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Endocrinology and Metabolism Clinics of... Dec 2019Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular... (Review)
Review
Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular dysplasia. It has long been recognized as the prototype of angiotensin-dependent hypertension. However, the mechanisms underlying the physiopathology of hypertensive occlusive vascular renal disease are complex and distinction between the different causes of RVD should be made. Recognition of these distinct types of RVD with different degrees of renal occlusive disease is important for management. The greatest challenge is to individualize and implement the best approach for each patient in the setting of widely different comorbidities.
Topics: Fibromuscular Dysplasia; Humans; Hypertension, Renal; Hypertension, Renovascular; Nephritis; Renal Artery Obstruction
PubMed: 31655775
DOI: 10.1016/j.ecl.2019.08.007 -
Clinical Reviews in Allergy & Immunology Jun 2023Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality... (Review)
Review
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains a serious complication, often necessitating level three care for patients affected. Whilst renal outcomes have significantly improved following the advent of angiotensin-converting enzyme inhibitor (ACEi) therapy, SRC remains a precarious challenge for clinicians, due to lack of preventative measures and the fact that patients can rapidly decline despite best medical management. Large cohort studies spanning decades have allowed clear identification of phenotypes particularly at risk of developing SRC thus allowing enhanced monitoring and early identification in those individuals. Novel urinary biomarkers for renal disease in SSc may offer a new window for early identification of SRC patients and response to treatment. Multiple studies have demonstrated increased activity of complement pathways in SRC with some anecdotal cases exhibiting serological response to treatment with eculizumab where ACEi and therapeutic plasma exchange (TPE) were not successful. Endothelin-1 blockade, a therapeutic strategy in other SSc vasculopathies, has shown potential as a target but clinical trials are yet to show a clear treatment benefit. Clear guidelines for the management of SRC are in place to standardise care and facilitate early collaboration between rheumatology and renal physicians. Outcomes following renal transplant have improved but the mortality of SRC remains high, indicating the need for continued exploration of the mechanisms precipitating and exacerbating SRC in order to develop novel therapies.
Topics: Humans; Hypertension, Renal; Acute Kidney Injury; Angiotensin-Converting Enzyme Inhibitors; Scleroderma, Systemic; Scleroderma, Localized
PubMed: 35648373
DOI: 10.1007/s12016-022-08945-x -
Kardiologia Polska 2018The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment- -resistant hypertension set the stage for a... (Meta-Analysis)
Meta-Analysis Review
The publication of the first non-randomised proof-of-concept trial of renal denervation as a treatment modality in treatment- -resistant hypertension set the stage for a search for novel devices with the expectation that technology would reduce the burden of hypertension by reducing or eliminating the costly and lifelong use of blood pressure-lowering medications. As we demonstrate in this review, this idea was so attractive to manufacturers and invasive cardiologists and radiologists that they overlooked decades of careful pathophysiological research in a disease that remains enigmatic but is still a major cause of cardio-vascular mortality worldwide. To make our point, we first reviewed the prevalence and risks associated with treatment-resistant hypertension. Next, we highlighted the key points required for the diagnosis of treatment-resistant hypertension, including the recording of ambulatory blood pressure and the assessment of adherence to medication. Finally, we summarised new insights in the management of treatment-resistant hypertension by medication and devices as well as in future research. Throughout our review, we focused on new evidence that had become available since 2013. Our conclusion is that optimising medical treatment based on simple algorithms remains the state of the art in treatment-resistant hypertension.
