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Biomedical subjects

S C Textor

Publications and source records attributed to S C Textor.

At least 37 records · Page 2Linked to original sources

Renal failure related to angiotensin-converting enzyme inhibitors.

The introduction of agents that block the renin-angiotensin system has provided major benefit to patients with hypertension, renal diseases, and congestive heart failure. Some of the therapeutic advantages related to the kidney derive from removing angiotensin II at the efferent arteriole. Under some circumstances when afferent blood supply is compromised, particularly beyond a renal arterial stenosis, use of angiotensin-converting enzyme (ACE) inhibitors can lead to decrements of glomerular filtration rate (GFR) and impaired potassium excretion, which clinicians should be prepared to identify and manage. How often this occurs and when such a decrement poses a hazard to renal parenchymal viability depends on the starting conditions of the renal vasculature and sodium balance. Although these observations have been made primarily with ACE inhibitors, the basic principles apply to other agents interacting with components of the renin-angiotensin system, including angiotensin II antagonists and renin-inhibitors. When promptly identified and treated, changes in kidney function under these conditions represent a modest and acceptable risk worth taking in exchange for major therapeutic benefits.

Angiotensin II↗

Role of steroid dose in hypertension early after liver transplantation with tacrolimus (FK506) and cyclosporine.

Transplant immunosuppression using either cyclosporine (CsA) or tacrolimus (FK506) leads to renal vasoconstriction and nephrotoxicity. Despite producing similar effects within the kidney and blood vessels, clinical hypertension occurs less frequently with tacrolimus during the first year after transplantation, compared with CsA. To examine the role of steroid dose in early posttransplant hypertension, we measured blood pressure and kidney function in liver transplant recipients treated with tacrolimus and either high-dose (TAC-HI-P, n = 19) or low-dose (TAC-LO-P,n = 20) prednisone, compared with CsA-treated recipients (n = 29) receiving prednisone doses similar to the TAC-HI-P group. At 1 month, hypertension occurred more often with CsA (72%) than with TAC-HI-P (42%, P < 0.05) or TAC-LO-P (30%, P < 0.05). By 4 months after transplantation, hypertension developed in nearly twice as many TAC-HI-P (63%) as TAC-LO-P patients (32%, P < 0.05), with no difference between TAC-HI-P and CsA (86%, NS). Daily prednisone dose at 1 month closely paralleled cumulative steroid dose in the first month in the TAC-HI-P and TAC-LO-P groups. Fourteen of 19 TAC-HI-P patients (74%) required bolus steroids for treatment of rejection within the first month, compared with 3/20 (15%) TAC-LO-P and 10/29 (34%) CsA recipients. Glomerular filtration rate fell from pretransplant levels at 1 month and 4 months to the same degree in CsA, TAC-HI-P, and TAC-LO-P patients. These results demonstrate a central role for steroid dose in the rate of onset of hypertension early after liver transplantation using tacrolimus immunosuppression. Both daily dose and cumulative dosage, including bolus treatment for rejection, may impact on the development of hypertension. Since prevalence rates rise to levels comparable to CsA by 24 months regardless of steroid dose, hypertension after liver transplant may be mediated by different mechanisms at different stages of the posttransplant course.

Blood Pressure↗

Computed tomography-derived intrarenal blood flow in renovascular and essential hypertension.

The effect of renal artery stenosis on intrarenal perfusion and volume in renovascular hypertensive patients is unclear. Alterations in these attributes may ultimately be involved in deterioration of renal function. We measured whole kidney, cortical, and medullary perfusion and volume with electron beam computed tomography (EBCT) in 33 hypertensive patients, with well-preserved renal function, scheduled for renal angiography. EBCT-derived whole kidney perfusion was lower in patients with atherosclerotic renal artery stenosis (RAS; N = 20) than in fibromuscular dysplasia (FMD; N = 10) or essential hypertension (N = 28; P < 0.05), as was cortical perfusion (2.44 +/- 0.16 vs. 3.26 +/- 0.17 and 3.07 +/- 0.09 ml/min/cc tissue, respectively, P < 0.005), but medullary perfusion was similar. Whole kidney, cortical, and medullary perfusion correlated inversely with degree of stenosis in FMD, but not in atherosclerotic RAS. Renal volumes were similar. These results demonstrate that, in contrast to patients with FMD, in patients with atherosclerotic RAS the decrease in cortical perfusion is not directly related to the degree of stenosis in the main renal artery. Factors other than the stenosis itself may play a role in the pathophysiology of atherosclerotic RAS and associated renal failure.

