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Renal vascular resistance in essential hypertension: duplex-Doppler ultrasonographic evaluation.

Duplex Doppler ultrasonography has been validated as a noninvasive method to evaluate hemodynamic features of renal blood flow in renal and intrarenal arteries in patients with various renal diseases. The significance of duplex Doppler sonography in the evaluation of renal vascular resistance in essential hypertension has not yet been clearly determined. The aim of the present study was to evaluate the renal vascular resistance in patients with essential hypertension by measuring intrarenal arterial resistance (RI) and to correlate RI with renal functional tests and other clinical and laboratory data. Duplex Doppler ultrasonography was used to measure RIs in intrarenal arteries in 128 patients with essential hypertension and 61 age-matched normotensive control examinees. The renal vascular resistance index (RI) was determined by use of Doppler ultrasound. Hypertension was classified according to the 1997 Joint National Committee Guidelines (JNC-VI). Mean RI in hypertensive patients was 0.66 +/- 0.05 (+/- sd) and in healthy controls 0.60 +/- 0.03 (+/- sd) (p = 0.0001). RI correlated significantly with patient's age (r = 0.577, p = 0.001), duration of hypertension (r = 0.335, p= 0.001), stage of hypertension according to the JNC-VI classification (r = 0.315, p = 0.006), creatinine clearance (r = -0.383, p = 0.001), systolic blood pressure (SBP, r = 0.41, p = 0.001) and mean blood pressure (MBP, r = 0.30, p = 0.002). RI values did not correlate significantly with plasma renin concentration (r = -0.198 NS), diastolic blood pressure (DBP, r = 0.17, p = 0.06), and cardiac pulse (r = -0.10, p = 0.16). Multiple regression analysis showed that independent variables for RI were the patient's age (multiple R = 0.53, signif. F = 0.001) and systolic blood pressure (multiple R = 0.57, signif. F = 0.03). The renal Doppler resistance index (RI) is increased in essential hypertension and it correlates with renal functional tests as well as with patient's age, duration of hypertension, with a stage of hypertension according to the JNC-VI classification, and with systolic and mean blood pressure. The increased renal vascular resistance (RI) in hypertensive patients could be a sign of developing hypertensive nephrosclerosis and consequently renal failure. The utilization of the renal vascular resistance index (RI), provides a new noninvasive parameter in the followup of patients with essential hypertension.

Adult↗

[Surgical treatment of arterial hypertension: experience and results].

Hypertension is a wide spread disease. In a small percentage of cases (nephrosclerosis, renovascular hypertension, endocrine hypertension) surgical treatment could be resolutive. The Authors describe their experience of the last five years about the subject, emphasize the technical detail taken and the results achieved; they outline the necessity to give the indications for surgery in wise manner considering clinical, laboratory and instrumental findings.

Humans↗

Kidney angiotensin receptors and their role in renal pathophysiology.

A considerable amount of data have implicated angiotensin receptors (AT receptors) in the development and maintenance of essential hypertension and renovascular hypertension as well as in progressive renal pathologies. Inhibition of angiotensin II (Ang II) action by blocking Ang II formation through angiotensin-converting enzyme (ACE) inhibitors, or by blocking AT1 receptors directly using subtype-selective nonpeptide antagonists, has been found to attenuate the proteinuria, microalbuminuria, glomerulosclerosis, and nephrosclerosis in a variety of experimental models and in clinical trials. This review will first broadly discuss AT receptor subtypes in terms of their structure, function, tissue distribution and signaling. Secondly, the mechanistic differences between ACE inhibition and AT1 receptor blockade will be examined because these pharmaceutical agents are widely used tools to investigate the role of AT receptors in renal disease. Lastly, experimental models of essential hypertension, renovascular hypertension and progressive renal disease will be presented, which include the Fawn-hooded rat, the stroke prone spontaneously hypertensive rat, renal mass ablation and the 2K1C and 1K1C animal models. The overall goal of this review is to critically evaluate the data regarding the role of AT receptors in the pathophysiology of renal disease.

Angiotensin II↗

[Two aged patients with chronic renal failure and chronic disseminated intravascular coagulation secondary to aortic aneurysms: effect of continuous subcutaneous heparin infusion therapy].

