Congestive heart failure in dialysis patients.

To determine the prevalence of congestive heart failure in dialysis patients and the disorders with which it is associated, 85% of 153 nondiabetic patients who were undergoing maintenance dialysis had echocardiography and gated cardiac scan. Ten percent (n = 15) had congestive heart failure, 53% (n = 8) of whom had dilated cardiomyopathy, and 47% (n = 7) had hypertrophic hyperkinetic cardiomyopathy. Ischemic heart disease was an additional independent risk factor for congestive heart failure. Significantly more of those patients with dilated cardiomyopathy were smokers and none were hypertensive, whereas all those patients with hypertrophic cardiomyopathy were hypertensive. The prevalence of hypertrophic hyperkinetic disease was 11%, of dilated cardiomyopathy 18%, and of symptomatic ischemic heart disease 18%. We concluded that congestive heart failure in dialysis patients is associated not only with dilated cardiomyopathy but also with hypertrophic cardiomyopathy, a disease that requires echocardiography for diagnosis and that has different risk factors and management.

Comparison of patients with idiopathic calcium phosphate and calcium oxalate stones.

Our primary objective was to test the hypothesis that a defect in acidification is more common in patients who have idiopathic calcium phosphate kidney stones than in those whose stones are formed mainly of calcium oxalate. Additionally, other risk factors might differ for these 2 stone types. Urine pH was measured serially over 24 hours, and along with ammonium and titratable acid, it was measured before and serially after ingestion of ammonium chloride in 3 groups of subjects: 24 patients with predominantly calcium phosphate stones, 30 patients with calcium oxalate stones, and 15 health non-stone-formers. Twenty-six parameters potentially related to stone formation and acidification were assayed on urines collected over 24 hours, and 15 parameters on blood. The data base was a computerized list of 5900 analyses of stones from patients living in Newfoundland. Patients not known by their physician to have had urinary tract infection, anatomical abnormality, hyperparathyroidism, or renal tubular acidosis were asked to participate in the study. Differences between means were considered significant if p values were less than 0.05 for F by analysis of variance and also less than 0.01 by t-test. In all patients with calcium oxalate stones and all non-stone-formers, urine acidified to pH less than 5.25, but in 8 of the 23 phosphate stone formers who completed the ammonium chloride study urine failed to acidify to pH less than 5.25. As all 8 had normal values for venous pH, total CO2, and chloride, they were considered to have incomplete renal tubular acidosis (IRTA). The 8 phosphate stone formers with IRTA had greater mean values for urine pH on all 9 specimens collected serially over 24 hours (all means greater than 6.2), and after administration of ammonium chloride (p less than 0.01), as well as lower mean values for urine titratable acid excretion (p less than 0.01), both after administration of ammonium chloride and in 24-hour urine samples, compared with the remaining phosphate stone formers whose urine acidified and the oxalate and non-stone-forming control groups. Nearly all the phosphate stone formers had 1 or more risk factors for stone formation, but with frequencies not significantly higher than those found in the oxalate group. Hypercalciuria and hypocitruria were the commonest, but increased oxalate or urate also occurred. Thus, idiopathic calcium phosphate stone formation can be associated with 1 or more of several risk factors, and, with the possible exception of those with IRTA, treatment should be similar to that given to patients with calcium oxalate stones.

Hepatitis B disease in dialysis and transplant patients. Further epidemiologic and serologic studies.

