Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.     

Plasma and muscle free amino acids in maintenance hemodialysis patients without protein malnutrition

To investigate how uremia modified by maintenance hemodialysis treatment influences the extra- and intracellular amino acid pattern, we collected muscle samples by percutaneous muscle biopsy and plasma samples for determination of free amino acids in 11 functionally anephric patients (creatinine clearance less than 1 ml/min), who had been treated with hemodialysis for greater than 6 months and had no clinical or laboratory signs of protein malnutrition. Five patients had mild acidosis (standard bicarbonate pre-dialysis 18 to 21 mmol/liter). The amino acid results were compared with data from age- and sex-matched healthy controls and with data obtained earlier from non-dialyzed patients with chronic uremia. In the hemodialysis patients threonine, serine and valine were significantly reduced in plasma compared to the controls, whereas the plasma concentrations of aspartate, glycine, citrulline, cysteine and arginine were elevated. In aspartate, glycine, citrulline, cysteine and arginine were elevated. In muscle, valine, serine and the tyrosine to phenylalanine ratio were low. Compared with the untreated uremic patients the hemodialysis patients exhibited fewer significant abnormalities, but the general pattern was similar, demonstrating that hemodialysis is unable to fully correct the amino acid abnormalities of chronic uremia. There was a significant positive correlation between both pre-dialysis and post-dialysis plasma bicarbonate and the muscle valine concentration, suggesting that mild acidosis may be causally related to the inbalance of the branched-chain amino acids in uremia. Extra- and intracellular serine depletion in the presence of high plasma glycine may reflect a defect in the metabolism of glycine to serine in hemodialysis patients, related to a lack of metabolizing renal tissue.     

Intradialytic parenteral nutrition treatment and biochemical marker assessment for malnutrition in adolescent maintenance hemodialysis patients.

Protein-energy malnutrition (PEM) is a significant cause of morbidity and mortality for patients receiving maintenance hemodialysis. Minimal study has evaluated therapeutic options for and biochemical marker assessment of pediatric patient PEM. In 2001, we expanded the indications for intradialytic parenteral nutrition (IDPN) treatment of PEM to all maintenance hemodialysis patients, regardless of etiology, who had a >10% weight loss and were at less than the 90th percentile of ideal body weight. Nine patients received thrice weekly IDPN from 3 to 22 months with minimal side effects. Six patients had weight and body mass index increase, 1 patient stopped losing weight, and 2 patients continued to lose weight during the initial 5 months of IDPN therapy. Cohort subanalysis showed that all patients with organic PEM responded to IDPN therapy, whereas patients with psychosocial causes of PEM did not. The normalized protein catabolic rate increased significantly for patients whose condition responded to IDPN therapy, whereas serum albumin did not change. The current study suggests that IDPN is effective treatment of organic causes of PEM in pediatric patients receiving maintenance hemodialysis and that normalized protein catabolic rate may be superior to serum albumin as a marker of nutrition status. The observation that IDPN was not sufficient to reverse PEM in patients with psychosocial PEM causes should direct caregivers to address the relevant underlying causes as well as to provide intensive nutrition therapy.     

Intradialytic parenteral nutrition does not improve survival in malnourished hemodialysis patients: a 2-year multicenter, prospective, randomized study

Although intradialytic parenteral nutrition (IDPN) is a method used widely to combat protein-calorie malnutrition in hemodialysis patients, its effect on survival has not been thoroughly studied. We conducted a prospective, randomized trial in which 186 malnourished hemodialysis patients received oral nutritional supplements with or without 1 year of IDPN. IDPN did not improve 2-year mortality (primary end point), hospitalization rate, Karnofsky score, body mass index, or laboratory markers of nutritional status. Instead, both groups demonstrated improvement in body mass index and the nutritional parameters serum albumin and prealbumin (P < 0.05). Multivariate analysis showed that an increase in prealbumin of >30 mg/L within 3 months, a marker of nutritional improvement, independently predicted a 54% decrease in 2-year mortality, as well as reduced hospitalizations and improved general well-being as measured by the Karnofsky score. Therefore, although we found no definite advantage of adding IDPN to oral nutritional supplementation, this is the first prospective study demonstrating that an improvement in prealbumin during nutritional therapy is associated with a decrease in morbidity and mortality in malnourished hemodialysis patients.     

