Urea Appearance Rate Research Articles

Effec Of Low Protein Diet On Chronic Renal Failure Due To Autosomal Dominant Polycystic Kidney Disease

There are few reports about therapeutic effects of low protein diet on the progression of chronic renal failure due to autosomal dominant polycystic kidney disease (ADPKD), although the disease is common.The annual incidence rate for end-stage renal disease caused by ADPKD is around 6 per million.In this retrospective study in one center, ten chronic renal failure patients due to ADPKD with creatinine clearnce of 17.0±3.3 mL/min /1.73 m 2 and serum creatinine (Cr) level of 4.4±0.7 mg/dL were studied for 40 months after the introduction of severe low protein diet (SLPD) (0.48±0.03 g/kgBW/day) without supplementation of essential amino acids or keto-analogues. Dietary protein intake was estimated by urea appearance rate from 24hr urine sample according to Mitch-Maroni's formula. The results clearly showed that ▵1/Cr/month(×10 −3 ) was significantly suppressed from 5.8±0.9 to 2.0±0.6 following the introduction of SLPD ( p p

Indicators of lean body mass catabolism: emphasis on the creatinine excretion rate

The major stress response to critical illness leads to a catabolic state and loss of lean body mass. To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process. Prospective observational study. Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium. Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine. Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

Minimal sampling protocol for accurate estimation of urea production: a study with oral [13C]urea in fed and fasted piglets

An oral [13C]urea protocol may provide a simple method for measurement of urea production. The validity of single pool calculations in relation to a reduced sampling protocol was assessed. In eight fed and five fasted piglets, plasma urea enrichments from a 10 h sampling protocol were measured following an intragastric [13C]urea bolus. Blood [13C]bicarbonate was measured to trace gut [13C]urea oxidation. Two-compartment and regression (single pool) computations were performed. Pool sizes were compared to urea distribution over total body water (TBW). Shorter protocol duration was tested in regression simulations. Differences in urea kinetics between fed and fasted piglets did not reach statistical significance. Mean (+/-SE) urea pool from TBW times plasma urea concentration was 2.2+/-0.16 mmol kg(-1). Two-compartment modelling yielded similar results for pool size (despite the oxidation of a small amount of urea tracer). Urea appearance rate was 306+/-18 micromol kg(-1)h(-1). Regression calculations overestimated urea appearance rate vs. compartmental model (P<0.05). When samples <2 h were discarded, results were comparable to compartmental calculations even if protocol length was 6 h (325+/-24 micromol kg(-1)h(-1), NS). Regression calculations using plasma enrichments sampled between 2 and 6 h after oral [13C]urea administration provide accurate rates of urea production, and are not affected by tracer oxidation.

The precision of estimating protein intake of patients with chronic renal failure

Biochemical methods for estimating protein intake are based on the concept that nitrogen-containing products of protein in diet plus the products arising from endogenous protein are excreted as either urea or non-urea nitrogen (NUN). This formulation is based on the fact that the urea is the principal end product of amino acid degradation and, hence, the urea appearance rate (or net urea production) is parallel to protein intake. The urea nitrogen appearance (UNA) rate is measured as the amount of urea excreted in urine plus the net amount accumulated in body water. A more difficult problem is how to estimate NUN, the sum of fecal nitrogen, and all forms of non-urea urinary nitrogen. Maroni, Steinman, and Mitch (Kidney Int 27:58-65, 1985) proposed estimating nitrogen intake (IN MARONI) from UNA plus NUN excretion rate of 0.031 g nitrogen/kg body weight/day, as they found NUN correlated with body weight but not with dietary nitrogen. Kopple, Gao, and Qing (Kidney Int 27:486-494, 1997) proposed a different equation for estimating nitrogen intake (IN KOPPLE) = 1.20 UNA + 1.74, concluding that dietary nitrogen directly correlates with fecal nitrogen and that NUN is constant for all patients. Their report prompted us to review all nitrogen balance measurements we had conducted in order to address the following questions. Does dietary protein increase fecal nitrogen excretion? Does NUN vary with weight or is it constant? How do the two methods (IN MARONI and IN KOPPLE) compare in estimating dietary protein from UNA? We examined nitrogen balance and its components measured in 33 patients with chronic renal failure (CRF) who were eating diets varying from 4.1 to 10.1 g nitrogen/day. We evaluated relationships between dietary nitrogen [intake nitrogen (IN)], NUN, fecal nitrogen, body weight, and the predictability of the two methods. Neither fecal nitrogen nor NUN were significantly correlated with IN (r = 0.04 and r = -0.07, respectively). NUN significantly correlated with body weight (P = 0.008). Measured IN averaged 5.75 +/- 0.41 g nitrogen/day; the estimated IN MARONI value was 5.61 +/- 0.27 g nitrogen/day; the estimated IN KOPPLE was 6.04 +/- 0.44 g nitrogen/day. The prediction errors associated with the IN KOPPLE equation were slightly but not statistically higher than that associated with IN MARONI. Fecal nitrogen is not correlated with IN. NUN is not constant but varies with weight, and the traditional method of estimating IN in stable chronic renal insufficiency (CRI) patients from UNA and weight as proposed by Maroni, Steinman, and Mitch is valid.

