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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A primary role for the kidney in hypertension has long been recognized, but the pathogenetic interactions among renal hemodynamics, hormonal and hereditary factors, and dietary sodium intake remain ill defined. Reduction in the filtration surface area, whether acquired in the course of intrinsic renal disease or after surgical renal ablation, leads to systemic hypertension as well as to progressive renal insufficiency, sequellae made even more severe by dietary sodium excess. Moreover, hypertension and progressive renal disease occur in some individuals born with a solitary kidney, and occur almost invariably with more severe degrees of dysgenesis. Hypertension is also commonly observed in certain inbred rat strains in which the filtration surface area is congenitally deficient. Based on these and other lines of evidence reviewed herein, we postulate that a renal abnormality that contributes to essential hypertension in the general population is a reduced number of glomeruli and tubules, the consequences of which are limitations in the ability to excrete sodium and thus salt-sensitive hypertension. Furthermore, congenitally decreased filtration surface area may explain why only some, but not all, patients exposed to potentially injurious renal stimuli eventually manifest chronic nephropathy, and may also account for the susceptibility of subsets of type I and type II diabetics to develop overt glomerulopathy. Clinically, tests of renal reserve capacity may serve as a useful guide to identification of those patients at risk for the development of hypertension and progressive renal disease.
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PMID:The interrelationships among filtration surface area, blood pressure, and chronic renal disease. 138 55

OBJECT OF TREATMENT: Antihypertensive treatment in hypertensive patients with insulin-dependent diabetes mellitus is intended to prevent long-term complications, particularly diabetic nephropathy. DIABETIC HYPERTENSIVES WITH ABNORMAL ALBUMINURIA: Antihypertensive therapy, particularly with angiotensin converting enzyme (ACE) inhibitors, typically produces a permanent reduction in the decline of the glomerular filtration rate (GFR) in diabetic patients with abnormal albuminuria. The rate of decline in the GFR during antihypertensive treatment is a well accepted end-point in diabetic renal disease. DIABETIC HYPERTENSIVES WITHOUT ABNORMAL ALBUMINURIA: In insulin-dependent diabetic patients with essential hypertension but with normal urinary albumin excretion there is no reduction in the GFR. Longitudinal studies have shown a fall in the GFR only in the presence of significantly increased urinary albumin excretion. ABNORMAL ALBUMINURIA AS A MARKER OF INCIPIENT NEPHROPATHY: Micro-albuminuria and proteinuria may be pathogenetic factors in the development of nephropathy, leading eventually to end-stage renal failure in diabetic patients. Measurements of micro-albuminuria and proteinuria, in addition to blood pressure recordings, might therefore be used as indications for initiating antihypertensive treatment. NEED TO MONITOR PATIENTS FOR ABNORMAL ALBUMINURIA: Transglomerular macromolecular traffic may produce mesangial damage, with subsequent glomerulopathy and diabetic nephropathy. Thus, close monitoring for micro-albuminuria and proteinuria is desirable in the management of diabetic hypertensive patients.
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PMID:Micro-albuminuria and the organ-damage concept in antihypertensive therapy for patients with insulin-dependent diabetes mellitus. 161 2

One-kidney, one-clip hypertension (1-K, 1-C HT) is initiated by increased preglomerular resistance which decreases nephron perfusion and causes several intrarenal changes that lead to increased mean arterial pressure (MAP). Elevated MAP serves to return nephron perfusion and sodium excretion to normal, so that fluid intake and output are balanced. Increased MAP usually occurs through volume homeostasis mechanisms that initially raise cardiac output and later elevate total peripheral vascular resistance via autoregulatory adjustments. However, if adequate volume is unavailable because of sodium restriction, sustained activation of the renin-angiotensin system increases blood pressure sufficiently to restore nephron perfusion. Thus, depending upon the availability of volume, renal perfusion and sodium balance can be restored either by volume retention or by increased angiotensin II (ANGII) formation and peripheral vasoconstriction. Similarities exist between 1-K, 1-C HT and low-renin essential hypertension (LRHT). In both cases, renal-pressure natriuresis is shifted to higher levels and there are marked increases in preglomerular resistance that necessitate increased MAP to maintain sodium balance. However, in 1-K, 1-C HT, there is a parallel shift of pressure natriuresis with little or no change in the slope of this curve, similar to that found in the normal-renin essential hypertension. In LRHT the slope of pressure natriuresis is decreased, indicating that blood pressure is much more salt sensitive than normal. Another difference is that PRA is low compared to normal PRA in 1-K, 1-C HT after compensatory increases in MAP. There is also no indication of glomerular membrane damage in 1-K, 1-C HT, whereas LRHT may have significant glomerulopathy, especially as hypertension progresses. These differences suggest that there may be additional factors besides preglomerular vasoconstriction involved in the etiology of LRHT. One possible factor is a reduction in nephron number in LRHT. Decreased functional nephrons would lead to glomerular hyperfiltration and increased distal tubular flow rate in the remaining nephrons, causing decreased PRA and eventually glomerular damage. Increased fractional sodium reabsorption, particularly in distal tubular segments, could also contribute to decreased PRA and cause blood pressure to be salt sensitive. These abnormalities, along with preglomerular vasoconstriction, may explain many of the characteristics of LRHT.
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PMID:Renal function in one-kidney, one-clip hypertension and low renin essential hypertension. 174 89

