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Tubulointerstitial nephritis: diagnosis, treatment, and monitoring

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Abstract

Tubulointerstitial nephritis (TIN) is a frequent cause of acute kidney injury (AKI) that can lead to chronic kidney disease (CKD). TIN is associated with an immune-mediated infiltration of the kidney interstitium by inflammatory cells, which may progress to fibrosis. Patients often present with nonspecific symptoms, which can lead to delayed diagnosis and treatment of the disease. Etiology can be drug-induced, infectious, idiopathic, genetic, or related to a systemic inflammatory condition such as tubulointerstitial nephritis and uveitis (TINU) syndrome, inflammatory bowel disease, or immunoglobulin G4 (IgG4)-associated immune complex multiorgan autoimmune disease (MAD). It is imperative to have a high clinical suspicion for TIN in order to remove potential offending agents and treat any associated systemic diseases. Treatment is ultimately dependent on underlying etiology. While there are no randomized controlled clinical trials to assess treatment choice and efficacy in TIN, corticosteroids have been a mainstay of therapy, and recent studies have suggested a possible role for mycophenolate mofetil. Urinary biomarkers such as alpha1- and beta2-microglobulin may help diagnose and monitor disease activity in TIN. Screening for TIN should be implemented in children with inflammatory bowel disease, uveitis, or IgG4-associated MAD.

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Emily Joyce & Agnieszka Swiatecka-Urban

  2. Department of Anaesthesiology and Intensive Therapy, Medical University of Gdansk and Department of Ophthalmology, 80-299, Gdańsk, Poland

    Paulina Glasner

  3. Department of Pediatric Pathology, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15224, USA

    Sarangarajan Ranganathan

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  1. Emily Joyce
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  3. Sarangarajan Ranganathan
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  4. Agnieszka Swiatecka-Urban
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Correspondence to Emily Joyce.

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Answers

1. A

2. A

3. C

4. D

5. A

Key summary points

1. Tubulointerstitial nephritis is often diagnosed late, so clinical suspicion is necessary for early identification and possible intervention (or removal of the offending agent).

2. Presenting signs and symptoms of TIN can include nonspecific systemic symptoms (fatigue, weight loss, headache, flank pain), fever, rash, eosinophilia/eosinophiluria, and evidence of elevated creatinine and Fanconi’s syndrome (glucosuria, aminoaciduria, acidosis).

3. Etiology of TIN can be drug-induced, infectious, idiopathic, genetic, or related to a systemic inflammatory condition such as tubulointerstitial nephritis and uveitis (TINU) syndrome or inflammatory bowel disease (IBD)

4. Treatment is based on etiology; aside from removal of offending agents, the mainstay of therapy is corticosteroids and, less often, mycophenolate mofetil.

5. Urinary biomarkers such as alpha1-microglobulin (A1M) and beta2-microglobulin (B2M) may help diagnose and monitor disease activity in TIN.

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Joyce, E., Glasner, P., Ranganathan, S. et al. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol 32, 577–587 (2017). https://doi.org/10.1007/s00467-016-3394-5

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