Cumulative dose of bevacizumab associates with albuminuria rather than podocyturia in cancer patients

Abstract

Angiogenesis inhibition with bevacizumab, a monoclonal antibody against vascular endothelial growth factor A (VEGF-A), is an anticancer treatment associated with hypertension and renal glomerular toxicity referred to as a preeclampsia-like syndrome. In preeclampsia, podocyturia predates proteinuria and clinical features of preeclampsia, and is regarded as a biomarker of ongoing glomerular injury. Using a quantitative polymerase chain reaction of the podocyte-specific molecules nephrin, podocin, and VEGF-A in the urine, we examined whether podocyturia is present in bevacizumab-treated cancer patients, and whether it relates to proteinuria and the cumulative dose of bevacizumab. Urine samples were cross-sectionally collected from 43 bevacizumab-treated patients, 21 chemotherapy-treated patients, and 7 healthy controls. Urinary protein-to-creatinine ratio (mean and range) was 32.0 mg/mmol (5.2–284.4) in the bevacizumab group, compared with 11.4 mg/mmol (1.1–21.0) in the chemotherapy group and 7.4 mg/mmol (3.9–16.5) (P < .05) in healthy controls, whereas urinary albumin-to-creatinine ratio values in the three groups were, respectively, 18.9 mg/mmol (0.1–227.7), 1.5 mg/mmol (0.2–3.5), and 0.2 mg/mmol (0.1–0.4) (P < .05). The cumulative dose of bevacizumab ranged from 550 to 93,628 mg. Urinary podocin mRNA expression was undetectable in 59% of participants, urinary nephrin mRNA expression per mmol creatinine ranged from 0.0 to 5.3 and urinary VEGF-A mRNA expression from 0.0 to 2.7. Urinary nephrin mRNA expression did not correlate to the albumin-to-creatinine ratio or the cumulative dose of bevacizumab, whereas the latter correlated with the albumin-to-creatinine ratio (r = 0.77; P < .001). Our results demonstrate that the cumulative dose of bevacizumab is closely correlated with albuminuria but not with podocyturia as measured with the quantitative polymerase chain reaction technique, challenging the feasibility of this measurement to monitor ongoing glomerular injury in patients chronically treated with bevacizumab.