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Clin Exp Nephrol (2009) 13:397401
DOI 10.1007/s10157-009-0167-5
CASE REPORT
Nephrotic-range proteinuria in a patient with a renal allograft treated with sorafenib for metastatic renal-cell carcinoma
Iris J. A. M. Jonkers Marjolijn van Buren
Received: 26 October 2008 / Accepted: 16 February 2009 / Published online: 21 April 2009 Japanese Society of Nephrology 2009
Abstract A 51-year-old man with immunoglobulin A (IgA) nephropathy developed metastatic renal-cell carcinoma of his native right kidney, 3.5 years post kidney transplant. At that time renal function was stable with the presence of only mild proteinuria. Shortly after chemo-therapy with sorafenib [anti-vascular endothelial growth factor (VEGF)] was initiated, progressive renal impairment, hypertension, and nephrotic-range proteinuria developed. Allograft biopsy showed extensive IgA nephropathy. After withdrawal of the anti-VEGF therapy, however, renal function and blood pressure improved, and proteinuria diminished. Based on the clinical course and histopathological ndings we hypothesize that sorafenib may induce nephrotic-range proteinuria and renal impairment, possibly through anti-VEGF-mediated effects on the progression of IgA nephropathy.
Keywords IgA nephropathy Proteinuria Sorafenib
VEGF
Introduction
Vascular endothelial growth factor (VEGF) promotes angiogenesis, which is essential for cancer development, survival and metastasis. Anti-VEGF therapy has become an effective chemotherapeutic strategy for the treatment of
metastatic renal-cell carcinoma, though with adverse effects such as thrombosis and hypertension [1, 2]. In addition, a recent trial demonstrated the presence of proteinuria in 53% of the patients with metastatic renal cancer treated with bevacizumab, a human monoclonal antibody against VEGF, whereas nephrotic-range proteinuria occurred in up to 6.5% of treated patients [3]. Recently, Eremina et al. [4] demonstrated thrombotic microangiopathy as the responsible underlying pathophysiological mechanism of anti-VEGF-induced nephrotic-range proteinuria. Sorafenib, another VEGF inhibitor, acts differently, being a small-molecule tyrosine kinase inhibitor with activity against VEGF receptor-2 and receptor-3, b-Raf, c-Raf, c-Kit, and Flt-3. Although it is known to cause hypertension, protein-uria has never been linked to sorafenib [2]. Here, we report the development of at least partly reversible progressive renal impairment, hypertension and nephrotic-range proteinuria during therapy with sorafenib.
Case report
In 1990, a 38-year-old Caucasian man presented with malignant hypertension, associated with renal insufciency, without a classifying diagnosis due to insufciently obtained kidney biopsy material. His renal function deteriorated gradually, resulting in peritoneal dialysis dependency in 2000. In 2003 he received a post-mortal renal allograft...