We describe here two cases of chronic disseminated intravascular coagulation(DIC) secondary to aortic aneurysms. The patients were 78- and 84-year-old males, who visited our hospital to receive hemodialysis therapy for chronic renal failure probably due to nephrosclerosis. They had mild bleeding tendency and thrombocytopenia(< 10 x 10(4)/microliter). Coagulation test revealed the findings of chronic DIC in both patients, and computed tomography showed abdominal and thoracoabdominal aortic aneurysms with mural thrombi, respectively. In one patient, subcutaneous hemorrhage after vascular access surgery had continued for a month. However, the hemorrhage and swelling of the limb disappeared after continuous subcutaneous heparin infusion(CSHI) therapy in a daily dose of 10,000-14,000 unit. These findings suggest that chronic DIC secondary to aortic aneurysm should be considered when bleeding tendency and thrombocytopenia are observed in aged patients, and that CSHI is the choice of therapy for the bleeding tendency of chronic DIC.

Aged↗

The use of bivalirudin in patients with renal impairment.

The majority of patients with acute coronary syndromes have renal impairment from either the aging process or from underlying disease, such as nephrosclerosis or diabetes. For example, in the phase 3 studies of bivalirudin use in PTCA, only 25% of patients had normal renal function: 46% had mild renal impairment, 28% had moderate renal impairment and about 1% had severe renal impairment. In patients with normal renal function, the intravenous pharmacokinetics of bivalirudin are dose proportional (linear) and are characterized by rapid plasma clearance (4.58 ml/minute/kg), a small volume of distribution (0.2 L/kg), and an elimination half-life of about 30 minutes. Renal clearance is the primary route of elimination of bivalirudin. As for other small polypeptides, bivalirudin is filtered at the glomerulus, secreted in the proximal convoluted tubule, reabsorbed in the distal convoluted tubule and degraded within intracellular lysosomes to constituent amino acids. There is a direct positive relationship between the dose of bivalirudin, plasma concentrations and the activated partial thromboplastin time (aPTT) or activated clotting time (ACT). A study comparing the pharmacokinetics and pharmacodynamics of bivalirudin with normal renal function (GFR greater than or = 90 ml/minute; n = 8), mild (GFR 60-89 ml/minute; n = 8), moderate (GFR 30-59 ml/minute; n = 7), or severe (GFR < 30 ml/minute; n = 10) renal impairment showed that while clearance was similar in the normal (4.58 ml/minute/kg) and mildly impaired (4.94 ml/minute/kg) groups, the clearance rate was reduced 45% in the moderate impairment (2.50 ml/minute/kg) group and about 68% in the severe impairment (1.46 ml/minute/kg) group. Clearance was further reduced (77%) in a group of 12 dialysis dependent patients (1.04 ml/minute/kg). There was a strong positive correlation between plasma bivalirudin concentrations and aPTT. The derived maximal effect (Emax) was similar for the normal (58.3 seconds), mildly impaired (44.7 seconds) and moderately impaired (56.8 seconds) groups, but prolonged in the severely renally impaired (79.4 seconds) and dialysis dependent (84.4 seconds) patients. These kinetic and dynamic results have recently been substantially confirmed in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), where reduced plasma clearance (20%) and elevated ACTs were observed in patients with moderate renal impairment. The bleeding results of the phase 3 PTCA clinical trial (involving 4,312 patients) in which patients were classified as having normal renal function, or mild, moderate or severe renal impairment (using the above criteria), is consistent with the pharmacokinetic data. The incidence of major bleeding was directly correlated with renal function for both bivalirudin (normal, 1.2%; mild, 1.9%; moderate, 6%; severe, 0%) and heparin (normal, 3.1%; mild, 8.5%; moderate, 12.7%; severe, 26.7%). Importantly, the incidence of major bleeding was significantly less on bivalirudin than heparin in patients with any degree of renal impairment. The mean 45-minute ACT values were similar (350-400 seconds) in the normal, mild and moderately impaired groups, but elevated in the severely impaired group (450 seconds). A multivariate analysis of bleeding covariates in this database indicated that GFR is an important risk factor for bleeding (r(2) = 0.054), and accounted for twice the variability in bleeding as either sex or age.

Angioplasty, Balloon, Coronary↗

Deterioration in renal function associated with fibrate therapy.

