Extremes of glycemic control (HbA1c) increase hospitalization risk in diabetic hemodialysis patients in the USA.

BACKGROUND/AIMS: Because the relation between glycemic control and clinical outcomes found in the general diabetic population has not been established in diabetic hemodialysis patients, we evaluated the association between glycemic control and hospitalization risk. METHODS: We performed a primary retrospective data analysis on 23,829 hemodialysis patients with diabetes mellitus. Hemoglobin A(1c) at baseline and hospitalization events over the subsequent 12 months were analyzed and logistic regression models constructed for unadjusted, case mix-adjusted and case mix plus lab- adjusted data. Models were also constructed for cardiovascular, vascular access and sepsis hospitalizations. RESULTS: Eighty percent had type 2 DM, 5% type 1 and 14% not specified. The groups had similar mean HbA(1c) levels, 6.8 +/- 1.6%. Among all patients, the mean HbA(1c) values were >7% in 35%. The odds ratio of hospitalizations grouped by baseline HbA(1c) was significant at extremes of <5% and >11%. Similar relationships were evident for the subset of type 2 DM and in the analysis for hospitalizations due to sepsis. CONCLUSION: Extremely high and low HbA(1c) values are associated with hospitalization risk in diabetic hemodialysis patients. Prospective studies are needed to determine whether meeting recommended HbA(1c) targets might improve outcomes without posing additional risks in this population.

Hemodialysis-associated platelet activation and thrombocytopenia.

The interactions between platelets and dialysis membranes were studied prospectively in 10 patients undergoing long-term stable dialysis. Transient but significant thrombocytopenia and platelet activation were found during dialysis with the commonly used cuprophane membrane. Platelet counts decreased from 231 +/- 21 X 10(3)/mm3 before dialysis to 127 +/- 28 X 10(3)/mm3 at 90 minutes following initiation of dialysis (p less than or equal to 0.007). Thromboxane B2, an index of platelet activation, also increased from a baseline level of 1.06 +/- 0.2 pg/10(6) platelets to 7.3 +/- 3.0 pg/10(6) platelets at 90 minutes (p less than or equal to 0.04). Cuprophane membranes were also shown to induce complement activation with C3a desArg, the stable derivative of C3 activation, showing a threefold increase from baseline 15 minutes after initiation of dialysis. In contrast, during dialysis with a non-complement-activating dialyzer membrane, polymethylmethacrylate, thrombocytopenia and platelet activation were not observed. These data suggest that platelet activation and thrombocytopenia during hemodialysis are associated with complement activation during hemodialysis in a manner similar to dialysis-associated neutropenia.

Proposed clinical trials in the evaluation of intradialytic parenteral nutrition.

New revised policies relating to intradialytic parenteral nutrition (IDPN) reimbursement by Medicare have made it difficult, if not impossible, to qualify malnourished hemodialysis patients for this potentially useful therapy. These policies were adopted by Medicare because of a lack of studies that provide clear documentation of the medical benefits of IDPN or their cost-effectiveness. We propose a limited study of the role of IDPN with and without anabolic growth factors to improve predefined nutritional parameters and document its cost-effectiveness by monitoring hospitalization and mortality. The proposed study will be multicenter, prospective, limited to severely malnourished patients, and will include a control group that would receive standard of care.

Prognosis of patients with acute renal failure requiring dialysis: results of a multicenter study.

Despite several decades of clinical experience, the mortality rate for patients with acute renal failure (ARF) requiring dialysis remains high, and the evaluation of the patients prognosis has been difficult. To date, the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system has been used more frequently for prediction in studies of ARF than any other scoring system, but has not been prospectively validated in controlled multicenter studies of this entity. In a multicenter, prospective, controlled trial evaluating the use of biocompatible hemodialysis membranes (BCMs) in patients with ARF, we evaluated the extent to which the APACHE II scoring system, based on the physiological variables in the 24 hours before the onset of dialysis and the presence or absence of oliguria, is predictive of outcome. Analysis of survival and recovery of renal function for the 153 patients treated in this study show that APACHE II scores are predictive both of survival and recovery of renal function, whether analyzed separately by type of dialysis membrane used (BCM or bioincompatible [BICM]) or for both groups combined (all P < 0.01). There was no evidence of a significant center effect or interaction of APACHE II score with dialysis membrane in our study. After adjusting for the APACHE II score, there was a positive effect of the BCM on both probability of survival (P < 0.05) and recovery of renal function (P < 0.01). In patients dialyzed with BCMs, oliguria at onset of dialysis had an adverse effect on both survival and recovery of renal function (both P < 0.01). Receiver operator curves (ROCs) using APACHE II score and the use of BCMs in nonoliguric patients yielded a statistically significant improvement versus the use of APACHE II score alone in the area under the curve (AUC) for survival (0.747 to 0.801; P < 0.05) and recovery of renal function (0.712 to 0.775; P < 0.05). We conclude that the use of the APACHE II score determined at the time of initiation of dialysis for patients with ARF is a statistically significant predictor of patient survival and recovery of renal function. The use of the APACHE II score measured at the time of dialysis initiation, especially when modified by the presence or absence of oliguria, should help in predicting outcome when evaluating interventions for patients with ARF.

