Urinary Podocyte Excretion and Proteinuria in Patients Treated with Antivascular Endothelial Growth Factor Therapy for Solid Tumor Malignancies

Abstract

Background: Urinary podocyte excretion (podocyturia) may function as a more specific marker of ongoing glomerular damage. This study sought to analyze the relationship between proteinuria and podocyturia in cancer patients treated with antivascular endothelial growth factor (anti-VEGF) agents. Methods: Thirty-seven patients treated with anti-VEGF medications were analyzed in a single-institution, cross-sectional study. Podocyte cultures were performed on random urine collections (50-100 ml), and podocytes were identified by positive podocin staining. The corresponding urine samples were analyzed for protein and creatinine (Cr) measurements. Results: Proteinuria ≥0.5 g/g Cr was found in 30% of the patients (median, 0.12; interquartile range, 0.04-0.86), and 62% had podocyturia. There was a significant difference in the amount of podocyturia between patients with proteinuria ≥0.5 g/g Cr and those with a value <0.5 g/g Cr (median podocyturia, 1.08 cells/mg Cr, range, 0-14.55 vs. 0.03 cells/mg Cr, range, 0-1.64, respectively; p < 0.001). A statistically significant correlation was observed between the cumulative dose of bevacizumab and both proteinuria (r = 0.48, p = 0.004) and podocyturia (r = 0.34, p = 0.045) as well as between proteinuria and podocyturia (r = 0.63, p < 0.001), suggesting that these are mechanistically related. Discussion: Ongoing podocyte loss may be mechanistically related to the onset and severity of proteinuria in patients treated with anti-VEGF agents.

Assessment of Urinary Podocin Level as an Early Indicator in Diabetic Nephropathy

“…Regarding our study, we found that Sensitivity of urinary podocin as an early marker to predict diabetic nephropathy in normoalbuminuria group (versus control) is 94.7% while specificity is 92%, with a positive predictive value of 94.7 and negative predictive value of 92% at cut off value >6.0 ng/ml (p<0.001) which comes in agreement with El Shaarawy et al [17] as urinary podocin is highly sensitive and specific marker to predict diabetic nephropathy. Our study also comes in agreement with Hayman et al [18] as urinary podocin levels may function as a more specific marker of ongoing glomerular damage as it was significantly increased in normoalbuminuric group compared to control group. Finally, our study show multiple strength points as it was started by a full bibliographic citation, full biographical information about the author was given, the general problem area and intentions toward it was discussed building on past researches and the objective of the research was clearly stated.…”

Preeclampsia: Novel Mechanisms and Potential Therapeutic Approaches

“…However, in the last decade, there is growing evidence that imbalance between the proangiogenic and anti angiogenic factors plays a key role in podocyte injury ( Genbacev et al, 1997 ; Fulton et al, 1999 ; Robertson et al, 2003 ; Venkatesha et al, 2006 ; Baelde et al, 2007 ; Sison et al, 2010 ; Bertuccio et al, 2011 ; Veron et al, 2012 ). This concept is supported by the observation that bevacizumab, an anti-VEGF antibody used to treat patients with various types of cancer or diabetic proliferative retinopathy causes hypertension and proteinuria mimicking the effect of sFlt-1 ( Eremina et al, 2008 ; Muller-Deile and Schiffer, 2011 ; Hayman et al, 2014 ). Interestingly, the renal findings in patients who were treated with bevacizumab including endotheliosis, thrombotic microangiopathy, and podocytes shedding, are similar to those found in preeclamptic state ( Eremina et al, 2008 ; Muller-Deile and Schiffer, 2011 ; Hayman et al, 2014 ).…”

“…The importance of VEGF for the maintenance of normal endothelial function and development of placental vasculature is derived from the consequences of impairment of VEGF activity due to certain drugs or elevation of sFlt-1 ( Ahmed, 1997 ; Kabbinavar et al, 2003 ; Sison et al, 2010 ; Bertuccio et al, 2011 ; Veron et al, 2012 ). In this context, anti- VEGF therapy with Avastin display preeclampsia-like symptoms, namely hypertension and proteinuria ( Kabbinavar et al, 2003 ; Eremina et al, 2008 ; Muller-Deile and Schiffer, 2011 ; Hayman et al, 2014 ). sFlt-1 is a splice variant of VEGF receptor fms-like tyrosine kinase 1 ( Maynard et al, 2003 ).…”

Deterioration of Glycemic Control Contributes to the Prevalence of Proteinuria among Bevacizumab-Treated Cancer Patients with Type 2 Diabetes Mellitus

“…Proteinuria is closely associated with the disintegration of the glomerular filtration barrier. 16) In this study, the mean eGFR, an index of renal glomerular function, in patients with and without proteinuria were found not to be significantly different (Table 4), indicating that proteinuria in BEV-treated patients with type 2 DM did not necessarily lead to a decrease in eGFR. Hayman et al reported that the onset of proteinuria caused by BEV treatment is related to podocyte loss.…”