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American Journal of Physiology. Renal... Oct 2015When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The... (Review)
Review
When introduced clinically 6 years ago, renal denervation was thought to be the solution for all patients whose blood pressure could not be controlled by medication. The initial two studies, SYMPLICITY HTN-1 and HTN-2, demonstrated great magnitudes of blood pressure reduction within 6 mo of the procedure and were based on a number of assumptions that may not have been true, including strict adherence to medication and absence of white-coat hypertension. The SYMPLICITY HTN-3 trial controlled for all possible factors believed to influence the outcome, including the addition of a sham arm, and ultimately proved the demise of the initial overly optimistic expectations. This trial yielded a much lower blood pressure reduction compared with the previous SYMPLICITY trials. Since its publication in 2014, there have been many analyses to try and understand what accounted for the differences. Of all the variables examined that could influence blood pressure outcomes, the extent of the denervation procedure was determined to be inadequate. Beyond this, the physiological mechanisms that account for the heterogeneous fall in arterial pressure following renal denervation remain unclear, and experimental studies indicate dependence on more than simply reduced renal sympathetic activity. These and other related issues are discussed in this paper. Our perspective is that renal denervation works if done properly and used in the appropriate patient population. New studies with new approaches and catheters and appropriate controls will be starting later this year to reassess the efficacy and safety of renal denervation in humans.
Topics: Denervation; Drug Resistance; Humans; Hypertension, Renal; Kidney; Renal Circulation; Sympathectomy
PubMed: 26224718
DOI: 10.1152/ajprenal.00246.2015 -
Renal Failure Oct 2016The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is...
The renal functional reserve (RFR) is the ability of the kidneys to increase renal plasma flow and glomerular filtration rate (GFR) in response to protein intake. It is a measure of functional and anatomic integrity of nephrons. It is not known what relation between RFR and kidney Doppler parameters. We aimed to study the relation between the RFR and renal hemodynamic parameters in hypertensive patients with and without nephropathy who had normal kidney function. Twenty-four hypertensive subjects with nephropathy (HTN-n, n = 10) and hypertension without nephropathy (HTN, n = 14) were included in the study. Control group included 11 healthy subjects. Baseline GFR (GFR1) and GFR after intake of egg protein 1 mg/kg of body weight were determined (GFR2). RFR was calculated by the following formula: (GFR2-GFR1)/GFR1 × 100%. Doppler ultrasonography was performed. Arterial blood pressure (BP), body mass index (BMI), and estimated GFR were also recorded. HTN and HTN-n groups had impaired levels of RFR compared with controls (p < 0.05), significantly decreased value of flow velocity parameters (Vmax, Vmin), and increased RRI compared with controls. There was significant negative correlation of RFR with blood pressure levels (sBP, r = -0.435, p = 0.009; dBP, r = -0.504, p = 0.002), RRI (r = -0.456, p = 0.008), micro albuminuria (MAU, r = -0.366, p = 0.031) and positive correlation with Vmax and Vmin (r = 0.556, p = 0.001 and r = 0.643, respectively, p < 0.001). Linear regression showed that RRI and MAU were independent predictors of decreased RFR. RFR is lower in hypertensive patients despite near-normal level of kidney function and is related to particular level of BP. RRI and MAU were independent predictors of decreased RFR.
Topics: Adult; Blood Pressure; Cross-Sectional Studies; Female; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Regional Blood Flow; Renal Artery; Renal Circulation; Ultrasonography, Doppler, Color
PubMed: 27470640
DOI: 10.1080/0886022X.2016.1214052 -
Current Hypertension Reports Jan 2019In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that... (Review)
Review
PURPOSE OF REVIEW
In this review, we summarized the current knowledge of connecting tubule-glomerular feedback (CTGF), a novel mechanism of renal microcirculation regulation that integrates sodium handling in the connecting tubule (CNT) with kidney hemodynamics.
RECENT FINDINGS
Connecting tubule-glomerular feedback is a crosstalk communication between the CNT and the afferent arteriole (Af-Art), initiated by sodium chloride through the epithelial sodium channel (ENaC). High sodium in the CNT induces Af-Art vasodilation, increasing glomerular pressure and the glomerular filtration rate and favoring sodium excretion. CTGF antagonized and reset tubuloglomerular feedback and thus increased sodium excretion. CTGF is absent in spontaneous hypertensive rats and is overactivated in Dahl salt-sensitive rats. CTGF is also modulated by angiotensin II and aldosterone. CTGF is a feedback mechanism that integrates sodium handling in the CNT with glomerular hemodynamics. Lack of CTGF could promote hypertension, and CTGF overactivation may favor glomerular damage and proteinuria. More studies are needed to explore the alterations in renal microcirculation and the role of these alterations in the genesis of hypertension and glomerular damage in animals and humans.
KEY POINTS
• CTGF is a vasodilator mechanism that regulates afferent arteriole resistance. • CTGF is absent in spontaneous hypertensive rats and overactivated in Dahl salt-sensitive rats. • CTGF in excess may promote glomerular damage and proteinuria, while the absence may participate in sodium retention and hypertension.
Topics: Animals; Feedback; Humans; Hypertension; Kidney Glomerulus; Kidney Tubules; Microcirculation; Proteinuria; Rats; Renal Circulation; Sodium
PubMed: 30659366
DOI: 10.1007/s11906-019-0911-5 -
Nature Reviews. Drug Discovery Aug 2016Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for this disease, with current treatment strategies relying on... (Review)
Review
Chronic kidney disease (CKD) represents a leading cause of death in the United States. There is no cure for this disease, with current treatment strategies relying on blood pressure control through blockade of the renin-angiotensin system. Such approaches only delay the development of end-stage kidney disease and can be associated with serious side effects. Recent identification of several novel mechanisms contributing to CKD development - including vascular changes, loss of podocytes and renal epithelial cells, matrix deposition, inflammation and metabolic dysregulation - has revealed new potential therapeutic approaches for CKD. This Review assesses emerging strategies and agents for CKD treatment, highlighting the associated challenges in their clinical development.