Prescribed versus delivered dialysis in acute renal failure patients.

The current study was designed first to determine separately the prescribed and delivered dose of dialysis and, second, to determine what factors lead to failure to deliver the prescribed dose of dialysis in patients with acute renal failure (ARF). Forty patients, who collectively underwent 136 dialysis treatments, were studied prospectively at two institutions. The results showed that almost half the prescriptions (49%) were for a Kt/V less than 1.2 and, more importantly, nearly 70% of the treatments delivered a Kt/V less than 1.2, the minimally acceptable dose defined in the Dialysis Outcomes Quality Initiative (DOQI) guidelines for chronic hemodialysis (CHD) patients. Patient predialysis weight was the most important variable associated with a low prescribed and delivered dose of dialysis, as well as lack of delivery of the prescribed dose of dialysis. From the statistical model, it is estimated that for every 10-kg increase in predialysis weight, the chance of prescribing or delivering a Kt/V less than 1.2 increased 4.6- and 1.95-fold, respectively. The lower than prescribed blood flow achieved by the temporary catheters and patients not receiving anticoagulation were variables also associated with not receiving the prescribed Kt/V. It is concluded that patients with ARF are prescribed and receive a dose of dialysis that would be considered inadequate for CHD patients. Until the association between dose of dialysis and outcome is better defined, it would be prudent that both the dialysis prescription and the delivery of dialysis to patients with ARF should be performed with the same care and goals as that currently received by patients with end-stage renal disease (ESRD).

Relationship of dialysis membrane and cause-specific mortality.

A number of studies have suggested that type of dialysis membrane is associated with differences in long-term outcome of patients undergoing hemodialysis, both in terms of morbidity and mortality. The purpose of this study was to determine the relationship of membrane type and specific causes of death. Data from the United States Renal Data System Case Mix Adequacy Study, a national random sample of hemodialysis patients who were alive on December 31, 1990, were used. Our study was limited to patients in this data set who were undergoing dialysis for at least 1 year (n = 4,055). For the main analytic models, membrane type was classified into two categories: unmodified cellulose or MC/SYN (which combines modified cellulose [MC] and synthetic membranes [SYN]). The relationships of membrane type and major causes of mortality were analyzed using Cox proportional hazards models, which adjusted for multiple (21) covariates, including demographics, comorbidity, Kt/V, and other parameters. Patients were censored at transplantation or 60 days after a switch to peritoneal dialysis. Compared with patients dialyzed with unmodified cellulose membranes, the adjusted relative mortality risk (RR) from infection was 31% lower (RR = 0.69; P = 0.03) and from coronary artery disease was 26% lower (RR = 0.74; P = 0.07) for patients dialyzed with MC/SYN membranes. No statistically significant difference (all P > 0.1) was found in mortality risk from cerebrovascular disease (RR = 1.08), other cardiac causes (RR = 0.86), malignancy (RR = 0.90), or other known causes (RR = 0.82) between patients dialyzed with MC/SYN compared with unmodified cellulose membranes. These results offer support to reported experimental and observational clinical studies that have found that unmodified cellulose membranes may increase the risk for both infection and atherogenesis. Further studies are necessary to evaluate the possibility of confounding factors, compare more specific membrane types, and determine the pathophysiology linking membrane type to cause-specific mortality.

Meaningful rehabilitation of the end-stage renal disease patient.

In this highly technological age, health care providers are called to attend to the patient as a whole person, with dreams and goals and a desire for purpose and meaning in life. In this article, we propose a broadened definition of rehabilitation and a rehabilitation program designed to effect an improvement in the quality of life of each renal patient by aiming to restore meaningful existence in each of their lives. An individualized plan for rehabilitation can be constructed and implemented with far-reaching success when the focus is on the life goals of the patient, whether physical, social, psychological, or intellectual. These programs not only enhance the quality of life of the patient with end-stage renal disease, but are cost-effective, both at the societal level and at the level of the dialysis clinic.