BACKGROUND: Fibric acid derivatives (fibrates) are commonly used for the treatment of hyperlipidemia. A side-effect of these medications that is not well recognized is deterioration in renal function during therapy. This study reviewed a series of patients who showed such a deterioration. METHODS: The design was a retrospective chart review. Data extracted included creatinine, urea, cyclosporine levels, medical history, and medications. Charts were examined for other potential reasons for a change in creatinine. RESULTS: There were a total of 10 patients. All were males between the ages of 37 and 71. All had a history of renal insufficiency. Six had received a renal transplant and, of these, 5 were on cyclosporine. Reasons for underlying renal impairment included diabetes, hypertension, nephrosclerosis, and renal disease of unknown etiology. Most patients had risk factors for or the presence of vascular disease. The mean pre-treatment creatinine was 182 +/- 14 micromol/l (2.1 +/- 0.2 mg/dl) (mean +/- SE), compared to a peak creatinine on the medication of 247 +/- 16 micromol/l (2.8 +/- 0.2 mg/dl) (p < 0.001). The post-medication mean was 183 +/- 13 (2.1 +/- 0.1 mg/dl) (p < 0.001 vs maximum creatinine). Urea values also increased with therapy and decreased following discontinuation of the fibrate. Cyclosporine levels did not change with treatment. All recorded creatine kinase values were within the normal range. CONCLUSIONS: A group of 10 men showed a reversible deterioration in renal function while being treated with a fibrate for hyperlipidemia. The mechanism involved in the deterioration in renal function is not clear. The most plausible mechanism is one based on renal hemodynamics, given the rapid and complete reversibility that was noted and the finding that most patients had risk factors for vascular disease. If patients with pre-existing renal dysfunction are to receive a trial of fibrate therapy, this should be done with caution and

Adult↗

[Fibronectin content in the urine of patients with chronic glomerulonephritis as a test for the efficiency of treatment].

Renal fibronectin synthesis is impaired in patients with chronic glomerulonephritis. We measured urinary fibronectin for evaluating the efficiency of various methods of treatment. Traditional therapy of patients with the nephrotic syndrome at the stage of renal failure leads to decrease of fibronectinuria, which can be indicative of the progress of nephrosclerotic process in the renal parenchyma; monotherapy with wobenzyme during the azothemic stage of disease in patients with the urinary and nephrotic syndrome does not cause statistically significant changes in the level of urinary fibronectin, which can be regarded as inhibition of nephrosclerosis process. Hence, wobenzyme is the drug of choice, decreasing the velocity of nephrosclerotic processes, when pathogenetic therapy is largely limited or precluded. Combination of wobenzyme with pathogenetic drugs in patients with the nephrotic syndrome and intact renal function suppresses fibronectinuria due to mutual potentiation of the antiinflammatory effect. Decrease of fibronectin concentration in the urine after wobenzyme monotherapy in patients with the urinary syndrome without signs of chronic renal insufficiency confirms the antiinflammatory effect of the drug.

Adjuvants, Immunologic↗

Levels of serum complement components in patients undergoing renal dialysis.

Following acceptance to a renal dialysis therapy program, 13 patients underwent serial examination of the serum complement system for periods of 6 to 12 months. Serum levels of C3 and C4 were examined at monthly intervals before the first dialysis of each month. The patients suffered from various primary renal diseases, including glomerulonephritis, obstructive uropathy with chronic pyelonephritis, nephrosclerosis and chronic nephropathy of undetermined nature. Levels of serum C3 were depressed at some time during the study period in all patients. Serum C4 levels were normal. The depression of serum C3 levels was significant and prolonged in nine patients. There seemed to be no relationship between the nature of the basic disease and the depression of serum C3 levels. Caution should be exercised in attributing depressed C3 levels to a particular type of underlying renal disease in patients on renal dialysis.

Complement C3↗

[The role of the selective blocking of angiotensin II receptors in the treatment of cardiovascular diseases].

Angiotensin II plays an important role in blood pressure control and in water and salt homeosthasis. It is involved in the pathogenesis of hypertension and structural alterations of the vasculature, kidney, and heart, including nephrosclerosis, post infarction remodelling and left ventricular hypertrophy. At least two subtypes of receptors have been identified, angiotensin type 1 (AT1) and type 2 (AT2). The AT1 receptor is responsible for all the known effects of Ang II on blood pressure, osmoregulation, and cell growth and consequently for the contribution to cardiovascular and renal pathology. Research has indicated that the AT1 receptor modulates cardiac and vascular hypertrophy, cellular growth and ventricular remodelling. Evidence suggests that, on the other hand, the AT2 receptor is involved in growth inhibition, inhibits cell proliferation, induces vasodilatation and reverses the AT1 induced hypertrophy. The accumulating evidence appears to demonstrate therefore that the function of these receptor subtypes may exerts opposite effects while stimulated by AngII. The angiotensin receptor antagonists are able to inhibit the renin angiotensin system by blocking selectively the AT1 receptor. It is supposed that AT1 receptor antagonists may provide end organ protection by blocking angiotensin II effects via the AT1 receptor leaving the AT2 receptor unopposed: it is conceivable that the stimulation of AT2 receptors may prevent the hypertropic effects seen in conditions such as LVH, hypertrophy, postinfarction remodeling and repair after injury. For this, the AT1/AT2 selectivity associated to these drugs may be important for their effects and to differentiate them from ACE inhibitors.