As hepatitis B virus (HBV) infection in renal transplant recipients is associated with a high incidence of progressive liver disease it may be inadvisable to transplant hemodialysis patients with hepatitis B antigenemia. To determine the natural history of HBV disease in hemodialysis patients, all 49 patients on hemodialysis treatment for at least 1 year, at 3 centers, who developed circulating hepatitis B surface antigen (HBsAG), were studied. A subgroup of these patients (n = 31) aged less than or equal to 50 years, followed for 55 +/- 6 months after detection of HBsAg was compared with 22 previously studied HBsAg-positive transplant patients followed for 81 +/- 9 months. Significantly more transplant patients developed chronic hepatitis defined biochemically (P less than .001) and none of the transplant patients became HBsAg-negative compared with 19% of the hemodialysis group. Taking difference in follow-up into account, mortality was significantly higher in the transplant recipients (P less than .005) following development of HBsAg antigenemia, and the mortality difference was attributable to deaths from liver disease. A total of 36 serum samples from 14 of the 22 HBsAg-positive renal transplant recipients was analyzed for hepatitis B e antigen (HBeAg), antibody to hepatitis D virus (anti-HD), and hepatitis B virus deoxyribonucleic acid (HBVDNA) concentration. No serum sample was anti-HD-positive. Twelve of the 14 patients were HBeAg-positive. Five patients became HBeAg-negative, 3 of whom developed aggressive liver disease. One HBeAg-negative anti-HBe-positive patient had progression of liver disease from asymptomatic carrier status to chronic active hepatitis (CAH). Of 14 patients, 9 developed progressive CAH. HBVDNA concentration was not diagnostic of disease activity on liver biopsy. However only 1 sample of 10 measured in 5 patients with nonprogressive disease had a level greater than 100 pg/L, compared with 9 of 17 in the group who progressed to CAH. During the interval when the liver histology progressed from asymptomatic carriage or chronic persistent hepatitis (CPH) to CAH, the HBVDNA concentration increased by greater than 10 times baseline in 4 of 5 patients who had serial samples, whereas this did not occur in 4 patients with nonprogressive disease. We conclude that the long-term outcome of hepatitis B infection in transplant recipients is significantly worse than in hemodialysis patients. Therefore it may be inadvisable to transplant HBsAg-positive hemodialysis patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Impact of renal transplantation on uremic cardiomyopathy.

In chronic uremia, cardiomyopathy manifests itself as systolic dysfunction, concentric left ventricular (LV) hypertrophy, or LV dilatation. To determine the impact of renal transplantation on uremic cardiomyopathy, all dialysis patients participating in a long-term cohort study who received a successful renal transplant were followed with echocardiography. The transplanted group comprised 102 of 433 (24%) endstage renal disease (ESRD) patients. They were significantly younger and, on starting ESRD therapy, had significantly less ischemic heart disease and cardiac failure than the overall ESRD cohort. During followup, ischemic heart disease developed in only 1 patient and none experienced cardiac failure. In the 12% (n = 12) of patients with systolic dysfunction before renal transplant, fractional shortening normalized in all patients, increasing from 21.5 +/- 4.6% to 33.5 +/- 5.6% after transplantation. In the 41% (n = 41) with concentric LV hypertrophy before transplantation, the LV mass index improved from 158 +/- 39 g/m2 to 132 +/- 39 g/m2. LV dilatation was present in 32% (n = 32) of patients before transplantation. After transplantation, LV volume fell from 116 +/- 3.1 ml/m2 to 89 +/- 21 ml/m2, and LV mass index in this group fell from 166 +/- 55 g/m2 to 135 +/- 37 g/m2. It was not possible to associate risk factors characteristic of the uremic state with the improvement in cardiac structure and function, although the fall in LV mass was significantly associated with fall in blood pressure. We conclude that correction of the uremic state by renal transplantation leads to normalization of LV contractility in systolic dysfunction, regression of hypertrophy in concentric LV hypertrophy, and improvement of cavity volume in LV dilatation. The degree of improvement suggests that dialysis patients with uremic cardiomyopathy would benefit from renal transplantation.

Investigation and management of renal stones.

Renal stones are a major source of morbidity and health care expenditure. Stone-forming patients may be grouped according to the etiological factors of their disease. Investigation begins with an appropriate history and physical examination, followed by selected laboratory tests aimed at discovering factors that may be contributing to stone formation and also at classifying the activity of the stone disease. Management depends on timely surgical procedures to deal with problematic stones and on advice concerning fluid intake, dietary modification, and in some cases, drug therapy to prevent further stone formation.

The management of cardiac disease in chronic uremia.

The burden of cardiac disease is high in chronic uremia. Cardiomyopathy results from a combination of cardiac disorders, particularly dilated cardiomyopathy, left ventricular hypertrophy with normal systolic function, and ischemic heart disease. The prognosis for these cardiac disorders is poor. Known potentially reversible risk factors include uremia, anemia, hypertension, smoking, coronary artery disease, hyperparathyroidism, hyperlipoproteinemia, and left ventricular hypertrophy. Randomized controlled clinical trials of interventions that may prevent or ameliorate cardiac disease in dialysis patients are required. These interventions include normalization of hematocrit with erythropoietin compared with partial correction of anemia, increased amount of dialysis compared with that provided by a dialysis prescription of KT/V of 1., control of blood pressure using angiotensin-converting enzyme inhibitors compared with other antihypertensive agents, control of hyperlipidemia, and treatment of diabetes with agents that prevent collagen cross-linking.