The current and future state of the ESRD program: a provider roundtable.

The decade of the 1990s have seen substantial consolidation of services in the dialysis industry in the United States. A small number of horizontally and/or vertically integrated companies oversee the care of over two-thirds of dialysis patients. There are many questions regarding this trends as well as the vision of these large organizations regarding the future of the ESRD program. The senior physicians in the four largest such organizations agreed to participate in a provider roundtable to share their thoughts on the following issues: What are the advantages and disadvantages of industry consolidation?; What steps has your organization taken to succeed?; What are the key issues facing this industry in the next decade?; What policy changes by the Federal Government do you anticipate?; What policy changes would you like to see? Although significant differences in specifics are clear in the responses, a recurrent theme relates to how value will be maintained in the program-the balance between high-quality outcomes and the costs of achieving these outcomes. This is clearly the challenge in the years ahead.

Nitrogen balance in hospitalized chronic hemodialysis patients.

Malnutrition is an important factor in the increased morbidity and mortality of chronic hemodialysis (CHD) patients. Dietary protein intake necessary to maintain neutral nitrogen balance appears to be higher in CHD patients due to various catabolic effects of the hemodialysis procedure, including nutrient losses and increased energy expenditure. Dietary intake may be further decreased in hospitalized CHD patients. We examined this issue in 18 CHD patients (9 male, 9 female) who were admitted to a regular ward. Daily protein intake (DPI) and daily caloric intake were measured for each patient. In addition, protein catabolic rate (PCR) calculated from interdialytic changes in BUN were calculated. Our results showed that mean (+/- SD) DPI was 0.79 +/- 0.41 g/kg/day, while PCR was 0.93 +/- 0.38 g/kg/day. Dietary protein and energy intake were 66% and 50% of suggested values, respectively, and DPI accounted for only 85% of PCR. Mean nitrogen balance was negative by -2.11 +/- 2.77 g of nitrogen/day (range -9.91 g of nitrogen/day to +3.89 g of nitrogen/day). Biochemical nutritional parameters such as serum albumin, cholesterol, prealbumin and transferrin obtained one week following admission were also indicative of undernutrition (3.16 +/- 0.39 g/dl, 132 +/- 30 mg/dl, 20 +/- 7.4 mg/dl, 154 +/- 49 mg/dl, respectively). We conclude that hospitalized CHD patients have inadequate protein and energy intake and this is evidenced by a significant deterioration in nutritional parameters during hospitalization. More aggressive nutritional interventions may be needed for this group of patients to prevent the adverse effects of hospitalization on nutritional status.

Clinical sequelae of complement activation in hemodialysis.

During clinical hemodialysis, interactions between blood and dialysis membranes lead to the activation of several pathways such as the coagulation, kallikrein and complement pathways. The sum of these interactions defines the biocompatibility of the dialysis membrane; Cuprophane membranes, the most widely used dialysis membranes elicit intense blood-membrane interactions. Complement activation can be measured by determining the concentration of the activated third and fifth component of the complement cascade, namely C3a and C5a. These active products lead to the well known neutropenia seen during the early phase of dialysis. However, the neutropenia is only the most visible manifestation of the effects of complement activation. C5a-induced secretion of granule enzymes from neutrophils and their subsequent desensitization to further chemotaxis and phagocytosis may be an important factor in the incidence of infections in the dialysis patient. Endothelial cell damage by complement stimulated granulocytes mediated via superoxide anion may also play a role in the pulmonary dysfunction seen in dialysis patients, and recent evidence suggests that complement products may lead to cardiac dysfunction manifested by impaired ventricular contractility. Although some of these events may not be mediated directly by activated complement products, recent studies suggest that they play a role in the activation of several other pathways and pathophysiological process.

Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.

