Tyrosine kinase inhibitor-induced hypertension-marker of anti-tumour treatment efficacy or cardiovascular risk factor?

Tyrosine kinase receptor inhibitors (TKIs) are a relatively new class of targeted anti-cancer agents with vascular endothelial growth factor signalling pathway-inhibiting properties. Hypertension is recognized as one of the most common adverse effects of this anti-angiogenic therapy and is the consequence of reduced production of vasodilatory nitric oxide and reduced prostacyclin production as well as increased production of vasoconstrictive endothelin-1. TKI-induced hypertension is dose dependent and it has been suggested as a marker of treatment effectiveness. In this issue, Saito et al. report the incidence of treatment-related hypertension in patients treated with lenvatinib, a newer TKI, for non-resectable hepatocellular carcinoma. The authors demonstrate that a subset of TKI-treated patients develop fluid retention 3 weeks after treatment initiation as a consequence of lower urinary sodium excretion and thus provides insights into the pathogenesis of blood pressure elevation in the second phase. These findings contribute to a better understanding of TKI-associated hypertension and help in choosing the most appropriate antihypertensive agents in this setting. Active control of hypertension may help more patients benefit from longer TKI therapy, possibly resulting in better cancer outcomes.

Changes in Kidney Function in a Population With Essential Hypertension in Real Life Settings.

INTRODUCTION: Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function. MATERIALS AND METHODS: We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied. RESULTS: Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P < .001). CONCLUSIONS: RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs.

The effect of antihypertensive drugs on chronic kidney disease: a comprehensive review.

Data from randomized clinical trials and epidemiological evidence identify systemic hypertension as the second most common modifiable risk factor for chronic kidney disease (CKD) progression after diabetes mellitus. CKD may progress silently over the years and early diagnosis and control of hypertension is of major importance in delaying renal function decline. Recent guidelines for the treatment of hypertension suggest the use of a variety of antihypertensive drugs in order to achieve the desired blood pressure levels. Renin-angiotensin system inhibitors have been undoubtedly studied the most and are suggested by guidelines and experts as first choice in patients with hypertension and renal injury, particularly in those with diabetes, as they have repeatedly shown to significantly reduce proteinuria. Other classes of antihypertensive drugs have been studied to a lesser extent and they have their own unique properties and effects. However, it is now common knowledge that adequate blood pressure control is the most important factor for the preservation of renal function, so every drug that effectively lowers hypertension is believed to be renoprotective. The present article will review the latest data on the role and properties of each class of antihypertensive drugs on CKD.

Effect of hospitalization on 24-h ambulatory blood pressure of hypertensive patients.

The aim of this study is to assess the effect of hospital admission on 24-h ambulatory blood pressure (ABP) in hypertensive subjects. Treated or untreated hypertensive adults with open-angle glaucoma underwent inpatient and outpatient 24-h ABP monitoring in a random order 4 weeks apart. Awake ambulatory hours, awake in-bed hours and sleep hours were reported by participants. The nighttime-to-daytime ABP dip (%) and the sleeping-to-awake dip (ambulatory and in-bed) were determined using the two ABP recordings. A total of 40 subjects were analyzed (mean age 65.7 ± 8.4 (s.d.) years, n=19 men). Daytime systolic BP (SBP) was lower in the hospital than in the outpatient setting (mean difference 4.3 ± 10.4 mm Hg, P=0.01), as was the awake ambulatory SBP (mean difference 5.0 ± 11.1 mm Hg, P=0.008). No differences were detected in 24 h, nighttime or sleeping SBP or in any of the respective diastolic outpatient vs. inpatient ABP measurements. The nighttime SBP dip (vs. daytime) was larger in the outpatient setting (8.9 ± 7.5% and 5.2 ± 4.7%, respectively; P=0.003). Sleeping SBP dip (vs. awake ambulatory and awake in-bed) was also larger in the outpatient setting (11.1 ± 7.3 and 7.8 ± 5.9%, respectively; P=0.02) with no difference in diastolic ABP. These data suggest that inpatient 24-h ABP monitoring does not reflect the usual BP level during routine daily life, nor does it represent the usual diurnal pattern of an individual. Relying on the 24-h ABP monitoring performed in the hospital environment may lead to an underestimation of ABP and an overdiagnosis of non-dippers. Therefore, 24-h ABP monitoring for decision making regarding diagnosis and treatment of hypertension should be performed only in the routine daily conditions of each individual.