The concept of crosstalk‐directed embryological target mining and its application to essential hypertension treatment failures

Sag, Alan A.; Şal, Oğuzhan; Kilic, Yagmur; Önal, Emine Meltem; Kanbay, Mehmet

doi:10.1111/jch.12978

Cited by 5 publications

(5 citation statements)

References 25 publications

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“…Percutaneous catheter-based radiofrequency ablation of afferent and efferent sympathetic nerves of renal arteries is one such technique and is the most widely researched to date. It is purported to address certain interorgan crosstalk pathways that may be upregulated in non-atherosclerotic nephrogenic hypertension [ 9 ]. Due to the risk of contrast-induced nephropathy associated with the use of iodinated contrast materials, patients with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m 2 have been excluded from major trials of renal sympathetic denervation (RSDN).…”

Section: Introductionmentioning

confidence: 99%

Renal denervation using carbon dioxide renal angiography in patients with uncontrolled hypertension and moderate to severe chronic kidney disease

Hameed

Freedman

Watkin

et al. 2017

Clinical Kidney Journal

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BackgroundChronic kidney disease (CKD) is the most common cause of secondary hypertension. More than half of the patients have uncontrolled hypertension (≥140/90 mmHg on three or more antihypertensive agents at optimum doses). Renal sympathetic denervation (RSDN) has been shown to reduce blood pressure (BP) in patients with resistant hypertension. Although patients with CKD have high sympathetic drive, all major clinical trials have excluded patients with estimated glomerular filtration rates (eGFRs) <45 mL/min/1.73m2 for risk of contrast-induced nephropathy.MethodsIn this pilot study, carbon dioxide (CO2) was used as the sole contrast agent to carry out renal angiography and RSDN in patients with moderate to severe CKD (eGFR 15–44 mL/min/1.73m2) and uncontrolled hypertension.ResultsEleven patients (eight males) underwent RSDN. The median age was 57 years [interquartile range (IQR) 49–66]. The median number of antihypertensives being taken at baseline was 4 (IQR 3–4). No statistically significant difference was observed in serum creatinine in the serial follow-ups until at 6 months[median difference 0.25 mg/dL (IQR 0.09–0.53); P = 0.008]. There was a non-significant reduction in median clinic BP from baseline to 6 months [−14 mmHg (IQR −24–5)] and a significant increase in daytime ambulatory systolic BP [7 mmHg (IQR −2–12); P= 0.045]. A trend towards a serial reduction in albuminuria was observed. Procedure-related complications included a groin haematoma (n = 1) and reported flank (n = 1) and groin pain (n = 1).ConclusionsThis pilot study shows that CO2 renal angiography can be used to perform RSDN in patients with significant renal impairment and may lead to associated improvements in clinic BP and albuminuria.

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Section: Introductionmentioning

confidence: 99%

Renal denervation using carbon dioxide renal angiography in patients with uncontrolled hypertension and moderate to severe chronic kidney disease

Hameed

Freedman

Watkin

et al. 2017

Clinical Kidney Journal

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“…These patients have more target organ damage compared with patients with hypertension who achieve target BPs with treatment. There is no accepted therapeutic norm for these patients, which has created a longstanding therapeutic dilemma . However, a new emerging technique was recently introduced: renal sympathetic denervation.…”

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confidence: 99%

“…There is no accepted therapeutic norm for these patients, which has created a longstanding therapeutic dilemma. 4,5 However, a new emerging technique was recently introduced: renal sympathetic denervation. In initial studies, renal sympathetic denervation was demonstrated to be effective in reducing BP in patients with resistant hypertension.…”

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confidence: 99%

Should we take renal denervation with a grain of salt?