AIMS: Cardiovascular mortality has been reported to be 10- to 20-fold higher in chronic dialysis patients than in the age-matched general population. It has been suggested that increased oxidant stress and resulting vascular wall injury due to uremia and the hemodialysis procedure may be one of the mechanisms predisposing to these cardiovascular complications. Further, hemodialysis membrane bioincompatibility can contribute to increased oxidative stress and prevalence of inflammation. MATERIALS: We studied 18 chronic hemodialysis (CHD) patients (age 62.8 +/- 14.7 years, 39% male, 61% African-American, 44% insulin-dependent diabetic, 61% smokers, 61% with documented coronary artery disease) during hemodialysis with 2 membranes with different flux and complement activating properties. METHODS: We have measured free and phospholipid-bound F2-isoprostane (F2-IsoP) levels, a sensitive marker of oxidative stress, in CHD patients and compared them to levels in healthy subjects. We have also examined the acute effects of the hemodialysis procedure using both biocompatible and bioincompatible membranes on F2-IsoP levels. RESULTS: The results indicated that, compared to controls, both free (96.2 +/- 48.8 pg/ml versus 37.6 +/- 17.2 pg/ml) and bound F2-IsoP (220.4 +/- 154.8 pg/ml versus 146.8 +/- 58.4 pg/ml) levels were significantly higher (p < 0.05 for both). There was a statistically significant decrease in free F2-IsoP concentrations at 15 and 30 minutes of HD, which rebounded to baseline levels at the completion of the procedure. There were no significant differences in F2-IsoP concentrations between the 2 study dialyzers at any time point. Age, smoking status, diabetes mellitus and presence of cardiovascular disease were also not correlated with F2-IsoP levels in this patient population. There was a significant association between predialysis F2-IsoP and C-reactive protein concentrations. CONCLUSION: Using a sensitive and specific assay for the measurement of F2-IsoP, we demonstrated that CHD patients are under increased oxidative stress. During a single hemodialysis treatment, the hemodialysis membrane appears to have no discernable effect on oxidative stress status. Measurement of F2-isoprostanes may be a useful biomarker of oxidative stress status as well as in developing new therapeutic strategies to ameliorate inflammatory and oxidative injury in this patient population.

Outcomes of patients with pelvic-ring fractures managed by open reduction internal fixation.

The purpose of this multiple-subject case report is to describe the physical impairments, disabilities, and handicaps of patients with multiple traumas and pelvic-ring fractures after management with open reduction internal fixation. Nineteen men and 12 women, with a mean age of 38+/-16 years (chi+/-SD), were interviewed and examined at least 1 year (chi+/-14.5 months) after sustaining multiple traumas, including an unstable pelvic-ring fracture that was repaired by open reduction internal fixation. Disabilities and handicaps were assessed using the Oswestry Low Back Pain Questionnaire and the Sickness Impact Profile (SIP). Assessments of physical performance consisted of lift capacity, the amount of forward bending, and gait. A descriptive analysis by age and pelvic fracture classification is reported. The < or = 50-year-old group had the best physical testing scores, except for the lifting test. The > 50-year-old group had the lowest scores. Subjects with B1-class "open-book" pelvic fractures had a tendency to score higher in individual SIP categories. The average SIP scores of 9.34+/-7.47 for the total SIP score, 7.79+/-6.93 for the physical dimension, and 8.24+/-9.61 for the psychosocial dimension represent mild disability. The mean Oswestry score of 13.26%+/-15.41% also represents mild disability. Some subjects demonstrated impairments, disabilities, and handicaps 1 year postoperatively, but for the most part the subjects recovered almost all lost function. The data and clinical management information can be used as a basis of comparison for treatment and research with these types of patients.

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.

Influence of the dialysis membrane on outcome of ESRD patients.

Data from the US Renal Data System (USRDS) document a substantial reduction in the use of cellulosic membranes, from approximately 70% in 1990 to less than 20% in 1996. These changes have been accompanied by a reduction in the adjusted mortality of patients with end-stage renal disease (ESRD) in the United States. The possibility that this association between the changes in the nature of the membrane and clinical outcome represents a cause-and-effect relationship is discussed in terms of the known biochemical actions of complement activation, consequent neutrophil and monocyte activation, and clinical studies that have been published comparing membranes with different biocompatibilities. Together, these studies support a role for the changes in the biocompatibility of dialysis membranes in the improvement of ESRD patient mortality in the United States.

Natural killer-cell function in hemodialysis patients: effect of the dialysis membrane.

Natural killer (NK) cells are specific peripheral blood lymphocytes which are involved in the lysis of malignant and virally transformed cells. In a prospective study of eight hemodialysis patients, we investigated the effects of recurrent exposure to the cuprophane (CU) membrane on the number and functional ability of NK cells, against both their classical in vitro target, K562 cell line, as well as the beta 2m/HLA negative cells that emerge during dialysis with CU membrane. The percent of NK cells, defined by the CD56 epitope, increased from 27.7 +/- 7.9% of cells at baseline to 59.2 +/- 12.0% after two weeks of dialysis with new CU membrane (P < 0.01). The ability of these cells to lyse K562 cells decreased from 28.7 +/- 16.5% at baseline to 12.5 +/- 6.2% (P < 0.001) after two weeks of dialysis with CU membrane, while their cytotoxicity against beta 2m negative cells increased during the same period from 32.5 +/- 12.4% to 61.3 +/- 23.7% (P < 0.001). These results are consistent with the observation that the cytolytic ability of NK cells is inversely related to target cell expression of HLA antigens and beta 2m expression on cell surfaces. In addition, the results of these studies confirm in vitro observations of the decrease in cytolytic activity of the NK cells when exposed to the CU membrane, and may explain the emergence of these beta 2m/HLA negative cells during dialysis with CU membrane. It is possible that these observations may also have a clinical relevance to the immune defects and increased incidence of malignancy in uremia.

