Erythropoietin and peritoneal dialysis: the efficacy of intraperitoneal dosing.
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Anemia↗
Biomedical subjects
A R Nissenson
Publications and source records attributed to A R Nissenson.
Quality of life on in-center hemodialysis versus CAPD.
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Humans↗
Epoetin and cognitive function.
The uremia of chronic renal failure (CRF) can alter brain electrophysiology and cognitive function, even in the well-dialyzed patient. The effect of uremia on brain function can be assessed by electrophysiologic techniques such as electroencephalogram (EEG), sensory-evoked potentials (EPs), and cognitive event-related potentials (ERPs), and through a series of neuropsychologic tests. Five tests have been used clinically to measure the speed and efficiency of cognitive functioning and include the following: Number Cancellation, Trailmaking Test, Symbol Digit Modalities Test, Rey Auditory Verbal Learning Test, and Controlled Oral Word Association Test. Test performance by patients with CRF is often below that of healthy controls. Auditory ERPs, a sensitive indicator of subtle changes in central nervous system (CNS) function in uremia, result in the generation of a P300 component wave that varies in amplitude and latency with patient variables such as attention and effort. Although dialysis tends to normalize P300 latencies, the waves remain somewhat prolonged in most patients. The anemia often observed in patients receiving chronic dialysis appears to aggravate uremic encephalopathy. This effect can be reversed when anemia is corrected following administration of recombinant human erythropoietin (epoetin). Improvement in P300 amplitudes, and, in some cases, decreases in P300 latencies correlated well with epoetin-induced increases in hematocrit levels. With the correction of anemia, that component of brain dysfunction not attributable to retention of uremic toxins can largely be reversed.
Anemia↗
Recombinant human erythropoietin and renal anemia: molecular biology, clinical efficacy, and nervous system effects.
Anemia (hematocrit less than 25%) predictably accompanies chronic renal failure and is present in over 90% of patients on chronic dialysis. Relative erythropoietin deficiency is the proximate cause. Recombinant human erythropoietin recently became available for research and clinical use. Erythropoietin production is regulated by a single copy gene located on chromosome 7; its expression has been shown in the kidney, liver, and macrophages. It is glycosylated protein of 166 amino acids with a molecular weight of 34,000 D. When given to patients with the anemia of renal failure, erythropoietin causes a dose-dependent rise in hematocrit to the normal range within 8 to 14 weeks. Complications of this response are minimal except for a significant incidence of hypertension. When the anemia is corrected, the patient's quality of life, cognitive function, and brain electrophysiology improve dramatically. Recombinant human erythropoietin represents a major breakthrough in the treatment of patients with chronic renal failure. Current reimbursement constraints limit its full application.
Anemia↗
Cognitive function, mood and P3 latency: effects of the amelioration of anemia in dialysis patients.
Attention difficulties and psychomotor slowing associated with depressed mood affect the ability of individuals to perform on most neuropsychological tests. It has been suggested that latency of the P3 (P300) component of the event-related EEG potential is an index of neurocognitive status which is not affected by mood. Dialysis patients, who experience diminished dysphoric mood with the reversal of anemia when treated with recombinant human erythropoietin (rHuEPO), were tested for neurocognitive performance, mood and latency of P3. Prior to rHuEPO treatment mood was dysphoric, and neurocognitive testing showed mild deficits, but P3 latency was normal. After treatment, mood improved and neurocognitive test performance was normal. P3 amplitude increased over frontal areas, while P3 latency remained unchanged. Thus, in the case of dysphoric mood, P3 latency may provide a more accurate index of cognitive capacity (as opposed to level of functioning) than neurocognitive test measures.
Affect↗
rHuEPO treatment improves brain and cognitive function of anemic dialysis patients.
Twenty-four patients with chronic renal failure, stabilized on hemodialysis, were treated with recombinant human erythropoietin. Before treatment, all patients were anemic (mean Hct = 23.7%). Hematocrits reached normal levels (36.5%) after three months of treatment. Brain event-related potentials and neuropsychological tests were used to assess changes in brain and cognitive functions associated with the correction of anemia. Assessments were done prior to and after three and twelve months of rHuEPO treatment. The P3 component of the event-related potential increased in amplitude significantly with treatment, while its latency was unaffected. Of the four neuropsychological tests administered, scores on two improved significantly with treatment, and the other two approached significance. Taken together, these findings suggest that the correction of anemia to hematocrits near normal in uremic patients by rHuEPO treatment improves brain and cognitive function by raising levels of sustained attention, thus increasing speed and efficiency of scanning and perceptual-motor functions and enhancing learning and memory. These findings also suggest that anemia, either directly or indirectly, may impair brain function.
Anemia↗
National cooperative rHu erythropoietin study in patients with chronic renal failure: a phase IV multicenter study. Report of National Cooperative rHu Erythropoietin Study Group.