Angiotensin I↗

The role of lifestyle management in the overall treatment plan for prevention and management of hypertension.

Hypertension is the most common cardiovascular risk factor in the U.S. population, and hypertensive nephrosclerosis is a common cause of progressive renal disease. Dietary and lifestyle modifications have shown promise in enhancing the effectiveness of blood pressure (BP) management. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNCVI) includes recommendations for prevention and management of hypertension. Recommendations include reducing sodium intake, increasing potassium, calcium, and magnesium intake, controlling obesity, and avoiding heavy alcohol intake, along with aggressive BP control. JNCVI guidelines provide a reasonable approach to lifestyle interventions, the benefits of which would outweigh the antihypertensive effects. The data suggest that such guidelines would benefit normotensive people as well.

Alcohol Drinking↗

Infliximab treatment in a patient with rheumatoid arthritis on hemodialysis.

We describe a 60-year-old woman with active rheumatoid arthritis (RA) and endstage renal disease secondary to hypertensive nephrosclerosis undergoing hemodialysis. She had tried multiple antirheumatic medications; however, their usefulness was limited due to toxic side effects or lack of efficacy. She was then treated with chimeric antitumor necrosis factor monoclonal antibody (infliximab), which resulted in immediate improvement in clinical and laboratory measures. After about 2 years of therapy, no side effects have been observed. This report expands the spectrum of infliximab to include RA patients with renal insufficiency.

Antibodies, Monoclonal↗

Pathogenesis of malignant hypertension: experimental evidence from the renal hypertensive rat.

In rats with unilateral renal artery stenosis, the malignant phase of hypertension is characterized by: systolic blood pressure above 180-190 mm Hg; sodium and water loss; polyuria and polydipsia; markedly activated renin-angiotensin-aldosterone system; impairment of renal function and malignant nephrosclerosis in the contralateral kidney; some rats exhibit signs of cerebral hemorrhage, heart failure, acute renal failure, and some rats die. After such a phase of malignant hypertension, a period of remission may occur, which is followed by another malignant phase, etc. When malignant hypertensive rats are offered, in addition to water, saline as drinking fluid, they compulsively drink the saline, BP falls transiently, and all signs of malignant hypertension nearly or completely disappear. These observations indicate that, at a critically high BP level, it is salt and water loss which, by activating the renin-angiotensin system, trigger the vicious circle of malignant renal hypertension in rats.

Animals↗

Renal vein renin in essential hypertension.

A frequency distribution curve and interval percentages of variations in right versus left renal vein renin (RVR) were calculated from 227 sets of renin data from patients with mild and moderate essential hypertension (EH). A renal vein renin ratio (RVRR), large/small, of approximately 2.0 or more falls beyond the 95 per cent confidence interval, and may therefore by considered to be abnormal. Although assay variability and sampling errors may contribute to artifactually large RVRR's in EH, they usually indicate true disparity, probably secondary to asymmetrical nephrosclerosis. Recent hypotheses regarding diagnostic value of RVR in hypertension are evaluated in light of data yielded by this investigation. Simultaneous and/or replicate sampling should reduced within-patient variability and improve clinical interpretation of test results.

Adult↗

[Pathogenesis of "Leningrad" (blockade) hypertension (60-th anniversary of the Leningrad blockade)].

Leningrad (blockade) hypertension observed in survivors of the Leningrad blockade during the World War II is a unique form of hypertension initiated and maintained pathogenetically by disturbed neuroregulation resultant from a severe psychoemotional stress. Pathogenesis of Leningrad hypertension involves mechanisms playing a key role in pathogenesis of other forms of essential hypertension. A characteristic feature of this pathogenesis is interaction of the initial and key neurogenic factor with such hypertensive factors of alimentary-dystrophic genesis as lesions of the vascular wall secondary to marked hypoproteinemia and hypovolemia. Later, in addition to hypertension the patients developed atherosclerosis, nephrosclerosis and other diseases.

Adult↗

Diazoxide in the management of severe hypertension.