Adult↗

Radiographic evaluation of the renal vasculature.

Renal artery stenosis is an important cause of hypertension and progressive renal insufficiency. Additionally, there is increasing concern that renovascular disease is a significant, but previously-unrecognized, cause of end-stage renal disease in certain subsets of patients. Advances in revascularization techniques offer a greater opportunity for blood pressure control and for the restoration or preservation of renal function. Accurate imaging of the renal vasculature, however, is essential for the proper selection of those individuals who might best benefit from such intervention. Although conventional or digital subtraction arteriography remains the gold standard diagnostic test, significant advances in non-invasive imaging techniques now offer the clinician several options for the accurate diagnosis of hemodynamically significant renovascular disease. These techniques include captopril renography, duplex ultrasonography, magnetic resonance angiography, and spiral/fast computed tomography. In this review, the advantages and limitations of these imaging techniques are compared and contrasted with an emphasis on their usefulness in screening for renovascular disease. Also reviewed are recent applications of these techniques for measurement of renal function, predicting outcome of revascularization, and the clinical monitoring of patients with renovascular disease managed either medically or by revascularization.

Diagnostic Imaging↗

Atherosclerotic renovascular disease as a cause of end-stage renal disease: cost considerations.

Atherosclerotic vascular disease affects an increasing number of patients with end-stage renal disease. A review of comorbid atherosclerotic disease in 7,200 end-stage renal disease patients indicated that occlusive disease of the renal arteries may contribute to progressive renal failure in 1.34% of the US dialysis population or in 14% of the Caucasian patients with hypertensive nephrosclerosis. The costs of dialytic care in such patients exceed USD 87 million annually. The risks and costs of surgical revascularization of such patients are large, however. These data argue that prospective trials of intervention in atherosclerotic renal artery disease are urgently needed.

Adult↗

Loss of nocturnal blood pressure fall after liver transplantation during immunosuppressive therapy.

Hypertension, which develops after organ transplantation during immunosuppression with cyclosporine (CSA), is often associated with a loss of nocturnal decrease in blood pressure. Few data correlate circadian blood pressure patterns before transplant with those observed at fixed time points after transplant, or address the role of alternate immunosuppressive agents such as FK506. FK506 is unrelated structurally to CSA and less often leads to hypertension early after transplant. The present study compared nocturnal blood pressure patterns in patients with end-stage liver disease (ESLD) before transplant to those of transplant recipients receiving either FK506 (0.15 mg/kg/day) plus prednisone or CSA (2 to 3 mg/kg/day) plus prednisone and azathioprine after orthotopic liver transplantation. Overnight ambulatory blood pressure profiles were studied in 13 pretransplant ESLD patients and in 34 patients (FK506: n = 13; CSA: n = 21) treated with different steroid doses (24 +/- 11 mg/day FK506; 34 +/- 3 mg/day CSA), according to protocol, 4 weeks (range, 2 to 7 weeks) after liver transplant. Mean blood pressure and heart rate values from awake and nocturnal 5-h time blocks were compared to 13 normotensive control subjects. Patients with ESLD were normotensive and maintained a normal nocturnal blood pressure fall (125 +/- 3/74 +/- 2 mm Hg awake; 109 +/- 3/60 +/- 2 mm Hg nocturnal). Awake ambulatory blood pressures were higher in CSA patients than in FK506 patients (148 +/- 3/95 +/- 2 v 128 +/- 3/78 +/- 2 mm Hg, respectively; P < .01), despite reduced glomerular filtration rates in both transplant groups. Both immunosuppressive regimens led to a loss of nocturnal blood pressure fall, as compared to ESLD patients or normotensive controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Advanced renovascular hypertension and renal insufficiency: trends in medical comorbidity and surgical approach from 1970 to 1993.