Initial experience with recombinant human erythropoietin (rHuEPO, epoetin alfa) was gained through research protocols in which patient selection and management were tightly controlled. When epoetin alfa was approved for use by the Food and Drug Administration (FDA) these constraints were removed. The present study was designed to examine the medical and social impact of epoetin alfa therapy, as well as to document its safety and efficacy as it is used in clinical practice. From 1,000 to 2,000 patients at 100 to 200 centers will be enrolled and monitored for 1 year. Two groups of patients are being studied--those already receiving epoetin alfa at study entry and those new to epoetin alfa therapy. Demographic data are collected initially and detailed outcome data are collected monthly. This interim report presents data from 68 participating dialysis centers on 447 enrolled patients. To date, 89% of the patients are on in-center hemodialysis, while 9% are on home dialysis (79% continuous ambulatory peritoneal dialysis [CAPD], 14% continuous cyclic peritoneal dialysis [CCPD]). Preliminary analyses suggest this population is similar in age and cause of chronic renal failure to the overall US dialysis population, although whites and males are somewhat underrepresented. Of those already on epoetin alfa at study entry, 62% were receiving 3,000 to 9,000 U/wk. In addition, those already on epoetin alfa had better self-rated general health than those new to therapy. Outcomes and epoetin alfa usage patterns are currently being fully analyzed. Three-month follow-up data on a cohort of patients new to epoetin alfa indicate that the average dose in these patients is less than 100 U/kg/wk; two thirds of the doses were administered intravenously. Hematocrit levels increased over the 3 months from a level of 25.1% at entry to 30.6% by month 3. The percentage of cohort patients who were transfusion-independent increased from 85.1% at study entry to 95.7% by month 3. No increases in the incidence of adverse events occurred in the cohort group and no changes in the safety profile were indicated. These preliminary findings suggest that low doses of rHuEPO are being used in general, with a resultant low mean hematocrit. Thus, patients do not seem to be realizing the full potential beneficial effects of this remarkable agent.
Adolescent↗
Leukocyte sequestration during hemodialysis.
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Humans↗
Peritoneal dialysis in the geriatric patient.
Elderly patients on chronic peritoneal dialysis (CPD) from two large chronic peritoneal dialysis programs were compared with younger patients in regard to peritonitis rates, catheter problems, hospital days, transfers to other forms of therapy, and mortality. Peritonitis rates and organisms were similar in younger and older patients. Catheter replacements were less common in the elderly. Differences in hospital days were attributable to hospitalization for vascular disease. The elderly were more likely to have the first episode of peritonitis, to die and to change dialysis modalities at all times after the first year of continuous ambulatory peritoneal dialysis (CAPD) treatment, although other than increased mortality, differences between the two groups were small. CPD appears to be an acceptable form of renal replacement therapy in the elderly.
Aged↗
Outcome of end-stage renal disease in patients with rare causes of renal failure. III. Systemic/vascular disorders.
This multicentre national study has provided demographic and outcome data on over 1700 patients with rare systemic/vascular diseases as a cause of ESRD. Except for those with Henoch-Schönlein purpura, polyarteritis nodosa and Wegener's granulomatosis, women predominated. On the other hand, black patients seem less susceptible to these illnesses than white patients except for SLE. Recovery of renal function sufficient for dialysis to be discontinued was more likely in each of these diseases except for SLE than for any of the other 'rare' diseases described by us, the usual causes of renal failure as reported by the EDTA Registry or our control patients. Overall survival was quite good except in those patients with progressive systemic sclerosis whose outlook was poor.
Adult↗
Selection of ESRD treatment: an international study.
Using the method of paired comparisons, we surveyed nephrologists in three different socioeconomic regions, North Carolina, Southern California, and Australia-New Zealand, to determine their preferences among the major end-stage renal disease (ESRD) treatment modalities. For comparison, we also determined how patients were assigned to the treatment modalities, based on registry data in the regions. Preferences were determined in for six standard ESRD treatment modalities--living related donor (LRD), four-antigen match, LRD two-antigen match, and cadaver (CAD) transplantation; and home peritoneal dialysis (HPD), home hemodialysis (HHD), and facility hemodialysis (FHD)--and for three categories of patients--patients with diabetes, patients over age 60, and patients in general. There was overall agreement in the ranking of treatments by the nephrologists from all three regions for each of the three patient categories; however, significant differences were noted between regions in preferences for certain modalities. Comparison within and between regions revealed striking disparities between preferences and practice. Analysis of these findings provides important insights into the process of ESRD treatment selection and identifies issues that merit further consideration.
Attitude of Health Personnel↗
Recombinant human erythropoietin treatment may improve quality of life and cognitive function in chronic hemodialysis patients.
