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    • Search Google Scholar
    • Export Citation
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    Arima H, et al. Mortality patterns in hypertension. J Hypertens 2011; 29 (Suppl 1):S3S7. doi: 10.1097/01.hjh.0000410246.59221.b1

  • 3.

    Gudsoorkar P, et al. Onco-hypertension: An emerging specialty. Adv Chronic Kidney Dis 2021; 28:477489.e1. doi: 10.1053/j.ackd.2021.09.011

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    Ruf R, et al. Onco-hypertension: Overview of hypertension with anti-cancer agents. JON 2021; 5:5769. doi: 10.1177/23993693211001374

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    Sufrin G, et al. Hormones in renal cancer. J Urol 1977; 117:433438. doi: 10.1016/s0022-5347(17)58490-6

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    Gandini S, et al. Anti-hypertensive drugs and skin cancer risk: A review of the literature and meta-analysis. Crit Rev Oncol Hematol 2018; 122:19. doi: 10.1016/j.critrevonc.2017.12.003

    • Search Google Scholar
    • Export Citation
  • 7.

    Abdel-Qadir H, et al. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: A systematic review and meta-analysis. Cancer Treat Rev 2017; 53:120127. doi: 10.1016/j.ctrv.2016.12.002

    • Search Google Scholar
    • Export Citation
  • 8.

    Lambrechts D, et al. Genetic markers of bevacizumab-induced hypertension. Angiogenesis 2014; 17:685694. doi: 10.1007/s10456-014-9424-7

  • 9.

    Caletti S, et al. Management of VEGF-targeted therapy-induced hypertension. Curr Hypertens Rep 2018; 20:68. doi: 10.1007/s11906-018-0871-1

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    Ketch T, et al. Four faces of baroreflex failure: Hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia. Circulation 2002; 105:25182523. doi: 10.1161/01.cir.0000017186.52382.f4

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Oncohypertension: A New Field in the Making

  • 1 Prakash Gudsoorkar, MD, FASN, FNKF, is Assistant Professor of Medicine with the Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH.
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In oncology, survivorship focuses on the health and well-being of a person with cancer from the time of diagnosis until the end of life (1). Hypertension is a growing global public health problem and a contributor to cardiovascular disease (CVD) (2). The relationship among hypertension, cancer, chronic kidney disease (CKD), and CVD is multifaceted, sharing common risk factors, such as smoking, obesity, and metabolic syndrome. For the same reasons, oncohypertension is an emerging subspecialty focusing on the close interplay between hypertension and cancer (3, 4). Hypertension in patients with cancer can be

In oncology, survivorship focuses on the health and well-being of a person with cancer from the time of diagnosis until the end of life (1). Hypertension is a growing global public health problem and a contributor to cardiovascular disease (CVD) (2). The relationship among hypertension, cancer, chronic kidney disease (CKD), and CVD is multifaceted, sharing common risk factors, such as smoking, obesity, and metabolic syndrome. For the same reasons, oncohypertension is an emerging subspecialty focusing on the close interplay between hypertension and cancer (3, 4). Hypertension in patients with cancer can be broadly categorized into worsening of preexisting hypertension, paraneoplastic syndrome (i.e., from cancer itself), and hypertension from chemotherapeutic agents and from adjuvant therapies used to treat cancer (Figure 1).

Figure 1
Figure 1

Hypertension in a patient with cancer

Citation: Kidney News 14, 6

Paraneoplastic hypertension

The prototype example of paraneoplastic hypertension in association with renal cell cancer occurs in 14% to 35% of the cases (5). Pathogenic mechanisms implicated are upregulation of the renin angiotensin aldosterone system (RAAS), ectopic production of erythropoietin, and secretion of vasoactive peptides, such as endothelin 1 and adrenomedullin.

Antihypertensive medications and cancer risk

Over the past few decades, several studies have examined the association between distinct classes of antihypertensive agents and cancer risk. However, each of these observational studies has important caveats and confounders, leaving conflicting results and uncertainty. Even if antihypertensives are associated with a small increased risk of cancer (e.g., thiazides and calcium channel blockers: skin cancer; angiotensin receptor blockers: lung cancer), they likely do not outweigh the known cardiovascular and mortality benefits (6).

