Nocturnal ultrafiltration profiles in patients on APD: impact on fluid and solute transport.

In order to prevent morbidity and mortality in peritoneal dialysis (PD), sodium and water balance as well as a minimal level of small-solute clearances are needed. The impact of three nocturnal peritoneal ultrafiltration (UF) profiles on UF and small solute clearance in patients on automated PD (APD) was studied: constant glucose concentration of 1.36% (flat) or modifying the glucose concentration of the heater bag (descendant: 3.86-1.36%; ascendant: 1.36-3.86%). Sixty-two patients were enrolled in the study and received each profile within a four-month period, thus serving as their own controls. UF was lower with the flat profile (367+/-420ml; P<0.01), but no difference was seen between the two higher glucose concentration profiles. Peritoneal Kt/V (pKt/V) and peritoneal creatinine clearance (CrpC) showed statistically higher values from the descendant vs ascendant vs flat profiles (pKt/V: 1.54+/-0.30 vs 1.45+/-0.30 vs 1.38+/-0.27, and CrpC: 36.9+/-7.9 vs 33.5+/-7.48 vs 29.92+/-7.5 mlmin(-1)). Multivariate analysis showed statistical significance for the following: in the intrasubject comparisons, the profile for pKt/V (F=9.109, P<0.001) and CrpC (F=11.697, P<0.001), and in the intersubjects comparisons, the effects of both gender (F=14.334, P<0.01) for pKt/V and peritoneal permeability for both parameters (pKt/V: F=4.37, P<0.05; CrpC: F=11.697, P<0.001). In conclusion, the application of ascendant and descendant UF profiles in automated PD is feasible and results in better UF and small solute clearances, thus preventing inadequate dialysis and volume overload..

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) : characterization of the cohort.

The Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD) was launched in December 2004 aiming to collect data monthly and continuously from a representative cohort, allowing for a continuous snapshot of the peritoneal dialysis (PD) reality in the country. This is an observational study of PD patients comprising follow-up from December 2004 to February 2007 (mean follow-up of 13.6 months-ranging from 1 to 26 months) in 114 Brazilian centers. All centers report data through a central web-based database. After an initial baseline retrospective data collection, all patients are followed prospectively every month until they drop out from the PD program. Total number of patients recruited until February 2007 was 3226 (2094 incident patients). Mean age was 54+/-19 years (37% above 65 years old), with 55% females and 64% Caucasians. The more frequent causes of renal failure were diabetic nephropathy (34%), renal vascular disease associated with hypertension (26%), and glomerulopathies (13%). The most common comorbidities were hypertension (76%), diabetes (36%), and ischemic heart disease (23%). Automated PD (APD) was the modality utilized in 53%. The estimated overall peritonitis rate was 1 episode per 30 patient-months (most frequently due to Staphylococcus aureus). The total dropout rate was 33%, mainly due to deaths, whereas 20% of dropouts were due to renal transplant. The gross mortality was 17.6% and the main causes of mortality were cardiovascular diseases (40%) and infections (15%). The initial results of this first Brazilian PD registry provide a unique opportunity to develop future clinical studies addressing specific PD questions in the Brazilian reality and context.

Are insulin-like growth factor and its binding proteins 1 and 3 clinically useful as markers of malnutrition, sarcopenia and inflammation in end-stage renal disease?

