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Cited by 21Renal Diseases and GlomerulopathiesAcute Kidney Injury ResearchComplement system in diseases

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Acute nephritic syndrome after anti‐VEGF therapy for renal cell carcinoma

Rolleman, E. J., Weening, J., Betjes, M. G. H.·2009·Nephrology Dialysis Transplantation
DOI 10.1093/ndt/gfp140
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Abstract

Sir, Two interesting recent publications in this journal reported biopsy-proven kidney damage after treatment with the vascular endothelial growth factor (VEGF) receptor blocker sunitinib [ 1,2 ]. We would like to report another case of acute renal failure during treatment with this drug, yet with a different histopathological picture. A 61-year-old woman was treated with sunitinib (50 mg once daily) for a renal cell carcinoma that was metastasized to lungs and abdominal lymph nodes. At baseline, the serum creatinine was 84 μmol/L with normal urine sediment and no proteinuria. Twenty-five days later, she was admitted because of nausea and vomiting and a risen serum creatinine level (362 μmol/L). Discontinuation of sunitinib and fluid repletion resulted in decline of the creatinine level to 150 μmol/L, but in the following days, the renal function rapidly deteriorated and haemodialysis was started (Figure 1 ). The urine analysis showed nephrotic range proteinuria, leucocyturia and erythrocyturia. Laboratory tests did not reveal thrombotic microangiopathy (TMA) and were negative for auto-antibodies, and serum complement levels were in the normal range. The kidney biopsy contained 10 glomeruli, all with massive influx of neutrophils and swelling and proliferation of endothelial cells. No signs of TMA were observed. Immunofluorescence microscopy was strongly positive for complement C3 in a starry sky distribution, without concomitant immunoglobulin depositions. Electron microscopy showed electron dense deposits along the endothelial side of the glomerular basement membrane. Course of serum creatinine concentration. The grey bar indicates treatment with sunitinib; the white bar indicates saline infusion therapy. The arrow indicates the day of biopsy and treatment with methylprednisolone. Haemodialysis was started on Day 40. Our patient presented with an acute nephritic syndrome with renal failure after anti-VEGF therapy for a metastasized renal cell carcinoma. The kidney biopsy showed an acute exudative immune-complex glomerulonephritis as can be seen after infections, during cryoglobulinaemia or in early MPGN. Toxicity of the newer anti-VEGF drug sunitinib seems the most likely explanation as no other cause could be identified. Another possibility would be a renal tumour-related glomerulonephropathy, a rare entity associated with a variety of unrelated histopathological diagnosis [ 3 ]. Formally, we cannot exclude this possibility but the acute onset of glomerulonephritis and time relationship with sunitinib treatment argue against such a diagnosis. With the growing use of anti-VEGF therapeutics, unexpected renal side effects, specifically TMA [ 4,5 ], become apparent. Our findings describe a histopathological picture that has not been reported before with the use of anti-VEGF blockers, specifically with the newest agent sunitinib. It adds on the recent findings of Bollee et al . [ 2 ] and Winn et al . [ 1 ] who reported cases of TMA and acute interstitial nephritis, respectively. Based on the information available now, different histopathological patterns can be elicited by sunitinib. Therefore, it seems advisable that during anti-VEGF therapy, kidney function and the urine sediment are monitored carefully and a kidney biopsy is taken when proteinuria or renal insufficiency develops. Conflict of interest statement . None declared.

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Metadata

Authors
Rolleman, E. J., Weening, J., & Betjes, M. G. H.
Affiliations
Erasmus MC (NL)
ORCID
Betjes, M. G. H.
Venue
Nephrology Dialysis Transplantation
Publisher
Oxford University Press (OUP)
Published
2009-03-30
Volume
24
Issue
6
Pages
2002-2003
ISSN
  • 0931-0509 (ISSN-L)
  • 1460-2385
DOI
10.1093/ndt/gfp140
OpenAlex
W2100157410
Cited by
21
References
5
Citations by year
2023: 1 · 2022: 1 · 2021: 3 · 2018: 3 · 2016: 1 · 2014: 1 · 2013: 3 · 2012: 2
FWCI
1.84
Type
journal article
Language
en
Open access
closed
Locations
  • Nephrology Dialysis Transplantation (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Topics
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
  • Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
Keywords
acute nephritic syndrome, sunitinib, anti-VEGF therapy, renal cell carcinoma, drug-induced nephrotoxicity, immune complex glomerulonephritis, complement C3, electron-dense deposits, acute kidney injury, nephrotic-range proteinuria, hemodialysis, methylprednisolone
MeSH terms
Sunitinib, Antineoplastic Agents, Carcinoma, Renal Cell, Female, Humans, Indoles, Kidney Neoplasms, Middle Aged, Nephrotic Syndrome, Pyrroles, Vascular Endothelial Growth Factor A, Acute Kidney Injury

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