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Biomedical subjects

B J Pereira

Publications and source records attributed to B J Pereira.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of disease-state management of dialysis patients.

Dialysis patients are the only Medicare beneficiaries prohibited from joining managed care plans. Concerns have been raised about the ability of such plans to provide the comprehensive care required by patients with this complex condition. However, more than 20,000 dialysis patients belong to such plans because they were enrolled before developing end-stage renal disease (ESRD). Disease-state management, successfully applied to patients with diabetes mellitus and congestive heart failure, is now being used in patients with ESRD. Standardized mortality ratios (SMRs) and standardized hospitalization ratios (SHRs) were calculated for 1998 and 1999 in 1,541 patients enrolled in the RMS Disease Management program of renal disease-state management using US Renal Data System methods. SMRs were 0.643 and 0.806 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). SHRs were 0.620 and 0.503 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). Although additional studies are needed to define the aspects of care that are most important for the outcomes seen, this study shows that favorable outcomes are achievable for this vulnerable patient population within a managed care setting that applies coordinated approaches to care.

Adolescent↗
PubMed2001

Trends in anemia at initiation of dialysis in the United States.

BACKGROUND: Anemia almost invariably develops in patients with chronic renal insufficiency (CRI) and is associated with a wide range of complications. The anemia of CRI can be effectively treated with recombinant human erythropoietin (rHuEPO). Recent studies suggest that the management of anemia of CRI is suboptimal in the United States. METHODS: We examined the trends in hematocrit and rHuEPO use among all patients who started chronic dialysis therapy between April 1, 1995, and December 31, 1999, from the End-stage Renal Disease Medical Evidence Form 2728 submitted to the Health Care Financing Administration of the United States. Follow-up data containing hematocrit levels after initiation were obtained from the Medicare Part A institutional outpatient dialysis provider claims for 1990 to 1998 prevalent patients. RESULTS: From June 1995 to June 1999, the mean hematocrit at initiation of dialysis increased from 28.1 to 29.3%. Likewise, the annual percentage of patients receiving pre-dialysis rHuEPO increased from 21.8 to 28.1%. Patients receiving predialysis rHuEPO had a higher mean hematocrit than patients without predialysis rHuEPO. The annual percentage of patients with hematocrit <24% fell 6.6% and the percentage with hematocrit > or =30% increased 9.2%. The trend toward higher hematocrit levels has been consistent across all age, gender, and race categories. Older patients, males, whites, and those who selected peritoneal dialysis had higher hematocrit levels than their counterparts. There were significant geographic differences in the prevalence of predialysis rHuEPO use. CONCLUSION: There has been a slight improvement in the management of anemia of CRI in the United States. However, a considerable fraction of patients still have hematocrit levels that are significantly lower than the currently recommended target. Furthermore, improvement in the management of anemia could result in improved clinical outcomes among patients with CRI.

Adolescent↗
PubMed2001

Apoptosis of leukocytes: basic concepts and implications in uremia.

Circulating blood leukocytes have short life expectancies and end their lives by committing programmed cell death or apoptosis. Apoptosis is an active form of cell death that is initiated by a number of stimuli and is intricately regulated. Apoptosis in both excessive and reduced amounts has pathological implications. Evidence suggests that apoptosis may play a role in the pathophysiology of immune dysfunction in uremia. Indeed, accelerated programmed cell death has been observed in lymphocytes, monocytes, and polymorphonuclear leukocytes among patients with chronic renal failure. This may be due in part to the retention of uremic toxins. The aim of this article is to review the evidence for accelerated leukocyte apoptosis, key regulatory apoptotic pathways, and the possible role of this highly organized process in the pathogenesis of immune dysfunction in uremia.

Apoptosis↗
PubMed2001

Prevalence and characteristics of individuals with chronic kidney disease in a large health maintenance organization.