Fourteen patients with severe hypertension have been given i.v. diazoxide in a dosage of 5 mg/kg b.wt. The material comprised 2 patients with malignant nephrosclerosis, 4 with chronic nephropathy and severe reduction of renal function, 1 patient with chronic pyelonephritis, 1 with renovascular hypertension and 6 patients with essential hypertension and in malignant phase. All patients attained a controllable blood pressure. Eight patients remaining needed only one injection, while the remaining patients required 2-5 injections, and concomitant furosemide therapy. The retinopathy improved in most patients and renal function was unchanged in the azotemic patients. No serious adverse effects were seen, except one hypotensive episode. Diazoxide is easy to handle, dosage can be predetermined, monitoring is simple and we find diazoxide to be a valuable drug in severe hypertension.

Adult↗

Management of chronic renal insufficiency: a call for a proactive approach.

As many as 6.2 million Americans may have chronic renal insufficiency (CRI), an insidious disease that can arise as a result of diabetes, hypertensive nephrosclerosis, chronic glomerulonephritis, and many other disorders. CRI usually progresses over time to end-stage renal disease, when patients require either dialysis or kidney transplantation in order to survive. With this population identified, primary care physicians, nephrologists, and payers have an opportunity to prevent or at least slow the progression of renal disease. The Renal Anemia Management Period (RAMP) may help raise awareness of the need for early diagnosis and aggressive treatment of anemia, one of the leading causes of morbidity in CRI patients. Such treatment has the potential to prevent or control the development of significant morbidity and mortality.

Anemia↗

First kidney transplantation from a non-heart-beating donor in the Czech Republic.

The long-lasting decline in the number of kidney donors with brain death in recent years is the reason for a quest for new sources of kidney donors in the Czech Republic. One possible source to increase the number of donor kidneys is the program of obtaining kidneys from non-heart-beating donors (NHBDs). Based on previous experience abroad, optimum hospital conditions, and, first of all, three years of experimental work, it was possible to realise an NHBD program for the first time in the Czech Republic, in the Transplant Centre of the Plzen Hospital in early 2002. The first two kidneys were obtained from a donor with a devastating gunshot brain injury (Maastricht criteria, Class III). After machine perfusion (RM3 renal perfusion system, Waters Medical) both kidneys were transplanted into two recipients with chronic renal insufficiency (chronic glomerulonephritis, nephrosclerosis). Both kidneys resumed their function immediately. For immunosuppression, basiliximab (Simulect, Novartis), rapamycin (Rapamune, Wyeth), and methylprednisolone (Urbason solubile forte, Hoechst) were used. To improve renal function, cyclosporine A (Sandimmune Neoral, Novartis) was started later in the course, simultaneously reducing the dose of rapamycin. The postoperative course was uneventful and both patients could be discharged on the twenty-first day of hospitalisation for further care at home.

Creatinine↗

An update on 'progression promoters' in renal diseases.

AIM: This paper reviews progression in renal diseases. METHODS: An English language literature search using Medline (1980 January-2001 July) was done to assess research and review articles on progression in renal diseases. RESULTS: Factors that increase the risk of progression in renal diseases are hypertension, dyslipidaemia, underlying nephropathy, high dietary protein intake and proteinuria. Others are smoking, hyperglycemia, low birth weight, obesity, metabolic syndrome X, genetic factors such as angiotensin converting enzyme 'DD' genotype and chromosome 1q21, and exposure to lead. Hypertension induces arteriolar nephrosclerosis. The mechanisms whereby lipids contribute to vascular and renal injury are incompletely understood. Glomerular hyperperfusion and increased proteinuria may explain the adverse effects of increased protein intake on renal disease progression. Proteinuria contains numerous toxic/inflammatory systems that promote progression. Cigarette smoking has vasoconstrictive, thrombotic and direct toxic effects on the vascular epithelium. Hyperglycemia is strongly implicated in the progression of complications in diabetics. Oligonephropathy in low birth weight has been suggested to increase the risk for systemic and glomerular hypertension in adult life. In obesity, the combination of hyperfiltration, glomerular hypertrophy and glomerular hypertension is a primary initiating event for glomerular injury manifesting as glomerulomegally and focal and segmental glomerulosclerosis and proteinuria. Angiotensin I, with enzyme insertion/deletion polymorphism, especially the "DD" genotype, predisposes to a rapid decline in renal function. Finally, long-term exposure to low levels of environmental lead affects renal function. CONCLUSION: The control of hypertension, dyslipidaemia, proteinuria, obesity, avoidance of low birth weight, smoking and heavy metals such as lead are intervention strategies for preventing progression of renal diseases.

Angiotensin II↗