NDT Advance Access originally published online on April 30, 2007
Nephrology Dialysis Transplantation 2007 22(8):2411; doi:10.1093/ndt/gfm199
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Interstitial nephritis in a patient taking sorafenib
Correspondence and offprint requests to: Email: hassan.izzedine{at}psl.aphp.frSir,
Sorafenib (Nexavar, Bayer-Onyx) is an oral multi-targeted kinase recently approved by the FDA for the treatment of advanced renal cell cancer (RCC). This treatment has been associated with an increased number of adverse events, as compared with placebo [1], but no renal failure has been noted. We report on a patient who developed a renal insufficiency related to acute interstitial nephritis (AIN) while taking sorafenib.
A 66-year-old male presented with a 2-day history of nausea and facial erythema. This episode began approximately 10 days after taking 200 mg of sorafenib, given orally twice daily for metastatic RCC. This treatment was prescribed after the failure of an 8-month sunitinib treatment (stopped one month previously). His past medical history included nephrectomy, hypertension and chronic renal failure related to focal segmental glomerulosclerosis. Physical examination revealed a painful erythematous rash on the face, upper trunk and proximal upper limbs as well as angio-oedema of the tongue. Body temperature was 38.5°C. Blood pressure rose from 140/90 to 170/100 mm Hg before and after sorafenib initiation. Urinalysis revealed 2+ protein and 3+ blood; the urine sediment contained dysmorphic red cells and white-cell casts. Laboratory data on admission included the following: leucocytes 11 450/mm3 with eosinophils 916/mm3 (normal < 700), urine proteins (from 0.7 to 240 g of protein in a 24-h collection), 70 leucocytes per high-power field, 20 erythrocytes per high-power field and negative urinary cultures. Serum creatinine concentration rose from 3.6 to 4.5 mg/dl (400 µmol/l). Renal biopsy revealed a focal AIN (Figure 1) associated with polynuclear infiltration in some glomerular capillary wall in the setting of chronic glomerulopathy (17 glomeruli, 6 sclerotic and 3 with focal segmental sclerosis, the other 8 glomeruli remained normal). The patient was treated with oral prednisone at a dose of 0.5 mg/kg for 4 weeks, followed by rapid tapering. Serum creatinine level fell to 3.4 mg/dl over the next 2 weeks without the need for dialysis and the urinary leucocytes disappeared despite maintenance of sorafenib therapy at 200 mg daily.
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Sorafenib prolongs progression-free survival in patients with metastatic RCC in second-line therapy after cytokine failure. In the phase 3 study against placebo, skin toxicity and diarrhoea were the main limiting toxicities reported. Erythema of the face, scalp and upper thorax were reported (40% and 16% with sorafenib and placebo, respectively) [1].
In large retrospective series, AIN represented 2–3% of all native renal biopsies [2], was drug-related in 92% of cases [3], and is associated with a generalized cutaneous rash in 25–30% [2,4].
In this report, we cannot totally eliminate the role of sunitinib in the occurence of this nephrotoxicity, although that possibility seems unlikely in view of the temporal relation with the use of sorafenib.
This case of AIN should serve as a warning that the use of sorafenib may be associated with renal injury. We suggest careful monitoring for urinalysis and serum creatinine of patients receiving sorafenib, especially those with dermatologic events.
Conflict of interest statement. None declared.
1Department of Nephrology
2Department of Pathology
3Department of Medical Oncology
La Pitié-Salpêtrière Hospital
47-80 Boulevard de l’Hôpital
Assistance Publique-Hopitaux de Paris
Pierre et Marie Curie University
75013 Paris, France
References
- Escudier B, Eisen T, Stadler WM, et al. Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma. N Engl J Med (2007) 356:125–134.
[Abstract/Free Full Text] - Rossert J. Drug-induced acute interstitial nephritis. Kidney Int (2001) 60:804–817.[CrossRef][Web of Science][Medline]
- Clarkson MR, Giblin L, O’Connell FP, et al. Acute interstitial nephritis: clinical features and response to corticosteroid therapy. Nephrol Dial Transplant (2004) 19:2778–2783.
[Abstract/Free Full Text] - Greising J, Trachtman H, Gauthier B, Valderrama E. Acute interstitial nephritis in adolescents and young adults. Child Nephrol Urol (1990) 10:189–195.[Web of Science][Medline]
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