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.

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.

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.

Familial hypercholesterolemia treated by plasma exchange and immunoadsorption.

IA clearly improved JL's HDL and LDL/HDL ratio because of its specificity, yet the extent of TC and LDL reduction per treatment was not as high as that obtained with TPE. Studies to achieve more efficient and specific extracorporeal lipid removal are in progress to help reduce the risk of CAD in FH patients and others. The continuity of procedural care and supportive needs provided by the nephrology nurses demonstrated a positive influence on J.L.'s acceptance of his familial genetic disorder and the prescribed chronic treatment regimen.

Immunoadsorption: a novel treatment for sensitized kidney transplant candidates.

Sensitized patients frequently have a positive crossmatch against kidneys available for transplant. A positive crossmatch precludes transplantation in most cases because it is usually predictive of rejection after transplant. Immunoadsorption is an extracorporeal treatment combined with immunosuppression to decrease sensitization in patients and thereby enable transplantation. This article discusses sensitization, its detection, and the benefits of immunoadsorption.

Extracorporeal treatment of familial hypercholesterolemia with monoclonal antibodies to low-density lipoprotein.

Plasma exchange (PE) is considered the most effective nonsurgical treatment modality for the reduction of low-density lipoprotein (LDL) in patients with familial hypercholesterolemia (FH). However, the concomitant reduction of high-density lipoprotein (HDL) and the necessity and cost of using blood products are major drawbacks of PE. We studied the effects of selective LDL reduction using monoclonal anti-LDL antibodies in an investigational immunoadsorption (IA) system. Results were compared with the effects of PE. During the study period, two homozygous FH patients with baseline cholesterol levels greater than 10.34 mmol/L (400 mg/dL) were treated sequentially for a combined total of 37 IA treatments and the results were compared with a total of 19 sequential PE treatments. The IA system consisted of on-line plasma processing over two columns of monoclonal anti-LDL antibodies in alternating cycles of column adsorption and regeneration. No replacement solution was needed. PE was performed with a centrifugal plasma separator using 5% albumin as replacement solution. Results showed that the reduction of lipids with IA was 43% +/- 0.9% for cholesterol, 51% +/- 1.0% for LDL, and 19% +/- 1.3% for HDL, resulting in a reduction in the LDL to HDL ratio of 41% +/- 1.7%. Compared with IA, percent reduction by PE was significantly greater (P less than 0.001) for all lipids, but was nonselective (cholesterol, 74% +/- 1.0%; LDL, 77% +/- 1.2%; HDL, 73% +/- 2.7%), and therefore the reduction of the LDL to HDL ratio was only 6% +/- 3.6%, which was significantly less than for IA (P less than 0.001). Pretreatment HDL concentration appeared to increase with repetitive IA treatment, but decreased back to prestudy levels with repetitive PE.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

The effect of membrane biocompatibility on plasma beta 2-microglobulin levels in chronic hemodialysis patients.

Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes. However, because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin, the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined. This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers (ten centers affiliated with Dallas Nephrology Associates and three with Vanderbilt University Medical Center) by using two low-flux membranes with widely different biocompatibilities. These patients were prospectively randomized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane. Plasma beta 2-microglobulin levels were measured at 0, 3, 6, 9, 12, and 18 months. Sixty-six patients completed the 18-month study. Plasma beta 2-microglobulin increased in all patients; however, the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane. In this group, beta 2-microglobulin increased from (mean +/- SD) 27.8 +/- 14.8 mg/L to 34.0 +/- 10.0 mg/L at 18 months (P = not significant), and the mean increase at 18 months was 2.6 +/- 14.7 mg/L. In contrast, the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 +/- 9.6 mg/L to 29.5 +/- 12.2 mg/L (P < 0.001); these increases continued to be significant until Month 18, when serum beta 2-microglobulin reached 36.8 +/- 13.9 mg/L with an average increase of 11.8 +/- 11.2 mg/L (P < 0.0001). The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed. There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study. It was concluded that over a period of 18 months, the use of biocompatible membranes, even in the low-flux configuration, is associated with a significantly slower increase in plasma beta 2-microglobulin, independent of the influence of residual renal function.

The effects of recombinant human growth hormone and intradialytic parenteral nutrition in malnourished hemodialysis patients.

