# Novel clinical application of urinary angiotensin-converting enzyme assay in renal sarcoidosis: a retrospective observational study

## TL;DR

A new urine test for angiotensin-converting enzyme may help diagnose kidney sarcoidosis more accurately than current methods.

## Contribution

This study introduces urinary ACE as a potential diagnostic biomarker for renal sarcoidosis with high sensitivity and specificity.

## Key findings

- Urinary ACE levels and the u/s ACE ratio were significantly higher in renal sarcoidosis patients compared to controls.
- The u/s ACE ratio showed strong correlations with tubulointerstitial injury, inflammatory cell infiltrates, and interstitial fibrosis.
- A cutoff u/s ACE ratio of 0.39% achieved 100% sensitivity and specificity for detecting diffuse tubulointerstitial injury.

## Abstract

Renal involvement, occurring in approximately −1% to 5% of patients with sarcoidosis, is characterized mainly by granulomatous interstitial nephritis. Angiotensin-converting enzyme (ACE) reflects the presence of granuloma; accordingly, serum ACE (sACE) and tubular injury markers are measured in renal sarcoidosis (RS). However, these markers possess low diagnostic accuracy; therefore, we hypothesized that urinary ACE (uACE) could reflect granuloma in the kidneys and be a disease-specific marker for RS.

In this single-center retrospective study, the sACE and uACE levels were measured and the creatinine-corrected ratio of uACE and sACE (u/s ACE ratio) was calculated. Additionally, patients with sarcoidosis without renal insufficiency (RI), sarcoidosis with RI, and tubulointerstitial nephritis (TIN) without a sarcoidosis etiology were included as controls.

This study included 18, 18, 14, and 10 patients in the RS, sarcoidosis without RI, sarcoidosis with RI, and TIN without sarcoidosis etiology groups, respectively. uACE and u/s ACE ratio in the RS group were higher than those in the control groups. In the RS group, u/s ACE ratio was positively correlated with the degree of tubulointerstitial injury (r = 0.69, P = 0.0045); the cutoff value of u/s ACE ratio for diffuse tubulointerstitial injury was 0.39%, with a sensitivity and specificity of 100.0% each. Furthermore, obvious positive correlations were observed among u/s ACE ratio, inflammatory cell infiltrates (r = 0.53, P = 0.044), and interstitial fibrosis (r = 0.56, P = 0.029) in the RS group.

u/s ACE ratio and sACE could be useful biomarkers for diagnosing RS in sarcoidosis and TIN, respectively. A simple uACE assay could help diagnose and assess disease severity in patients with RS.

The online version contains supplementary material available at 10.1007/s10157-025-02803-8.