PURPOSE: The primary aims of this study were to delineate trends in medical comorbidity and surgical approach in patients with renal atherosclerosis and azotemia. METHODS: We reviewed 1643 patients undergoing renovascular surgery between 1970 and 1993. We focused on those with the most advanced kidney disease (serum creatinine > 2 mg/dl) (n = 402). Attention was focused specifically on trends in sex, age, medical risk factors, surgical technique (bypass vs endarterectomy), and outcome including eventual need for long-term dialysis. RESULTS: From 1970 to 1980, 652 patients underwent renovascular surgery, with 98 (15%) having a serum creatinine > 2 mg/dl. From 1980 to 1993, the percentage of patients with renal insufficiency increased to 31% (304 of 991) (p < 0.001). Gender distribution did not change, but median age rose from 63.5 years in the first decade to 68.0 in the past 13 years. A remarkable increase in all serious medical risk factors also occurred (first vs second decade). Another significant trend was a shift toward bilateral simultaneous transaortic endarterectomy (18% from 1980 to 1985 vs 53% from 1986 to 1993; p < 0.01), which simplified and achieved complete renal revascularization, especially in patients having multiple renal artery stenoses and those needing aortic grafting for occlusive or aneurysmal disease (56% from 1970 to 1980 vs 75% from 1980 to 1993). Patients at low risk (0 to 1 comorbid medical conditions) had a 30-day mortality rate of 5.6% compared with patients at high risk (2 to 3 comorbid conditions) (15.5%) (p = 0.016). The eventual need for long-term dialysis remained low (9%) for patients with a preoperative serum creatinine of 2 to 2.9 mg/dl compared with those with a serum creatinine greater than 3 mg/dl (35%, p < 0.01). CONCLUSIONS: In the past 20 years, there has been a remarkable increase in the medical comorbidity and extent of aortic disease in patients undergoing surgical revascularization for advanced renovascular hypertension and renal insufficiency. However, the surgical approach can be simplified and expedited by bilateral transaortic endarterectomy, and the risk of late dialysis can be reduced significantly by operating before the serum creatinine exceeds 3 mg/dl.

Adult↗

Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation.

Transplant immunosuppression using either cyclosporine (CsA) or FK506 leads to renal vasoconstriction. To examine the role of endothelin (ET) in this process, we measured plasma and urinary ET before and at intervals for two years after liver transplantation. Urinary prostacyclin (as 6-keto-PG-F1 alpha), thromboxane, glomerular filtration rate and renal plasma flow were also measured. Forty-four patients were treated with CsA-based regimens and 31 patients with FK506-based regimens. Prednisone doses after one year were lower with FK506 (5.5 +/- 0.5 vs. 10.5 +/- 0.5 mg/day) by study design. Circulating plasma ET remained above normal, but not different from pre-transplant levels. Urinary ET was elevated before transplant (24.6 +/- 3.4 ng/day vs. normal 16 +/- 1.5 ng/day, P < 0.05) and rose further after transplantation (48.5 +/- 13 ng/day, P < 0.05), remaining elevated for two years. 6-keto-PG-F1 alpha fell from 2567 +/- 338 ng/day to subnormal levels and remained suppressed (1158 +/- 128 ng/day, P < 0.01). Over the same period GFR fell (84 +/- 3 ml/min to 60 +/- 3 ml/min, P < 0.01) and renal vascular resistance index rose (11,119 +/- 561 to 23,279 +/- 1692 d.s.cm-5.m-2, P < 0.01). Similar changes were observed both with CsA and FK506-based immunosuppression. No changes in ET were attributable to dihydropyridine calcium channel blockers. These results demonstrate that urinary ET changes independently from plasma ET after transplantation. Elevated ET and suppression of endothelium-derived prostacyclin persist with intense renal vasoconstriction for at least two years after transplant.

