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Biomedical subjects

R M Hakim

Publications and source records attributed to R M Hakim.

At least 55 records · Page 3Linked to original sources
PubMed1995

Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin.

Iron supplementation is required by most dialysis patients receiving recombinant human erythropoietin. The efficacy of oral iron is variable in these patients, and many require the use of intravenous iron dextran to maintain adequate iron levels, defined as transferrin saturation greater than 20%, serum ferritin greater than 100 ng/mL, and serum iron greater than 80 micrograms/dL. To determine the efficacy of different oral iron preparations in maintenance of iron status, we prospectively studied 46 recombinant human erythropoietin-treated patients and randomized them to receive different oral iron preparations. These four preparations included Chromagen (ferrous fumarate; Savage Laboratories, Melville, NY), Feosol (ferrous sulfate; SmithKline Beecham, Inc, Pittsburgh, PA), Niferex (polysaccharide; Central Pharmaceuticals, Inc, Seymour, IN), or Tabron (ferrous fumarate; Parke-Davis, Morris Plains, NJ). All patients were prescribed approximately 200 mg of elemental iron daily of their assigned iron preparation with at least 100 mg ascorbic acid daily for 6 months. At baseline and bimonthly during the study, serum iron, transferrin saturation, ferritin, hematocrit, and recombinant human erythropoietin dose were monitored; in addition, compliance and side effects were recorded by patient interview. All patients were able to maintain target hematocrit during the 6 months of study. However, there were differences in the trends of serum iron, percent transferrin saturation, and ferritin when considered singly or in combination between the four groups of iron medications. The percent of laboratory values measured over the study period in each group that met the criteria of transferrin saturation more than 20% was greatest in the Tabron group (58%), followed by the Feosol (47%), Chromagen (33%), and Niferex (31%) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Defective platelet aggregation in uremia is transiently worsened by hemodialysis.

Bleeding is a prominent feature of uremia and remains a significant cause of morbidity in hemodialysis (HD)-dependent patients. To measure the impact of the HD procedure, we performed a prospective cross-over study in eight patients placed consecutively for 2-week periods each on low-flux biocompatible polymethylmethacrylate, low-flux complement-activating cuprophane, and high-flux biocompatible polysulfone membranes. The primary measure of platelet function studied was shear-induced platelet aggregation (SIPA), which has been shown to be a physiologically relevant marker of platelet function and involves the interaction of von Willebrand factor (vWf) with platelet membrane glycoproteins (GP) Ib and IIb-IIIa. Flow-cytometric analysis of the surface expression of platelet membrane GP Ib and GP IIb-IIIa was performed using fluorescein isothiocyanate (FITC)-conjugated monoclonal antibodies CD42b and CD41a, respectively. Multivariate analysis did not demonstrate a statistically significant effect of the type of dialysis membrane on platelet aggregation, calcium flux, or thromboxane B2 production. There was a marked decrease of SIPA in HD patients (pre-HD, mean +/- SEM, 19% +/- 3%) compared with normal controls (43% +/- 3%, P < 0.001), with a further decrease after the HD procedure (post-HD, 12% +/- 2%, P = 0.015 compared with pre-HD). This intradialytic decrease in SIPA correlated with a decrease in GP Ib (pre-HD, 385 +/- 21 mean fluorescence intensity [MFI]; post-HD, 285 +/- 21 MFI, P = 0.0001). GP IIb-IIIa was also significantly decreased post-HD (pre-HD, 1,022 +/- 70 MFI; post-HD, 881 +/- 64 MFI, P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1995

Interventions to treat malnutrition in dialysis patients: the role of the dose of dialysis, intradialytic parenteral nutrition, and growth hormone.

Protein and calorie malnutrition often starts before initiation of dialysis, and reflects the anorexia and the catabolic state of chronic renal failure. In the face of inadequate dialysis, which perpetuates the uremic state, malnutrition often worsens. Several studies, though not all, suggest that optimal dialysis improves nutritional status of dialysis patients. Such optimal dialysis now must include the use of biocompatible membranes to deliver Kt/V > 1.4 (urea reduction ratio > 65%). Additional interventions can include the use of enteral or intravenous hyperalimentation, and recombinant growth factors such as growth hormone or insulin-like growth factor-1. Importantly, studies to document the improvement in the morbidity and mortality of patients with these interventions are still needed and require large multicenter trials.