Mechanisms of urea tolerance in urea-adapted populations of Drosophila melanogaster.

When behavioral avoidance cannot prevent an animal from being exposed to novel environmental toxins, physiological mechanisms must cope with the toxin and its effects. We are investigating the basis of urea tolerance in populations of Drosophila melanogaster that have been selected to survive and develop in food containing 300 mmol l(-1) urea. Previous research has demonstrated that the urea-selected larvae have lower levels of urea in their body than control larvae reared under the same conditions. The current series of experiments focuses on three possible ways of reducing urea levels in the body: urea metabolism, increased urea excretion and decreased urea uptake from the environment. We tested for urea metabolism directly, by assaying for activity of two urea-metabolizing enzymes, and indirectly, by looking for reduced urea content of their medium. To measure urea excretion rates in whole animals, we reared control and urea-selected larvae on urea-containing food (urea food), switched them to normal food and monitored the loss of urea from their hemolymph. We measured urea uptake by rearing control and selected larvae on normal food, switching them to urea food and monitoring the rate of urea appearance in the hemolymph. We found no evidence for urea metabolism by either direct or indirect methods. Control larvae excreted urea at a higher rate than selected, probably because they contained more urea than the selected larvae and thus had a greater gradient for urea loss. The rate of urea uptake in selected larvae was 2 mmol l(-1) h(-1) slower than the rate in control larvae, a difference that could account for the measured differences in body urea levels. Thus the selected larvae appear to have adapted to urea exposure primarily by decreasing the ability of urea to enter their body in the first place. The mechanism responsible for this reduction in uptake is uncertain.

Plasma Urea Appearance Rate Is Lower When Children with Kwashiorkor and Infection Are Fed Egg White-Tryptophan Rather than Milk Protein

In kwashiorkor, there is less endogenous proteolysis in response to acute infection than in a well-nourished state. Thus the amino acid composition of dietary protein may be more important in facilitating the acute phase response in kwashiorkor. This study tested the hypothesis that during the treatment of kwashiorkor with infection, there is a lower rate of urea appearance when the dietary intake of amino acids more closely resembles the amino acid composition of acute phase proteins. Thirty children in Malawi with kwashiorkor and acute infection were fed isoenergetic, isonitrogenous meals containing either egg white-tryptophan or milk as a protein source. After 24 h, the rates of urea appearance and whole-body protein breakdown and synthesis were measured with the use of 1-13C-leucine and 15N2-urea tracers. Plasma concentrations of seven acute phase proteins, interleukin 6 and tumor necrosis factor-alpha were measured on admission, and at 24 and 48 h. The 16 children who received egg white-tryptophan had lower rates of urea appearance than those who received milk [57+/-30 vs. 87+/-36 micromol/(kg x h), mean +/- SD, P<0.02]. No significant differences were found in the rates of whole-body protein turnover or in the concentration of any of the acute phase proteins or cytokines. The concentration of interleukin 6 was consistent with an appropriate proinflammatory response and correlated directly with the concentrations of C-reactive protein (r = 0.67, P<0.01) and alpha1-antitrypsin (r = 0.40, P<0.05). The findings suggest that egg white-tryptophan is associated with less amino acid oxidation in kwashiorkor and acute infection than is milk.

