Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporine is a specially useful immunosuppressor agent in children subjected to renal transplantation, minimizing the deleterious effect of steroids on growth and the development of Cushing syndrome. However, side effects which require close supervision are well known, including liver, kidney and central nervous system toxicity. Seizures, cerebellar ataxia, aphasia, paresthesia and behavioral disorders are characteristic of the latter. Hypertension and hypomagnesemia have been identified as risk factors. In contrast to nephrotoxicity, CNS toxicity is not related to plasma levels of cyclosporine. In this paper 2 patients, 10 and 11 year old, manifesting cyclosporine neurotoxicity after renal transplant, are reported.
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PMID:[Neurotoxicity caused by cyclosporin A in renal transplantation in children]. 134 84

Orthotopic heart transplant recipients treated with immunosuppressive regimens based on cyclosporine have a high incidence of hypertension. Cyclosporine-induced nephrotoxicity characterized by afferent glomerular arteriolar vasoconstriction also develops in these patients. Calcium channel antagonists produce afferent glomerular arteriolar vasodilation. Angiotensin-converting enzyme inhibitors (ACEI) dilate the efferent arteriole and have been suggested to decrease glomerular filtration rate in subjects taking cyclosporine. To test the hypothesis that calcium channel antagonists would improve glomerular filtration rate in heart transplant patients receiving ACEI treatment, we reviewed the charts of our patients whose treatment for hypertension had been changed from an ACEI to a calcium channel antagonist. A change in renal function was assessed by the average of serum creatinine level, blood urea nitrogen, and creatinine clearance within 3 months before and after the change from ACEI to calcium channel antagonist. Blood pressure was assessed on two different occasions before and after conversion to calcium channel antagonist. The data were analyzed by a paired Student t test. Serum blood urea nitrogen and creatinine levels decreased significantly when patients were treated with calcium channel antagonists (p < 0.05). Creatinine clearance increased in all patients when the treatment was converted to a calcium channel antagonist (CCA) (ACEI = 56.4 +/- 19.3 ml/min versus CCA = 71.06 +/- 23.77, N = 9; p < 0.005). A 5-mm Hg decrease occurred in mean arterial pressure when treatment was changed from ACEI to calcium channel antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of calcium channel antagonists on renal function in hypertensive heart transplant recipients. 145 46

Cyclosporin A (CsA) is an effective therapy for severe intraocular inflammation but nephrotoxicity and hypertension are major side effects even in low dose in combination with oral corticosteroids and clinical studies on the long-term effects of low-dose CsA therapy outside the field of organ transplantation are lacking. This multicentre, open, longitudinal study has been established to evaluate the long-term efficacy and side effects of low-dose CsA therapy (initial dose less than or equal to 5 mg/kg/day, with a maximum dose of 7 mg/kg/day, and total treatment duration greater than 3 months) in severe ocular inflammation where conventional therapy had failed to control the disease or caused intolerable side effects. Visual response to treatment, clinical signs and symptoms of side effects, biochemical and haematological parameters have been recorded at 3-monthly intervals since January 1987 and will continue until December 1993. Data for 74 patients (age 35.5 +/- 16.6 years) and 293 follow up visits are presented in this preliminary report. [table: see text] Other side effects include (% of all visits): hypertrichosis (4.2), headache (2.8), cramps (1.8), arthropathy (1.8), paraesthesiae (1.8), abdominal pain (1.5), weakness (1.5), dyspepsia (1.4), nausea (1.4), others (4).
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PMID:Low-dose cyclosporin therapy of ocular inflammation: preliminary report of a long-term follow-up study. 150 18

This investigation is an assessment of the cyclosporin A-prednisone treatment which has been employed in all cases of therapy-resistant nephrotic syndrome in adults (n = 18) since January 1985 at the Department of Nephrology at the State University Hospital. Following an average duration of treatment of 20.7 months, five patients were in complete and eight in partial remission. All of the patients with minimal change disease (three patients) achieved complete remission. Recurrence after withdrawal of cyclosporin A occurred in three out of five patients. Cyclosporin A was withdrawn in five patients on account of suspected cyclosporin A nephrotoxicity. Hypertension, which was slight to moderate in the majority of cases, occurred frequently during treatment. Compared with the prognosis and frequency of complications in the untreated nephrotic syndrome and the frequency of side effects with the previously administered immunosuppressive treatment, the frequency of side effects with cyclosporin A treatment was acceptable. Until the indications are elucidated, adult patients with otherwise intractable nephrotic syndrome should be referred to special nephrological departments for possible cyclosporin A treatment.
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PMID:[Cyclosporin A treatment of adult patients with severe nephrotic syndrome]. 150 56