INTRODUCTION: Malnutrition is common in end-stage renal disease (ESRD) and affects both morbidity and mortality. The growth hormone-dependent insulin-like growth factor (IGF)-I may be a good marker of malnutrition because of its short half-life. In the present study, we investigate the influence of decreasing residual renal function as well as of chronic inflammation on the IGF system to assess its usefulness in this patient group. PATIENTS AND METHODS: Cross-sectional analysis of 220 ESRD patients (140 males) with a mean age of 52+/-1 years. Biochemical analyses of insulin, IGF-I, IGFBP-1, IGFBP-3, IL-6, high sensitivity (hs)-CRP and other routine markers. Malnutrition status was recorded using subjective global assessment (SGA), body mass index, estimated protein intake from nitrogen appearance (nPNA), handgrip strength (HGS) and insulin resistance (HOMA-IR). Dual energy X-ray absorptiometry was used to assess body composition. RESULTS: Both IGF-I and IGFBP-1 showed significant and opposite correlations with most markers of nutritional status, including SGA (rho=-0.29 and 0.27; P<0.001), nPNA (rho=0.18 and -0.22; P<0.05), S-creatinine (rho=0.19 and -0.19; P<0.01) and HGS (rho=0.21 and -0.25; P<0.01). IFG-I was strongly correlated with IGFBP-3 (rho=0.62; P<0.001) and inversely correlated with IGFBP-1 (rho=0.44; P<0.001). Both IGF-I and IGFBP-3, but not IGFBP-1, were significantly correlated with age (rho=-0.25 for IGF-I and -0.35 for IGFBP-3; P<0.001) and hsCRP (rho=-0.21 and -0.32; P<0.01). In multivariate analysis, SGA and s-albumin were independent predictors of both IGF-I and IGFBP-1. CONCLUSION: Both IGF-I and IGFBP-1 appear to correlate well with markers of protein-energy malnutrition and sarcopenia. However, IGF-I is also influenced by age, whereas IGFBP-1 is influenced by glucose metabolism. IGFBP-3 does not correlate with nutritional status in ESRD, perhaps because of a strong association with inflammation.

Glutamate concentration in plasma, erythrocyte and muscle in relation to plasma levels of insulin-like growth factor (IGF)-I, IGF binding protein-1 and insulin in patients on haemodialysis.

Elevated insulin-like growth factor binding protein (IGFBP) levels, including IGFBP-1, occur in renal failure, and may contribute towards reduced IGF bioactivity in uraemia. The reduced IGF bioactivity may, in turn, contribute towards the disturbances in protein metabolism present in renal failure. In this study, the relationships between intra- and extracellular amino acid (AA) levels and IGF-I and/or IGFBP-1 levels were studied in 30 adult patients (aged 24-70 years) on haemodialysis who had no clinical signs of malnutrition. Blood samples (n = 30) and muscle biopsies (n = 13) were collected for determination of free AA in erythrocytes (RBC), plasma and muscle by reverse-phase HPLC while IGFBP-1, IGF-I and insulin plasma levels were determined by radioimmunoassay The patients on haemodialysis had elevated glutamate concentrations in RBC and plasma compared with healthy controls (524 +/- 26 vs 448 +/- 17 mumol/l, P < 0.05 and 45 +/- 4 vs 32 +/- 4 mumol/l, P < 0.01 respectively), although glutamate levels in muscle were within the normal range. The mean IGF-I level was slightly increased (s.d. score +0.74 +/- 0.30) but insulin levels were within the normal range. IGFBP-1 levels, which were inversely correlated to insulin (r = -0.40, P < 0.02), were elevated threefold compared with controls. No plasma AA level displayed a significant correlation with IGF-I, IGFBP-1 or insulin levels. However, glutamate concentrations in RBC were positively correlated to IGFBP-1 (r = 0.51, P < 0.01) and inversely correlated to IGF-I (r = -0.46. P < 0.01), although unrelated to insulin. Muscle glutamate, which was inversely related to RBC glutamate, displayed an opposite pattern with an inverse relation to IGFBP-1 levels (r = - 0.73, P < 0.01) and a positive correlation to IGF-I levels (r = 0.64, P < 0.02). Glutamate was the only AA to display an inverse correlation between RBC and muscle (r = -0.65, P < 0.02, n = 12). These findings lead us to propose that, in uraemia, the elevated IGFBP-I levels, which reduce the bioavailability of IGFs, are linked to glutamate uptake in muscle, resulting in accumulation of RBC glutamate. Whether there is a causal relationship or the correlation is due to some common regulator is not clarified in the present study.

Children on continuous ambulatorial peritoneal dialysis: muscle and plasma proteins, amino acids and nutritional status.