Loss of amino acids during hemodialysis: effect of oral essential amino acid supplementation

The aim of this study was to investigate the effect of amino acid (AA) supplementation on the loss and its time course of free AA, during hemodialysis. 2 uremic patients on regular hemodialysis received an increasing number of essential AA tablets during the dialysis. The loss and its time course of 6 essential and 7 nonessential free AA during dialysis was assayed in the dialysate. The loss per dialysis treatment of the administered essential AA increased almost proportionally with the doses of AA tablets. For the nonessential AA, no definite relationship between doses of AA tablets and losses was observed. At all levels of supplementation, methionine was retained best: 90% of the amount present in the tablets. Threonine showed the lowest retention: 15-55%.     

Intradialytic dobutamine therapy in maintenance hemodialysis patients with persistent hypotension.

Intradialysis hypotension is a common problem, especially in patients with poor left-ventricular function. We studied 6 patients who were on maintenance hemodialysis with left-ventricular ejection fraction of <40%, whose dialysis sessions were often complicated with severe hypotension (systolic blood pressure <90 mm Hg). Dobutamine infusion during dialysis significantly reduced the number of hypotensive episodes, increased left-ventricular ejection fraction, and decreased the number of emergency admissions to the hospital.     

Sexual dysfunction in female hemodialysis patients: a multicenter study

BACKGROUND: Sexual function is one aspect of physical functioning. Sexual dysfunction, no matter the etiology, could cause distress. In female hemodialysis patients, sexual problems have often been neglected in clinical performance and research. METHODS: We conducted this study by use of self-reported questionnaires. A total of 578 female hemodialysis patients in northern Taiwan were included in this study. Demographic data, comorbid diseases, medications in use, biochemical, and hematologic parameters were analyzed. All patients were asked to complete by themselves three questionnaires: (1) the Index of Female Sexual Function (IFSF) to assess sexual function; (2) the Beck Depression Inventory (BDI) (Chinese version) to rate the severity of depressive symptoms; and (3) the 36-item Short Form Health Survey Questionnaire (SF-36, Taiwan Standard Version 1.0) to survey their quality of life. RESULTS: A total of 138 female patients were enrolled into further analysis. The mean age was 48.7 +/- 11.2 years old. The mean IFSF score was 24.5 +/- 9.3. Age, BDI score, and serum triglyceride levels were the independent factors of dysfunction in each sexual functional dimension. Patients with higher IFSF scores had significantly higher scores in physical functioning and mental health (P= 0.007 and 0.018, respectively). Patients with higher intercourse satisfaction had significantly higher general health scores (P= 0.001). CONCLUSION: Sexual dysfunction is frequent in the female hemodialysis population. It is strongly associated with increasing age, dyslipidemia, and depression. The subjects with sexual dysfunction had poorer quality of life. The diagnosis and treatment of sexual dysfunction should be included in the clinical assessment.     

Timing of the first cannulation and survival of arteriovenous grafts in hemodialysis patients: a multicenter retrospective cohort study

Arteriovenous graft (AVG) is an important vascular access route in hemodialysis patients. The optimal waiting time between AVG creation and the first cannulation is still undetermined, therefore the current study investigated the association between ideal timing for cannulation and AVG survival. This retrospective cohort study used data from the Taiwan National Health Insurance Database, which included 6,493 hemodialysis patients with AVGs between July 1^st 2008 and June 30^th 2012. The waiting cannulation time was defined as the time from the date of shunt creation to the first successful cannulation. Patients were categorized according to the waiting cannulation time of their AVGs as follows: ≤30 days, between 31 and 90 days, between 91 and 180 days, and >180 days. The primary outcome was functional cumulative survival, measured as the time from the first cannulation to shunt abandonment. The AVGs which were cannulated between 31 and 90 days (reference group) after construction had significantly superior functional cumulative survival compared with those cannulated ≤30 days (adjusted HR = 1.651 with 95% CI 1.482–1.839; p < 0.0001) and >180 days (adjusted HR = 1.197 with 95% CI 1.012–1.417; p = 0.0363) after construction. An analysis of the hazard ratios in patients with different demographic characteristics, revealed that the functional cumulative survival of AVGs in most groups was better when they received cannulation >30 days after construction. Consequently, in order to achieve the best long-term survival, AVGs should be cannulated at least 1 month after construction, but you should avoid waiting for >3 months.     