Cyclosporine↗

Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation.

Hypertension is common after orthotopic liver transplantation and may be due, in part, to cyclosporin A-induced renal dysfunction and/or enhanced proximal tubular sodium reabsorption. To determine whether enhanced proximal tubular sodium reabsorption is central to the development of posttransplant hypertension, measurements of renal hemodynamics and fractional clearances of lithium and sodium were compared 1 month after orthotopic liver transplantation in previously normotensive patients receiving either cyclosporin A (N = 24) or FK506 (N = 18), an immunosuppressive agent that is structurally unlike cyclosporin A and that has a lower reported incidence of hypertension. Median prednisone doses were 20 and 13 mg/day in the cyclosporin A and FK506 groups, respectively (P < 0.05). At 1 month, mean arterial blood pressure was higher in the cyclosporin A versus the FK506 group: 108 +/- 2 versus 95 +/- 3 mm Hg (P < 0.05). GFR, RBF, and renal vascular resistance were not different between the two groups: 59 +/- 4 and 53 +/- 5 mL/min per 1.73 m2, 439 +/- 28 and 440 +/- 41 mL/min per 1.73 m2, and 22,429 +/- 1,822 and 22,977 +/- 3,506 dyne s/cm5 per 1.73 m2, respectively. Fractional lithium excretion was similar in the cyclosporin A and FK506 groups: 19.9 +/- 2.2 and 19.4 +/- 2.0% (P = not significant) although both values were lower than those of normal controls (25.5 +/- 1.1%) (P < 0.05). Fractional sodium excretion was 2.7 +/- 0.3 and 2.3 +/- 0.4% in the cyclosporin A and FK506 groups, respectively (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Renal artery angioplasty: technical results and clinical outcome in 320 patients.

OBJECTIVE: To review the results of percutaneous transluminal renal artery angioplasty (PTRA), including technical success and clinical outcome, at Mayo Clinic Rochester. DESIGN: We retrospectively reviewed our experience with 320 patients who underwent PTRA for stenosis of 396 arteries during a 14-year period. MATERIAL AND METHODS: We reviewed medical records and angiograms of patients who underwent PTRA at Mayo Clinic Rochester between January 1980 and December 1993. The patients were divided into four groups, based on clinical history and angiographic appearance of the stenosing lesion: renal artery atherosclerosis (ASO group), fibromuscular dysplasia (FMD group), previous renal artery bypass or endarterectomy, and renal artery stenosis in a solitary kidney. Technical results of the PTRA were determined by evaluation of angiograms obtained before and after the procedure. Data on patient demographics, blood pressure, antihypertensive medications, and serum creatinine were recorded for the period preceding PTRA, after the procedure, and at last follow-up. RESULTS: All groups had statistically significant reductions in mean arterial pressure and antihypertensive medications after PTRA. The percentage of patients who benefited after renal artery angioplasty was 70% for patients with ASO (8.4% cured), 63% for patients with FMD (22% cured), 53.8% for patients with prior surgical revascularization (23.1% cured), and 91.7% for patients with a solitary kidney (0% cured). No significant overall change in serum creatinine level was noted after the procedure in any group. Complications were comparable to those reported in other studies. The 30-day all-cause mortality rate was 2.2% for the current study, all deaths occurring in the ASO group. CONCLUSION: PTRA rarely leads to a "cure" of renovascular hypertension but provides effective control of blood pressure and decreases the medication requirements in selected patients.

Adult↗

Postural tachycardia syndrome (POTS).

In orthostatic intolerance, the patient develops symptoms while standing that are relieved when the patient assumes a supine position. Different degrees of orthostatic intolerance exist, but not a system of grading severity. We have developed a system that grades the severity of orthostatic intolerance by the three-pronged criteria of the rapidity of development and the severity of orthostatic symptoms, the ability of the subject to withstand orthostatic stresses, and the degree of interference with daily living. In this article, this system is presented, and one disorder, postural tachycardia syndrome (POTS), is examined in some detail.