The aim of the study was to investigate plasma and muscle amino acid (AA) levels in children on continuous ambulatory peritoneal dialysis (CAPD) and their relationship to various indices of nutritional status. Ten children with a mean age of 6.4 +/- 5.6 yrs were evaluated. Muscle biopsies and venous blood samples were taken after an overnight fast. Muscle samples were obtained from rectus abdominis. Data were compared with those of a control group of 22 children who were undergoing elective surgery. Informed consent was obtained from the parents. The plasma concentration of most of the essential AA (valine, leucine, isoleucine, lysine, methionine and tyrosine) were significantly reduced and the levels of some non essential AA (aspartic acid, glycine, citrulline, 1-3 methihystidine, taurine + alanine) were significantly higher than in the controls. Muscle intracellular free essential AA concentrations, except the low levels of valine and leucine did not differ significantly from values in the controls. Among non essential AA, aspartic acid, glutamic acid and ornitine showed significantly increased intracellular concentrations. No significant correlations were found between plasma and muscle AA concentration and ASP (alkali-soluble protein)/DNA ratio, serum albumin, transferrin, bicarbonate levels and duration of CAPD. Instead, a significant correlation was noted between the muscle ASP/DNA ratio, an indicator of the amount of cell proteins per cell unit, and age (r = 0.714, p < 0.05). Muscle Branched chain AA levels were significantly correlated to body mass index (BMI) (r = 0.648, p < 0.05).

High C-reactive protein is a strong predictor of resistance to erythropoietin in hemodialysis patients.

Inflammation is one of the major causes of resistance to erythropoietin (EPO) treatment. In the present study, the relationship between serum C-reactive protein (s-CRP) and the dose of recombinant human EPO required to maintain hemoglobin levels at approximately 12 g/dL was analyzed in 30 hemodialysis patients. The weekly EPO dose in patients with s-CRP > or = 20 mg/L was, on average, 80% higher than in patients with s-CRP less than 20 mg/L. The EPO doses and s-CRP were both inversely correlated to the levels of serum albumin and serum iron, suggesting that the principal mechanism by which inflammatory cytokines inhibit erythropoiesis is coupled to iron metabolism, ie, functional iron deficiency. Our results demonstrate the usefulness of s-CRP as a predictor of resistance to EPO treatment.

Free amino-acid levels simultaneously collected in plasma, muscle, and erythrocytes of uraemic patients.

BACKGROUND: Disturbances in amino acid (AA) metabolism in uraemia have mainly been reported to occur in plasma and muscle. The erythrocytes (RBC) constitute a large proportion of the free AA in blood and may play an important role in the interogan transport of AA. This report presents the first data on AA levels obtained simultaneously from three different compartments in uraemic patients. METHODS: Muscle biopsy and blood samples were obtained from 38 haemodialysis (HD), 22 continuous peritoneal dialysis (CPD) and 10 end-stage renal failure patients for determination of free amino acids by reversed-phase HPLC. The results are compared to data obtained from 27 healthy subjects under the same conditions. RESULTS: For a number of non-essential AA (alanine, glycine, asparagine, arginine) and for lysine, elevated concentrations were present simultaneously in RBC and in muscle but not in plasma. On the other hand, low concentration of some essential AA (leucine, valine, phenylalanine, tyrosine) were observed in RBC and in plasma, while the concentrations in muscle were normal. Most of the non-essential AA (NEAA), especially taurine and glutamine, had much higher muscle/plasma gradients than RBC/plasma gradients, although an accumulation in RBC of glycine, serine, arginine, asparagine, ornithine, glutamate and taurine was observed. Most of the essential AA (EAA) showed higher muscle/plasma gradients, whereas the RBC/ plasma gradients were approximately 1.0. CONCLUSION: Our findings are in agreement with studies that have shown that RBC and plasma play independent and opposing roles in AA interorgan transport. The results indicate that there are several AA abnormalities in all three compartments in uraemic patients. They also suggest that there may be some specific common changes of selected transport systems for both RBC and muscle in uraemia. Determination of AA in RBC should be considered when undertaking metabolic and clinical studies of AA disturbances.

Suicidal chloral hydrate poisoning.

BACKGROUND: The cumulative reports of chlorate hydrate toxicity suggest an unacceptable risk for this commonly used sleep aid. CASE REPORT: A 29-year-old male was admitted after ingestion of 70 g of chloral hydrate. He was hypotensive and hypothermic. Spontaneous respiration was insufficient. Fluid resuscitation did not restore adequate blood pressure levels. Low dose catecholamine infusion resulted in ventricular arrhythmias. The patient was treated with combined hemoperfusion and hemodialysis during an eight hour period. During this time, serum concentrations of trichlorethanol fell. Blood pressure and heart rate increased and consciousness was regained without signs of neurological deficits. CONCLUSIONS: Although outcome was favorable, this case report illustrates the potentially high acute toxicity of chloral hydrate and supports its removal from the market.

Muscle and plasma amino acids and nutritional status in kidney-transplanted children.