Hypertension from cancer therapy

To prevent acute and long-term cardiovascular effects, optimal and timely management of hypertension in survivors of cancer cannot be overstated. Antihypertensive therapies need to be tailored to underlying comorbidities, such as diabetes, heart failure, and others. Hypertension is one of the most common vascular toxicities (class effect) seen in 25%−30% of patients treated with vascular endothelial growth factor inhibition (VEGFi; e.g., bevacizumab, sorafenib, and sunitinib) (7). It is mediated by vasoconstriction (decreased production of endothelial nitric oxide synthase [eNOS]), decreased vascular compliance, and kidney injury (e.g., thrombotic microangiopathy phenotype) (Figure 2).

Figure 2
Figure 2

Pathophysiology of development of hypertension and proteinuria from VEGFi

Citation: Kidney News 14, 6

Polymorphisms in the VEGF gene predispose certain patients to the vasculotoxic effect of VEGFi, for example, single nucleotide polymorphisms in Egl nine homolog 3, epidermal growth factor, WNK lysine-deficient protein kinase 1, and the kinase insert domain receptor gene (8). The current data obtained from clinical trials and physiological studies suggest that dihydropyridine calcium channel blockers (avoid diltiazem or verapamil and inhibit cytochrome P450 3A4 leading to higher levels of drugs, such as sunitinib and sorafenib) and RAAS blockers can be considered as first-line antihypertensive therapies for hypertension mediated by VEGFi (Figure 3) (9). RAAS blockers directly cause vascular smooth muscle relaxation and upregulate NO production leading to microcirculatory changes and decreased blood pressure. In addition, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) help reduce proteinuria that commonly occurs with VEGFi.

Figure 3
Figure 3

Approach to management of hypertension from VEGFi

Citation: Kidney News 14, 6

Radiation exposure and hypertension

Radiation therapy that involves the head or neck can lead to baroreflex failure and to associated difficult-to-treat labile hypertension and hypertensive crisis (10). Radiation nephropathy occurs in approximately 20% of irradiated subjects and can have various clinical presentations, such as acute radiation nephritis, chronic radiation nephropathy (chronic thrombotic microangiopathy), malignant hypertension, and benign hypertension.

Oncohypertension is an emerging subspecialty in the field of onconephrology and cardio-oncology, as hypertension lies at the intersection of both specialties. Hence, a multidisciplinary team—consisting of oncologist, nephrologist, cardiologist, pharmacist, and primary care physician—should form the framework of an oncohypertension clinic.

References

  • 1.

    Denlinger CS, et al. Survivorship: Introduction and definition. Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2014; 12:3445. doi: 10.6004/jnccn.2014.0005

    • Search Google Scholar
    • Export Citation
  • 2.

    Arima H, et al. Mortality patterns in hypertension. J Hypertens 2011; 29 (Suppl 1):S3S7. doi: 10.1097/01.hjh.0000410246.59221.b1

  • 3.

    Gudsoorkar P, et al. Onco-hypertension: An emerging specialty. Adv Chronic Kidney Dis 2021; 28:477489.e1. doi: 10.1053/j.ackd.2021.09.011

  • 4.

    Ruf R, et al. Onco-hypertension: Overview of hypertension with anti-cancer agents. JON 2021; 5:5769. doi: 10.1177/23993693211001374

  • 5.

    Sufrin G, et al. Hormones in renal cancer. J Urol 1977; 117:433438. doi: 10.1016/s0022-5347(17)58490-6

  • 6.

    Gandini S, et al. Anti-hypertensive drugs and skin cancer risk: A review of the literature and meta-analysis. Crit Rev Oncol Hematol 2018; 122:19. doi: 10.1016/j.critrevonc.2017.12.003

    • Search Google Scholar
    • Export Citation
  • 7.

    Abdel-Qadir H, et al. Cardiovascular toxicity of angiogenesis inhibitors in treatment of malignancy: A systematic review and meta-analysis. Cancer Treat Rev 2017; 53:120127. doi: 10.1016/j.ctrv.2016.12.002

    • Search Google Scholar
    • Export Citation
  • 8.

    Lambrechts D, et al. Genetic markers of bevacizumab-induced hypertension. Angiogenesis 2014; 17:685694. doi: 10.1007/s10456-014-9424-7

  • 9.

    Caletti S, et al. Management of VEGF-targeted therapy-induced hypertension. Curr Hypertens Rep 2018; 20:68. doi: 10.1007/s11906-018-0871-1

  • 10.

    Ketch T, et al. Four faces of baroreflex failure: Hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia. Circulation 2002; 105:25182523. doi: 10.1161/01.cir.0000017186.52382.f4

    • Search Google Scholar
    • Export Citation
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