Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis
Open accessAbstract
Background: We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. Methods: In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. Results: In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27–69) and 28 (13–47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, −6.0 (−9.4 to −2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. Conclusions: Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.
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Moledina et al. observed higher levels of urinary CXCL9, IL-9 and TNF-α in patients with AIN.
“Despite the findings of Moledina et al. [60, 62, 94], who observed a higher level of urinary C-X-C motif ligand 9 (CXCL9), interleukin-9 (IL-9) and tumor necrosis factor-α (TNF-α) levels in patients with AIN”
From The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review (2024) · cites this paper as [94]
The Discussion (page unavailable) says urinary IL-9 and TNF-α were previously shown to distinguish AIN from other causes of acute kidney injury. This paper does not report the claimed higher urinary CXCL9 level, so it supports only the IL-9 and TNF-α portion of the sentence. (LLM, conf=0.88)
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- Authors
- Moledina, D. G., Wilson, F. P., Kukova, L., Obeid, W., Luciano, R., Kuperman, M., Moeckel, G. W., Kashgarian, M., Perazella, M. A., Cantley, L. G., & Parikh, C. R.
- Affiliations
- Yale University (US)
- Albert Einstein College of Medicine (US)
- Johns Hopkins University (US)
- Arkana Laboratories (US)
- Corresponding author
- Moledina, Dennis G
- ORCID
- Venue
- Nephrology Dialysis Transplantation
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-10-28
- Volume
- 36
- Issue
- 10
- Pages
- 1851-1858
- ISSN
- 0931-0509 (ISSN-L)
- 1460-2385
- PMC
- PMC8476079
- OpenAlex
- W3096976558
- Cited by
- 47
- References
- 41
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 13 · 2023: 10 · 2022: 10 · 2021: 5
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Nephrology Dialysis Transplantation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (K23DK117065, T32DK007276, K24DK090203, R01DK113191, UG3DK114866, P30DK079310)
- Department of Health and Human Services
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Transplantation › Renal Transplantation Outcomes and Treatments
- Keywords
- acute interstitial nephritis, TNF-α, urinary biomarkers, prognosis, estimated glomerular filtration rate, corticosteroid therapy, interstitial fibrosis, acute kidney injury, immunosuppressive therapy
- MeSH terms
- Glomerular Filtration Rate, Humans, Nephritis, Interstitial, Prognosis, Tumor Necrosis Factor-alpha, Interleukin-9
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