Growth Hormone↗
PubMed1995

Analysis of the genomic sequence for the autosomal dominant polycystic kidney disease (PKD1) gene predicts the presence of a leucine-rich repeat. The American PKD1 Consortium (APKD1 Consortium).

The complete genomic sequence of the gene responsible for the predominant form of polycystic kidney disease, PKD1, was determined to provide a framework for understanding the biology and evolution of the gene, and to aid in the development of molecular diagnostics. The DNA sequence of a 54 kb interval immediately upstream of the poly(A) addition signal sequence of the PKD1 transcript was determined, and then analyzed using computer methods. A leucine-rich repeat (LRR) motif was identified within the resulting predicted protein sequence of the PKD1 gene. By analogy with other LRR-containing proteins, this may explain some of the disease-related renal alterations such as mislocalization of membrane protein constituents and changes in the extracellular matrix organization. Finally, comparison of the genomic sequence and the published partial cDNA sequence showed several differences between the two sequences. The most significant difference detected predicts a novel carboxy-terminus for the PKD1 gene product.

Amino Acid Sequence↗
PubMed1995

Initiation of dialysis.

The decision to initiate dialysis in a patient with progressive renal disease often depends on the physician's assessment of the patient's subjective symptoms of uremia. There is an increasing need to identify objective criteria for such a decision. Recent evidence suggests that malnutrition at the initiation of dialysis is a strong predictor of subsequent increased relative risk of death on dialysis. In this context, the role of prescribed protein restriction as well as the influence of the progression of renal disease on spontaneous dietary protein intake is examined. It is proposed that the indices of malnutrition such as progressive weight loss, serum albumin levels below 4.0 g/dL, serum transferrin levels below 200 mg/dL, and spontaneous dietary protein intake (using 24-hr urinary nitrogen measurement) below 0.8 to 0.7 g/kg per day be considered as objective criteria for the initiation of dialysis. Studies that have examined the role of "early" versus "late" dialysis have consistently shown a better outcome in the patients starting dialysis early. Other studies also suggest that early referral to nephrologists results in improved morbidity and mortality as well as hospitalization costs. An adequate vascular access, as well as social and psychological preparation of the patient, is an important early step in the process.

Humans↗
PubMed1995

Spontaneous dietary protein intake during progression of chronic renal failure.

Malnutrition at the initiation of dialysis is a strong predictor of subsequent increased mortality on dialysis. Few studies have documented the relationship between the progression of renal failure and spontaneous dietary protein intake (DPI) and other indices of malnutrition. In this prospective study, renal function was sequentially measured by creatinine clearance (CrCl) and DPI by 24-h urine collection; simultaneously, multiple sequential biochemical nutritional indices, including serum albumin, transferrin, prealbumin, and insulin-like growth factor-I (IGF-I) concentrations, were measured. The study involved 90 patients (46 men and 44 women) with chronic renal failure (CRF) of various causes monitored in an outpatient clinic. Dietary interventions were minimal. The mean duration of follow-up was 16.5 +/- 11.8 months. The results show that the mean (+/- SD) DPI was 1.01 +/- 0.21 g/kg per day for patients with CrCl over 50 mL/min and decreased to 0.85 +/- 0.23 g/kg per day for patients with CrCl between 25 and 50 mL/min. The DPI further decreased to a level of 0.70 +/- 0.17 g/kg per day for patients with CrCl between 10 and 25 mL/min and was 0.54 +/- 0.16 g/kg per day for patients with CrCl below 10 mL/min. This trend was statistically significant (P < 0.001). A similar statistically significant trend was observed for serum cholesterol, transferrin, and total creatinine excretion (all P < 0.01). A mixed model analysis indicated that for each 10 mL/min decrease in CrCl, DPI decreased by 0.064 +/- 0.007 g/kg per day, transferrin decreased by 16.7 +/- 4.1 mg/dL, weight decreased by 0.38 +/- 0.13% of initial weight, and IGF-I decreased by 6.2 +/- 1.9 ng/mL. It was concluded that the progression of renal failure is associated with a spontaneous decrease in DPI, especially below a CrCl of 25 mL/min, and that most nutritional indices in CRF patients worsen as CrCl and DPI decrease. Dietary protein restriction should be used cautiously in CRF patients when CrCl falls below 25 mL/min.

