Differentiating acute interstitial nephritis from acute tubular injury: a challenge for clinicians
Open accessAbstract
Background: Differentiating etiologies of acute kidney injury (AKI) is critical in determining the course of care in clinical practice. For example, acute interstitial nephritis (AIN) requires withdrawal of the offending drug and immunosuppressive therapy, while acute tubular injury (ATI) does not have any disease-specific therapies. Failure to distinguish AIN from ATI in a timely manner can lead to kidney fibrosis and chronic kidney disease. In this review, we discuss current tests and novel biomarkers to distinguish ATI from AIN. Summary: In a prospective cohort study of 32 participants with AIN and 41 with ATI, clinical features and current, laboratory tests did not provide sufficient distinction between the 2 subpopulations of AKI. The findings in our cohort are consistent with our review of the literature. Given the limitations of clinical features and laboratory assessments, clinical practice relies on kidney biopsy for histological diagnosis, which is not always feasible, and is associated with bleeding complications in high-risk populations. In addition, histological diagnosis is prone to sampling errors and inter-rater variability. In the interest of identifying a novel biomarker, we compared urine and plasma levels of cytokines in the Th1, Th2, and Th9 pathways, which have been implicated in the pathogenesis of AIN. Urine TNF-α and interleukin-9 were higher in AIN participants than in ATI controls and helped discriminate AIN from ATI (area under curve 0.83 [0.73–0.92]). Key Messages: Differentiation between AIN and ATI in patients with AKI using currently available tests is challenging. Urine TNF-α and interleukin-9 may help clinicians separate AIN from ATI.
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IL-9 and IL-5 are implicated in allergic responses and promote mast cell accumulation, which is a source of TNF-α.
“As IL-9 and IL-5 are implicated in allergic responses and promotes mast cell accumulation, which in turn is a source of TNF-α [60, 61, 95–98]”
From The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review (2024) · cites this paper as [61]
The Introduction’s Novel Biomarkers section (page unavailable) lists IL-5, IL-9, and TNF-α as cytokines studied in acute interstitial nephritis, but does not link them through allergic responses or mast-cell accumulation. A reference title mentions mast-cell activation, but our copy does not say that IL-5 or IL-9 promotes mast-cell accumulation or that mast cells are a source of TNF-α. Searches for the claimed mechanism found no supporting passage. (LLM, conf=0.74)
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- Authors
- Moledina, D. G., & Parikh, C. R.
- Affiliations
- Yale University (US)
- Johns Hopkins University (US)
- Venue
- Nephron
- Publisher
- S. Karger AG
- Published
- 2019
- Volume
- 143
- Issue
- 3
- Pages
- 211-216
- ISSN
- 1660-8151 (ISSN-L)
- 2235-3186
- PMC
- PMC6821567
- OpenAlex
- W2950921882
- Cited by
- 40
- References
- 15
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 8 · 2020: 3 · 2019: 2
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Nephron journals/Nephron journals (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale University
- National Heart, Lung, and Blood Institute (R01HL085757)
- National Institute of Diabetes and Digestive and Kidney Diseases (UG3DK114866, P30DK079337, K23DK117065, P30DK079310, K24DK090203)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Nephrotoxicity and Medicinal Plants
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- acute interstitial nephritis, acute tubular injury, acute kidney injury, differential diagnosis, biomarkers, TNF-α, IL-9, cytokines, renal biopsy, urinary biomarkers, drug-induced nephrotoxicity
- MeSH terms
- Acute Disease, Adult, Aged, Diagnosis, Differential, Female, Humans, Kidney Diseases, Kidney Tubules, Male, Middle Aged, Nephritis, Interstitial, Acute Kidney Injury
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