Hyperglycemia During Normothermic Cardiopulmonary Bypass: The Role of the Kidney

Background. Hyperglycemia commonly occurs during cardiopulmonary bypass. We studied the quantitative impact of glucose input and its renal excretion on hyperglycemia during cardiopulmonary bypass. Methods. The quantity of glucose infused and metabolite and hormone concentrations in plasma, as well as oxygen consumption, carbon dioxide production, and renal glucose excretion, were determined before, during, and after cardiopulmonary bypass in 8 patients. Results. Hyperglycemia (14 to 29 mmol/L) was accompanied by an increase in plasma insulin levels. The degree of hyperglycemia was directly related to the amount of glucose infused. The rate of oxygen consumption did not decrease and the rate of urea appearance (gluconeogenesis) did not rise. Despite a very high filtered load of glucose, there was very little glucosuria, indicating a markedly enhanced renal absorption of glucose. Conclusions. Hormonal and metabolic factors permit the development of hyperglycemia during cardiopulmonary bypass but its severity depends on the quantity of glucose infused and, what appears to be a new finding, a markedly enhanced renal reabsorption of filtered glucose. Thus the kidney plays an important role in the development of severe hyperglycemia during cardiopulmonary bypass.

Protein metabolism in children with edematous malnutrition and acute lower respiratory infection

This study tested the hypothesis that wholebody protein kinetics remain low in children with edematous malnutrition and acute infection. Thirteen children with edematous malnutrition and acute infection (subjects) were compared with 14 uninfected children with edematous malnutrition early in recovery (control children). Protein kinetics were determined by using a primed, constant intravenous infusion of [13C]leucine and [15N2]urea in the postabsorptive state. Calculations of rates of whole-body protein synthesis and breakdown were based on the rate of leucine appearance; the rate of leucine oxidation was estimated from the rate of urea appearance. Protein synthesis and breakdown rates were lower in subjects than in control children (97 +/- 30 compared with 153 +/- 67, P < 0.01, and 103 +/- 30 compared with 160 +/- 67 mumol leucine.kg-1.h-1, P < 0.01). No difference was found between the two groups in the rate of urea appearance, but this analysis only had a statistical power of 54%. The absence of the expected increase in the rate of protein turnover during acute infection in edematous malnutrition implies that acute phase proteins are made with a corresponding depletion of muscle, hepatic, and other body proteins such as albumin, and that there may also be a blunting of the acute phase response.

Urea production in normal breast-fed infants measured with primed/intermittent oral doses of [15N, 15N]urea.

Urea kinetics were measured on 11 occasions in six normal, breast-fed infants aged 29-88 days. Prime and intermittent oral doses of [15N, 15N]urea with measurement of enrichment of urea in urine were used. The rate at which urea appeared in the urea pool was 265 mgN/kg per hour, 85% of which derived from endogenous production and 15% from the diet. Urinary excretion of urea was 87 mgN/kg per hour. Therefore, 60% of the urea entering the pool each day was hydrolysed by the metabolic activity of the colonic microflora and the nitrogen was made available for further metabolic interaction. The rate of urea appearance and the extent to which urea nitrogen was salvaged were greater in infants under 6 weeks than in those over 6 weeks, indicating that urea kinetics is a more active process at an early age, and slows with time. With respect to factors influencing urea kinetics, the apparently conflicting results which have appeared in the literature may be explained. The results may help explain the growth of breast-fed infants on low protein intakes.

