Abstract: FR-PO339
Hypertension and Proteinuria After Antiangiogenic Drugs: Role of the Renin-Angiotensin-Aldosterone System
Session Information
- Hypertension and CVD: Mechanisms - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Shingarev, Roman A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Latcha, Sheron, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Jaffer Sathick, Insara, Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Prieto, Minolfa C., Tulane University, New Orleans, Louisiana, United States
- Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background
Antiangiogenic drugs (AAD) are an effective treatment for many cancers. Hypertension (HTN) and proteinuria (PTN) are frequent side effects of AAD and are common reasons for therapy discontinuation. These effects are thought to be due at least in part to blockade of VEGF in the vasculature and podocytes, but the mechanisms involved are not well understood. Renin-angiotensin-aldosterone system (RAAS) blockade is commonly used for treatment despite the lack of evidence of RAAS activation in this setting. Here, we examine the link bewteen the development of HTN and PTN and intrarenal (IR) RAAS activation.
Methods
Urine albumin/creatinine ratio (ACR) and blood pressure (BP) were measured in 28 prospectively enrolled patients before AAD and on subsequent follow-up visit. Urine angiotensinogen (uAGT) was used as marker of IR RAAS activation and quantified by ELISA, corrected for urine creatinine and assessed for association with HTN and PTN. HTN was defined as BP ≥ 140/90. PTN was defined as > "trace" on urinalysis.
Results
HTN was present in 8 patients at the study start with 50% developing worsening HTN. New HTN developed in 12 patients (60%) and PTN in 10 patients (36%). Mean fold uAGT increase was significantly correlated with fold increase in urine ACR (r=0.39, p=0.04). A 6-fold increase in uAGT was associated with development of HTN and/or PTN, RR= 1.5 (95% confidence interval, 1.1-2.02). Mean fold uAGT increase was greater in patients with incident HTN vs non-HTN and with incident PTN vs non-PTN; however, this trend did not reach statistical significance. Mean baseline uAGT was not predictive of subsequent HTN or PTN.
Conclusion
This study suggests that IR RAAS activation after AAD drugs is responsible at least in part for the development of HTN and PTN in these patients. Larger studies will be needed to better determine whether IR RAAS activation mediates the development of isolated HTN without PTN after AAD.
Association of Hypertension and Proteinuria with Urine Angiotensinogen
| Outcome | Neither HTN nor PTN | HTN and/or PTN | Non-HTN | HTN | Non-PTN | PTN |
| n (%) | 7 (25) | 21 (75) | 12 (43) | 16 (57) | 18 (64) | 10 (36) |
| Mean baseline uAGT/Cr, SD | 14.07 ± 3.75 ng/mg | 7.23 ± 2.69 ng/mg | 10.27 ± 8.87 ng/mg | 7.94 ± 10.98 ng/mg | 8.76 ± 8.90 ng/mg | 9.26 ± 12.30 ng/mg |
| p value | 0.14 | 0.54 | 0.91 | |||
| Fold increase uAGT/Cr, SD | 1.64 ± 1.14 | 5.26 ± 6.01 | 3.40 ± 4.86 | 5.06 ± 5.89 | 3.27 ± 4.25 | 6.30 ± 6.93 |
| p value | 0.02 | 0.42 | 0.23 | |||
Cr, creatinine; HTN, hypertension; PTN, proteinuria; uAGT, urine angiotensinogen