Clinical aspects of cardiomyopathy in dialysis patients.

The burden of cardiac disease in dialysis patients is high. Congestive heart failure, ischemic heart disease, left ventricular hypertrophy, and systolic dysfunction occur frequently and are associated with an adverse prognosis. In addition, during dialysis therapy anemia, hypoalbuminemia, low blood pressure, and lower serum creatinine levels are adverse predictors of mortality. Risk factors for systolic dysfunction include older age, ischemic heart disease, hyperparathyroidism, and smoking. Risk factors for left ventricular hypertrophy include older age, hypertension, anemia, and diabetes mellitus. Interventions with potential for improving cardiomyopathy include normalization of hematocrit with erythropoietin, improved uremia therapy, and angiotensin-converting enzyme inhibitors. Trials to determine the most appropriate interventions to reduce the impact of cardiac disease in chronic uremia are urgently required.

The natural history of myocardial disease in dialysis patients.

Among dialysis patients, only 23% have a normal echocardiogram, about 10% have recurrent or chronic congestive heart failure, and 17% have asymptomatic ischemic heart disease. The predisposing factors for congestive heart failure are dilated cardiomyopathy, hypertrophic hyperkinetic disease, and ischemic heart disease. Dilated cardiomyopathy, a disorder of systolic function, includes among its risk factors age, hyperparathyroidism, and smoking. Hypertrophic disease results in diastolic dysfunction, and its predictors include age, hypertension, aluminum accumulation, anemia, and, perhaps, hyperparathyroidism. Ischemic heart disease is due to the presence of coronary artery disease and also to nonatherosclerotic disease caused by the reduction in coronary vasodilator reserve and altered myocardial oxygen delivery and use. The clinical outcome of congestive heart failure is comparable to that of nonrenal patients with medically refractory heart failure. Left ventricular hypertrophy is an important independent determinant of survival. A subset have hyperkinetic disease with severe hypertrophy and have a bad survival, as low as 43% have a 2-yr survival after the first admission to hospital with cardiac failure. The prognosis for those with dilated cardiomyopathy is less severe but is worse than those with normal echocardiogram. The survival of patients with symptomatic ischemic heart disease was little different from that of patients without symptoms, suggesting that the underlying cardiomyopathies had an adverse impact on survival independent of ischemic disease. Much research needs to be undertaken on the risk factors, natural history, and therapy of the various types of cardiac disease prevalent in dialysis patients.

The reliability and validity of echocardiographic measurement of left ventricular mass index in hemodialysis patients.

We assessed the reliability and validity of a formula, based on echocardiographically derived parameters, to calculate left ventricular mass index (LVMI) in a group of 15 chronic hemodialysis patients. All patients had M-mode echocardiography before and after a hemodialysis session. Echocardiograms were interpreted by 2 observers blind to each other's measurements. Interobserver reliability for LVMI was high (r = 0.94, p < 0.0007). LVMI decreased in 11 of 15 patients during dialysis and increased in 4. The mean difference in LVMI between pre- and posthemodialysis was 26.2 +/- 15 g/m2 (p < 0.0001). End-diastolic diameter decreased from 53.5 +/- 5.9 to 49.5 +/- 7.5 mm (p = 0.0016). These data indicate that measurement of LVMI is highly reproducible in hemodialysis patients but that it changes significantly over the course of a hemodialysis session. Its use as an outcome measure in clinical trials in hemodialysis patients should be interpreted with caution.

Recurrent hemoperitoneum in women receiving continuous ambulatory peritoneal dialysis.

Of 27 women in the reproductive age group receiving continuous ambulatory peritoneal dialysis for more than 3 months, 4 of 7 who menstruated developed recurrent hemoperitoneum. Tubal ligation had been done in 3 of these 4 women. There were 37 episodes of hemoperitoneum; 22 occurred at midcycle and 15 with menstruation. One patient required repeated blood transfusion, but after oral anovulant therapy no further bleeding occurred and no transfusion was required. Two patients needed laparotomy: one for heavy intraperitoneal bleeding originating from a luteal cyst, and the other for severe lower abdominal pain from follicular and luteal cysts. Ultrasound examinations suggested the presence of small ovarian cysts in the two remaining patients. Recurrent midcycle hemoperitoneum in women on continuous ambulatory peritoneal dialysis may be triggered by ovulation and associated ovarian cyst formation. Suppression of ovulation should be considered.