A primary role for the kidney in the initiation and maintenance of hypertension has long been recognized, but the pathogenetic interactions among renal hemodynamics, hormonal and hereditary factors, and dietary sodium intake remain enigmatic. Reduction in filtration surface area, whether acquired in the course of intrinsic renal disease or after surgical renal ablation, leads to systemic hypertension as well as to progressive renal insufficiency, sequellae made even more severe by dietary sodium excess. Moreover, hypertension and progressive renal disease eventuate in some individuals born with a solitary kidney, as well as in those with more severe degrees of dysgenesis (ie, oligomeganephronia). Hypertension is also commonly observed in certain inbred rat strains in which filtration surface area is congenitally deficient. Based on these and other lines of evidence reviewed herein, we postulate that a renal abnormality that contributes to essential hypertension in the general population is a reduced number of nephrons. The consequences of this abnormality are limitations in the ability to excrete sodium and thus, salt-sensitive hypertension. Finally, congenital variability in filtration surface area may explain why only some, but not all, patients exposed to potentially injurious renal stimuli eventually manifest chronic nephropathy. This may also account for the susceptibility of subsets of Type I and Type II diabetics to develop overt glomerulopathy.
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PMID:Glomeruli and blood pressure. Less of one, more the other? 1691 17

Captopril (Capoten; Squibb) is a specific orally active antagonist of peptidyl-dipeptide carboxyhydrolase, the enzyme which converts angiotensin I to angiotensin II and which inactivates bradykinin. Captopril therefore reduces blood pressure in a variety of animal models of hypertension. In 96 studies on 1570 patients, captopril has been shown to be superior to placebo and equivalent to either propranolol or a diuretic in the treatment of essential hypertension. In the management of severe treatment-resistant hypertension, the response to captopril (alone or in combination with a diuretic and/or propranolol) was better than the response to standard triple therapy. Captopril, with digitalis and a diuretic, also improved the haemodynamic and clinical status of patients with refractory congestive heart failure. Side-effects include skin rashes (15%), proteinuria (1,1%, or 0,4% of patients with no prior renal disease) and the nephrotic syndrome (0,9%, or 0,3% of patients with no prior renal disease). Nearly all patients with the nephrotic syndrome in whom renal biopsies were performed were found to have membranous glomerulopathy. Neutropenia (total white cell count less than 1,000/microliter) was found in 33 of over 6,000 patients (0,4%), but in all cases there were other possible causes for this. Captopril is the first of an important group of antihypertensive and afterload-reducing drugs; its major indications are likely to be in the treatment of refractory severe hypertension or congestive heart failure.
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PMID:Captopril--an overview. 621 58

This case report describes a patient with essential hypertension in whom captopril during seven months resulted in a nephrotic syndrome. A renal biopsy specimen revealed membranous glomerulopathy stage I. After withdrawal of the drug, urinary protein loss disappeared within ten days. However, a second biopsy three months later still showed granular deposition of IgA, IgG, IgM and C3 in the glomerular basement membrane and unchanged subepithelial electron-dense deposits on electron microscopy. Glomerular filtration rate remained normal during the observation period.
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PMID:Membranous glomerulopathy in a patient on captopril. 700 96