Arterial hypertension (HT) is a common complication after renal transplantation. We evaluated ambulatory blood pressure profiles during 24 h in 30 pediatric patients (pts) aged 6-22 years who had been transplanted 2 months to 7 years previously. Creatinine clearance was 14-121 (median 57) ml/min/1.73 m2. Twenty-three pts were being treated with ciclosporin. Sixteen pts received antihypertensive drugs. Using the monitor Nippon Collins 630 (Baxter), blood-pressure (BP) values were taken every 20 min during the day and overnight (10 p.m.-7 a.m.). Five out of 10 pts with elevated office BP readings were normotensive by ambulatory blood pressure monitoring (ABPM). Ambulatory hypertension was discovered in one child with normal office BP. Echocardiography was performed in 23 pts. Five of six pts with significant left-ventricular hypertrophy (LVH), but none of the 17 pts without LVH had ambulatory HT (p less than 0.01). The physiological decline of BP during the night was significantly reduced when compared to 21 subjects of similar age with essential HT (-9.2% vs. -15.4%; p less than 0.02); no correlation was found with renal function or prednisone dose. Ciclosporin tended to reduce the day-night gradient (-14.5% vs. -9.2%; p = 0.11). One child showed a severe nocturnal BP rise of 25 mmHg. We conclude that abnormalities of nyctohemeral BP rhythm, as described in transplanted adults, can be observed to a lesser extent in children. ABPM allows a better evaluation of BP compared to office BP and, thus, may contribute to a better management of these patients.
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PMID:[Ambulatory blood pressure measurement in children and adolescents with kidney transplants]. 151 16

Cyclosporine's toxic side effects are widely recognized as a cause of major morbidity. Peripheral vasoconstriction has been suggested as the pathophysiological mechanism for hypertension and renal failure caused by cyclosporine. To study vascular effects on peripheral arterial circulation, cyclosporine was injected into isolated hind limbs perfused at constant flow in the dog. Pure powder cyclosporine was dissolved in a 10% fat emulsion and infused directly into the arterial inflow of the perfused hind limb (n = 7) at a concentration of 5 mg/kg body weight. Reactivity of the vascular bed was first shown by an average decrease of 72 +/- 4 mmHg (95% confidence interval 63 to 81, P less than 0.01) in hind limb perfusion pressure after infusion of 5 mg nitroglycerin. Infusion of fat emulsion did not cause any significant changes. The infusion of cyclosporine caused an average increase of 29 +/- 5 mmHg (95% confidence interval 17 to 41, P less than 0.01) in hind limb perfusion pressure after 4 mins' infusion. After cyclosporine infusion, the vascular bed still responded to nitroglycerin by an average decrease of 56 +/- 5 mmHg (95% confidence interval 42 to 69, P less than 0.01) in perfusion pressure. Blockade of alpha-receptors with phentolamine in five dogs and ipsilateral lumbar sympathectomy in four prevented the increase in perfusion pressure following cyclosporine injection. In conclusion, cyclosporine injected at high doses causes a small vasoconstriction of the peripheral arterial circulation in the hind limb through stimulation of alpha-adrenergic receptors mediated by the sympathetic nervous system. Since the response is completely abolished by sympathectomy, it is probably caused by reflex activation. A direct effect of cyclosporine on the arterial vessel walls of the limb can therefore be excluded.
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PMID:Effect of direct injection of cyclosporine on the arterial vessels of the isolated hind limb in the dog. 164 70

Cyclosporine is the core component of all immunosuppressive protocols. Renal insufficiency and hypertension are the two major side effects of cyclosporine use. A vascular effect of cyclosporine could explain these complications. To study the effect of cyclosporine on vessel wall, a model of isolated renal and femoral artery perfusion was used in the dog. The injection of 0.5, 1, 5 and 10 mg of cyclosporine in the renal artery caused an average increase in renal perfusion pressure of 8 +/- 4, 15 +/- 8, 32 +/- 12 and 81 +/- 21 mmHg (p less than 0.05) respectively. Blockade of alpha-adrenergic receptors and renal sympathectomy did not modify the renal vascular response to cyclosporine. The injection of 1, 5, 10 and 20 mg of cyclosporine in the femoral artery caused an average increase in perfusion pressure of 4 +/- 2, 10 +/- 4, 9 +/- 2 and 20 +/- 8 mmHg (p less than 0.05) respectively. Blockade of alpha-adrenergic receptors and lumbar sympathectomy prevented the vasoconstrictive effect of cyclosporine on the femoral artery. Therefore, cyclosporine caused a significant increase in renal perfusion pressure and a modest vasoconstriction of the femoral artery. This effect appears to be related to an adrenergic mechanism only in the femoral circulation. We conclude that other studies are needed to define the mechanism responsible for the vasoconstrictive effect of cyclosporine.
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PMID:[Effect of therapeutic doses of cyclosporine injected into the renal and femoral arteries in dogs]. 166 94