Risk factors for the development of left ventricular hypertrophy in a prospectively followed cohort of dialysis patients.

The objective of this study was to determine the role of hypertension, age, anemia, and hyperparathyroidism in the pathogenesis of left ventricular hypertrophy (LVH) developing after the initiation of dialysis for ESRD. A cohort of dialysis patients who were being treated for ESRD and whose initial echocardiograms after the start of dialysis therapy do not show LVH were studied. Three hundred and thirty-nine patients have been monitored at three centers since 1985. Serial echocardiograms have been performed with M-mode and two-dimensional echocardiography. Data on blood pressure, height, weight, hemoglobin, number and type of antihypertensive medications, and the presence of functioning vascular access have been collected prospectively. Prospective data on serum calcium, serum phosphorus, alkaline phosphatase, and parathyroid hormone levels and skeletal x-rays have also been collected. By the use of set criteria and blinding to echocardiographic outcome, the presence and severity of hyperparathyroidism were graded by consensus. Fifty-one patients met eligibility criteria for inclusion; of these, 14 developed LVH (cases) and 37 did not (controls). Cases had significantly higher systolic blood pressure (P = 0.009) and were older (P = 0.01) than controls. Systolic blood pressure correlated significantly with final posterior left ventricular wall thickness (r = 0.39; P < 0.01). By the use of multivariate analysis, age and systolic blood pressure were significantly and independently associated with increased left ventricular mass index. The frequency of hyperparathyroidism was low and equal in both groups. There was a trend toward more severe anemia in cases that did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac function and hematocrit level.

Patients on dialysis have an age-adjusted death rate 3.5 times that of the general population. The most common cause of death in patients on dialysis is cardiovascular disease. We prospectively followed a cohort of 433 patients in three centers for a mean of 41 months. Mean hemoglobin level at the beginning of dialysis was 8.39 (+/- 1.7) g/dL, and the mean hemoglobin level during follow-up was 8.84 (+/- 1.5) g/dL. Using Cox's regression model, we found that anemia predicted mortality independently of age, diabetes mellitus, cardiac failure, hypoalbuminemia, serum creatinine, mean arterial pressure, or echocardiographic heart disease. The independent relative risk (RR) of mortality was 1.18 per 1.0 g/dL decrease in hemoglobin level. Anemia also independently predicted the de novo occurrence of congestive heart failure when the same covariates were controlled for (RR, 1.49 per 1.0 g/dL decrease). Anemia was also independently predictive of heart failure at the start of dialysis (RR, 1.14 per 1.0 g/dL decrease) and heart failure recurrence (RR, 1.25 per 1.0 g/dL decrease). Left ventricular hypertrophy is present in 75% of patients on dialysis at the start of therapy for end-stage renal disease. It independently predicts mortality. Our prospective cohort study identified increasing age, hypertension, and anemia as risk factors for its development. One controlled study and several uncontrolled studies demonstrated improvement (but not complete regression) of elevated left ventricular mass in patients on dialysis treated with recombinant human erythropoietin (epoetin).

Outcome of congestive heart failure, dilated cardiomyopathy, hypertrophic hyperkinetic disease, and ischemic heart disease in dialysis patients.

Congestive heart failure in dialysis patients is associated with dilated cardiomyopathy, hypertrophic hyperkinetic disease and ischemic heart disease. To determine the natural history of these four diseases, 150 dialysis patients were prospectively followed for 3-5 years. The 2-year cumulative survival rate was 33% in those with recurrent or persistent congestive heart failure vs. 80% in dialysis patients without. Survival was significantly worse in patients with an echocardiographic diagnosis of dilated cardiomyopathy compared to patients with normal echo-cardiogram (2-year survival rate 67 vs. 90%). In hypertrophic hyperkinetic disease the 2-year survival rate was 30% after entry into the study, and 43% after first admission with congestive heart failure. Symptomatic ischemic heart disease did not have an adverse impact on mortality when compared to those without ischemic heart disease. We conclude that congestive heart failure in dialysis patients has a bad prognosis. Its associated disorders include dilated cardiomyopathy and hypertrophic hyperkinetic disease, the latter being associated with a high mortality. As the prognosis for patients with overt ischemic heart disease was not different from patients without, it is likely that the underlying cardiomyopathy directly influenced survival.