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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Hypertension and VEGF (Vascular Endothelial Growth Factor) Receptor Tyrosine Kinase Inhibition: Effects on Renal
Brian C Boursiquot1, Emily C Zabor1, Ilya G Glezerman1
1From the Stanford University School of Medicine, CA (B.C.B.); Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY (E.C.Z.); Department of Medicine, Division of Nephrology & Hypertension, Weill-Cornell Medical College, New York, NY (I.G.G., E.A.J.); and Department of Medicine, Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY (I.G.G., E.A.J.).
Abstract:
VEGF (vascular endothelial growth factor) receptor tyrosine kinase inhibitors have become first-line therapy for metastatic renal cell carcinoma. Their use commonly leads to hypertension, but their effects on long-term renal function are not known. In addition, it has been suggested that the development of hypertension is linked to treatment efficacy. The objective of this study was to determine the effects of these drugs on long-term renal function, especially in those with renal dysfunction at baseline, and to examine the role of hypertension on these effects. Serum creatinine measurements were used to calculate the estimated glomerular filtration rate for 130 renal cell carcinoma patients who were treated with this class of tyrosine kinase inhibitors. New or worsening hypertension was defined by documented start or addition of antihypertensive medications. Overall, the use of tyrosine kinase inhibitors in patients with estimated glomerular filtration <60 or ≥60 mL/min per 1.73 m2 was not associated with a decline in long-term renal function. During follow-up, 41 patients developed new or worsening hypertension within 30 days from first drug administration, and this was not linked to further reductions in glomerular filtration. These patients seemed to survive longer than those who did not develop hypertension within 30 days, although this was not statistically significant (P=0.07). Our findings suggest that the use of VEGF tyrosine kinase inhibitors does not adversely affect long-term renal function even in the setting of new-onset hypertension or reduced renal function at baseline.
Insights
Vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors do not harm long-term kidney function in metastatic renal cell carcinoma patients, even with existing or developing hypertension.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- VEGF receptor tyrosine kinase inhibitors are first-line for metastatic renal cell carcinoma.
- Hypertension is a common side effect, but long-term renal function effects are unknown.
- Hypertension development may correlate with treatment efficacy.
Purpose of the Study:
- To assess long-term renal function in patients treated with VEGF inhibitors.
- To investigate effects in patients with baseline renal dysfunction.
- To examine the role of hypertension in these renal effects.
Main Methods:
- Retrospective analysis of 130 renal cell carcinoma patients treated with VEGF inhibitors.
- Serum creatinine used to calculate estimated glomerular filtration rate (eGFR).
- Hypertension defined by new or intensified antihypertensive medication use.
Main Results:
- VEGF inhibitor use was not associated with declining long-term renal function, regardless of baseline eGFR.
- New or worsening hypertension within 30 days did not correlate with further eGFR reduction.
- Patients developing hypertension showed a trend towards longer survival (P=0.07).
Conclusions:
- VEGF tyrosine kinase inhibitors do not negatively impact long-term renal function.
- This holds true even with new-onset hypertension or pre-existing renal dysfunction.
- Hypertension development may not be detrimental to renal outcomes in this patient group.
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