Biochemical parameters in chronic renal failure.

We analyzed biochemical data derived from 911 patients with renal insufficiency observed at our institution for periods up to 7 years. During early renal failure (RF) (creatinine less than 5 mg/dL), the rate of change of hematocrit, total CO2 (tCO2) and urea per unit change of creatinine was significantly higher than during moderate (creatinine between 5 and 10 mg/dL) or advanced (creatinine greater than 10 mg/dL) RF. For example, the rate of change of hematocrit (%, volume/volume [v/v]) was (mean +/- SEM) -2.15 +/- 0.15% for each 1 mg/dL increase in creatinine in the range of creatinine less than 5 mg/dL, whereas for the range of creatinine greater than 10 mg/dL, the rate of change was only -0.48 +/- 0.06% (P less than 0.001). Similarly, the rate of change of tCO2 was -1.68 +/- 0.09 mEq/L for each 1 mg/dL increment in creatinine concentration during early RF, and -0.19 +/- 0.09 mEq/L per unit increase in creatinine during advanced RF (P less than 0.001). Chloride concentration initially increased as a function of creatinine in early RF, but decreased in advanced RF, whereas the anion gap increased throughout the course of RF. Mean serum phosphate concentration also increased steadily, but remained below the upper range of normal (4.7 mg/dL) during early RF without the use of phosphate binders. These data suggest that different biochemical parameters change at different rates as a function of the severity of renal dysfunction, and that although phosphate retention may occur, hyperphosphatemia is not a hallmark of early RF.

Progression of chronic renal failure.

Rates of progression of renal failure were calculated for a group of 277 patients who had five or more clinic visits. The goals of therapy in the absence of ongoing immunological processes were control of blood pressure to diastolic pressures less than 85 mm Hg and serum phosphate less than 1.60 mmol/L (5 mg/dL). The mean rate of progression expressed as the slope of the reciprocal creatinine versus time was -0.0054 +/- 0.0009 dL/mg/mo (mean +/- SEM), and the median was -0.00315 dL/mg/mo. Approximately 25% of these patients had rates of progression less than -0.001 dL/mg/mo. The rate of progression was inversely correlated with the creatinine concentration at entry (P less than 0.004) and with the frequency of clinic visits (P less than 0.01). The "renal survival" time from a creatinine of 880 mumol/L (10 mg/dL) to dialysis was 10.0 +/- 1.2 months (mean +/- SEM). These data provide rates of progression for a group of patients without specific dietary intervention but with vigorous control of blood pressure and phosphorus.

Malnutrition in hemodialysis patients.

Increasing attention has been paid recently to the problem of protein and energy malnutrition and its effects on mortality and morbidity in hemodialysis (HD) patients. Protein deficiency has received more attention than other nutritional problems, largely because its consequences are more easily measured and large population studies have demonstrated the adverse effects of even small decreases in serum albumin on patient's survival. This review discusses these findings and presents other indicators of early malnutrition, which range from static measurements of plasma constituents such as transferrin and insulin-like growth factor 1 (IGF-1), kinetic measurements of protein catabolic rate (PCR) derived from urea kinetic modeling, and noninvasive measurements of body composition. In addition, the predialytic and dialytic factors that influence nutritional status, including the adverse effects of uremia, inadequate dialysis, membrane bioincompatibility, and intercurrent illness requiring hospitalization, as well as socioeconomic factors, are discussed. While some of these are difficult to deal with, the review emphasizes simple interventions that are likely to benefit the patient, including the delivery of optimal dialysis, appropriate choice of medications, and dietary interventions. Once malnutrition is established, parenteral nutrition may reverse the objective evidence of malnutrition, but its effects on survival have not yet been documented. Finally, the review addresses the effects of therapeutic substances such as growth hormone (GH) and erythropoietin (EPO) in combination with nutrients that at present appear to be favorable but are still being evaluated.