Prognosis of acute renal failure in the elderly

Life expectancy is uncertain in the elderly with ARF. In order to determine whether a costly supportive management is worthwhile, we have studied a group of 68 elderly patients (over 65 years of age) admitted to the ICU with ARF. 47 male; 21 female; 72 +/- 6 years old. Types of ARF include prerenal 24; obstructive 9; intrinsic 35 (acute tubular necrosis 30; glomerulonephritis 4; vascular 1). The mean simplified acute physiology score (SAPS) was 14 +/- 4; 39 patients (57.3%) had more than two underlying diseases; 42 patients (61.7%) were on mechanical ventilation; 40 patients (60%) underwent haemodialysis. The overall survival rate was 36.7%. Among the parameters studied, organic systemic failure index (OSF), diuresis, blood lactate, systolic blood pressure, urea appearance rate (UAR), differed significantly in survivors and deceased. From these results we conclude that the elderly with non-oliguric ARF, normal blood lactate, low catabolic state, and no more than two organ failures have a fair chance of recovering and should therefore be treated aggressively. In other cases, decisions to proceed with intensive supportive measures should be made according to individual characteristics.

Assessment of Urea Appearance Rates and Net Nitrogen Deficits in Patients With Acute Renal Failure Receiving Continuous Venovenous Hemofiltration

■ Objective: To investigate the impact of the nutritional regimen on the urea appearance rate (UAR) and net nitrogen deficit (NND) in patients with acute renal failure (ARF) receiving continuous venovenous hemofiltration (CWH). Comparison of estimated energy expenditure using a modification of the Harris-Benedict equation versus measured energy expenditure was performed. ■ Design: Noninterventional study with prospective data collection. ■ Setting: Tertiary care hospital. ■ Patients: Forty consecutive patients age 52 ± 20 years (mean ± SD) with ARF who required CWH between June 1991 and June 1992. ■ Interventions: Noninterventional study. ■ Main outcome measures: UAR and NND were calculated for each study day. Total calories, nonprotein calories, and grams of protein per day, and estimated energy needs were quantified for all patients. Energy expenditure was measured for 10 patients. ■ Results: Patients were treated with CWH for a total of 357 days. Estimated energy needs (2,408 ± 515 kcal/d) correlated well with measured energy needs (2,348 ± 706 kcal/d; r = 0.78). The mean UAR was 13.2 ± 4.7 g N/d. There was no difference in mean UAR between patients receiving less than 1.0 g versus 1.0 g or more of protein/kg/d. The mean NND was −8.3 ± 6.1 g N/d. Those patients receiving 1.0 g or more of protein/kg/d (n = 16) had a significantly lower NND than those patients who received less. Five patients receiving 1.0 g or more of protein/kg/d achieved a positive nitrogen balance. These patients had a nonprotein calorie-to-nitrogen ratio (132 ± 37) that was significantly less than that administered to patients who did not achieve a positive nitrogen balance (169 ± 33; P > 0.05). ■ Conclusions: Estimated energy expenditures using a modified Harris-Benedict equation provided moderate predictability with measured energy expenditures. The provision of 1.0 g or more of protein/kg/d did not increase the UAR and was associated with a decreased NND. The provision of a lower nonprotein calorie-to-nitrogen ratio in patients receiving 1.0 g or more of protein/kg/d was associated with a positive nitrogen balance.

Relationships between Dialysis Quantification and Normalized Protein Catabolic Rate in Peritoneal Dialysis

Normalized protein catabolic rates (NPCR) and urea clearances (Kt/V urea) correlate significantly in peritoneal dialysis suggesting that the adequacy of dietary protein intake and dialysis dose are interrelated. However, both of these calculated parameters are mathematical functions of the normalized urea appearance rate (GN). NPCR, GN, Kt/V urea, total creatinine clearance, residual renal clearance, and peritoneal urea and creatinine clearances were determined in 29 stable peritoneal dialysis patients with no history of recent peritonitis or other catabolic illness. Multiple linear regression analysis showed that NPCR correlated closely with both GN (r = 0.96; p < 0.0001) and Kt/V urea (r = 0.77; p < 0.0001), whereas GN also correlated with Kt/V urea (r = 0.66; p < 0.0001). Total weekly creatinine clearances rather than Kt/V urea should be utilized in peritoneal dialysis to permit independent estimations of dialysis dose and NPCR, since both Kt/V and NPCR are related closely to GN. Total weekly creatinine clearances correlated with NPCR (r = 0.59; p < 0.0002), which supports the hypothesis that dietary protein intake is dependent on the delivered dialysis dose.

