Katharine A. Kirk

Renal insufficiency in treated essential hypertension

We analyzed the clinical courses of 94 patients with treated primary hypertension and initially normal serum creatinine concentrations (less than or equal to 133 mumol per liter [less than or equal to 1.5 mg per deciliter]) who were followed for a mean (+/- SD) of 58 +/- 34 months (range, 12 to 174) to determine the frequency with which renal function deteriorated and the factors associated with deterioration. Fourteen patients (15 percent) had an increase in serum creatinine concentrations (greater than or equal to 35 mumol per liter [greater than or equal to 0.4 mg per deciliter]); in 16 percent of the 61 patients with apparently good control of blood pressure, the serum creatinine concentration rose 59 +/- 33 mumol per liter (0.67 +/- 0.38 mg per deciliter). Despite good control of diastolic blood pressure (less than or equal to 90 mm Hg), black patients were twice as likely as white patients to have elevations in serum creatinine (23 percent vs. 11 percent). Stepwise discriminant function analysis showed that a significant rise in the serum creatinine concentration was most likely to occur in association with older age, black race, a higher number of missed office visits, and employment as a laborer. We conclude that although renal function was preserved in 85 percent of patients with treated hypertension, it may deteriorate in some patients despite good blood-pressure control. Our observations may partly explain why hypertension, particularly among black persons, remains a leading cause of renal disease in the United States.

Clinical characteristics and outcome of patients with high defibrillation thresholds. A multicenter study.

BackgroundSuccessful defibrillation by an implantable cardioverter-defibrillator (ICD) depends on its ability to deliver shocks that exceed the defibrillation threshold. This study was designed to identify clinical characteristics that may predict the finding of an elevated defibrillation threshold and to describe the outcome of patients with high defibrillation thresholds Methods and ResultsThe records of 1,946 patients from 12 centers were screened to identify 90 patients (4.6%) with a defibrillation threshold ≥25 J. Excluding three patients who received ICDs that delivered >30 J, there were 81 men and six women with a mean age of 59.5plusmn;10.1 years, a mean left ventricular ejection fraction of 0.32plusmn;0.14, and a 76% prevalence of coronary artery disease. Sixty-one patients (70%) were receiving antiarrhythmic drugs, and 45 (52%) were receiving amiodarone. Seventy-one patients (82%) received an ICD. Death occurred in 27 patients −19 of the 71 (27%) with an ICD (eight arrhythmic), and eight of the 16 (50%) without an ICD (four arrhythmic). Actuarial survival for all patients at 5 years was 67%. Actuarial survival rates at 2 years for patients with and without an ICD were 81% and 36%, respectively (p = 0.0024). Actuarial survival at 5 years for the ICD patients was 73%; no patient without an ICD has lived longer than 32 months. Actuarial survival free of arrhythmic death in the ICD patients at 5 years was 84%. Although the only variable to predict survival was ICD implantation (p = 0.003), it is entirely possible that in this retrospective analysis, clinical selection decisions to implant or to not implant an ICD differentiated patients destined to have better or worse outcomes, respectively. ConclusionsAntiarrhythmic drug use may be causally related to the finding of an elevated defibrillation threshold. When patients with high defibrillation thresholds receive an ICD, arrhythmic death remains an important risk (42% of deaths in these patients were arrhythmia related, with 16% actuarial incidence at 5 years). Vigorous testing to optimize patch location can potentially benefit patients by enhancing the margin of safety for effective defibrillation.

Myocardial calcification and cardiac dysfunction in chronic renal failure

PURPOSE Myocardial calcium content may have clinical importance in end-stage renal disease (ESRD), but it is difficult to detect during life. Our goal was to assess the effect of myocardial calcium content on left ventricular ejection fraction (LVEF) in uremic patients undergoing dialysis. PATIENTS AND METHODS Energy subtraction radiography of the chest was used to measure myocardial calcium content in 43 patients undergoing dialysis, in 32 control subjects, and in nine patients with advanced cardiomyopathy. LVEF and left ventricular end-diastolic dimension were measured by two-dimensional echocardiography. The concentration of parathyroid hormone was measured by radioimmunoassay; calcium-phosphorus product, alkaline phosphatase, and serum bicarbonate were also assessed. RESULTS Patients undergoing dialysis had a greater myocardial calcium content than control subjects [262 +/- 15.4 (mean +/- SE) versus 187 +/- 8 mg/cm2, p less than 0.05]. Ten patients with the highest myocardial calcium content (Group I) had the lowest LVEF values and highest left ventricular end-diastolic dimension. Significant inverse linear associations between LVEF and myocardial calcium content (r = -0.425, p = 0.013) and between parathyroid hormone concentration and LVEF (r = -0.352, p = 0.047) were noted. There was no association between parathyroid hormone concentration and myocardial calcium content. Stepwise regression analysis showed a strong positive correlation between myocardial calcium content and calcium-phosphorus product, vascular calcification, race (black), and parathyroidectomy. Similar analysis shows that LVEF was significantly associated with myocardial calcium content, lung calcium, calcium-phosphorus product, and race (black). CONCLUSION We suggest that increased myocardial calcium content results from poor calcium and phosphorus control and may be enhanced by parathyroid hormone hyperactivity. Increased myocardial calcium content is strongly associated with myocardial dysfunction in patients undergoing dialysis.