This study is designed to estimate the prevalence of and gain further insight into the characteristics of the chronic kidney disease (CKD) population in a large US health maintenance organization (HMO) to better understand the CKD population in the United States overall. Analyses were performed using data from a staff and network model HMO in the southwestern United States with more than 150,000 members per year during 1994 to 1997. The estimated prevalence of CKD in the HMO population varied from 0.4% to 7.1%, depending on the definition of CKD used. Regardless of the definition, CKD was more common in men compared with women and in patients with diabetes mellitus and/or hypertension. Applying the age- and sex-specific prevalence rates in the HMO to the US population in 1990, we estimate there were approximately 9.1 million Americans with at least one elevated sex-specific creatinine (Cr) value and approximately 4.2 million Americans with at least two elevated Cr values separated by 90 days or greater, a more rigorous definition of CKD. From these results, it is apparent that there are a large number of patients in the United States with CKD. Most have not been identified because screening for CKD generally is not performed. Considering the high prevalence of CKD and the high cost and clinical morbidity associated with end-stage renal disease (ESRD), it is clear that CKD is an important public health problem. Early identification of patients with CKD would allow treatment that could slow the progression to ESRD, improve clinical outcomes, and constrain the growth of costs in the ESRD program. The time has come for a structured public and professional educational program to address this serious condition.

Adult↗
PubMed2001

Anemia: an early complication of chronic renal insufficiency.

The strong association between anemia and cardiovascular complications among patients with end-stage renal disease suggests that anemia during chronic renal insufficiency (CRI) may also have important consequences. We performed a retrospective cohort study to identify factors associated with severe anemia (hematocrit [Hct] < 30%) and examine anemia management practices in CRI. The CRI cohort was composed of 604 adult patients with elevated serum creatinine levels. There was a direct correlation between predicted glomerular filtration rate and Hct (r = 0.49) and an inverse correlation between serum creatinine level and Hct (r = -0.37). Anemia was noted early in CRI; 45% of patients with serum creatinine levels of 2 mg/dL or less had an Hct less than 36%, and 8% had an Hct less than 30%. During the course of the study, mean Hct decreased from 35.1% +/- 5.6% to 31.8% +/- 5.6%. Iron studies were obtained in only 19% of patients, and among these, the prevalence of iron deficiency (transferrin saturation < 20%) was 54%. Only 30% and 26% of patients were administered recombinant human erythropoietin (rHuEPO) and iron, respectively. Multivariate analyses showed that diabetes as the cause of renal disease, greater serum creatinine level, and having a single nephrology visit were associated with greater odds for the presence of anemia. A lower Hct and having a single nephrology visit were associated with greater odds for rHuEPO use. These results show that anemia begins early in the course of CRI, and management of anemia is suboptimal, even among patients under the care of nephrologists. Educational programs to optimize anemia management among patients with CRI are needed.

Administration, Oral↗
PubMed2001

Mechanisms of neutrophil apoptosis in uremia and relevance of the Fas (APO-1, CD95)/Fas ligand system.

The regulation of neutrophil apoptosis in chronic renal failure (CRF) has not been clearly defined. The Fas/FasL system is an important apoptotic regulatory pathway in a wide variety of cells. Fas is a widely expressed cell surface protein that transduces an apoptotic signal after interaction with its natural ligand FasL. In contrast to the extensive tissue distribution of Fas, constitutive expression of FasL is relatively limited. We examined Fas and FasL expression by neutrophils in healthy subjects, patients with CRF, and patients on hemodialysis (HD) and peritoneal dialysis (PD). Fas expression was significantly higher among patients with CRF compared with control subjects, HD patients, and PD patients. FasL expression was significantly higher among patients with CRF compared with control subjects. At 24 h, neutrophil apoptosis was higher among patients with CRF compared with control subjects. Furthermore, high-neutrophil Fas expression was paralleled by a higher sensitivity to Fas-mediated apoptosis. There was a strong correlation between Fas-stimulated apoptosis and creatinine clearance as well as Fas expression. Finally, we found that uremic serum increased the expression of neutrophil-associated Fas and FasL proteins, when compared with normal serum. Further studies are under way to examine the regulation of this pathway in the uremic environment.