Nutritional status, assessed by anthropometric and biochemical methods, protein and amino-acid (AA) composition and muscle water were evaluated in 11 kidney transplanted children and in a control group of 10 children with normal renal function who were undergoing elective surgery. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when the peritoneal catheter was removed in the transplanted children. The mean time from the transplantation to the study time was 97 +/- 14 days (range 72-114 days). Height was reduced in the transplanted children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were normal. The body mass index was over the 50 degree percentile in nine of the eleven children. The muscle contents of total, extracellular, and intracellular water, alkali-soluble protein (ASP), DNA and the ASP/DNA ratio were not significantly different in transplanted children from those in the controls. Plasma leucine and taurine levels were significantly decreased, whereas plasma citrulline and alanine levels and the glycine/serine ratio were increased. Muscle threonine, alanine+taurine, glycine and aspartic acid levels as well as the glycine/serine ratio were increased in the transplanted children. Transplanted children show an almost normal muscle AA profile and a plasma AA pattern that seems to be related to the prednisone therapy.

Nutritional status and muscle amino acids in children with end-stage renal failure.

Nutritional status, assessed by anthropometric and biochemical methods, and muscle water, protein and amino acid composition, were evaluated in a control group of 10 children with normal renal function who were undergoing elective surgery, and in 15 children with end-stage chronic renal failure. Samples of the rectus abdominis muscle were taken when surgery was performed in the control children and when a peritoneal catheter was implanted in the uremic children. Height and body weight were reduced in the uremic children compared to the controls but skinfold thickness, arm muscle circumference and serum proteins (total protein, albumin, transferrin, pseudocholinesterase) were essentially normal. The muscle contents of total, extracellular and intracellular water, and of alkali-soluble protein (ASP), DNA and the ASP-DNA ratio were not significantly different in uremic children from those in the controls. Plasma leucine, isoleucine, tyrosine, valine, and serine levels were significantly decreased, whereas plasma citrulline, 1-methylhistidine and 3-methylhistidine levels were increased. Muscle isoleucine and valine levels and the valine/glycine ratio were low in the uremic children. Our results demonstrate that children with chronic renal failure and growth retardation may maintain a satisfactory nutritional status but exhibit amino acid abnormalities typical of uremia.

Multifrequency bioimpedance in assessment of dry weight in haemodialysis.

The use of multifrequency bioimpedance (MFB) for determination of dry weight (DW) in haemodialysis (HD) patients was evaluated in three studies. In Study 1, the fluid state [total body water (TBW) and extracellular volume (ECV)] was measured by MFB in 82 normotensive patients. 41 hypertensive patients and in 30 healthy subjects. TBW and ECV were expressed as per cent of body weight (BW). In Study 2, DW of five hypertensive HD patients was gradually decreased during 3 months and ECV (MFB) and blood pressure (48 h ambulatory blood pressure monitoring) were measured at the beginning and end of study. In Study 3, we measured the fluid status repeatedly by MFB and the diameter of the inferior vena cava (DIVC) by ultrasound before, during and 2 h post-HD. In Study 1, the hypertensive patients had significantly greater TBW (P < 0.05) than the normotensive patients before (50.3 +/- 6.5% vs 47.6 +/- 5.8%) and after HD (48.8 +/- 7.8% vs 45.7 +/- 6.4%) and ECV (P < 0.001) before (29.4 +/- 3.6% vs 26.8 +/- 3.5%) and after HD (27.0 +/- 4.0% vs 24.6 +/- 3.5%), Post-HD ECV in the normotensive patients was similar to that in the healthy subjects. In Study 2, more efficient ultrafiltration resulted in reduction of BW and ECV along with a decrease in blood pressure and need for antihypertensive medication. In Study 3, both ECV and DIVC decreased following the removal of fluid during HD. ECV maintained stable values during the post-HD period, unlike DIVC which increased significantly (P < 0.005) due to refilling from the interstitial space. We conclude that MFB is an appropriate non-invasive method for DW determination, which is highly reproducible and technically simple to use.

Factors predicting malnutrition in hemodialysis patients: a cross-sectional study.