Afsar

Sag

Kanbay

2017

J of Clinical Hypertension

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In the current issue of the Journal of Clinical Hypertension, De Beus and colleagues investigated the effect of salt intake on blood pressure (BP) response after percutaneous renal denervation in patients with resistant hypertension. The authors found no relationship between baseline sodium excretion and change in BP. 1 Hypertension is one of the leading attributable risk factors for kidney disease and cardiovascular morbidity and mortality.2 A subgroup of patients with hypertension do not achieve target BP levels despite concurrent use of three or more antihypertensive agents (one being diuretic). These patients are considered to have "resistant hypertension." The incidence of resistant hypertension ranges from 10% to 12%. 3 These patients have more target organ damage compared with patients with hypertension who achieve target BPs with treatment. There is no accepted therapeutic norm for these patients, which has created a longstanding therapeutic dilemma. Dietary sodium intake is also known to be related to sympathetic activity, and lower intake is associated with higher sympathetic drive.14 Conversely, efferent sympathetic activity directly increases tubular sodium absorption. 15 Thus, hypothetically, it can be concluded that renal sympathetic denervation can cause decreased vasoconstriction, renin release, and decreased sodium and water retention. In this context it can be hypothesized that sodium intake may be an important factor for the success of renal sympathetic denervation.These data, taken into account alongside the study in which deBeus and colleagues investigated the role of basal sodium intake on BP response after percutaneous renal denervation in patients with resistant hypertension, yielded no statistically significant relationship between baseline sodium excretion and change in BP. Percutaneous renal denervation decreased BP with similar salt intake, suggesting a decrease in salt sensitivity. However, the same decline in BP was also observed in the control group; thus, percutaneous renal denervation did not seem to impact this decrease in BP. 1 Although the study is informative, the results must be interpreted with caution.First, the generalizability of the study should be considered. The trial excluded patients with severe renal ınsufficiency (estimated glomerular filtration rate <20 mL/min per 1.73 m 2 ). The relationship

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“…Finally, the inclusion of only patients naïve to anti-RAAS medication is especially interesting from the perspective of purported cross-talk pathways underlying ARVH pathophysiology (e.g. the mechanism of RAAS activation as a mechanism of thiazide resistance) [ 4 , 5 ]. Since most atherosclerotic patients are not candidates for renal denervation (due to inability to provide catheter/true vessel wall contact deep to plaque), the future of intervention for ARVH (until endovascular regenerative techniques such as stem cell embolization come to fruition) will focus on angioplasty and stenting (with or without drug-eluting technology) in the near term [ 2 ].…”

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confidence: 99%

Revisiting angioplasty for renovascular hypertension

Sag

Kanbay

2017

Clinical Kidney Journal

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Following contemporary trends in arterial endovascular therapy of the lower extremities, recent major trials in anti-hypertensive renovascular revascularization have focused on outcomes after primary stenting of the renal artery. Angioplasty-only therapy has not been studied in a major trial since the year 2000. As such, the current study by Saeed et al. presents an updated data set on the technique with one unique aspect: patients underwent post-procedural physiologic scintigraphy to document the effects of unilateral intervention in patients with two kidneys. Although these physiologic changes should not supersede the clinically relevant outcome of blood pressure reduction (which was also accomplished in this study albeit to a modest but statistically significant degree), the physiologic consequences of unilateral intervention are elegantly presented in this short-term follow-up study. Furthermore, while current renovascular intervention is trending towards treatment of global renal ischemia (i.e. bilateral renal artery stenosis or renal artery stenosis in a congenitally or acquired solitary functional kidney scenario), the current study provides a useful data set for reference in guiding future renovascular revascularization studies and treatment algorithms.

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The concept of crosstalk‐directed embryological target mining and its application to essential hypertension treatment failures

Cited by 5 publications

References 25 publications

Renal denervation using carbon dioxide renal angiography in patients with uncontrolled hypertension and moderate to severe chronic kidney disease

Renal denervation using carbon dioxide renal angiography in patients with uncontrolled hypertension and moderate to severe chronic kidney disease

Should we take renal denervation with a grain of salt?

Revisiting angioplasty for renovascular hypertension

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