Malnutrition in hemodialysis patients is associated with increased morbidity and mortality. The use of intradialytic parenteral nutrition (IDPN) to improve nutritional parameters has been shown to be of limited benefit in most studies. We studied the use of recombinant human growth hormone (rHuGH) in potentiating the effects of IDPN in seven hemodialysis patients dialyzed with a Kt/V of 1.03 +/- 0.11 (mean +/- SEM), but with evidence of malnutrition: albumin, 3.2 +/- 0.18 g/dL; transferrin, 215 +/- 30 mg/dL; insulin-like growth factor-1 (IGF-1), 115 +/- 19 ng/mL, protein catabolic rate (PCR), 0.70 +/- 0.05 g/kg/d; and weight, 12.3% +/- 4.0% below ideal body weight. During 6 weeks of IDPN, resulting in an additional 18 +/- 4 kcal and 0.69 +/- 0.03 g of protein/kg body weight per dialysis session, albumin concentration increased to 3.5 +/- 0.14 g/dL (compared with baseline, P = NS), transferrin increased to 279 +/- 36 mg/dL (P < 0.002), IGF-1 increased to 152 +/- 32 ng/mL (P = NS), and PCR increased to 0.81 +/- 0.04 g/kg/d (P = NS). During the next 6 weeks, IDPN administration was continued and rHuGH, at a dose of 5 mg subcutaneously during each dialysis, was added to the regimen. This resulted in an increase in albumin concentration to 3.8 +/- 0.08 g/dL (P < or = 0.04 compared with end of IDPN phase), an increase in transferrin to 298 +/- 41 mg/dL (P = NS compared with end of IDPN phase), and an increase in IGF-1 to 212 +/- 45 ng/mL (P = 0.05 compared with end of IDPN phase).(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study.

BACKGROUND: Numerous studies suggest a strong association between nutrition and clinical outcome in chronic hemodialysis (CHD) patients. Nevertheless, the pathophysiological link between malnutrition and morbidity remains to be clarified. In addition, recent evidence suggests that nutritional indices may reflect an inflammatory response, as well as protein-calorie malnutrition. In this study, we prospectively assessed the relative importance of markers of nutritional status and inflammatory response as determinants of hospitalization in CHD patients. METHODS: The study consisted of serial measurements of concentrations of serum albumin, creatinine, transferrin, prealbumin, C-reactive protein (CRP), and reactance values by bio-electrical impedance analysis (BIA) as an indirect measure of lean body mass every 3 months over a period of 15 months in 73 CHD patients. Outcome was determined by hospitalizations over the subsequent three months following each collection of data. RESULTS: Patients who required hospitalization in the three months following each of the measurement sets had significantly different values for all parameters than patients who were not hospitalized. Thus, serum albumin (3.93 +/- 0.39 vs. 3.74 +/- 0.39 g/dl), serum creatinine (11.0 +/- 3.7 vs. 9.1 +/- 3.5 mg/dl), serum transferrin (181 +/- 35 vs. 170 +/- 34 mg/dl), serum prealbumin (33.6 +/- 9.2 vs. 30.0 +/- 10.1 mg/dl), and reactance (50.4 +/- 15.6 vs. 43.0 +/- 13.0 ohms) were higher for patients not hospitalized, whereas CRP (0.78 +/- 0.89 vs. 2.25 +/- 2.72 mg/dl) was lower in patients who were not hospitalized. All differences were statistically significant (P < 0.05 for all parameters). When multivariate analysis was performed, serum CRP and reactance values were the only statistically significant predictors of hospitalization (P < 0.05 for both). When a serum CRP concentration of 0.12 mg/dl was considered as a reference range (relative risk 1.0), the relative risk for hospitalization was 7% higher (relative risk = 1.07) for a CRP concentration of 0.92 mg/dl and was 30% (relative risk = 1.30) higher for a CRP concentration of 3.4 mg/dl. When a reactance value of 70 ohms was considered as a reference range with a relative risk of 1.0, the relative risk of hospitalization increased to 1.09 for a reactance value of 43 ohms and further increased to 1.14 for a reactance value of 31 ohms. CONCLUSIONS: The results of this study strongly indicate that both nutritional status and inflammatory response are independent predictors of hospitalization in CHD patients. CRP and reactance values by BIA are reliable indicators of hospitalization. Visceral proteins such as serum albumin, prealbumin, and transferrin are influenced by inflammation when predicting hospitalization. When short-term clinical outcomes such as hospitalizations are considered, markers of both inflammation and nutrition should be evaluated.

Vascular access blood flow monitoring reduces access morbidity and costs.