Relationships between Dialysis Quantification and Normalized Protein Catabolic Rate in Peritoneal Dialysis

Normalized protein catabolic rates (NPCR) and urea clearances (Kt/V urea) correlate significantly in peritoneal dialysis suggesting that the adequacy of dietary protein Intake and dialysis dose are Interrelated. However, both of these calculated parameters are mathematical functions of the normalized urea appearance rate (GN). NPCR, GN, Kt/V urea, total creatinine clearance, residual renal clearance, and peritoneal urea and creatinine clearances were determined In 29 stable peritoneal dialysis patients with no history of recent peritonitis or other catabolic illness. Multiple linear regression analysis showed that NPCR correlated closely with both GN (r=0.96; p&lt;0.0001) and Kt/V urea (r=0.77; p&lt;0.0001), whereas GN also correlated with Kt/V urea (r=0.66; p&lt;0.0001). Total weekly creatinine clearances rather than Kt/V urea should be utilized in peritoneal dialysis to permit independent estimations of dialysis dose and NPCR, since both Kt/V and NPCR are related closely to GN. Total weekly creatinine clearances correlated with NPCR (r=0.59; p&lt;0.0002), which supports the hypothesis that dietary protein Intake is dependent on the delivered dialysis dose.

The effect of tumor bulk on the metabolic response to cancer.

The aim of this study was to examine the association between tumor bulk and degree of metabolic abnormalities in patients with cancer. Patient data were obtained from a retrospective review of metabolic data collected from patients over a 5‐year period. Some of the data have been used in other previously published studies.1, 2, 3 Patients were included in this study if metabolic data had been collected preoperatively, if they had no “significant” sepsis and concurrent endocrine disease, and if they had not received total parenteral nutrition. Solid tumor volume was calculated based on the tumor dimensions recorded in the pathologic records of the patients reviewed. The authors made the assumption that solid tumors were uniformly spherical and 1 cm3 of tumor tissue weighed 1 g. The volume and weight of hepatic or pulmonary metastases were similarly calculated using dimensions obtained with ultrasound or computed tomographic scanning. The volume of myeloproliferative tumors was calculated assuming that all hematopoietic tissue, except the spleen, was uniformly malignant and the myeloid tissue composed 5.9% of the patient's body weight. The following metabolic parameters were measured: oxygen consumption, rates of plasma glucose appearance and clearance, rate of plasma glucose oxidation and recycling, and rate of net protein catabolism. Glucose kinetics were measured by using primed constant infusions of [14C]glucose and [6‐3H]glucose. The rate of protein catabolism was determined by using primed constant infusions of [14C]urea or [di‐15N]urea. Blood samples were drawn after 120 minutes of isotope infusion over a 60‐minute interval. Indirect calorimetry was performed and oxygen consumption determined.Eighty‐five patients were included in the study. Approximately 81% were patients with solid tumors. The majority of these patients had gastrointestinal and head and neck malignancies. The remaining 19% had leukemias or lymphomas. The rates of plasma glucose appearance and clearance were determined in all 85 patients as was the rate of net protein catabolism. However, the rates of plasma glucose oxidation and recycling were determined in only 52 patients (61%).A positive correlation was found between the rate of plasma urea appearance and the rate of net protein catabolism and tumor bulk (r 2 =.80). The bulk of tumor present was positively correlated with the rate of plasma glucose appearance (r 2 =.72) and the rate of plasma glucose clearance (r 2 =.70). However, a negative correlation was demonstrated when the percentage of glucose uptake oxidized by tissue was compared to tumor bulk (r 2 =.75); this was associated with an increase in the percentage of tissue glucose uptake recycled to lactate (r 2 =.62). Oxygen consumption was also positively correlated with tumor bulk (r 2 =.79).Based on these data, the authors concluded that progressive increase in tumor size is associated with an increase in peripheral substrate mobilization, an increase in the rate of glucose production, an increase in the rate of tissue glucose uptake, and an increase in glucose recycling and protein loss.

Permeability changes in hepatic mitochondria and altered glucose and urea metabolism in aroclor 1254-treated rats.