Signs of protein-energy malnutrition are common in maintenance hemodialysis (HD) patients and are associated with increased morbidity and mortality. To evaluate the nutritional status and relationship between various parameters used for assessing malnutrition, we performed a cross-sectional study in 128 unselected patients treated with hemodialysis (HD) thrice weekly for at least two weeks. Global nutritional status was evaluated by the subjective global nutritional assessment (SGNA). Body weight, skinfold thicknesses converted into % body fat mass (BFM), mid-arm muscle circumference, hand-grip strength and several laboratory values, including serum albumin (SA1b), plasma insulin-like growth factor I (p-IGF-I), serum C-reactive protein (SCRP) and plasma free amino acids, were recorded. Dose of dialysis and protein equivalence of nitrogen appearance (nPNA) were evaluated by urea kinetic modeling. The patients were subdivided into three groups based on SGNA: group I, normal nutritional status (36%); group II, mild malnutrition (51%); and group III, moderate or (in 2 cases) severe malnutrition (13%). Clinical factors associated with malnutrition were: high age, presence of cardiovascular disease and diabetes mellitus. nPNA and Kt/V(urea) were similar in the three groups. However, when normalized to desirable body wt, both were lower in groups II and III than in group I. Anthropometric factors associated with malnutrition were low body wt, skinfold thickness, mid-arm muscle circumference (MAMC), and handgrip strength. Biochemical factors associated with malnutrition were low serum levels of albumin and creatinine and low plasma levels of insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (isoleucine, leucine and valine). The serum albumin (SAlb) level was not only a predictor of nutritional status, but was independently influenced by age, sex and SCRP. Plasma IGF-1 levels also reflected the presence and severity of malnutrition and appeared to be more closely associated than SAlb with anthropometric and biochemical indices of somatic protein mass. Elevated SCRP (> 20 mg/liter), which mainly reflected the presence of infection/inflammation and was associated with hypoalbuminemia, was more common in malnourished patients than in patients with normal nutritional status, and also more common in elderly than in younger patients. Plasma amino acid levels, with the possible exception of the branched-chain amino acids (isoleucine, leucine, valine), seem to be poor predictors of nutritional status in hemodialysis patients.

Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

Fluid state and blood pressure control in patients treated with long and short haemodialysis.

BACKGROUND: Patients treated at the haemodialysis (HD) centre in Tassin, France have been reported to have superior survival and blood pressure (BP) control. This control has been ascribed to maintenance of an adequate fluid state, antihypertensive drugs being required in < 5% of the patients, although it could not be excluded that a high dose of HD regarding removal of uraemic toxins might also have been of value. METHODS: The aim of the study was to assess the fluid state and BP in normotensive patients on long HD (8 h) in Tassin (group TN) using bioimpedance to measure extracellular volume (ECV), ultrasound for determining the inferior vena cava diameter (IVCD), and 'on-line' monitoring of the change in blood volume (BV), and to compare them with normotensive (group SN) and hypertensive (group SH) patients on short HD (3-5 h) at centres in Sweden. ECV was normalized (ECVn) by arbitrarily setting the median ECV (in % of body weight) in SN patients at 100% for each gender, recalculating the individual values and combining the results for male and female patients in each group. RESULTS: The dose of HD (Kt/V urea) was higher for TN patients than for Swedish patients who had a similar Kt/V, whether hypertensive or not. SH patients had significantly higher ECVn and IVCD than TN and SN patients. TN and SN patients did not differ significantly regarding ECVn and IVCD before and after HD. However, in a subgroup of eight TN patients, ECVn was below the range of that in SH and SN patients, due to obesity with a high body mass index. Another subgroup of 14 TN patients had a higher ECVn than most of the SN patients and also higher than the median ECVn in the SH group, without any difference in body mass index, but they were nevertheless normotensive. The fall in BV was greater in SN than in TN patients, presumably due to a higher ultrafiltration rate in SN patients. However, SH patients had a smaller change in BV than SN patients, presumably because their state of overhydration facilitated refilling of BV from the interstitial fluid. CONCLUSIONS: Normotension can be achieved independently of the duration and dose (Kt/V urea) of HD, if the control of post-dialysis ECV is adequate. However, this is more difficult to achieve with short than with more prolonged HD during which the ultrafiltration rate is lower, BV changes are smaller and intradialysis symptoms less frequent. The results in the subgroup of patients with high ECVn at Tassin suggest that normotension may also be achieved in patients with fluid overload provided that the dialysis time is long enough to ensure more efficient removal of one or more vasoactive factors that cause or contribute to hypertension.