Kidney disease in the first-degree relatives of African-Americans with hypertensive end-stage renal disease☆

The incidence of treated end-stage renal disease (ESRD) in the United States is four times more frequent in African-Americans (AAs) than in whites. This is explained neither by a greater prevalence of hypertension and diabetes mellitus nor by socioeconomic issues. To investigate familial risk of renal disease in AAs, we examined the records of 472 AA dialysis patients in Jefferson County, Alabama. Applying strict criteria, we identified 85 index cases of ESRD associated only with hypertension (H-ESRD). We examined the records of 75 index cases and studied the first-degree relatives of 40 patients. The numbers of men and women with H-ESRD were similar (38 and 37, respectively). There was no statistical difference in age at the onset of dialysis (women 53.7 +/- 13.5 years [+/-SD] and men 49.2 +/- 12.2 years; P = 0.0863). We found evidence for renal disease in 26 of 40 (65%) index cases with participating families. Hypertension was present in all 40 families (100%) and diabetes mellitus was present in 24 families (60%). Eighteen of the 75 H-ESRD index patients had a first-degree relative with ESRD. In total, we found evidence for renal disease in 35 of 75 (47%) We conclude that there is a strong concordance of renal disease in the families of AAs with H-ESRD.

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Interstudy reproducibility of biplane cine nuclear magnetic resonance measurements of left ventricular function

Cine nuclear magnetic resonance (NMR) imaging, as a noninvasive and high-resolution imaging modality, has been shown to be reliable for determining absolute left ventricular (LV) volumes and ejection fraction. A relatively new gradient echo cine NMR approach using 2 orthogonal long-axis planes (2- and 4-chamber) aligned with the true axes of the left ventricle has been previously developed and validated against radiographic biplane LV cineangiography. The aim of the present investigation was to determine the reproducibility of this more rapid cine NMR approach for the measurement of LV volumes and ejection fraction. Eighteen normal subjects underwent 2 cine NMR studies, on different days, using a 1.5-tesla clinical imaging system. Studies were analyzed on-line and blindly by 2 independent observers. Intraobserver error was also determined in a blinded manner. Mean values of measurements determined by this method in this group of normal subjects were end-diastolic volume (120 +/- 20 ml), end-systolic volume (39 +/- 9 ml) and ejection fraction (67 +/- 4%). Paired analysis of data revealed no significant bias between interstudy, interobserver or intraobserver measurements, except for interobserver end-diastolic volume, where the first observer measurements were slightly elevated (5.6 +/- 7.8 ml) compared with the second. This resulted in a small difference in ejection fraction (1.7 +/- 2.3%) between observers. The absolute variation between measurements (square root of variance components) was low for all interstudy, interobserver and intraobserver comparisons: end-diastolic volume was less than +/- 6.7 ml, end-systolic volume less than +/- 3.5 ml and ejection fraction less than +/- 2.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of leptin and hunger-satiety ratings in obese women.

OBJECTIVE: To measure leptin, insulin and cholecystokinin (CCK) concentrations in obese women on calorie restriction and to determine their correlation with hunger-satiety ratings. Although it has been proposed to play a role in appetite regulation, the effects of physiological concentrations of these hormones on hunger-satiety in humans have not yet been well established.DESIGN: Prospective metabolic study. A two week `wash-in period’ followed by a three-week observation period, during which each subject underwent six measurements of satiety, blood parameters and body weight.SETTING: Energy Metabolism Research Unit, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.SUBJECTS: 22 moderately to severely overweight women (mean age: 45±8 y; body mass index (BMI): 33±6 kg/m2).INTERVENTION: Energy restriction, in the form of a 3.3 MJ (800 kcal) diet during five weeks.MAIN OUTCOME MEASUREMENTS: Fasting blood levels of leptin, insulin, glucose and CCK, fasting hunger-satiety scores and body weight.RESULTS: The mean (±s.d.) fasting serum leptin concentration at the beginning of the observation period was 26.1±15.9 ng/ml (range: 6.7–59.8 ng/ml). Leptin concentrations correlated positively with body weight (P<0.0001). Furthermore, reductions in body weight were associated with decreases in fasting leptin levels (P=0.002). Leptin concentrations correlated with serum levels of insulin (P=0.0001) and CCK (P=0.06), but in multivariate analysis including insulin, CCK and glucose, only leptin had a significant relationship with satiety (P=0.04). This relationship was linear.CONCLUSIONS: These results confirm the association between leptin levels, body weight and serum insulin. We also showed that higher serum leptin levels correlated with greater feelings of fullness, a relationship which was not blunted in the more obese subjects. These findings suggest that leptin is a satiety hormone that reduces appetite, even in obese individuals, and that weight gain must be due to other factors, overriding this feed-back regulation.