Creatinine↗
PubMed1995

Malnutrition in peritoneal dialysis patients: etiologic factors and treatment options.

It is clear that malnutrition is common in chronic dialysis patients and is associated with increased morbidity and mortality. Evidence is accumulating that several measures can be taken to improve the nutritional status of these patients. An early start of dialysis, an increase in dialysis dose, the use of biocompatible membranes or dialysis solutions, and intensive nutritional counseling should be applied when necessary. If these measures fail, additional interventions, such as parenteral or enteral nutritional supplements, rhGH, and rhIGF-1, alone or in combination, should be tried.

Anabolic Agents↗
PubMed1994

Effect of the dialysis membrane in the treatment of patients with acute renal failure.

BACKGROUND: The mortality rate among patients with acute renal failure remains high, and the role of the biocompatibility of the dialysis membrane in the resolution of this disorder is not known. METHODS: We prospectively studied 72 patients with acute renal failure who required hemodialysis and assigned them to two treatment groups. One group underwent dialysis with the widely used cuprophane dialysis membrane, which activates the complement system and leukocytes, and the other group underwent dialysis with a synthetic polymethyl methacrylate membrane, which has a more limited effect on complement and leukocytes. Scores on the Acute Physiology, Age, and Chronic Health Evaluation (APACHE II) were calculated at the initiation of dialysis. Survival and the recovery of renal function were determined with the use of proportional-hazards and exact logistic-regression analyses. RESULTS: When dialysis was initiated, the patients in the two groups were similar in terms of age, APACHE II scores, the prevalence of oliguria, and biochemical indexes of renal failure. Twenty-three of the 37 patients (62 percent) in the group undergoing dialysis with the polymethyl methacrylate membrane recovered renal function, as compared with 13 of the 35 patients (37 percent) in the group undergoing dialysis with the cuprophane membrane (P = 0.04 after adjustment for the APACHE II score). The median number of dialysis treatments required before the recovery of renal function was 5 in the former group and 17 in the latter group (P = 0.02). Twenty-one patients (57 percent) undergoing dialysis with the polymethyl methacrylate membrane survived, as compared with 13 patients (37 percent) undergoing dialysis with the cuprophane membrane (P = 0.11). Of the 20 patients in each group who initially had nonoliguric acute renal failure, the survival rates were 80 percent with the polymethyl methacrylate membrane and 40 percent with the cuprophane membrane (P = 0.01). CONCLUSIONS: Among patients with acute renal failure requiring hemodialysis, the use of the polymethyl methacrylate membrane, as compared with the cuprophane membrane, resulted in improved recovery of renal function.

APACHE↗
PubMed1994

Effects of dose of dialysis on morbidity and mortality.

The annual mortality rate of patients on hemodialysis in the United States is 24.3%, substantially higher than the mortality of age-matched patients in Europe and Japan. Differences in the dose of dialysis received by US patients has been proposed as an important factor contributing to this high mortality rate. We undertook a prospective effort to increase the dose of dialysis delivered to 130 patients treated at an urban dialysis center affiliated with Vanderbilt University. From 1988 to 1991 the dose of dialysis, represented by the urea kinetic modelling parameter Kt/V (K = dialyzer clearance, t = dialysis time, V = volume of distribution of urea), has been gradually increased from a dose of 0.82 +/- 0.32 to 1.33 +/- 0.23. Concurrent with this increase, there was a reduction of the gross annual mortality rate from 22.8% in 1988 to 9.1% in 1991. To account for potential differences in patient characteristics during those years, we also calculated the number of expected deaths, based on data from the United States Renal Data System. The ratio of observed to expected deaths, termed the "standardized mortality rate," decreased from a value of 1.03 in 1988 to a value of 0.611 in 1991. In addition, the number of hospital days per patient per year decreased from 15.2 d/patient/yr to 10.3 d/patient/yr. We conclude that increasing the dose of delivered dialysis decreases the hospitalization and mortality rates of hemodialysis-dependent patients.