Medical, psychological, and social adaptation (quality of life) as well as cognitive function were studied in 15 chronic stable hemodialysis patients before the onset of treatment with recombinant human erythropoietin (r-HuEPO), 1 month after stabilization of normal hematocrit levels, and 10 to 15 months after treatment onset. After r-HuEPO treatment, subjects had significantly higher hematocrits, markedly improved energy levels, and marginally improved global health. r-HuEPO treatment was also associated with progressively decreased levels of subject mood disturbance and dialysis-related stresses. Subjects had no increased participation in paid employment and only minimally increased participation in social and leisure activities at posttreatment data points. There was no significant improvement in cognitive function after treatment. r-HuEPO treatment appears to be associated with higher energy levels, significant psychological benefits, and minimal improvements in social adaptation. The effects on cognitive function merit further study.
Adaptation, Psychological↗
End-stage renal disease and the practice of nephrology.
Data from a national survey of 336 nephrologists who provide dialysis care on capitation reimbursement show differences in practice activity associated with the proportion of patients with end-stage renal disease (ESRD). On the average, ESRD patients account for 53% of patients seen by these physicians. Nephrologists who have the majority of their visits with ESRD patients average more than 120 patient encounters per week, approximating the practice workloads of primary care physicians. Nephrologists spend comparable amounts of time providing treatment for ESRD and non-ESRD patients in the same settings, schedule additional office visits for facility dialysis patients, and provide treatment and advice for problems not related to dialysis. Whereas care for acute renal failure patients is primarily based on consultations and involves a narrow focus, treatment for ESRD involves the provision of comprehensive primary medical care by nephrologists to their patients being treated with dialysis.
Ambulatory Care↗
Dialysis for chronic renal failure: comorbidity and treatment differences by disease etiology.
A national sample of dialysis physicians was used to obtain data for a comparison of patient characteristics, comorbid conditions and treatment patterns associated with the five leading causes of end-stage renal disease (ESRD). The data are used to assess trends in physician care for ESRD patients and likely changes in program costs. The analysis shows that patients with glomerulonephritis are the youngest. Those with hypertensive nephropathy are the oldest, and include the highest proportion of blacks, while those with polycystic kidney disease include the lowest proportion of blacks. Patients with diabetic nephropathy have the most problems noted at the time of physician contact, the most emergent and severe problems, the highest number of diagnostic tests utilized, the most complex treatments required and the longest physician time spent per encounter. Patients with 'other interstitial nephritis' are significantly more likely to have infections, musculoskeletal disorders, chronic obstructive pulmonary disease and neoplasms noted as comorbid conditions. They also have the highest number of therapeutic procedures and the greatest percentage of referrals for consultations. Survey data highlight the evolving nature of Medicare's ESRD program. With increasing numbers of elderly and diabetic patients, more physician time will be required for the overall care of the dialysis patient, and increasing costs associated with necessary diagnostic tests and referrals can be expected.
Cohort Studies↗
Outcome of end-stage renal disease in patients with rare causes of renal failure. I. Inherited and metabolic disorders.
This study represents the first national multi-center evaluation of treatment for end-stage renal disease outcome in patients with rare metabolic and inherited disorders in the United States. Because of the small number of such patients at single centers only a co-operative study could provide adequate data on enough patients for meaningful conclusions. By co-ordinating such data, the Network Forum provides a model for the newly organized U.S. Renal Data System and demonstrates the potential for useful special studies in the future. It is clear from these data that despite the systemic nature of these illnesses, treatment for ESRD can be applied to achieve excellent survival rates.
Adult↗
Recombinant human erythropoietin: impact on brain and cognitive function, exercise tolerance, sexual potency, and quality of life.
The clinical manifestations of uremia are only incompletely reversed by chronic hemodialysis. Signs and symptoms can include abnormalities in electrophysiologic indices, clinical mental status, and neuropsychological test performance, as well as decreases in exercise tolerance, sexual potency, and general quality of life. Though retention of uremic toxins is responsible for many of these symptom complexes, some may be caused, or substantially aggravated, by the anemia that almost invariably accompanies chronic renal failure. Treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) increases hematocrit values and thus reduces the anemia, in turn improving brain and cognitive function, exercise tolerance, sexual potency, and quality of life.
Anemia↗
Outcome of end-stage renal disease in patients with rare causes of renal failure. II. Renal or systemic neoplasms.
We describe a large experience with patients with end-stage renal disease (ESRD) whose primary cause was considered multiple myeloma, renal cell carcinoma and amyloidosis. Data were obtained by a collaboration of the majority of the ESRD Networks of the United States. The data presented reflect recent practice in the United States. Even though it is likely that some selection bias plays an important role, the demographic characteristics, choice of early treatment and overall survival data provide some assistance to physicians when advising their patients with these rare conditions. More detailed analyses are needed to assess the outcome by choice of treatment as well as the age- and treatment-adjusted survival for these diagnoses.
Actuarial Analysis↗