Results of Coronary Artery Bypass Grafting in End-Stage Renal Disease

We examined the results of coronary artery bypass grafting (CABG) in patients with end-stage renal disease and symptomatic ischemic heart disease who had significant arteriosclerotic narrowing of one or more coronary vessels between 1970 and 1984. Twenty-four such patients underwent bypass grafting, 20 dialysis patients and four who had been transplanted. Bypass grafting completely or partially relieved symptoms in 83%. The hospital mortality associated with this surgery for the 20 dialysis patients was 20% compared with a lower overall hospital mortality for bypass grafting in nondialysis patients of 1.3%. Greater hospital mortality was noted for patients over age 60 undergoing bypass grafting, 33.3% v 1.9% in nondialysis patients. In this study, the most significant factor associated with mortality was older age. We conclude that bypass grafting has an acceptable mortality in younger end-stage renal disease patients anticipating or having had renal transplantation, but it is associated with a high hospital mortality in older dialysis patients.

Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: A double-blind, placebo-controlled trial during controlled weight loss

OBJECTIVE: To evaluate the effects of a completely soluble fiber on fasting and postprandial hormone levels, respiratory quotient (RQ) and subjective ratings of satiety during a controlled weight-loss program.DESIGN: In a five-week prospective, randomized, double-blind study, a 3.3 MJ (800 kcal)/d diet was provided during a two-week wash-in period. Then, during the intervention weeks, separated by a one-week wash-out period, a 3.3 MJ (800 kcal) formula containing either 20 g fiber or placebo daily, was given in a cross-over design and on days 1, 3 and 7 of the intervention weeks (weeks 3 and 5) measurements were taken after an overnight fast.SUBJECTS: 25 obese but otherwise healthy females (age: 46±6 y, body mass index (BMI): 35±6 kg/m2) were studied.MEASUREMENTS: Body weight; hunger/satiety ratings; glucose, insulin, cholecystokinin (CCK) and leptin concentrations; RQ during the intervention weeks.RESULTS: In the fasting state, the supplement had no effect on any of the measured parameters, including blood concentrations of glucose, insulin, CCK, and leptin, RQ and satiety ratings. In the 2 h postprandial period following the test meal, none of the measured parameters differed significantly from that following the non-fiber-supplemented meal, except for the CCK response. CCK demonstrated an overall higher concentration after the fiber-supplemented meal (P=0.007), even after adjustment for age, weight, height and treatment sequence. The postprandial peak in CCK also occurred earlier (at 15 min vs 30 min) after completion of the fiber-supplemented meal.CONCLUSIONS: The results indicated that a hydrolyzed guar gum fiber supplement produced a heightened postprandial CCK response, but did not alter other satiety hormones or increase satiety ratings, in either the fasting or the postprandial state.

Physiologic levels of uric acid inhibit xanthine oxidase in human plasma.

ABSTRACT: Xanthine oxidasc, a key source of reactive oxygen species, and purine substrates are detected in the circulation after ischemia-reperfusion. High levels of uric acid, produced by a lanthine oxidase-catalyzed reaction, are found in human plasma. We studied whether uric acid could alter xanthine oxidasc activity in plasma obtained from eight adults and eight neonates. Known amounts of uric acid were added to xanthine and xanthine oxidase-supplemented buffer and plasma, and the production of uric acid and superoxide was determined. Uric acid, 150 and 300 μM, decreased the oxidation of xanthine to uric acid in adult plasma by 37.5 ± 5.6 and 48.9 ± 6.1% and formation of superoxide by 23.2 ± 1.9 and 32.0 ± 2.3%, respectively, compared with plasma without uric acid. In newborn plasma, a similar pattern and extent of inhibition was observed. Superoxide formation, however, was inhibited to a greater extent than in adult plasma. Endogenous xanthine oxidase was detected in newborn plasma in nine additional neonates using HPLC. These results indicate that uric acid is an effective inhibitor of the formation of superoxide and hydrogen peroxide by xanthine oxidase at the levels found in human plasma. Plasma uric acid may play an important role in attenuating the oxidant-mcdiated tissue damage caused by xanthine oxidase released into the circulation during ischemia-reperfusion.