total of 14 participants across groups had urinary ACE levels below the detection limit, and were excluded from the final urine analysis. Data demonstrated that people with renal sarcoidosis had significantly higher urinary ACE levels and urine-to-blood ACE ratio compared with the other three groups.
When assessing the ability of blood ACE levels, urinary ACE levels, and urine-to-blood ACE ratio to detect kidney involvement among people with sarcoidosis, the urine-to-blood ACE ratio showed the strongest overall discriminative performance, as shown by an area under the curve (AUC) value of 0.89, according to the researchers.
AUC ranges from zero to one, and the higher the AUC value, the better the classifier is at distinguishing people with a given disease from those without it. By comparison, urinary ACE levels alone had an AUC of 0.83, while blood ACE levels performed worst, with an AUC of 0.57.
Blood ACE levels were found to be more useful for distinguishing renal sarcoidosis from other causes of TIN, showing an AUC value of 0.92, per study data.
[The results suggest the urine-to-blood ACE ratio] is a useful biomarker for screening [kidney] involvement in sarcoidosis and is positively correlated with [disease] severity.
In renal sarcoidosis patients, the urine-to-blood ACE ratio also appeared to reflect disease severity, with higher values being significantly associated with more extensive injury in kidneys’ filtering tubes and surrounding tissue.
A higher ratio was also significantly linked to greater infiltration of immune cells and scarring in the kidneys. Also, renal sarcoidosis patients with more extensive scarring tended to have higher urine-to-blood ACE ratios.
Overall, the results suggest that the urine-to-blood ACE ratio “is a useful biomarker for screening renal involvement in sarcoidosis and is positively correlated with [disease] severity in RS,” the researchers wrote. Relative to kidney biopsy, this ratio would represent a less invasive tool, that can be repeated over time, the team emphasized.
Still, further studies are needed to confirm the findings, the scientists concluded.