In suspensions of permeabilized human neutrophils, the free Ca2+ concentration was measured to test the effects of ciclosporin. Free Ca2+ concentration was measured with a Ca2(+)-selective electrode. Ciclosporin (500 ng/ml) induced a transient increase in free Ca2+ concentration (maximum delta pCa, 0.41 +/- 0.17). Thereafter, the free Ca2+ concentration decreased again, but did not reach the baseline level in most experiments. Ruthenium red, but not orthovanadate, abolished the slow decline of free Ca2+ concentration after the initial increase. The experiments suggest that ciclosporin may induce a release of Ca2+ from cellular organelles, e.g. the endoplasmic reticulum, and a partial reuptake in mitochondria. A release of cellular Ca2+ may play a role in ciclosporin-induced hypertension.
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PMID:Ca2+ release in permeabilized human neutrophils induced by ciclosporin. 170 Mar 14

Five of 182 recipients of allogeneic bone marrow transplants performed between 2/84 and 6/90 developed seizures while receiving cyclosporine and methylprednisolone to prevent acute graft-versus-host disease. All received a radiation-free regimen of busulfan and cyclophosphamide as preparative therapy. Two patients received HLA-mismatched allografts; and three patients received marrow from HLA-identical sibling donors. Two patients had received extensive intrathecal therapy prior to transplantation. All patients were receiving standard prophylactic doses of CsA and MP at the time of onset (median 31 days posttransplantation) of seizures. Three patients had mild-to-moderate hypertension and varying degrees of morphologic evidence of microangiopathic hemolytic anemia. None had unusually low magnesium levels. Cyclosporine levels were not in the toxic range. Cranial magnetic resonance imaging and computed tomography (CT) showed bilateral abnormalities primarily in the posterior temporal, occipital, and parietal lobes. These abnormalities were shown to be transient on sequential MRI exams in two patients. Seizures as well as radiologic abnormalities resolved on stopping CsA and did not recur in 2 patients who subsequently received CsA in lower doses. These findings confirm and expand previous observations of CsA-associated seizures and demonstrate that they occur in allogeneic bone marrow transplant recipients following a radiation-free preparative regimen of busulfan and cyclophosphamide.
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PMID:Cyclosporine-associated seizures in bone marrow transplant recipients given busulfan and cyclophosphamide preparative therapy. 187 5

The effects of cyclosporine A treatment on arterial pressure and renal function were assessed in 11 young patients with type I diabetes of short duration. Cyclosporine was started at 7.5 mg/kg/day, progressively decreased to 6.3 mg/kg/day at 6 months, and then continued at a lower dose (4.1 mg/kg/day) for an additional 3 months in patients in whom remission of insulin dependency was obtained (n = 6). After 3 months of cyclosporine, a slight but significant increase in arterial pressure (+5.2 +/- 1.5 mm Hg), a rise in renal vascular resistance (approximately 20%), a decrease in glomerular filtration rate (approximately 25%), and a fall in filtration fraction were observed. Such changes were sustained after 6 and eventually 9 months of therapy. The decrease in glomerular filtration rate observed during cyclosporine treatment contrasted with the lack of change in simultaneously estimated creatinine clearance; in fact, the creatinine clearance/glomerular filtration ratio increased from 1.07 +/- 0.05% to 1.33 +/- 0.09% within 3 months of cyclosporine therapy, thus suggesting an enhanced tubular secretion of creatinine. Plasma renin activity and urinary excretion of kallikrein decreased significantly (approximately 50%), whereas plasma aldosterone concentration remained unaltered and plasma concentration of potassium increased during cyclosporine therapy. These changes were observed in the presence of a constant urinary excretion of sodium and potassium and a constant body weight. All parameters returned to pretreatment values within 3 months after cessation of cyclosporine. These results indicate that cyclosporine given for 6-9 months at a moderate dose causes a deleterious but reversible effect on arterial pressure and renal function in young diabetic patients.
Hypertension 1991 Sep
PMID:Renal changes associated with cyclosporine in recent type I diabetes mellitus. 188 46


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