Adult↗
PubMed2001

Management of chronic renal insufficiency: a call for a proactive approach.

As many as 6.2 million Americans may have chronic renal insufficiency (CRI), an insidious disease that can arise as a result of diabetes, hypertensive nephrosclerosis, chronic glomerulonephritis, and many other disorders. CRI usually progresses over time to end-stage renal disease, when patients require either dialysis or kidney transplantation in order to survive. With this population identified, primary care physicians, nephrologists, and payers have an opportunity to prevent or at least slow the progression of renal disease. The Renal Anemia Management Period (RAMP) may help raise awareness of the need for early diagnosis and aggressive treatment of anemia, one of the leading causes of morbidity in CRI patients. Such treatment has the potential to prevent or control the development of significant morbidity and mortality.

Anemia↗
PubMed2000

Impact of intermittent hemodialysis variables on clinical outcomes in acute renal failure.

When hospital-acquired acute renal failure (ARF) is severe enough to require renal replacement therapy, mortality rates are extremely high, exceeding 50%. The potential impact of renal replacement therapy on clinical outcomes in ARF remains a subject of ongoing investigation and controversy. This article reviews in depth all of the clinical trials that have examined the effect of dialysis-related variables on clinical outcomes in patients with ARF requiring intermittent hemodialysis. In particular, the role of biocompatibility of dialyzer membranes, and timing, intensity, and adequacy of dialysis are discussed.

Acute Kidney Injury↗
PubMed2000

Hepatitis C virus mixed genotype infection in patients on haemodialysis.

Hepatitis C virus (HCV) has been classified into different genotypes/subtypes with demonstrated clinical implications. Whether there is biological difference between genotypes is unknown. We determined HCV genotype in 120 anti-HCV-positive patients with end-stage renal disease and on haemodialysis, by both serological assay (which showed evidence of previous exposure) and by two molecular assays: restriction fragment length polymorphism (RFLP) and line-probe reverse hybridization (LiPA). In mixing experiments, RFLP and LiPA was able to detect the minor HCV genotypes (if present) in 5-30% and 1-2% of the viral population, respectively. Of the 120 patients studied, genotype-specific antibodies were detected in 50 (42%), and eight patients had reactivities to peptides derived from multiple genotypes (genotypes 1 and 2 and/or 3). Only genotype 1 infection was found by RFLP/LiPA in these eight patients with reactivities to multiple HCV genotypes. One-hundred and five of the 120 (88%) patients were positive for HCV RNA by reverse transcription-polymerase chain reaction (RT-PCR) analysis and 14 were found to have mixed genotype infection. Follow-up serum samples (4-21 months later) were available in five patients (genotype 1a with another genotype/subtype). All five patients had a reduced number of HCV genotypes detected during follow-up; four of the five patients still had detectable genotype 1a, and one patient lost genotype 1a and was positive for genotype 2b only. These data showed that HCV mixed infection can be reliably detected by molecular methods and, in patients with end-stage renal disease and mixed genotype infection, there is a trend that during follow-up, HCV genotype 1 may prevail, or 'take over' the genotype 2 and 3 infection.

Cloning, Molecular↗
PubMed2000

Impact of dialyzer membrane selection on cellular responses in acute renal failure: a crossover study.