Adult↗
PubMed1994

Renal replacement therapies in the elderly: Part II. Renal transplantation.

The United States end-stage renal disease (ESRD) population is growing progressively older. As a percentage of the overall ESRD population, the number of patients 65 years of age and older approached 40% by 1989. However, the percentage of ESRD patients with a functioning transplant was only 2.7% in this age group. Success of transplantation in geriatric ESRD patients over the last decade is due to improved patient selection as well as the use of cyclosporine A and lower doses of corticosteroids, with the achievement of 1-year patient and graft survival rates of 85% and 75%, respectively. For patients older than 60 or 65 years, the 5-year "functional" graft survival is 55% to 60%. Although overall results are excellent, the management of transplantation in the elderly requires an understanding of pharmacology, immunology, and physiology peculiar to this age group. Since the elderly have a degree of immune incompetence, they require less aggressive immunotherapy. Elderly patients have decreased hepatic enzyme activity, especially the P450 system, and therefore require a lower cyclosporine dose. Although elderly patients experience less rejection episodes than younger patients, graft loss in the elderly transplant recipient is due mainly to patient death. Most common causes of death in the elderly transplant recipient are cardiovascular disease and infection related to peaks of immunosuppression. Shortage of cadaver kidneys and limited life expectancy of the geriatric ESRD patient make allocation of cadaver kidneys to patients over 70 years (and even 65 years) a controversial issue and an ethical dilemma. Use of elderly cadaver donors (over 55 to 60 years) is associated with inferior success rates and is not an optimal solution to shortage of cadaver kidneys.

Aged↗
PubMed1994

Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study.

Hemodialysis (HD) vascular access thrombosis remains a major cause of morbidity, accounting for 17.4% of all HD patient hospital admissions in 1986. We initiated this prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded polytetrafluoroethylene (ePTFE) grafts in HD patients. Two patient groups were studied: Type I--with a new ePTFE graft; and Type II--with thrombectomy and/or revision of a previously placed ePTFE graft. One hundred and seven patients were followed for 18 months or until the first thrombotic episode. Actuarial analysis of Type I patients showed cumulative thrombosis rates (mean +/- SEM) of 21 +/- 9% on dipyridamole alone, compared with 25 +/- 11% on dipyridamole and aspirin combination, 42 +/- 13% on placebo, and 80 +/- 12% on aspirin alone. The relative risk of thrombosis with dipyridamole was 0.35 (P = 0.02) and that for aspirin was 1.99 (P = 0.18). In Type II patients, the rate of thrombosis was high in all study drug and placebo groups (overall 78% thrombosis) and actuarial analysis was not carried out because of the small number of patients enrolled. We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts. Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts.

Adult↗
PubMed1994

Amino acid and albumin losses during hemodialysis.

Protein and calorie malnutrition are prevalent in chronic hemodialysis (HD) patients and has been linked to increased mortality and morbidity in this patient population. Concern has been raised that the open pore structure of high flux membranes may induce the loss of more amino acids (AA) compared to low flux membranes. To address this issue, we prospectively analyzed pre- and post-HD plasma AA profiles with three different membranes in nine patients. Simultaneously, we measured dialysate AA losses during HD. The membranes studied were: cellulosic (cuprophane-CU), low flux polymethylmethacrylate (LF-PMMA), and high flux polysulfone (HF-PS) during their first use. Our results show that pre-HD plasma AA profiles were abnormal compared to controls and decreased significantly during HD with all dialyzers. The use of HF-PS membranes resulted in significantly more AA losses into the dialysate when compared to LF-PMMA membranes (mean +/- SD; 8.0 +/- 2.8 g/dialysis for HF-PS, 6.1 +/- 1.5 g/dialysis for LF-PMMA, p < 0.05, and 7.2 +/- 2.6 g/dialysis for CU membranes, P = NS). When adjusted for surface area and blood flow, AA losses were not different between any of the dialyzers. We also measured dialysate AA losses during the sixth reuse of the HF-PS membrane. Losses of total AA increased by 50% during the sixth reuse of HF-PS membrane compared to its first use. In addition, albumin was detected in the dialysate during the sixth reuse of HF-PS membrane. We therefore measured albumin losses in all patients dialyzed with HF-PS membranes as a function of reuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Short-term effects of recombinant human growth hormone in CAPD patients.