Intradialytic blood volume monitoring in ambulatory hemodialysis patients: a randomized trial

Complications related to inadequate volume management are common during hemodialysis. This trial tested the hypothesis that availability of an intradialytic blood volume monitoring (IBVM) device improves fluid removal, reducing morbidity. A six-center, randomized trial with 6 mo of intervention comparing IBVM using Crit-Line versus conventional clinical monitoring was conducted. The average rate of non-access-related hospitalizations was compared across treatment groups using Poisson regression. Mortality analysis used the Kaplan Meier method. A total of 227 patients were randomized to Crit-Line, and 216 were randomized to conventional monitoring. Both groups had similar baseline characteristics. During the study, no differences in weight, BP, or number of dialysis-related complications were observed. There were 120 and 81 non-access-related hospitalizations in the Crit-Line and conventional monitoring groups. The adjusted risk ratio for non-access-related and access-related hospitalization was 1.61 (95% confidence interval 1.15 to 2.25; P = 0.01) and 1.52 (95% confidence interval 1.02 to 2.28; P = 0.04) for the Crit-Line monitoring group. Mortality was 8.7% in the Crit-Line monitoring group and 3.3% in the conventional group (P = 0.021). Standardized mortality ratios comparing the Crit-Line and conventional monitoring groups to the prevalent hemodialysis population were 0.77 (NS) and 0.26 (P < 0.001). Hospitalization rates were 1.51 and 1.03 events/yr in the Crit-Line and standard monitoring groups, compared with 2.01 for the prevalent hemodialysis population. IBVM was associated with higher nonvascular and vascular access-related hospitalizations and mortality compared with conventional monitoring. The atypically low hospitalization and mortality rates for the conventional monitoring group suggest that these findings should be generalized to the US hemodialysis population with caution.     

Blood pressure stability in hemodialysis patients confers a survival advantage: results from a large retrospective cohort study

The association between changes in systolic and diastolic blood pressure, and the use of cardioprotective drugs on survival of incident hemodialysis patients, was examined in this retrospective cohort study. Pre-hemodialysis systolic and diastolic blood pressures were averaged over the first month of hemodialysis. Slopes, reflecting temporal changes, were computed by linear regression of systolic blood pressures and Cox regression was used for survival analyses. Patients were initially stratified into four cohorts (below 120, 120 to 150, 151 to 180, and above 180 mm Hg) and further subdivided into groups with stable (no more than a 1-mm Hg change per month), increasing (over 1-mm Hg per month), and decreasing (less than 1-mm Hg per month) slopes during the first year. Analyses were repeated for patients who were treated with cardioprotective drugs for 1 month or more in the second year. In 10,245 patients (59% prescribed cardioprotective drugs), both increases and decreases in all ranges of blood pressure were associated with worse outcomes, whereas stable blood pressure had a survival advantage at all levels of systolic and diastolic pressures. Use of cardioprotective drugs attenuated changes and improved survival. Validation and sensitivity analyses confirmed the primary findings. Therefore, previous temporal trends need to be considered in patient care, and the use of cardioprotective agents is associated with enhanced survival at all blood pressure levels.     

Oral essential amino acid supplementation in patients on maintenance hemodialysis

Sixteen patients with chronic renal failure on maintenance hemodialysis were studied before and during oral treatment with essential amino acids. The patients received their usual diets (60-100 g protein/day) throughout the study. Plasma amino acids were studied pre-dialysis before supplements were started, after one month and after three months treatment; some measurements were also carried out post-dialysis. Before treatment 63% of patients pre-dialysis, and 82% post dialysis, had at least one essential amino acid value which was lower than our normal range. After one month of treatment 38% of patients pre-dialysis, and 67% post-dialysis, had one or more low essential amino acid value. After 3 months only 2 patients had an abnormal essential amino acid chromatogram pre-dialysis. Changes in non-essential amino acids, blood urea, serum proteins and hemoglobin are also reported. The data show that low plasma essential amino acid concentrations are frequently present in patients on maintenance hemodialysis even when the diet contains theoretically adequate amounts of protein. This deficiency can be corrected successfully with oral essential amino acid supplements.     

