Edwin A. Rutsky

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.

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.

Treatment of Uremic Pericarditis and Pericardial Effusion

Pericarditis occurred 161 times in 136 of 1,058 patients undergoing chronic dialysis during a period of 13.7 years. Cardiac tamponade occurred during 27 episodes, while pretamponade occurred in 30. Tamponade was less frequent and resolution of pericarditis without invasive intervention more frequent when pericarditis occurred within 2 weeks of initiation of chronic dialysis. Similarly, resolution with conservative therapy was more frequent with first episodes than with recurrences, and when pericarditis occurred within 3 months of initiation of chronic dialysis. The overall survival was 89.7% and was the same irrespective of the duration of dialysis or whether the pericarditis was a first episode or a recurrence. We recommend that patients with pericarditis and no hemodynamic alterations receive intensive hemodialysis, with careful hemodynamic and echocardiographic monitoring, as primary treatment. Invasive intervention is indicated if cardiac tamponade or pretamponade develops, if a pericardial effusion increases progressively in size, or if a large effusion persists after ten to 14 days of intensive dialysis. In our experience, the invasive intervention of choice is either formal pericardiectomy or subxiphoid pericardiotomy with intrapericardial steroid instillation. In our experience, pericardiocentesis has proven to be a high-risk procedure. It is reserved for emergency circumstances, and then is preferably performed in the operating room just prior to induction of anesthesia for definitive surgical drainage.

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.

Staphylococcus Aureus Bacteremia in Patients on Chronic Hemodialysis

Staphylococcus aureus bacteremia occurred 96 times in 58 of 671 patients on chronic hemodialysis during a nine-year period. Seventy-one instances of bacteremia originated in the vascular access site and resulted in the loss of the access device in 45 episodes. The overall mortality was 8%, and the incidence of infective endocarditis was 4%. Death occurred more often when bacteremia arose from an identifiable site other than the vascular access device (P less than .02). Patients who developed one or more metastatic foci of infection had a higher incidence of primary treatment failure (P less than .001) and a higher mortality (P less than .001) than did those with no metastatic infection. Although meaningful comparisons of differing antibiotic regimens could not be made, patients receiving antibiotic therapy for 28 days or longer relapsed less frequently (P less than .05). These data suggest that chronic hemodialysis patients with S aureus bacteremia have a relatively low mortality and a low risk of infective endocarditis. Antibiotic treatment, however, should be given for at least 28 days in order to minimize the risk of relapse.

Changing patterns of end-stage renal disease due to hypertension

We analyzed the records of all residents of Jefferson County, Alabama, accepted for renal replacement therapy between 1982 and 1987 and compared them with those accepted between 1974 and 1978 to determine any changes in the distribution and frequency of end-stage renal disease (ESRD) due to hypertension (H-ESRD). H-ESRD increased from 6.4 to 9.6 per 100,000 in blacks and from 0.36 to 0.62 per 100,000 in whites. Smoothed age- and race-specific yearly H-ESRD rates decreased in blacks under age 50. Peak incidence of H-ESRD shifted from age 40 to 49 in 1974 through 1978 to age 50 to 59 in 1982 through 1987 (P less than 0.0001). Blacks were referred for care with significantly higher blood pressure levels and serum creatinine concentrations than whites, and had more severe retinal vascular disease. Factors significantly associated with a shorter time from referral to renal replacement therapy were black race, female gender, blood urea nitrogen and serum creatinine concentrations, carbohydrate intolerance, and the use of alpha-agonist and/or angiotensin-converting enzyme (ACE) inhibitor. We conclude that racial distribution and risk for H-ESRD have not changed. Peak rates of H-ESRD have been delayed nearly a decade, suggesting a possible effect of better awareness and treatment of hypertension.

Treatment of secondary hyperparathyroidism in patients with chronic renal failure by total parathyroidectomy and parathyroid autograft.

Sixty-one patients with chronic renal failure and secondary hyperparathyroidism underwent total parathyroidectomy and parathyroid autograft. Symptoms relieved by parathyroidectomy included bone pain, pruritus, soft tissue calcification, muscle weakness and healing of fractures. Serum parathormone levels measured before and after operation in 48 patients returned to normal in all but two patients. Serum alkaline phosphatase levels also returned toward normal after operation, except in one patient with a retained parathyroid gland. Complete radiographic studies before and after operation were available in 30 of 61 patients. Twenty-three of 24 patients with osteitis fibrosa had evidence of healing, and in one patient no change occurred. Osteosclerosis noticed in 23 patients improved slightly in eight patients, did not change in 14 and became worse in one. Pathologic examinations revealed 45 patients to have diffuse hyperplasia and 16 nodular hyperplasia. There were two early postoperative deaths, in the first 30 days, and 16 late postoperative deaths, from four months to four years afterward. In no case did the operation contribute to the death. Some patients required the administration of supplemental calcium after operation, but in no instance did profound hypocalcemia occur. No patient developed recurrent hyperparathyroidism.