The influence of Aroclor 1254 (ARO) treatment or pair-feeding (PF) on gluconeogenesis and urea synthesis and on isolated hepatic mitochondria was studied in rats of different ages. ARO (300 mg/kg, po on 4 consecutive days) induced variable weight loss in young (153 +/- 10 g (initial wt), -10.9%), intermediate-age (195 +/- 10 g, -17.0%), and old (232 +/- 23 g, -4.9%) rats. Isolated mitochondria contained equal amounts of cytochromes aa3, b, c1 and c with exception that c1 and c were lower in the young ARO rats than in the PF controls. Mitochondria from ARO rats, which lost more weight than ad libitum-fed (AF) rats, showed suppression of ADP-stimulated H+ and oxygen uptake and succinate plus valinomycin maximal swelling in a potassium acetate and sucrose medium. Mitochondria from young ARO rats absorbed less incident light than mitochondria from PF or AF rats. Maximally swollen mitochondria from intermediate-age ARO rats, contracted more rapidly with antimycin addition than those from PF or AF controls. These findings showed greater permeability of ARO mitochondria to impermeable and accumulated ions. In contrast, mitochondria from ARO rats without significant weight loss showed activation of ADP-stimulated H+ and oxygen uptake and maximal swelling in comparison to mitochondria from AF and PF rats, but contracted like these controls after the antimycin addition. Urea synthesis in ARO rats, which lost 9.9% of initial body wt (173 +/- 6 g) and experienced a nitrogen deficit (Ebner et al., 1986), was significantly increased 12 min postinjection of NH4 acetate, and was greater than the urea level in AF rats at this time point. In comparison, gluconeogenesis was significantly increased in AF rats 12 min postinjection of NH4 acetate and was greater than in ARO rats at this time point. These differences were also observed when the data were expressed as the rate of glucose or urea appearance in peripheral blood per 100 g body wt. In PF rats, blood glucose and urea concentrations were intermediate to and indistinguishable from the ARO and AF groups. These data demonstrate that hepatic mitochondria from ARO rats that experienced a significant loss of body weight were suppressed and more permeable to ions than AF and PF controls. These mitochondrial properties may have predisposed the ARO rats toward urea formation rather than glucose synthesis and nitrogen retention.

Contribution of the urea appearance rate to diuretic–induced azotemia in the rat

Studies were performed to evaluate the contribution of the urea appearance rate to the elevated plasma urea concentration found during diuretic-induced sodium depletion. Negative sodium balance of -1162 + 29 microEq/100 g body wt was induced over a four day period by the administration of furosemide, 20 to 30 mg/kg/d i.p., to rats ingesting a sodium free diet. When compared with sodium replete controls, sodium depletion significantly increased the plasma urea concentration (65.0 +/- 3.1 vs. 26.4 +/- 1.1 mg/dl) through both an increase in the urea appearance rate (160 +/- 5.2 vs. 125 +/- 3.5 mg/day/100 g body wt), and a decrease in the urea clearance rate (1.99 +/- 0.14 vs. 3.16 +/- 0.12 ml/min/kg). The urea appearance rate increased on the first day of diuretic administration, remained elevated three days after stopping diuretics, rapidly returned to control levels after sodium repletion, and was significantly correlated with the magnitude of sodium deficit. Similar results were obtained when diuretic-induced sodium depletion was produced in adrenalectomized animals. After four days of sodium depletion the plasma concentration was increased for some amino acids but not for the plasma total amino acid, nitrogen concentration. The results indicate that sodium depletion increases the urea appearance rate through a mechanism that is independent of adrenal function. Thirty to sixty percent of the elevation in plasma urea concentration that occurs in the rat during diuretic-induced sodium depletion can be accounted for by an enhanced urea appearance rate.