Resistant starch supplementation attenuates inflammation in hemodialysis patients: a pilot study

Purpose

In chronic kidney disease (CKD) patients, dysbiosis is associated with inflammation and cardiovascular risk, so many nutritional strategies are being studied to reduce these complications. Resistant starch (RS) can be considered a prebiotic that promotes many benefits, including modulation of gut microbiota which is linked to immune-modulatory effects. The aim of this study was to evaluate the effects of RS supplementation on proinflammatory cytokines in CKD patients on hemodialysis (HD).

Methods

A double-blind, placebo-controlled, randomized trial was conducted with sixteen HD patients (55.3?±?10.05 years, body mass index (BMI) 25.9?±?5.42 kg/m², 56% men, time on dialysis 38.9?±?29.23 months). They were allocated to the RS group (16 g RS/day) or placebo group (manioc flour). The serum concentration of ten cytokines and growth factors was detected through a multiparametric immunoassay based on XMap-labeled magnetic microbeads (Luminex Corp, USA) before and after 4 weeks with RS supplementation.

Results

After RS supplementation, there was a reduction of Regulated upon Activation, Normal T-Cell Expressed and Secreted (p?<?0.001), platelet-derived growth factor (two B subunits) (p?=?0.014) and interferon-inducible protein 10 (IP-10) (p?=?0.027). The other parameters did not change significantly.

Conclusion

This preliminary result indicates that RS may contribute to a desirable profile of inflammatory markers in CKD patients.

     

Renal outcome after tonsillectomy plus corticosteroid pulse therapy in patients with immunoglobulin A nephropathy: results of a multicenter cohort study

Background

In addition to renin–angiotensin system inhibition (RAS), corticosteroids are recommended for patients who have immunoglobulin A nephropathy (IgAN) with ≧1 g/day proteinuria. Tonsillectomy plus corticosteroid pulse therapy (TSP) had been reported as more effective in producing clinical remission of IgAN than just oral-corticosteroid (OS) or steroid-pulse (SP) therapy—but that remained unconfirmed. Accordingly, this study compared the effects of TSP, corticosteroid therapies, and RAS on a multicenter, large-scale, long-term cohort.

Methods

1127 biopsy-proven IgAN patients with chronic kidney disease (CKD), G1-3, treated in our hospitals March 1981–December 2013 with TSP (n = 209), SP (n = 103), OS (n = 300), or RAS, alone (n = 515), were followed until end-stage renal disease (ESRD) or death, renal survival compared by treatment and proteinuria level. Hazard ratios (HRs) of ESRD were analyzed after adjusting for sex, age, BMI, eGFR, albumin, proteinuria, hematuria, blood pressure, medications, and renal-biopsy year, with propensity-score-matched analyses performed.

Results

With TSP as referent, the overall HRs of SP, OS, and RAS were, respectively, 1.33 (0.44–4.04), 3.56 (1.45–8.71), and 3.64 (1.48–8.96); with proteinuria ≧1.0 g/gCre, respective HRs were 2.99 (0.71–12.54), 5.04 (1.44–17.67), and 7.23 (1.98–26.40); with proteinuria <1.0 g/gCre, 0.42 (0.04–4.89), 3.24 (0.79–13.30), and 2.05 (0.52–8.05); and for patients with CKD G3, 0.37 (0.10–1.41), 2.14 (0.77–5.94), and 2.03 (0.72–5.72). Similar results were observed in models including pathological grading and/or propensity-score matching.

Conclusion

TSP may decrease the risk of ESRD in IgAN patients better than other therapies in CKD G1-2, with proteinuria ≧1.0 g/gCre, while outcome was similar to SP in CKD G3, or with proteinuria <1.0 g/gCre.

     

Relationships between homocysteine and related amino acids in chronic hemodialysis patients.