Humans↗

Hypertension after liver transplantation.

Hypertension developing after liver transplantation is nearly universal and likely reflects several pathogenic mechanisms. Foremost among these are altered vascular reactivity and vasoconstriction related to CSA, and probably FK506, administration, impaired GFR and sodium excretion, and the effects of steroids. This disorder is of both theoretical and practical importance in understanding blood pressure regulation in humans. Most importantly, it poses a considerable long-term cardiovascular risk for the transplant recipient. Recognition of acquired hypertension and timely intervention are among the primary management challenges for the transplant clinician.

Animals↗

Comparison of the postural tachycardia syndrome (POTS) with orthostatic hypotension due to autonomic failure.

Postural tachycardia syndrome (POTS) is characterized by orthostatic dizziness, tremulousness, tachycardia and variable blood pressure changes. Since some POTS patients have a marked reduction in pulse pressure on standing, a major mechanism of their symptoms might be venous pooling. We therefore studied the cardiovascular response to head-up tilt, Valsalva maneuver and deep breathing in: control subjects (n = 11; F = 8; M = 3; 39.2 +/- 14.4 years); patients with orthostatic hypotension secondary to autonomic failure (n = 11; F = 9; M = 2; 61.7 +/- 13.0 years), and patients with POTS (n = 15); F = 13; M = 2; 32.3 +/- 10.6 years). Blood pressure was measured with a Finapres, and cardiac output, stroke volume, end-diastolic volume and thoracic impedance (TFI) were measured by thoracic electrical bioimpedance. During tilt (in contrast to patients with orthostatic hypotensiom), patients with POTS had excessive tachycardia (P < 0.001), a normal to excessive total peripheral resistance increase, and an exaggerated decrease in stroke volume (P < 0.001) and end-diastolic volume (P < 0.001). These findings suggest that sympathetic arteriolar function remains relatively intact but that sympathetic venomotor function is selectively impaired. These findings may have significant implications for the treatment of patients with POTS.

Adult↗

Nephrotoxic effects of primary immunosuppression with FK-506 and cyclosporine regimens after liver transplantation.

OBJECTIVE: We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A (CSA) in liver transplant recipients. DESIGN: Between October 1990 and October 1991, 37 patients were enrolled in an open-labeled, randomized study of two immunosuppressive regimens after liver transplantation. MATERIAL AND METHODS: Of the 23 men and 14 women, 20 received FK-506 plus prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function was assessed before and after transplantation (day 1, month 1, month 4, and month 12) by measurements of serum creatinine (SCr) and glomerular filtration rate (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK-506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2 and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid chromatography) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated withdrawal of study medication for more than 48 hours. Mean patient age and values for SCr and GFR were comparable between the two groups at entry. RESULTS: Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up, although patients who received FK-506 had a significantly (P < 0.05) lower GFR when measured at 12 months than did patients treated with CSA (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and 10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients, all of whom were in the FK-506 group. These severe nephrotoxic reactions to FK-506 occurred early after transplantation, often during intravenous administration of the drug, and were not associated with poor liver allograft function or drug levels outside the therapeutic range. CONCLUSION: Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients. In this trial, however, we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506.

Acute Kidney Injury↗

Noninvasive diagnosis of renovascular disease.