BACKGROUND: When acute renal failure (ARF) is severe enough to require dialysis, in-hospital mortality rates approach 60%. These alarming figures have been ascribed in part to advanced age and the high prevalence of comorbid conditions. In the past several years, a number of attempts have been made to investigate the impact of dialyzer membrane type on clinical outcomes. Unfortunately, to date, clinical studies addressing this question have reported conflicting results. METHODS: This crossover study examined the effect of dialyzer membrane type on cytokine synthesis by peripheral blood mononuclear cells (PBMCs), superoxide release by neutrophils, and apoptosis or programmed cell death of neutrophils in 24 patients with ARF requiring intermittent hemodialysis. The patients were assigned in an alternate order to a low-flux cellulose acetate (CA) or polysulfone (PS) dialyzer. After three consecutive dialysis sessions, patients were crossed over to the second dialyzer for three additional treatments. These cellular responses were measured upon dialyzer assignment and at the third and sixth dialysis session in relationship to the dialyzer type. RESULTS: The results of the study showed no impact of dialyzer biocompatibility on synthesis of tumor necrosis factor-alpha (TNF-alpha) or interleukin 10 (IL-10) by PBMCs, superoxide release by neutrophils, or neutrophil apoptosis. This held true regardless of the initial dialyzer assignment. Furthermore, there was no correlation between dialysis adequacy (measured by single-pool Kt/V) and postdialysis cellular responses. CONCLUSIONS: In summary, this study refines the question of biocompatibility by comparing a substituted cellulose rather than unsubstituted cellulose dialyzer to a PS dialyzer in the setting of ARF. The results failed to demonstrate a dialyzer advantage on the selected cellular responses.

Acute Kidney Injury↗
PubMed2000

Characteristics and treatment of patients not reusing dialyzers in reuse units.

Dialyzer reuse is practiced in more than 75% of the patients and dialysis units in the United States. However, reuse is not practiced in a small fraction of patients treated in reuse units (RUUs). This study evaluates both patient and facility characteristics associated with nonreuse in RUUs. The data source is from the Dialysis Mortality and Morbidity Study, Waves 1, 3, and 4, of the US Renal Data System. Only facilities that practiced dialyzer reuse were included in the analysis. A total of 12,094 patients from 1,095 reuse facilities were studied. Patients undergoing hemodialysis as of December 31, 1993, were selected. Of all patients treated in RUUs, 8% did not reuse dialyzers. Nonreuse was significantly (P < 0.02) more common, based on adjusted odds ratios (ORs), among patients who were younger (OR = 1.16 per 10 years younger), had primary glomerulonephritis (OR = 1.26 versus diabetes), had lower serum albumin level (OR = 1.72 per 1 g/dL lower), had more years on dialysis, and had higher level of education. Nonreuse patients were more likely to be treated with low-flux dialyzers (OR = 7.35; P < 0. 0001) and have a lower dialysis dose. No reuse was more likely in larger units and in not-for-profit and hospital-based units. Patient refusal accounted for one fourth of nonreuse in RUUs and was associated with the same factors, as well as with fewer comorbid conditions and non-Hispanic ethnicity. Significant geographic variations (up to eightfold) were documented. Nonreuse patients are treated with smaller, low-flux dialyzers and, on average, receive a lower Kt/V than reuse patients in the same units.

Ambulatory Care Facilities↗
PubMed2000

Anemia management in patients with chronic renal insufficiency.

The introduction of recombinant human erythropoietin (rHuEPO) more than a decade ago provided the first effective treatment for the anemia of chronic renal insufficiency (CRI). The use of rHuEPO in the treatment of anemia has been associated with partial regression of left ventricular hypertrophy among both dialysis and nondialysis patients, and has been shown to reduce the frequency of cardiac complications such as congestive heart failure and number of days of hospitalization among dialysis patients. Despite this evidence, the anemia of CRI remains highly prevalent, underrecognized, and undertreated. A number of considerations arise regarding the management of anemia among patients with CRI. In this article, we review the rationale for treatment of anemia, current management practices, proposed treatment strategies, and the economic implications of improved anemia treatment.

Anemia↗
PubMed2000

Serum soluble Fas (CD95) and Fas ligand profiles in chronic kidney failure.