Topics: Blood Pressure Monitoring, Ambulatory; Denervation; Humans; Hypertension; Hypertension, Renal; Kidney; Prevalence; Treatment Outcome
PubMed: 29905926
DOI: 10.5603/KP.a2018.0129 -
Kidney International. Supplement May 2002There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP,... (Review)
Review
There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that "blood pressure goes with the kidney," a normotensive recipient of a kidney genetically programmed for hypertension (HT) will develop HT, while conversely hypertensive patients with renal failure receiving the kidney of a normotensive donor may develop normotension. Family studies showed higher BP values and more frequent HT in first degree relatives of patients with primary glomerulonephritis or diabetic nephropathy, both type 1 and type 2. The notion that HT accelerates the loss of renal function has been proposed at the turn of the century, but definite evidence by observational and interventional studies has only been provided in the last two decades. The issue has been much confounded by the mistaken believe that damaged kidneys require higher BP values in order to function properly. The mechanisms of BP increase in renal disease comprise: salt retention, inappropriate activity of the renin-angiotensin system (RAS) and of the sympathetic nerve system as well as impaired endothelial cell-mediated vasodilatation. There is ample evidence both in primary renal disease (AIPRI and REIN trials) and in nephropathy of type 1 and type 2 diabetes (IDNT, RENAAL) that pharmacological blockade of the RAS by angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers has BP-independent renoprotective effects. More recently, it has also been shown that blockade of the sympathetic nerve system has BP-independent effects on albuminuria and on glomerulosclerosis.
Topics: Humans; Hypertension, Renal
PubMed: 11982815
DOI: 10.1046/j.1523-1755.61.s80.28.x -
Kidney & Blood Pressure Research 2020Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena. (Review)
Review
BACKGROUND
Systemic sclerosis is an immune-mediated rheumatic disease characterized by vascular abnormalities, tissue fibrosis and autoimmune phenomena.
SUMMARY
Renal disease occurring in patients with systemic sclerosis may have a variable clinicopathological picture. The most specific renal condition associated with systemic sclerosis is scleroderma renal crisis, characterized by acute onset of renal failure and severe hypertension. Although the management of scleroderma renal crisis was revolutionized by the introduction of angiotensin-converting enzyme inhibitors, there is still a significant proportion of patients with poor outcomes. Therefore, research on establishing disease markers (clinical, ultrasonographical and serological) and clear diagnostic criteria, which could limit the risk of developing scleroderma renal crisis and facilitate diagnosis of this complication, is ongoing. Other forms of renal involvement in systemic sclerosis include vasculitis, an isolated reduced glomerular filtration rate in systemic sclerosis, antiphospholipid-associated nephropathy, high intrarenal arterial stiffness and proteinuria. Key Messages: Scleroderma renal crisis is the most specific and life-threatening renal presentation of systemic sclerosis, albeit with declining prevalence. In patients with scleroderma renal crisis, it is mandatory to control blood pressure early with increasing doses of angiotensin-converting enzyme inhibitors, along with other antihypertensive drugs if necessary. There is a strong association between renal involvement and patients' outcomes in systemic sclerosis; consequently, it becomes mandatory to find markers that may be used to identify patients with an especially high risk of scleroderma renal crisis.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Scleroderma, Systemic
PubMed: 32521536
DOI: 10.1159/000507886 -
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 -
Cardiology 2016The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The... (Review)
Review
The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research.
Topics: Blood Pressure; Humans; Hypertension, Renal; Kidney; Learning Curve; Randomized Controlled Trials as Topic; Renal Artery; Sympathectomy; Sympathetic Nervous System; Vasodilator Agents
PubMed: 27287994
DOI: 10.1159/000446909 -
Current Opinion in Nephrology and... Jan 2013Despite apparent blood pressure (BP) control and renin-angiotensin system (RAS) blockade, the chronic kidney disease (CKD) outcomes have been suboptimal. Accordingly,... (Review)
Review
PURPOSE OF REVIEW
Despite apparent blood pressure (BP) control and renin-angiotensin system (RAS) blockade, the chronic kidney disease (CKD) outcomes have been suboptimal. Accordingly, this review is addressed to renal microvascular and autoregulatory impairments that underlie the enhanced dynamic glomerular BP transmission in CKD progression.
RECENT FINDINGS
Clinical data suggest that failure to achieve adequate 24-h BP control is likely contributing to the suboptimal outcomes in CKD. Whereas evidence continues to accumulate regarding the importance of preglomerular autoregulatory impairment to the dynamic glomerular BP transmission, emerging data indicate that nitric oxide-mediated efferent vasodilation may play an important role in mitigating the consequences of glomerular hypertension. By contrast, the vasoconstrictor effects of angiotensin II are expected to potentially reduce glomerular barotrauma and possibly enhance ischemic injury. When adequate BP measurement methods are used, the evidence for BP-independent injury initiating mechanisms is considerably weaker and the renoprotection by RAS blockade largely parallels its antihypertensive effectiveness.
