CASE PRESENTATION
A 63-year-old man with metastatic renal cell carcinoma, diagnosed five
years ago and treated with 50 mg of Sunitinib daily for about four
months, presented to the emergency department of Imam Reza Hospital in
Tabriz with altered mental status and petechia. The patient had been
experiencing progressive symptoms of weakness and lethargy since last
week. Gradually, petechiae and purpura appeared on the skin and the oral
cavity. Physical examinations and imaging did not show any CNS lesion.
Initial laboratory data showed a decrease in platelets(PLT: 14,000/mm3)
and hemoglobin(Hb:10.5g/dL), white blood cell:10000 per
microliter, elevated serum level of lactate dehydrogenase, and
total bilirubin. High serum creatinine and granular cast in urine
sedimentation suggested acute kidney injury. Initial and secondary urine
analysis did not show evidence of proteinuria. Schistocytes were found
in the peripheral blood smear.
Upon diagnosis of TMA, the patient underwent four plasmapheresis
sessions for four consecutive days. Improvement in consciousness and
renal function was observed after four days. The patient was discharged
in good general condition after two weeks of ICU admission.
DISCUSSION
Renal cell carcinoma (RCC) is the most common kidney cancer, and it
represents about 3% of the whole adult malignancies (12, 13). In
addition, about Thirty percent of RCC patients present with metastatic
disease (14). Anti-VEGF antibody therapy is increasingly used in renal
cell carcinoma and metastatic colorectal cancer therapy (15-17). The two
main treatments for metastatic RCC are immunotherapy and vascular
endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKIs) (18).
The oral multi-targeted kinase inhibitors (MTKI) such as Sunitinib,
Sorafenib, and Brivanib block the VEGF signalling pathway, while
Bevacizumab blocks the action of circulating VEGF. Sunitinib is a
multi-targeted tyrosine kinase that inhibits VEGF receptor 1 and 2
platelet-derived growth factor receptors (PDGFR) (19).
Although The most frequent side effects reported in these drugs are
diarrhea, nausea, hypertension, fatigue, and skin lesions, After therapy
with this agent, multiple studies have reported the development of
proteinuria or acute renal failure. Recent studies described several
patients treated with Sunitinib who developed a preeclampsia-like
syndrome characterised by proteinuria, edema, and severe hypertension(7,
20, 21).
Studies showed that Genetic deletion or drugs that disrupted VEGF
signalling lead to the loss of normal glomerular capillary endothelial
cells, microvascular injury, and TMA (22,23).In the kidney, podocytes
consistently express VEGF, and its receptors are expressed by glomerular
endothelial cells(23). Anti-VEGF therapy by blocking VEGF receptors
caused Endothelial injury is implicated in the pathogenesis of
hypertension and arterial thrombosis and TMA (24). Daniel Roncone et al.
(25) study shows the damage of glomerular capillary endothelial suggests
thrombotic microangiopathy. Hohenstein et al. (26) demonstrate that
following glomerular endothelium injury, platelets influx and after
activation, they form microthrombi. This finding explains that VEFG has
a crucial role in glomerular capillary integrity and the prevention of
endothelial damage.