Controlled comparison of hemodialysis and peritoneal dialysis: Veterans Administration multicenter study

We measured mortality and morbidity among 114 patients assigned randomly to home hemodialysis (HD) and home intermittent peritoneal dialysis (IPD). Data were collected during the time of home training and for 12 months after initiation of home dialysis. Training time was shorter for the IPD than for the HD patients (P less than 0.001) with median time 1.8 months for IPD and 3.9 months for HD. Switching to the alternative mode of treatment was more frequent for the IPD group (29/59 vs. 5/55, P less than 0.001). Survival time was not different, perhaps because of the modality change. More IPD patients were hospitalized in the first 6 months (20 for IPD vs. 9 for HD, P = 0.02), but they had fewer troublesome cardiovascular events in the first year (0 vs. 12, P less than 0.001). The HD patients maintained better nutritional status as reflected in body weight and arm muscle circumference and possibly in urea appearance rate. Thus, these data suggest that for most patients, IPD is a less satisfactory form of therapy than HD, but certain advantages of IPD did emerge. Applications of this information to the currently more popular mode of CAPD await further study.

Effect of nitrogen intake on urea appearance in patients receiving total parenteral nutrition and hemodialysis.

Hemodialysis results in significant amino acid and protein losses and increases the patient's need for, and tolerance to, standard doses of protein. Since urea accumulation increases proportionately with increasing doses of protein in patients with normal renal function, urea accumulation may result when protein intake is increased to offset losses occurring in the dialysate. As a consequence, an increased requirement for dialysis may occur that might be poorly tolerated by the critically ill patient. This study was designed to determine the relationship between nitrogen intake and urea appearance in five patients requiring hemodialysis and total parenteral nutrition. Daily caloric and nitrogen intakes were determined. Urea appearance was calculated from measures of urine urea nitrogen excretion and daily body urea accumulation. Results of 108 measurements in treatment courses ranging from 23-79 days found that the average caloric intake (1984 +/- 55 calories/d) and nitrogen intake (11.0 +/- 0.4 g/d) resulted in a positive nitrogen balance (0.8 +/- 0.4 g/d) and a urea appearance rate of 9.4 +/- 0.8 g/d. Nitrogen intake correlated both with urea appearance (r = 0.59, p less than 0.001) and nitrogen balance (r = 0.49, p less than 0.001). Positive nitrogen balance was associated with improvements in measures of total iron binding capacity (p less than 0.05). Nitrogen intake directly relates to urea appearance, and positive nitrogen balance can be achieved without increasing dialysis requirements. In this group of patients, 28.3 calories per kg ideal body weight and 0.8 g of protein per kg ideal body weight were required to achieve nitrogen equilibrium.

Amino acid release from the hindquarter and urea appearance in acute uremia.

Hepatic urea production is increased in acutely uremic rats, but it is not known whether this is related to release of nitrogen from nonhepatic tissues. Rats with acute uremia had lower arterial concentrations of alanine, glutamine, and alpha-amino nitrogen when compared to sham-operated rats and released significantly more alpha-amino nitrogen from the hindquarter in situ. Release of alpha-amino nitrogen, alanine, and glutamine from the perfused hindquarter of acutely uremic rats was greater than that of sham-operated rats. These changes in situ and in the perfused hindquarter were more pronounced in rats deprived of food and water compared to fed animals and were not due to depletion of intracellular amino acids. In addition to increased amino acid nitrogen release, there was a higher urea appearance rate (excretion plus accumulation) in starved, uremic rats compared to sham-operated controls (244.7 +/- 11.2 vs. 182.0 +/- 12.4 mg. 100 g-1 .48 h-1); urea appearance also was suppressed partially by feeding. Both peripheral release of amino acids and diet influence waste nitrogen production in acute uremia.

Modulated nitrogen intake for patients on low-protein diets

In order to overcome malnutrition and poor palatability associated with long lasting low-protein intakes, a diet was devised based on modulated nitrogen intake and energy supply of at least 155 KJ/kg a day. Each patient underwent three different regimens (A, B, C) of protein intake. In period A, the protein intake was 0.33 g/kg a day. In period B, the patients were given 0.33 g/kg a day during day 1, 2, 3, 5, 6 and 1.00 g/kg a day during day 4 and day 7 of the week. In period C the daily protein intake was the mean of the weekly value from day 1 to 7 of period B. Data obtained show that in period A the urea appearance rate was equal to that in period B and lower than that in period C.