Topics: Animals; Fibrosis; Humans; Mice; Renal Agents; Renal Circulation; Renal Insufficiency, Chronic
PubMed: 27230798
DOI: 10.1038/nrd.2016.67 -
International Journal of Molecular... Nov 2023The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The... (Review)
Review
The rapid growth of the elderly population is making the need for extensive and advanced information about age-related organ dysfunction a crucial research area. The kidney is one of the organs most affected by aging. Aged kidneys undergo functional decline, characterized by a reduction in kidney size, decreased glomerular filtration rate, alterations in renal blood flow, and increased inflammation and fibrosis. This review offers a foundation for understanding the functional and molecular mechanisms of aging kidneys and for selecting identifying appropriate targets for future treatments of age-related kidney issues.
Topics: Aged; Humans; Kidney; Aging; Kidney Diseases; Renal Circulation; Fibrosis; Glomerular Filtration Rate
PubMed: 38069234
DOI: 10.3390/ijms242316912 -
Seminars in Nephrology Nov 2019A gradually developing reduction in renal blood flow from atherosclerotic renovascular disease results in loss of kidney volume and a decrease in glomerular filtration... (Review)
Review
A gradually developing reduction in renal blood flow from atherosclerotic renovascular disease results in loss of kidney volume and a decrease in glomerular filtration rate that eventually becomes irreversible. Whether this process fundamentally reflects tissue hypoxia has been difficult to establish. Studies of human renovascular disease have indicated that reductions in blood flow of up to 30% to 40% can be tolerated with preservation of normal oxygenation and structural integrity. These observations are consistent with remarkable stability of poststenotic kidney function during sustained medical antihypertensive drug therapy in moderate renovascular disease. With more severe and sustained reductions, however, cortical oxygenation decreases and the magnitude of medullary hypoxia expands. These changes are associated with increasing renal venous levels of inflammatory cytokines, angiogenic markers, and infiltration of inflammatory cells, including tissue macrophages and T cells. Although restoring large-vessel blood flow can improve oxygenation, some of these processes reflect microvascular rarefication, remain activated, and do not depend on hemodynamic factors alone. Elucidation of tissue injury pathways associated with hypoxia opens the possibility of adjunctive therapeutic measures beyond renal revascularization. These include cell-based regeneration, mitochondrial protection, and/or angiogenic cytokine therapy to restore or preserve renal function in ischemic nephropathy.
Topics: Disease Progression; Humans; Hypoxia; Ischemia; Kidney; Renal Artery Obstruction; Renal Circulation; Renal Insufficiency, Chronic
PubMed: 31836041
DOI: 10.1016/j.semnephrol.2019.10.008 -
Intensive Care Medicine Oct 2022
Topics: Extracorporeal Circulation; Humans; Kidney; Perfusion; Renal Circulation
PubMed: 36053317
DOI: 10.1007/s00134-022-06857-0 -
Cardiovascular Drugs and Therapy Dec 2017Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Given the increasing incidence of diabetes, many experts hold the view that... (Review)
Review
Diabetic nephropathy (DN) is currently the leading cause of end-stage renal disease globally. Given the increasing incidence of diabetes, many experts hold the view that DN will eventually progress toward pandemic proportions. Whilst hyperglycaemia-induced vascular dysfunction is the primary initiating mechanism in DN, its progression is also driven by a heterogeneous set of pathological mechanisms, including oxidative stress, inflammation and fibrosis. Current treatment strategies for DN are targeted against the fundamental dysregulation of glycaemia and hypertension. Unfortunately, these standards of care can delay but do not prevent disease progression or the significant emotional, physical and financial costs associated with this disease. As such, there is a pressing need to develop novel therapeutics that are both effective and safe. Set against the genomic era, numerous potential target pathways in DN have been identified. However, the clinical translation of basic DN research has been met with a number of challenges. Moreover, the notion of DN as a purely vascular disease is outdated and it has become clear that DN is a multi-dimensional, multi-cellular condition. The review will highlight the current therapeutic approaches for DN and provide an insight into how the inherent complexity of DN is shaping the research pathways toward the development and clinical translation of novel therapeutic strategies.
Topics: Antihypertensive Agents; Diabetic Nephropathies; Fibrosis; Humans; Hypoglycemic Agents; Kidney Failure, Chronic; Oxidative Stress; Renal Circulation; Renin-Angiotensin System
PubMed: 28956186
DOI: 10.1007/s10557-017-6755-9 -
British Journal of Anaesthesia Apr 2016
Topics: Colloids; Coronary Artery Bypass; Female; Humans; Isotonic Solutions; Male; Plasma Substitutes; Renal Circulation
PubMed: 26873176
DOI: 10.1093/bja/aev542 -
Critical Care Medicine Jun 2018Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate,...
OBJECTIVE
Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock.
DESIGN
Prospective comparative study.
SETTING
General and cardiothoracic ICUs.
PATIENTS
Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58).
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated.
CONCLUSIONS
In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.
Topics: Aged; Aged, 80 and over; Case-Control Studies; Female; Glomerular Filtration Rate; Humans; Kidney; Male; Middle Aged; Prospective Studies; Renal Circulation; Shock, Septic; Young Adult
PubMed: 29517549
DOI: 10.1097/CCM.0000000000003088