BACKGROUND: Vascular access morbidity results in suboptimal patient outcomes and costs more than $8000 per patient-year at risk, representing approximately 15% of total Medicare expenditures for ESRD patients annually. In recent years, the rate of access thrombosis has improved following the advent of vascular access blood flow monitoring (VABFM) programs to identify and treat stenosis prior to thrombosis. To define further both the clinical and financial impact of such programs, we used the ultrasound dilution method to study the effects of VABFM on thrombosis-related morbid events and associated costs, compared with both dynamic venous pressure monitoring (DVPM) and no monitoring (NM) in arteriovenous fistulas (AVF) and grafts. METHODS: A total of 132 chronic hemodialysis patients were followed prospectively for three consecutive study phases (I, 11 months of NM; II, 12 months of DVPM; III, 10 months of VABFM). All vascular access-related information (thrombosis rate, hospitalization, angiogram, angioplasty, access surgery, thrombectomy, catheter placement, missed treatments) was collected during the three study periods. RESULTS: During the three study phases, graft thrombosis rate was reduced from 0.71 (phase I), to 0.67 (phase II), to 0.16 (phase III) events per patient-year at risk (P < 0.001 phase III vs. phases I and II). Similarly, hospital days, missed treatments, and catheter use related to thrombotic events were significantly reduced during phase III compared to phases I and II. Hospital days related to vascular access morbidity and adjusted for patient-year at risk were 1.8, 1.6, and 0.4 and missed dialysis treatments were 0.98, 0.86, and 0.26 treatments per patient-year at risk for phases I, II, and III, respectively (P < 0.001 for phase III vs. phases I and II). Catheter use was also significantly reduced during phases II and III, from 0.29 (phase I) to 0.17 and further to 0.07 catheters per patient-year at risk, respectively (P < 0.05 for phase III vs. phase I). Percutaneous angioplasty procedures increased during phases II and III from 0.09 to 0.32 to 0.54 procedures per patient-year at risk for phases I, II, and III, respectively (P < 0.01 for phase III vs. phase I). When the total cost of treatment for thrombosis-related events for grafts was estimated, it was found that during phase III, the adjusted yearly billed amount was reduced by 49% versus phase I and 54% versus phase II to $158,550. Similar trends in reduced thrombosis-related morbid events and cost were observed for AVFs. CONCLUSIONS: VABFM for early detection of vascular access malfunction coupled with preventive intervention reduces thrombosis rates in both polytetrafluoroethylene (PTFE) grafts and native AVFs. While there was a significant increase in the number of angioplasties done during the flow monitoring phase, the comprehensive cost is markedly reduced due to the decreased number of hospitalizations, catheters placed, missed treatments, and surgical interventions. Vascular access blood flow monitoring along with preventive interventions should be the standard of care in chronic hemodialysis patients.

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)

Increased energy expenditure in hemodialysis patients.

Malnutrition is prevalent in chronic hemodialysis patients and is related to multiple factors; the hemodialysis procedure itself has been suggested as a catabolic factor. To examine the possible role of hemodialysis on energy metabolism, resting energy expenditure and respiratory quotient in ten chronic hemodialysis patients was measured in this study, using a whole-room indirect calorimeter. Measurements were done continuously: for 2 h before hemodialysis, during 4 h of hemodialysis, for 2 h after hemodialysis, and separately on a nondialysis day after 12 h of fasting. Age-, sex-, and body mass index-matched healthy volunteers were used as control subjects. Chronic hemodialysis patients have a significantly higher resting energy expenditure on a nondialysis day (1.18 +/- 0.15 kcal/min; P < 0.01) as compared with control subjects (1.10 +/- 0.16 kcal/ min). Resting energy expenditure further increased significantly during the hemodialysis procedure (1.32 +/- 0.18 kcal/min, averaged over the 4 h of hemodialysis; P < 0.01 versus predialysis) and was also significantly higher compared with the postdialysis period and nondialysis day resting energy expenditure (P < 0.001 for both). This effect was most pronounced during the first (1.37 +/- 0.19 kcal/min) and second (1.33 +/- 0.18 kcal/min) hours of hemodialysis (P < 0.001 for both). Respiratory quotient was not significantly affected by hemodialysis. It was concluded that chronic hemodialysis patients have higher than normal resting energy expenditure levels, which is further increased during hemodialysis. This process may significantly potentiate the protein-calorie malnutrition seen in this patient population.

