14th International HLA and Immunogenetics Workshop: report on the Prospective Chronic Rejection Project.

An international collaborative study of 45 transplant centers was undertaken at the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop to see if HLA antibodies detected posttransplant are predictive of chronic graft failure. With the newly developed assay, MICA (major histocompatibility complex class I-related chain A) antibodies were also measured and their effect analyzed. Total of 5219 sera from patients who were more than 6 months posttransplant with functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The method of antibody testing did not have a marked influence on the frequency of antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30% of heart patients, and 31% of liver patients. Among 948 kidney patients who had HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death occurred in 1.4% of total kidney patients and did not correlate to the presence of antibodies. We conclude that patients with posttransplant HLA antibodies indeed have a higher rate of chronic graft failure and that posttransplant antibodies are predictive of chronic rejection.

Prevention of peritonitis with disconnect systems in CAPD: a randomized controlled trial. The Mexican Nephrology Collaborative Study Group.

BACKGROUND: Recently, disconnect systems for CAPD that are associated with a reduced frequency of peritonitis have been introduced. Our objective was to compare the incidence of peritonitis using three current CAPD systems in a high-risk population with low educational and socioeconomic levels, and high prevalence of malnutrition. METHODS: In a prospective controlled trial, 147 patients commencing CAPD were randomly assigned to one of three groups: 29 to the conventional, 57 to the Y-set, and 61 to the twin bag systems. The number of peritonitis episodes was registered, and patients were followed up for an average of 11.3 months. RESULTS: The average peritonitis-free interval for the conventional group was 6.1 months, for the Y system was 12.0 months, and for the twin bag was 24.8 months (P < 0.001). By multivariate analysis, the only factor associated with peritonitis was the CAPD system. Peritonitis-related hospitalization was 5.3 +/- 2.0, 2.7 +/- 1.0, and 1.5 +/- 0.9 days/patient/year in the conventional, Y system, and twin bag groups, respectively. The cost per bag was similar for the conventional and Y system, but higher for the twin bag. However, the total costs of treatment (pesos/patient/year) were lower for twin bag (62,159 for the conventional, 70,275 for the Y system, and 54,387 for the twin bag), due to the lower peritonitis incidence and associated hospitalizations. CONCLUSIONS: Y system and twin bag use was associated with a reduction of 50 and 75% peritonitis incidence, respectively, in patients on CAPD. The cost of the twin bag was actually lower, because of savings from a decreased usage of antibiotics and fewer hospitalizations.

Effect of energy intake on nutritional status in maintenance hemodialysis patients.

Although maintenance hemodialysis (MHD) patients are often wasted, little is known about their dietary energy needs. We studied four men and two women in a clinical research center while they received diets providing 45, 35 and 25 kcal/kg desirable body weight/day; diets were fed, in random order, for 21 to 23 days each. Protein intake, 1.13 +/- 0.02 (SEM) g protein/kg/day, was similar with all three diets. Body weight rose with 45 and 35 kcal/kg/day (P less than 0.05) and fell with 25 kcal/kg/day (P less than 0.05). Nitrogen balance, adjusted for estimated unmeasured losses, was neutral with 45 and 35 kcal/kg/day and negative with 25 kcal/kg/day. Balance was neutral or positive in 6 of 6, 4 of 6, and 0 of 6 patients fed 45, 35, 25 kcal/kg/day, respectively. Nitrogen balance, many plasma amino acids and changes in body weight, mid-arm circumference, mid-arm muscle area and body fat each correlated with energy intake. Resting energy expenditure was normal. The energy intake estimated from regression equations to maintain neutral nitrogen balance was 38.5 kcal/kg desirable weight/day; for body fat and weight, it was 32 kcal/kg/day. These data suggest that MHD patients have normal energy expenditure and approximately normal requirements for maintenance of protein balance, body weight and body fat. An average energy intake of about 38 kcal/kg desirable weight/day may be necessary to maintain nitrogen balance in these patients.

Energy expenditure in patients with chronic renal failure.

Although nondialyzed, chronically uremic patients and patients undergoing maintenance hemodialysis often show evidence for wasting and calorie malnutrition and have low dietary energy intakes, their energy expenditure has never been systematically evaluated. It is possible that low energy intakes are an adaptive response to reduced energy needs; alternatively, energy expenditure could be normal or high and the low energy intakes would be inappropriate. Energy expenditure was therefore measured by indirect calorimetry in 12 normal individuals, 10 nondialyzed patients with chronic renal failure, and 16 patients undergoing maintenance hemodialysis. Energy expenditure was measured in the resting state, during quiet sitting, during controlled exercise on an exercise bicycle, and for four hours after ingestion of a test meal. Resting energy expenditure (kcal/min/1.73 m2) in the normal subjects, chronically uremic patients and hemodialysis patients was, respectively, 0.94 +/- 0.24 (SD), 0.91 +/- 0.20, and 0.97 +/- 0.10. There was also no difference among the three groups in energy expenditure during sitting, exercise, or the postprandial state. Within each group, energy expenditure during resting and sitting was directly correlated. During bicycling, energy expenditure was directly correlated with work performed, and the regression equation for this relationship was similar in each of the three groups. These findings suggest that for a given physical activity, energy expenditure in nondialyzed, chronically uremic patients and maintenance hemodialysis patients is not different from normal. The low energy intakes of many of these patients may be inadequate for their needs.

Effect of energy intake on nitrogen metabolism in nondialyzed patients with chronic renal failure.

Dietary energy requirements were evaluated during 16 studies that were carried out in six clinically stable nondialyzed chronically uremic patients who lived in a clinical research center and were fed diets providing 45, 35, 25 or 15 kcal/kg/day. Each diet was fed for 23.7 +/- 5.7 SD days and provided about 0.55 to 0.60 g protein/kg/day. Nitrogen balance after equilibration and adjusted for changes in body urea nitrogen, and change in body weight each correlated directly with energy intake. Correcting for estimated unmeasured nitrogen losses of about 0.58 g/day, nitrogen balance was negative in one of four patients fed 45 kcal/kg/day, one of five patients receiving 35 kcal/kg/day, three of five patients ingesting 25 kcal/kg/day and both patients fed 15 kcal/kg/day. The urea nitrogen appearance (UNA), the UNA divided by nitrogen intake, and several plasma amino acids, determined after an overnight fast, each correlated inversely with dietary energy intake. Resting energy expenditure measured by indirect calorimetry did not differ from normal and averaged 0.012 +/- 0.0033 kcal/kg/min with the different diets. These observations suggest that although some clinically stable nondialyzed chronically uremic patients ingesting 0.55 to 0.60 g protein/kg/day may maintain nitrogen balance with energy intakes below 30 kcal/kg/day, a dietary intake providing approximately 35 kcal/kg/day may be more likely to maintain neutral or positive nitrogen balance, maintain or increase body mass, and reduce net urea generation.