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Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis
Open accessAbstract
The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.
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“during the case of an antibiotic-related AIN, clinicians may require the use of alternative antibiotic drugs along with the application of an immunosuppressant [3, 6, 16, 17]”
From The diagnosis of acute interstitial nephritis caused by infection versus antibiotic-induced interstitial nephritis: a narrative review (2024) · cites this paper as [17]
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BackgroundResultGranulomatous interstitial nephritis
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“observed in patients with AIN [9].”
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“The authors showed that early initiation of the treatment was considered beneficial, probably because of decreased fibrinogenesis in the interstitium [9].”
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Lee, M. D., Seethapathy, H. S., Strohbehn, I. A., Zhao, S. H., Boland, G. M., Fadden, R. M., Sullivan, R. J., Reynolds, K. L., & Sise, M. E. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002292 · Cited by 42
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“The evidence behind the use of steroids in DI-AIN is mixed, but there are reports suggesting early treatment with steroids is beneficial [8, 10].”
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“Mechanisms of acute kidney failure due to tubular necrosis and interstitial nephritis caused by antibiotics are beyond the scope of this review and are reviewed elsewhere [21, 22].”
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Zhou, P., Gao, Y., Kong, Z., Wang, J., Si, S., Han, W., Li, J., Lv, Z., & Wang, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353339 · Cited by 33
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“…study of 61 patients with biopsy-proven drug-induced AIN (mostly on antibiotics and NSAIDs), serum creatinine was lower in those treated with steroids; therefore, prompt treatment after diagnosis of AIN would avoid subsequent interstitial fibrosis and an incomplete recovery of renal function [93].”
BackgroundHosohata, K., Inada, A., Oyama, S., & Iwanaga, K. (2018) · InTech eBooks · doi:10.5772/intechopen.79348 · Cited by 3
“In the treatment of drug-induced acute interstitial nephritis, we may consider steroid therapy after early withdrawal of drugs (within 2 weeks), when kidney disorder hangover occurs under the discontinuation of the suspected drug [20].”
BackgroundRamachandran, R., Kumar, K., Nada, R., Jha, V., Gupta, K., & Kohli, H. (2015) · Indian Journal of Nephrology · doi:10.4103/0971-4065.147766 · Cited by 31
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“While we do not have historical data with which to compare, we postulate that if steroids are protective against drug-induced AIN, the occurrence of this hypersensitivity reaction may increase as more transplant centers move away from routine use of glucocorticoids.”
ResultInfluentialTucci, M., Passarelli, A. M., Todisco, A., Mannavola, F., Stucci, L. S., D’Oronzo, S., Rossini, M., Taurisano, M., Gesualdo, L., & Silvestris, F. (2019) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919875549 · Cited by 33
Adverse effects of drugs on the kidney.
Bartoli, E. (2016) · European journal of internal medicine · doi:10.1016/j.ejim.2015.12.001 · Cited by 30
“drawal, prednisone administration [25], continuous follow-up of renal function and clinical conditions.”
BackgroundMethodCefepime induced acute interstitial nephritis – a case report
Mac, K., Chavada, R., Paull, S., Howlin, K., & Wong, J. (2015) · BMC Nephrology · doi:10.1186/s12882-015-0004-x · Cited by 30
“While some retrospective and uncontrolled studies have shown benefit of early administration of corticosteroids in preventing interstitial fibrosis, consistent benefits have not been observed in others [24,25].”
ResultRenal dysfunction in end-stage liver disease and post-liver transplant.
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Diagnosing acute interstitial nephritis: considerations for clinicians
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“Two subsequent studies found that eosinophilia was present in 36% [17] and 34% [18] of biopsy-proven cases of AIN.”
BackgroundShimamura, Y., Watanabe, S., Maeda, T., Abe, K., Ogawa, Y., & Takizawa, H. (2021) · Clinical and Experimental Nephrology · doi:10.1007/s10157-020-02008-1 · Cited by 37
“While a guideline recommends glucocorticoid therapy [27], the results of previous observational studies are controversial [28, 29].”