Protein and calorie malnutrition is common in chronic dialysis patients. Several interventions have been proposed to prevent and/or to treat malnutrition. Recombinant human growth hormone (rhGH) is a drug with anabolic properties and has been used in several catabolic conditions, such as patients with severe burns as well as in pediatric patients with chronic renal failure. In this study, we evaluated the short-term effects and safety of rhGH on urea kinetics and commonly measured biochemical parameters in 10 stable adult continuous ambulatory peritoneal dialysis (CAPD) patients. The design of the study was prospective, cross-over with the patients serving as their own controls. There were three study periods: baseline (PreGH), treatment (Tx), and follow-up (PostGH). During the seven day Tx period, patients self-administered 5 mg/day s.c. of rhGH. During this time, there was a significant decrease in blood urea nitrogen (BUN) (54 +/- 15 to 40 +/- 12 mg/dl), as well as in the combined dialysate and urine urea nitrogen excretion rate (5.69 +/- 1.86 to 4.04 +/- 1.13 g/day), and protein catabolic rate (0.82 +/- 0.13 to 0.67 +/- 0.09 g/kg/day), (all P < 0.001). Serum phosphorus (4.8 +/- 1.6 to 4.4 +/- 1.8 mg/dl) and potassium (4.0 +/- 0.4 to 3.6 +/- 0.2 mEq/liter) levels also showed a small but statistically significant decrease, in conjunction with a statistically significant increase in serum creatinine levels (12.2 +/- 5.7 to 12.9 +/- 5.7 mg/dl). Dietary protein intake, determined by dietary recall, did not change during the study (66.1 +/- 20.5 vs. 75.8 +/- 22.1 grams/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The effects of the dialysis membrane on cytokine release.

The immune response requires the coordinated release of a network of cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF), and IL-2. The potential role of the dialysis membrane on the elaboration of these cytokines by peripheral blood mononuclear cells (PBMNC) harvested from hemodialysis patients was investigated in a prospective crossover study. Eight hemodialysis patients, chronically dialyzed with a biocompatible membrane, were sequentially dialyzed for 2 wk with new cuprophane membranes (Phase I), 2 wk with a low-flux, low-complement-activating membrane (Phase II), and then switched back for a further 2 wk of dialysis with a cuprophane membrane (Phase III). At the end of 2 wk of exposure to the cuprophane membrane, during both Phase I and Phase III, the ability of PBMNC to elaborate IL-1 beta, tumor necrosis factor-alpha, and IL-2, as well as soluble IL-2 receptors, in response to phytohemagglutinin was significantly reduced compared with their respective levels at the beginning of the phase; dialysis with a biocompatible membrane increased these levels, and at the end of 2 wk, the response of the PBMNC to phytohemagglutinin was close to that in normal controls. These findings may explain some of the conflicting results in the measurement of cytokine levels in hemodialysis patients and may have clinical implications.

Aged↗
PubMed1994

Biocompatibility and risk of infection in haemodialysis patients.

Infection remains a major cause of morbidity and mortality in the dialysis patient. Most of these infections are bacterial and often lead to sepsis. In this review the possible influence of the biocompatibility of the dialysis membrane on the incidence of bacterial infections is discussed. Specifically, the role of the membrane on granulocyte function such as phagocytosis, adhesion, and production of reactive oxygen species is shown to be adversely affected by recurrent exposure to complement-activating membranes. Recent clinical studies also support the notion that dialysis with bioincompatible membranes is associated with a higher incidence of clinical infections than membranes that are more biocompatible.

Biocompatible Materials↗