Tubulointerstitial nephritis and cancer chemotherapy: update on a neglected clinical entity

Nephrol Dial Transplant. 2013 Oct;28(10):2502-9. doi: 10.1093/ndt/gft241. Epub 2013 Sep 5.


Background: Cancer patients are particularly vulnerable to drug-induced kidney injury during their chemotherapy. Whereas the direct nephrotoxic effects of these drugs are well recognized, that of tubulointerstitial nephritis (TIN) is less well known, underdiagnosed and often reported only as a functional tubular disorder. The diagnosis of acute TIN is important because of its insidious onset with tubular dysfunction, its potential reversibility if detected early and the possibility of its response to steroid treatment.

Methods: We performed a literature review (44 cases) and reviewed our institutional biopsy register (12 cases) of patients on cancer chemotherapy with documented TIN. Biopsies were considered in three groups: acute TIN, chronic TIN and acute on chronic TIN. The outcomes that were evaluated were recovery of kidney function, development of chronic kidney disease and onset of end-stage renal disease (ESRD).

Results: Ifosfamide, BCG, tyrosine kinase inhibitors and premetrexed were the most commonly implicated drugs. Ifosfamide and premetrexed were associated with worst outcomes. Recovery of kidney function was better in acute TIN (ATIN) (29%) with fewer progressing to ESRD (12.9%) than with chronic TIN (7.6% recovery, 15.3% ESRD). Steroid use appeared to favorably alter outcomes in ATIN (40% recovery) compared with conservative treatment (18.75% recovery). Peak serum creatinine, age, gender and type of malignancy did not influence outcomes.

Conclusions: As a potentially reversible lesion that can respond to withdrawal of the suspected agent, and in some cases to a short course of steroid therapy, it is important to consider ATIN in the differential diagnosis of all cases of acute kidney injury in cancer patients on chemotherapy.

Keywords: acute kidney injury; cancer chemotherapy toxicity; nephrotoxicity; tubulointerstitial nephritis.

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications*
  • Neoplasms / drug therapy
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / diagnosis
  • Prognosis