SUMMARY
Adequate 24-h BP control presently offers the most feasible intervention for reducing glomerular BP transmission and improving suboptimal outcomes in CKD. Investigations addressed to improving myogenic autoregulation and/or enhancing nitric oxide-mediated efferent dilation in addition to the more downstream mediators may provide additional future therapeutic targets.
Topics: Angiotensin II; Blood Pressure; Disease Progression; Homeostasis; Humans; Hypertension, Renal; Kidney Glomerulus; Microvessels; Nitric Oxide; Renal Insufficiency, Chronic
PubMed: 23132368
DOI: 10.1097/MNH.0b013e32835b36c1 -
Kidney International. Supplement Dec 2005The link between the kidney and hypertension has been considered a villain-victim relationship. High blood pressure levels are a well-recognized feature in chronic renal... (Review)
Review
The link between the kidney and hypertension has been considered a villain-victim relationship. High blood pressure levels are a well-recognized feature in chronic renal disease, but the ability of mild-to-moderate hypertension to produce renal insufficiency has been questioned. Nephrosclerosis, benign nephrosclerosis, and hypertensive kidney disease are terms that clinicians use when renal damage is thought to be secondary to essential hypertension. Many cases of end-stage renal disease are ascribed to so-called benign nephrosclerosis. This entity could actually be a primary renal disease affecting the preglomerular microvasculature, perhaps genetically mediated and ethnically influenced, and showing a heterogeneous clinical expression. African Americans suffer from nephrosclerosis more frequently than Caucasians. Nephrosclerosis affecting Caucasians seems to show a less aggressive pattern and could represent early age-related renal sclerosis. The risk of end-stage renal disease is increased when atherosclerotic lesions in large renal arteries coexist. Age, systolic blood pressure, proteinuria, and concomitant cardiovascular disease are well-known promoters of renal failure. A multifactorial strategy, including antihypertensive and antiproteinuric drugs, and lipid-lowering and anti-platelet agents, could improve cardiovascular and renal outcomes in patients with nephrosclerosis.
Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Diseases; Chronic Disease; Disease Progression; Female; Humans; Hypertension; Hypertension, Renal; Kidney Diseases; Kidney Failure, Chronic; Male; Nephrosclerosis; Prognosis
PubMed: 16336577
DOI: 10.1111/j.1523-1755.2005.09910.x -
Experimental and Clinical... Apr 2013Arterial hypertension is prevalent among kidney transplant recipients. The multifactorial pathogenesis involves the interaction of the donor and the recipient's genetic... (Review)
Review
Arterial hypertension is prevalent among kidney transplant recipients. The multifactorial pathogenesis involves the interaction of the donor and the recipient's genetic backgrounds with several environmental parameters that may precede or follow the transplant procedure (eg, the nature of the renal disease, the duration of the chronic kidney disease phase and maintenance dialytic therapy, the commonly associated cardiovascular disease with atherosclerosis and arteriosclerosis, the renal mass at implantation, the immunosuppressive regimen used, life of the graft, and de novo medical and surgical complications that may occur after a transplant). Among calcineurin inhibitors, tacrolimus seems to have a better cardiovascular profile. Steroid-free protocols and calcineurin inhibitor-free regimens seem to be associated with better blood pressure control. Posttransplant hypertension is a major amplifier of the chronic kidney disease-cardiovascular disease continuum. Despite the adverse effects of hypertension on graft and patient survival, blood pressure control remains poor because of the high cardiovascular risk profile of the donor-recipient pair. Although the optimal blood pressure level remains unknown, it is recommended to maintain the blood pressure at < 130/80 mm Hg and < 125/75 mm Hg in the absence or presence of proteinuria.
Topics: Antihypertensive Agents; Graft Rejection; Humans; Hypertension, Renal; Immunosuppressive Agents; Kidney Transplantation; Postoperative Complications; Prevalence
PubMed: 23473421
DOI: 10.6002/ect.2012.0311