Pazopanib-Induced Hypertension in Patients With Renal Cell Carcinoma Is Associated With Low Urine Excretion of NO Metabolites
| Autor: | Lars Bastholt, Kirsten Madsen, Niels Viggo Jensen, Anne Robdrup Tinning, Boye L. Jensen, Camilla Bengtsen |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Time Factors Denmark Administration Oral 030204 cardiovascular system & hematology Kidney Cohort Studies Hospitals University chemistry.chemical_compound 0302 clinical medicine Renal cell carcinoma Prospective Studies Sulfonamides Proteinuria Endothelin-1 Middle Aged Kidney Neoplasms Kidney Neoplasms/drug therapy medicine.anatomical_structure Vascular endothelial growth factor A Hypertension Neoplasm Invasiveness/pathology Female medicine.symptom medicine.drug Glomerular Filtration Rate medicine.medical_specialty Indazoles Renal function Nitric Oxide Risk Assessment Drug Administration Schedule Pazopanib 03 medical and health sciences Internal medicine Journal Article Internal Medicine medicine Renal medulla Humans Neoplasm Invasiveness Carcinoma Renal Cell Aged Neoplasm Staging Creatinine Dose-Response Relationship Drug Pyrimidines/adverse effects business.industry Hypertension/chemically induced Nitric oxide Sulfonamides/adverse effects medicine.disease 030104 developmental biology Endocrinology Blood pressure Pyrimidines chemistry Nitric Oxide/metabolism Carcinoma Renal Cell/drug therapy business Follow-Up Studies |
| Zdroj: | Tinning, A R, Bengtsen, C, Jensen, N V, Bastholt, L, Jensen, B L & Madsen, K 2018, ' Pazopanib-Induced Hypertension in Patients With Renal Cell Carcinoma Is Associated With Low Urine Excretion of NO Metabolites ', Hypertension, vol. 71, no. 3, pp. 473-480 . https://doi.org/10.1161/HYPERTENSIONAHA.117.10225 |
| ISSN: | 1524-4563 |
| DOI: | 10.1161/HYPERTENSIONAHA.117.10225 |
| Popis: | Drugs targeting VEGF (vascular endothelial growth factor) are often associated with rapid development of hypertension by a yet not fully understood mechanism. VEGF is expressed in renal epithelial cells and stimulates NO production. In the renal medulla, inhibition of NO formation by local L-NAME or by impaired endothelin-1 leads to hypertension. The present study was designed to test the hypothesis that VEGF receptor inhibitor treatment leads to hypertension through decreased renal medullary formation of NO and endothelin-1. With a single-center prospective observational design, patients with metastatic renal cell carcinoma (n=27) treated with the receptor tyrosine kinase inhibitor pazopanib were included in the study. Home blood pressure was measured, and plasma and urine samples were collected at baseline and after 4 and 8 weeks of treatment. After 4 weeks, systolic and diastolic blood pressures increased, whereas heart rate decreased significantly; urine protein/creatinine ratio increased significantly, whereas estimated glomerular filtration rate was unchanged. Urine nitrite/nitrate (NOx) and cGMP/creatinine ratios decreased significantly, whereas urine endothelin-1/creatinine ratio and FE Na+ were unchanged. In plasma, NOx, cGMP, and brain natriuretic peptide decreased significantly, whereas endothelin-1 was significantly elevated. Blood leukocyte count decreased significantly with unchanged CRP (C-reactive protein). In summary, pazopanib treatment of patients with advanced renal cell carcinoma is associated with hypertension, proteinuria, myelosuppression, and decreased urine and plasma NO metabolites. Results are compatible with a significant role of reduced renal medullary NO bioavailability in VEGF inhibitor–induced hypertension. |
| Databáze: | OpenAIRE |
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