Acute tubulointerstitial nephritis (ATIN) occurs in approximately 15% of patients who are hospitalized with acute kidney injury (AKI). Medications are the most common cause with antimicrobial agents, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, and immune-checkpoint inhibitors (ICPIs) as notable offenders (1). An early ATIN diagnosis is paramount to promoting kidney function recovery; however, the lack of suitably diagnostic clinical, laboratory, and imaging tests is a major impediment (2). The dearth of reliable tests makes kidney biopsy the best option despite its limitations and invasive nature.
Promising serum and urine biomarkers have the potential to fill the gap in diagnostic tests for ATIN (3). The imaging modality 2-deoxy-2-[18F]fluoro-D-glucose (F18-FDG) positron emission tomography-computed tomography (PET-CT) scan has shown potential in the diagnosis of ATIN (4). It is widely used in the diagnosis, staging, and restaging of many cancers, as well as in diagnosing various nononcologic disorders (5, 6). The test is based on F18-FDG uptake in glucose-using cells with high rates of anaerobic glycolysis, such as metabolically active tumor cells, and infected and inflamed tissues (Figure). Renewed interest in this diagnostic test, especially for ICPI-associated ATIN, is based on case reports and a study that reported increased renal parenchymal F18-FDG activity in 14 patients with ATIN who were treated with ICPIs (7).
Uptake of F18-FDG by renal interstitial inflammatory cells
Citation: Kidney News 16, 12
A recent publication by Gupta et al. in The Journal of Clinical Investigation demonstrates utility for F18-FDG PET-CT in diagnosing ICPI-AKI (8). The authors used data from a previously published study of 429 patients with ICPI-AKI, many with biopsy-proven ATIN (9). Patients with non-ICPI-AKI and ICPI treated without AKI were included as controls. Inclusion required F18-FDG PET-CT scans at baseline and within 14 days of AKI onset or at follow-up for patients without AKI. After appropriate exclusion, 53 patients were included (9 with ICPI-AKI, 24 with non-ICPI-AKI, and 20 treated with ICPI without AKI). Of the nine patients with ICPI-AKI, three had biopsy-proven ATIN, and six had clinically adjudicated ATIN. The patients with non-ICPI-AKIs had prerenal AKI (n = 10), ischemic or septic acute tubular necrosis (n = 10), or other AKI etiologies (n = 4).
Patients with ICPI-AKI had a significantly increased F18-FDG uptake compared with controls. The mean standardized uptake value (SUVmean) from baseline to follow-up was 57.4%, whereas the SUVmean increased by only 8.5% in patients with non-ICPI-AKI and decreased by 0.8% in patients treated with ICPI without AKI. The area under the curve was 0.97 (95% confidence interval, 0.93–1.00) for the differentiation of the SUVmean percent change for ICPI-AKI versus the two control groups. These results suggest that this scan has diagnostic utility in noninvasively differentiating ICPI-AKI from non-ICPI-AKI.
However, there are drawbacks to acknowledge. Notably, six of nine patients with ICPI-AKI in this study did not have definitive (biopsy-proven) ATIN. Additionally, patients require a baseline F18-FDG PET-CT scan to allow comparison. This could be quite limiting in the setting of routine clinical care.
What should we take away from this study? I believe we should be optimistic that this test may be helpful in our quest to noninvasively diagnose ATIN—including both ICPI-associated ATIN and other causes of ATIN. There is no reason to think that the F18-FDG PET-CT scan will not light up positively in most types of ATIN since the inflammatory interstitial infiltrate is quite similar across all forms of ATIN. Since differentiating ATIN from acute tubular necrosis as the cause for hospital-acquired AKI is a common dilemma for clinicians, a positive F18-FDG PET-CT may be sufficiently diagnostic to avert kidney biopsy for many patients. Perhaps combining F18-FDG PET-CT with serum or urine biomarkers will be the answer. Ultimately, this modality requires prospective study to validate these findings.
Footnotes
References
- 1.↑
Sanchez-Alamo B, et al. Facing the challenge of drug-induced acute interstitial nephritis. Nephron 2023; 147:78–90. doi: 10.1159/000525561
- 2.↑
Nussbaum EZ, Perazella MA. Diagnosing acute interstitial nephritis: Considerations for clinicians. Clin Kidney J 2019; 12:808–813. https://academic.oup.com/ckj/article/12/6/808/5531252
- 3.↑
Moledina DG, et al. Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis. J Clin Invest 2024; 134:e180583. doi: 10.1172/JCI168950
- 4.↑
Krishnan N, Perazella MA. The role of PET scanning in the evaluation of patients with kidney disease. Adv Chronic Kidney Dis 2017; 24:154–161. doi: 10.1053/j.ackd.2017.01.002
- 5.↑
Weitzer F, et al. Diagnostic value of F-18 FDG PET/CT in fever or inflammation of unknown origin in a large single-center retrospective study. Sci Rep 2022; 12:1883. doi: 10.1038/s41598-022-05911-7
- 6.↑
Ghodsi A, et al. PET/computed tomography transformation of oncology: Immunotherapy assessment. PET Clin 2024; 19:291–306. doi: 10.1016/j.cpet.2023.12.012
- 7.↑
Awiwi MO, et al. Imaging features of immune checkpoint inhibitor-related nephritis with clinical correlation: A retrospective series of biopsy-proven cases. Eur Radiol 2023; 33:2227–2238. doi: 10.1007/s00330-022-09158-8
- 8.↑
Gupta S, et al. F18-FDG PET imaging as a diagnostic tool for immune checkpoint inhibitor-associated acute kidney injury. J Clin Invest 2024; 134:e182275. doi: 10.1172/JCI182275
- 9.↑
Gupta S, et al.; ICPi-AKI Consortium Investigators. Acute kidney injury in patients treated with immune checkpoint inhibitors. J Immunother Cancer 2021; 9:e003467. doi: 10.1136/jitc-2021-003467