A multicenter comparison of dialysis membranes in the treatment of acute renal failure requiring dialysis.

The mortality of patients with acute renal failure (ARF) remains high, and in several large studies approaches 60%. This mortality is particularly high in patients with ARF who require dialysis and has not changed substantially over several years, despite the introduction of major advances in monitoring and treatment. Increasing prevalence of comorbidities has been suggested as the major factor in this persistently high mortality. This study investigates the potential role of the dialysis membrane on patient outcome in a prospective multicenter study of 153 patients with ARF requiring dialysis. The membrane assignment was made in alternating order and was limited to membranes with low complement activation (Biocompatible [BCM]) and cellulosic, high complement activation (Bioincompatible [BICM]). Both types of membranes were low-flux membranes. Patients were dialyzed with the assigned membrane until recovery, discharge from hospital, or death. The severity of illness of each patient was assessed using the APACHE II score at the time of initiation of dialysis. A logistic regression analysis was used to adjust for the APACHE II score. The results of the study showed a statistically significant difference in survival (57% in patients on BCM, 46% in patients on BICM; P = 0.03) and in recovery of renal function (64% in patients on BICM and 43% in patients on BICM; P = 0.001). These differences were particularly marked in the patients who were nonoliguric (>400 ml/d of urine output) at initiation of the study. In the subset of patients who were nonoliguric at the start of dialysis, a larger fraction (70%) became oliguric after initiating dialysis on a BICM membrane, in contrast to 44% who were initiated on a BCM membrane (P = 0.03). It is concluded that the biocompatibility of the dialysis membrane plays a role in the outcome of patients with ARF, particularly those who are nonoliguric at the time of initiation of dialysis.

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.

Effects of recombinant human growth hormone on plasma and dialysate amino acid profiles 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 including the use of recombinant human growth hormone (rhGH) as an anabolic agent. We have previously reported a significant decrease in net urea nitrogen appearance along with modest but statistically significant decrements in several blood chemistries including serum potassium, phosphorus, albumin and a small increase in creatinine concentration during rhGH administration in CAPD patients. In order to evaluate the underlying mechanism of these changes, we systematically evaluated the plasma and dialysate amino acid profiles in blood and dialysate samples of the same patients during their participation in the study. 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 days Tx period, patients self-administered 5 mg/day s.c of rhGH. Compared to PreGH period, administration of rhGH resulted in a significant decrease in essential amino acids (EAA), in both plasma (935 +/- 243 mumol/liter vs. 801 +/- 186 mumol/liter; P < 0.05) and dialysate (623 +/- 244 mumol/liter vs. 415 +/- 122 mumol/liter; P < 0.05). This decrease was evident in 8 out of 10 individual EAA, and the extent of decrease ranged from 15% to 28% for plasma EAA and from 30% to 45% for dialysate EAA. On the other hand, plasma non-essential AA levels increased significantly during treatment (2537 +/- 776 mumol/liter vs. 3177 +/- 1259 mumol/liter; P < 0.05). All changes returned to baseline values after discontinuation of rhGH. Our findings suggest that the net anabolic processes induced by rhGH reflect a shift in AA metabolism towards peripheral muscle tissues.

Effect of the membrane biocompatibility on nutritional parameters in chronic hemodialysis patients.

Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality. Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor. In a prospective study of 159 new hemodialysis patients from two centers randomized to either a low-flux biocompatible (BCM) membrane or a low-flux bioincompatible (BICM) membrane, we measured the long-term effects of biocompatibility on several nutritional parameters, including estimated dry weight, serum albumin, insulin-like growth factor-1 (IGF-1), and prealbumin over 18 months. Our results show that the BCM group had a mean (+/- SD) increase in their dry weight of 2.96 +/- 6.88 kg at month 12 and 4.36 +/- 8.57 kg at month 18 (P < 0.05 vs. baseline for both), whereas no change in mean weight was observed in BICM group. Following initiation of hemodialysis, a significant increase was observed in serum albumin levels in both groups of patients. However, the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group. The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group, but did not reach this level until 12 months after initiation of dialysis in the BICM group. The difference between the groups was statistically significant at months 7, 8, and 10 (P < 0.05, higher in the BCM group). Furthermore, the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent (P < 0.001). A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group (P = NS). In a further analysis, changes in IGF-1 levels, but not prealbumin, predicted the subsequent changes in serum albumin. We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients, independently of the flux characteristics of the membranes, and that IGF-1 may be an early marker of nutritional status.