ResultTreatment of Drug-Induced Acute Tubulointerstitial Nephritis
Moledina, D. G., & Perazella, M. A. (2018) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.12001018 · Cited by 36
A Case Series of Acute Kidney Injury During Anti-tuberculosis Treatment
Sakashita, K., Murata, K., Takahashi, Y., Yamamoto, M., Oohashi, K., Sato, Y., Kitazono, M., Wada, A., & Takamori, M. (2018) · Internal medicine · doi:10.2169/internalmedicine.0813-18 · Cited by 28
“Although the use of steroids for AIN remains controversial (12, 13), one study clearly showed that the early administration of steroids resulted in a higher rate of successful renal function recovery after the development of AIN (14).”
BackgroundAcid‐suppressive drugs and risk of kidney disease: A systematic review and meta‐analysis
Qiu, T., Zhou, J., & Zhang, C. (2018) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.14157 · Cited by 30
Mizushima, I., Yamamoto, M., Inoue, D., Nishi, S., Taniguchi, Y., Ubara, Y., Matsui, S., Yasuno, T., Nakashima, H., Takahashi, H., et al. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-1175-y · Cited by 28
The use of gallium-67 scintigraphy in the diagnosis of acute interstitial nephritis
Graham, F., Lord, M., Froment, D., Cardinal, H., & Bollée, G. (2015) · Clinical Kidney Journal · doi:10.1093/ckj/sfv129 · Cited by 27
“such as fever, rash or eosinophilia are present in only 25–35% of patients with drug-induced AIN, making the clinical diagnosis often difficult [1, 5].”
BackgroundManagement of nonimmediate hypersensitivity reactions to drugs.
Roujeau, J., Haddad, C., Paulmann, M., & Mockenhaupt, M. (2014) · Immunology and allergy clinics of North America · doi:10.1016/j.iac.2014.04.012 · Cited by 27
Borghi, S. M., Fattori, V., Ruiz-Miyazawa, K. W., Bertozzi, M. M., Lourenco-Gonzalez, Y., Tatakihara, R. I., Bussmann, A. J. C., Mazzuco, T. L., Casagrande, R., & Verri, W. A., Jr. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.07.038 · Cited by 30
Lysosomal protease cathepsin D; a new driver of apoptosis during acute kidney injury
Cocchiaro, P., Fox, C. P., Tregidgo, N., Howarth, R., Wood, K. M., Situmorang, G. R., Pavone, L. M., Sheerin, N., & Moles, A. (2016) · Scientific Reports · doi:10.1038/srep27112 · Cited by 29
Urinary eosinophils in AIN: farewell to an old biomarker?
Perazella, M., & Bomback, A. (2013) · American Society of Nephrology. Clinical Journal · doi:10.2215/cjn.08620813 · Cited by 26
Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis
Xia, W., He, Y., Gan, Y., Zhang, B., Dai, G., Ru, F., Jiang, Z., Chen, Z., & Chen, X. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.682904 · Cited by 25
“Many diseases are associated with RF development, including obstructive kidney disease, chronic glomerulonephritis, chronic pyelonephritis, systemic lupus erythematosus nephropathy, and hereditary nephropathies, such as Alport syndrome, diabetic nephropathy (DN), hypertensive nephropathy, and drug-induced nephropathy…”
BackgroundWente-Schulz, S., Aksenova, M., Awan, A., Ambarsari, C., Becherucci, F., Emma, F., Fila, M., Francisco, T., Gokce, I., Gülhan, B., et al. (2021) · BMJ Open · doi:10.1136/bmjopen-2020-047059 · Cited by 25
Sustained Tubulointerstitial Inflammation in Kidney with Severe Leptospirosis
Tanaka, K., Tanabe, K., Nishii, N., Takiue, K., Sugiyama, H., & Wada, J. (2017) · Internal medicine · doi:10.2169/internalmedicine.56.8084 · Cited by 25
“Furthermore, a recent report suggested that a small percentage of patients who survived acute leptospirosis had a persistently abnormal renal function consistent with early-stage CKD over a three-year follow-up period.”