Vascular nephropathies are a steadily increasing cause of end-stage renal failure. Arterionephrosclerosis and arteriolonephrosclerosis are common features in the hypertensive patient. This is especially true for blacks of African descent, in whom hypertension and nephrovasculopathies are a major cause of renal insufficiency. That primary hypertension leads to renal vascular lesions, glomerular obsolescence and interstitial fibrosis has long been established. It should not, however, obscure the fact that renal vascular lesions can be observed in animal models as well as in some humans, especially young blacks, in the absence of, or anticipating the onset of hypertension. This leads to considering the hypothesis that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed and that this defect is strongly associated with the hypertensive trait. Atherosclerotic renal disease is a major, potentially treatable cause of chronic renal disease is a major, potentially treatable cause of chronic renal failure, especially in whites. It leads to renal atrophy, but the ischemic kidney retains a vigorous potential for tubular cell regeneration, which pleads for early recognition and treatment. Recent data suggest that renal ischemia, be it due to renal artery stenosis or to cholesterol crystal embolism, ranks among the multiple causes of secondary focal segmental glomerulosclerosis. Irrespective of its initial mechanism, ischemia induces renal fibrosis, the pathophysiology of which is centered on increased generation of angiotensin II. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension, and the relationship between these lesions and the unfavorable prognosis of glomerulopathies, especially primary focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis, remains to be elucidated. Expanding knowledge of the spectrum of nephrovasculopathies opens perspectives for investigating, understanding and treating a major mechanism of progressive renal insufficiency.
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PMID:Ischemic renal diseases: new insights into old entities. 964 58

Nephrovasculopathies are an increasing cause of end-stage renal failure. Nephrosclerosis is a common finding in the hypertensive patient. However, genetic factors play a prominent role in its incidence. Nephrosclerosis is a common cause of early renal failure in blacks of African ancestry, as opposed to white Europeans, in whom hypertensive nephrosclerosis rarely and slowly leads to uremia. That primary hypertension is accompanied by arterionephrosclerosis and arteriolonephrosclerosis, by focal and segmental glomerulosclerosis leading to glomerular obsolescence and by interstitial fibrosis has been established for nearly a century. However, renal vascular lesions can be observed in animal models as well as in some humans, especially blacks, in the absence of, or preceding the onset of hypertension. This suggests that nephroangiosclerosis might stem from a genetic defect in the renal vascular bed, a defect closely associated with the hypertensive trait. Atherosclerotic renal artery stenosis is a major, potentially remediable cause of chronic renal failure, especially in whites. Its prevalence in the atherosclerotic population is in the order of 15 percent. This figure has obvious bearing in terms of health cost. Early diagnosis and treatment by angioplasty or surgery can preclude development to end-stage renal disease and maintenance hemodialysis, as renal atrophy due to chronic ischemia resulting from renal artery stenosis can be halted or partially reversed by revascularization before extensive fibrosis sets in. Finally, renal vascular lesions are commonly observed in the course of various nephropathies, even in the absence of hypertension. The relationship between fibrogenesis and these vascular lesions, which develop along with interstitial fibrosis and entail an unfavorable prognosis in various glomerulopathies, remains to be elucidated. This is especially the case for focal-segmental glomerulosclerosis, membranous glomerulopathy and IgA glomerulonephritis. The pathophysiology of renal fibrosis induced by ischemia is centered on increased generation of angiotensin II that is fibrogenic owing to interaction with endothelin 1, PDGF-BB and TGF-beta. These notions open perspectives toward pharmacologic means to retard or even prevent the development of such various ischemic conditions to end-stage renal failure.
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PMID:[Vascular mechanisms of renal fibrosis. Vasculonephropathies and arterial hypertension]. 1037 63

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
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PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

African Americans are prone to develop not only essential hypertension but also progressive renal injury. We present a simple model to explain salt-induced renal injury (sodium glomerulopathy) in African Americans, the central features of which are the tubuloglomerular feedback and the balance/imbalance between the vascular tones of the afferent and efferent glomerular arterioles. We propose that in African Americans, habitual consumption of high salt causes chronic intermittent tubular hyperperfusion of the macula densa, resulting in a rightward and upward resetting of the operating point for the tubuloglomerular feedback. The resetting of the operating point causes an imbalance between the vascular tones of the afferent/efferent arterioles, a rise in the glomerular capillary hydraulic pressure, and consequent hyperfiltration. Increased susceptibility to glomerular hyperfiltration of African Americans on a high salt intake may explain their proclivity to progressive renal injury associated with essential hypertension.
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PMID:Sodium glomerulopathy: tubuloglomerular feedback and renal injury in African Americans. 1471 6


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