Ischemic Heart Disease in Chronic Renal Failure: Management Considerations

Ischemic heart disease remains a leading cause of death in patients with end-stage renal disease (ESRD) undergoing renal replacement therapy with either dialysis or transplantation. The reasons for this are debated. The increased prevalence of risk factors for coronary artery disease (especially hypertension), serum lipoprotein abnormalities, (including elevated LDL cholesterol and depressed HDL cholesterol fractions) and left ventricular hypertrophy, has led to the idea that atherogenesis is accelerated in uremia ( 1-5). However, coexisting abnormalities in platelet function and coagulation may impede the atherogenic process (6-8). The latter observation together with epidemiologic and demographic data that reveal no differences in the distribution of coronary artery disease between dialysis populations and the general population make the concept of accelerated atherosclerosis less certain. Irrespective of one’s view about rates of atherogenesis in uremia, it is clear that the increased acceptance of diabetics into dialysis programs and the progressive aging of dialysis patients have created in the end-stage renal disease population a reservoir of patients at high risk for atherosclerotic coronary artery disease and its complications. It is important to recognize that 25 to 30% of dialysis patients with symptoms of ischemic heart disease have no angiographic evidence of significant coronary obstruction; about the same proportion found in symptomatic patients in the general population (9). Myocardial ischemia in this setting may be caused by disease of the small coronary vessels or by functional abnormalities of the coronary arteries, such as a reduction in the level of vasodilator reserve below that needed to meet cardiac oxygen demands in the presence of left ventricular hypertrophy and anemia (1013). Hemodialysis, too, frequently pre-

Coronary Artery Bypass Graft Surgery in End‐Stage Renal Disease: Indications, Contraindications, and Uncertainties

Cardiovascular disease of all types has been the leading cause of death in patients on chronic dialysis in the United States for the past two decades, and its frequency (as a percentage of all adult endstage renal disease (ESRD) dialysis patient deaths) has increased from 30% between 1969 and 1971 ( 1 ) . and to 43.1% between 1984 and 1990 (2). Myocardial infarction was second only to “all other cardiovascular events” as a cause of death among adult chronic dialysis patients in the U.S. between 1987 and 1989 (3), and accounted for 27.3% of all such deaths in 1988 (4). A similarly high prevalence of death due to cardiovascular disease in general, and myocardial infarction in particular, has been noted in Europe (5). At the same time, in the general population, there has been a steady decline in mortality due to cardiovascular disease, including myocardial infarction (6, 7). This decline probably relates to several factors, including both changing prevalence of risk factors and improved case-fatality rates (7). Since coronary artery bypass graft (CABG) surgery rapidly has become one of the most often performed surgical procedures in the United States, one might presume that it has played a major role in the declining mortality of coronary heart disease. However, it has been estimated that, while direct medical interventions accounted for 40% of the improved survival, only 3.5% to 5.5% of the improvement resulted from CABG surgery (8). There is a paucity of information regarding either the indications for CABG surgery or its outcome in the ESRD patient with coronary atherosclerosis; still, CABG surgery is increasingly performed in ESRD patients. The ESRD population is probably quite different from the patient populations studied in prior large trials of CABG surgery in the United States and Europe. The ESRD population is growing older (median age = 60 years for new patients initiating chronic dialysis in the United States between 1987 and 1989) (3), and this aging is accompanied by a shorter life expectancy. Thus, the mean life expectancy of dialysis patients, age 45-54 at the time of ESRD, in the United States between 1982 and 1987 was 6.1 years (median = 4.3 years), while that for the 55to 64-year-old group was four years (median = three years) (9). Similarly, the Eu-

The Management of Coronary Artery Disease in Patients with End-Stage Renal Disease

Ischemic heart disease (IHD) has been a leading cause of death for more than two decades in patients undergoing chronic dialysis for end-stage renal disease (ESRD). While the reasons for this are debated [1–5], it is generally accepted that dialysis patients have an increased prevalence of coronary risk factors [2–11], including hypertension, left ventricular hypertrophy (LVH), and abnormalities of serum lipoproteins. Furthermore, the mean age of new patients receiving renal replacement therapy has increased, as has the prevalence of diabetes mellitus [12]. As a result, clinical nephrologists must make diagnostic and therapeutic decisions in an aging and increasingly sick patient population with ESRD and chest pain. In this chapter, we review the problems of diagnosis and management of IHD in patients undergoing chronic dialysis.