BackgroundInfluentialPantoprazole-induced acute interstitial nephritis
Klassen, S., Krepinsky, J., & Prebtani, A. (2013) · Canadian Medical Association Journal · doi:10.1503/cmaj.120954 · Cited by 25
“5–1 mg/kg daily) over 4–6 weeks has been suggested.(2,7) The most recent retrospective multicentre study examining steroid use in druginduced acute interstitial nephritis confirmed by biopsy found that patients not given steroid therapy (n = 9) had significantly higher creatinine levels at the end of the follow-up per…”
BackgroundInfluentialAcute and Chronic Tubulointerstitial Nephritis of Rheumatic Causes
Oliva-Dámaso, N., Oliva-Dámaso, E., & Payán, J. (2018) · Rheumatic Disease Clinics of North America · doi:10.1016/j.rdc.2018.06.009 · Cited by 26
Gupta, S., Mistry, K., Alikhan, F. M., Mejia, S. M., Sadarangani, S. S., Cao, A., Wells, S. L., Коваль, Е. А., Liang, C. G., Ortega, J. L., et al. (2025) · Kidney International · doi:10.1016/j.kint.2025.05.029 · Cited by 24
El-Maadawy, W. H., Hassan, M., Abdou, R., Eldine, R. S., Aboushousha, T., El-Tanbouly, N., & El-sayed, A. (2022) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2022.103817 · Cited by 23
Rifampicin-associated acute renal failure and hemolysis: a rather uncommon but severe complication
Manika, K., Tasiopoulou, K., Vlogiaris, L., Lada, M., Papaemmanouil, S., Zarogoulidis, K., & Kioumis, I. (2013) · Renal Failure · doi:10.3109/0886022x.2013.815567 · Cited by 23
“The administration of steroid treatment in patients with druginduced AIN is a matter of debate.(11,16,17) Previous reports did not support the routine administration of steroids in the management of AIN since they were not found to decrease the risk of chronic renal failure.”
BackgroundResultJoaquim, A. I., Mendes, G. E., Ribeiro, P. F. F., Baptista, M., & Burdmann, E. (2010) · Nephrology, Dialysis and Transplantation · doi:10.1093/ndt/gfq152 · Cited by 23
Increased prevalence of acute interstitial nephritis: more disease or simply more detection?
Bomback, A., & Markowitz, G. (2013) · Nephrology, Dialysis and Transplantation · doi:10.1093/ndt/gfs318 · Cited by 23
Effect of steroids and relevant cytokine analysis in acute tubulointerstitial nephritis
Yun, D., Jang, M.-J., An, J. N., Lee, J. P., Kim, D. K., Chin, H. J., Kim, Y. S., Lee, D.-S., & Han, S. S. (2019) · BMC Nephrology · doi:10.1186/s12882-019-1277-2 · Cited by 22
Tureyen, A., Demirel, H., Demirkapi, E. N., Eryavuz, A. M., & Ince, S. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17968 · Cited by 22
“8 Therefore, new therapeutic agents are needed to mitigate both NSAID-induced gastrointestinal damage and renal damage caused by glucocorticoid therapy.”
BackgroundDiagnóstico diferencial de la insuficiencia renal aguda
Galeano, C., Rodríguez, N., & Liaño, F. (2010) · doi:10.3265/nefroplus.pre2010.jul.10548 · Cited by 22
Self-citation
Metadata
- Authors
- González, E., Gutiérrez, E., Galeano, C., Chevia, C., de Sequera, P., Bernis, C., Parra, E. G., Delgado, R., Sanz, M., Ortiz, M., Goicoechea, M., Quereda, C., Olea, T., Bouarich, H., Hernández, Y., Segovia, B., & Praga, M.
- Affiliations
- Hospital Universitario 12 De Octubre (ES)
- Hospital Universitario Ramón y Cajal (ES)
- Hospital Universitario La Paz (ES)
- Hospital Universitario de La Princesa (ES)
- Hospital Ruber Internacional (ES)
- Hospital Universitario de Getafe (ES)
- Hospital Universitario Severo Ochoa (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Corresponding author
- Praga, M.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 73
- Issue
- 8
- Pages
- 940-946
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2128802116
- Cited by
- 466
- References
- 0
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 32 · 2023: 23 · 2022: 32 · 2021: 34 · 2020: 30 · 2019: 38 · 2018: 27 · 2017: 28 · 2016: 23 · 2015: 28 · 2014: 23 · 2013: 18 · 2012: 23
- FWCI
- 16.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Nephrotoxicity and Medicinal Plants
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- drug-induced acute interstitial nephritis, corticosteroid therapy, renal function recovery, interstitial fibrosis, nonsteroidal anti-inflammatory drugs, serum creatinine, dialysis dependence, renal biopsy
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Biopsy, Creatinine, Drug Administration Schedule, Female, Humans, Kidney, Male, Middle Aged, Nephritis, Interstitial, Retrospective Studies, Steroids
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