Apoptosis, or programmed cell death, is an active form of cell death that is initiated by a number of stimuli and is intricately regulated. Apoptosis in both excessive and reduced amounts has pathophysiologic implications. Accelerated programmed cell death has been observed in leukocytes among patients with chronic renal failure (CRF). This has been ascribed in part to the retention of uremic toxins. The Fas/Fas ligand (FasL) system is a key regulatory apoptotic pathway. Membrane-bound Fas is a cell-surface receptor that transduces apoptosis after interaction with membrane-bound or soluble FasL (sFasL). By contrast, soluble Fas (sFas) binds sFasL and inhibits its activity. In an attempt to examine the balance between these soluble factors in uremia, we measured soluble sFas and sFasL levels in the serum of healthy control subjects and patients with various degrees of CRF and examined the distribution of the various molecular mass fractions of these proteins in uremic serum. In brief, serum was obtained from 15 healthy volunteers, 17 patients with CRF, 11 patients undergoing maintenance hemodialysis (HD), and 7 patients undergoing peritoneal dialysis (PD). Serum sFas and sFasL were measured by enzyme-linked immunosorbent assay, and their molecular distribution was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot. Compared with results in healthy control subjects, sFas levels were significantly higher in patients with CRF and in patients undergoing dialysis. There was a significant inverse correlation between sFas levels and creatinine clearance. Serum sFasL levels were not different among the four groups. However, the sFas-to-sFasL ratio was significantly lower in healthy control subjects as compared with patients with CRF and patients undergoing dialysis. Immunoblots and densitometric analyses of sFas and sFasL depicted a known 48-kd sFas, a known 27-kd sFasL, and a 60-kd sFas-sFasL protein aggregate signal. In conclusion, serum sFas levels are increased in patients with various degrees of CRF and may bind circulating sFasL, thereby minimizing mediation of cellular apoptosis.

Adult↗
PubMed1999

Effect of dialysis membranes and middle molecule removal on chronic hemodialysis patient survival.

The type of dialysis membrane used for routine therapy has been recently shown to correlate with the survival of chronic hemodialysis patients. We examined whether this effect of dialysis membrane could be explained by differences in dialyzer removal of middle molecules using data from the 1991 Case Mix Adequacy Study of the United States Renal Data System. The sample analyzed included patients who had been treated by hemodialysis for 1 year or more, who were dialyzed with the 19 most commonly used dialyzers in 1991, and for whom delivered urea Kt/V could be calculated from predialysis and postdialysis blood urea nitrogen concentrations. Vitamin B12 (1,355 daltons) was used as a marker for middle molecules, and the clearance of vitamin B12 was estimated based on in vitro data. After adjustments for case mix, comorbidities, and urea Kt/V, the relative risk of mortality for a 10% higher calculated total cleared volume of vitamin B12 was 0.953 (P < 0.0001 v 1.000). Similar results were obtained when middle molecule removal was adjusted for body size. We conclude that both small and middle molecule removal indices appear to be independently associated with the risk of mortality in chronic hemodialysis patients. Differences in mortality when using different types of dialysis membrane may be explained by differences in middle molecule removal.

Humans↗
PubMed1999

Hematopoietic effect of Radix angelicae sinensis in a hemodialysis patient.

The primary cause of anemia of chronic renal failure (CRF) is insufficient production of erythropoietin by the diseased kidneys. Although most patients receiving hemodialysis (HD) respond to recombinant human erythropoietin (rHuEPO) treatment, 4% prove to be rHuEPO resistant. The patient presented in this case study suffered from anemia of CRF that was resistant to rHuEPO therapy. He experienced marked improvement in the anemia after self-initiating regular consumption of the Chinese herb Dang qui (botanical name: Radix angelicae sinensis). The significant hematologic amelioration occurred in the face of a major decrease in the amount of rHuEPO administered. The causes and mechanisms of inadequate response to rHuEPO, as well as the possible beneficial hematopoietic effects of this herbal preparation, are discussed.

Anemia↗