OBJECTIVE: To present the epidemiologic and clinical features of renovascular disease and discuss various diagnostic approaches. DESIGN: We describe the findings in patients with fibromuscular dysplasia or atherosclerotic disease of the renal arteries and review pertinent studies from the literature. RESULTS: Renovascular disease is an important cause of resistant hypertension and progressive renal insufficiency, particularly in the elderly population. Improved blood pressure control and renal function after revascularization have generated intense interest in identifying those patients likely to benefit from this intervention. Fibromuscular dysplasia and atherosclerotic renal artery stenosis account for most cases of renovascular disease. Both entities produce resistant hypertension; the latter is the more common cause of progressive renal insufficiency--occasionally leading to end-stage renal disease. Angiotensin-converting enzyme inhibitor-related renal dysfunction, otherwise unexplained renal insufficiency, and recurrent pulmonary edema are increasingly recognized clinical manifestations of renovascular disease. Traditional screening tests such as intravenous pyelography, intravenous digital subtraction angiography, radionuclide scintirenography, and measurement of the peripheral venous plasma renin activity have limited accuracy for diagnosing renal artery stenosis and do not accurately predict the blood pressure response to revascularization. In comparison, recently developed noninvasive tests such as captopril renography, renal artery duplex sonography, and magnetic resonance angiography seem to be more accurate and, in the case of captopril renography, may be more predictive of the blood pressure response to revascularization. CONCLUSION: Future directions in the area of renovascular disease should include a direct comparison among these new noninvasive diagnostic techniques, with a particular focus on the identification of those patients most likely to benefit from revascularization in terms of both blood pressure control and improved renal function.

Humans↗

Cyclosporine-induced hypertension after transplantation.

OBJECTIVE: To describe the features and mechanisms of posttransplantation hypertension and suggest appropriate management of the disorder. DESIGN: We review our own experience and reports from the literature on hypertension in cyclosporine A (CSA)-treated transplant recipients. RESULTS: Soon after immunosuppression with CSA and corticosteroids, hypertension develops in most patients who undergo transplantation. The blood pressure increases, which are usually moderate, occur universally because of increased peripheral vascular resistance. Disturbances in circadian patterns of blood pressure lead to loss of the normal nocturnal decline, a feature that magnifies hypertensive target effects. Changes in blood pressure sometimes are severe and associated with rapidly developing target injury, including intracranial hemorrhage, left ventricular hypertrophy, and microangiopathic hemolysis. The complex mechanisms that underlie this disorder include alterations in vascular reactivity that cause widespread vasoconstriction. Vascular effects in the kidney lead to reduced glomerular filtration and impaired sodium excretion. Many of these changes affect local regulation of vascular tone, including stimulation of endothelin and suppression of vasodilating prostaglandins. Effective therapy includes use of vasodilating agents, often calcium channel blocking drugs. Caution must be exercised to avoid interfering with the disposition of CSA or aggravating adverse effects relative to kidney and electrolyte homeostasis. CONCLUSION: Recognition and treatment of CSA-induced hypertension and vascular injury are important elements in managing the transplant recipient.

Antihypertensive Agents↗

Pathophysiology of renal failure in renovascular disease.

Recent attention has focused on renovascular compromise as a cause of chronic renal failure. The sequence by which kidneys functioning near the limits of "critical perfusion pressures" develop parenchymal injury is not well understood. We studied poststenotic renal pressures, glomerular volume, and renal function in conscious rats using an aortic coarct model during antihypertensive therapy with sodium restriction and angiotensin-converting enzyme inhibition over 4 weeks. These were compared with acute reduction of renal pressures using aortic ligation. Both models reduced poststenotic pressures to 50 to 60 mm Hg. Total aortic ligation produced tubular necrosis and glomerular collapse with 40-fold elevated urinary N-acetyl-glucosaminidase excretion. In contrast, angiotensin-converting enzyme inhibition reduced renal blood flow by 30% without evident disruption in tubular function, reflected by low fractional excretion of sodium levels and normal excretion of N-acetyl-glucosaminidase. The glomerular filtration rate and filtration fraction were reduced. These results indicate that gradual reduction of renal perfusion pressure produces functional and morphologic consequences different from those observed with acute ischemic injury. Mechanisms by which chronic renal perfusion deficits produce tissue injury are reviewed and may include disruption of vascular regulation, energy storage molecules, cellular ion gradients, free radical generation, and disruption of cytoskeletal configuration and repair mechanisms. Further study of the pathways of chronic renal parenchymal injury beyond arterial stenosis is essential to achieve rational intervention and revascularization in humans.

Animals↗