AIMS: Homocysteine (Hcy) has emerged as an important risk factor for atherosclerotic disease. Elevated levels in chronic dialysis patients may contribute to high vascular mortality, but little is known about levels of related amino acids in this group. In an observational study in the clinical setting we sought to document these. METHODS: In 114 hemodialysis patients pre-dialysis total plasma homocysteine, vitamin B12 and red blood cell (RBC) folate concentrations were measured. In a subgroup of patients (n = 42), other plasma amino acids were measured pre- and post-dialysis. All patients were routinely taking oral folic acid supplements (1.2 mg per week). RESULTS: Elevated homocysteine concentrations were found in all patients (geometric mean 33.1 umol/l, range 13.8 - 69.2 umol/l, laboratory reference range (RR) 3-13 umol/l). RBC folate levels were high (1223 +/- 54.5 nmol/l mean +/- SE, RR 300 - 710 nmol/l) and inversely related to pre-dialysis plasma Hcy (r = -0.44, p < 0.001). Hcy levels were not related to vitamin B12 levels. A history of vascular disease was not associated with higher concentrations of Hcy. Hcy clearance on dialysis was substantial (mean Hcy reduction 33 +/- 14%). While plasma methionine levels were normal, serine levels were significantly lower than the reference range (59.3 +/- 2.39 umol/l (mean +/- SE, RR 70 - 195 umol/l)) and directly related to levels of glycine (r = 0.52, p < 0.001). Glycine levels were within normal range. Although overall levels were low, higher serine levels were related to elevated homocysteine (r = 0.42, p < 0.01). Dialytic loss of glycine, serine and methionine was moderate. CONCLUSION: An inverse association between RBC folate and homocysteine levels extended to 3 times the upper limit of normal for folate, suggesting a role for high dose folic acid supplementation in the treatment of renal-failure related hyperhomocysteinemia. Low serine levels are expected as it is primarily synthesized in the kidney. The direct relationship between serine and homocysteine is consistent with the reported lack of effect of serine supplements on high Hcy levels.     

Oral supplementation of branched-chain amino acids reduces early recurrence after hepatic resection in patients with hepatocellular carcinoma: a prospective study

Purposes

The long-term outcomes of branched-chain amino acids (BCAA) administration after hepatic resection in patients with hepatocellular carcinoma (HCC) remain unclear. This study assessed the effect of oral supplementation with BCAA on the development of liver tumorigenesis after hepatic resection in HCC patients.

Methods

Fifty-six patients were randomly assigned to receive either BCAA supplementation (Livact group, n = 26) or a conventional diet (Control group, n = 30). Twenty-six patients in the BCAA group were treated orally for 2 weeks before and 6 months after hepatic resection. Postoperative tumor recurrence was continuously evaluated in all patients by measuring various clinical parameters.

Results

There was no significant difference in the overall survival rate between the two patient groups; however, the recurrence rate at 30 months after surgery was significantly better in the Livact group in comparison to the Control group. Interestingly, the tumor markers, such as AFP and PIVKA-II, significantly decreased at 36 months after liver resection in the Livact group in comparison to the Control group.

Conclusions

Oral supplementation of BCAA reduces early recurrence after hepatic resection in patients with HCC. This treatment regimen offers potential benefits for clinical use in such patients, even in cases with a well-preserved preoperative liver function.     

Insomnia in diabetic hemodialysis patients. Prevalence and risk factors by a multicenter study

BACKGROUND: Insomnia is one of the most common problems in dialysis patients, and likely to contribute impairment in quality of life, which has a positive correlation with patients' survival. In diabetic patients, morbidity and mortality are substantially higher than in the nondiabetic counterparts, and also the incidence of sleep disturbances. However, there is no means to predict sleep disturbance in the dialysis patients especially in diabetics. To define the prevalence and risk factors for insomnia in diabetic patients on hemodialysis, we undertook a cross-sectional multicenter study. METHODS: Eighty-two diabetic patients (50 men/32 women, aged 58.7 +/- 9.23 years) on maintenance hemodialysis for more than 6 months from 12 different hospitals were enrolled. The demographic data, subjective symptoms, depression scale, and insomnia were assessed by questionnaires, and lean body mass, BMI, Kt/V, subjective global assessment, nursing assessment score (NAS), and biochemical parameters were examined. RESULTS: The number of patients with and without insomnia were 56 and 26, respectively, which amounted to 68.2% for insomnia. NAS (28.1 +/- 3.81 vs. 30.8 +/- 2.88, p = 0.002), serum albumin concentration (3.82 +/- 0.44 vs. 4.09 +/- 0.36 g/dl, p = 0.008), and depression scale (25.2 +/- 12.1 vs. 18.9 +/- 10.3, p = 0.025) were significantly different between them. Patients with insomnia were older (60.5 +/- 9.0 vs. 56. 1 +/- 9.60 years, p = 0.053) and felt pain (38.5 vs. 15.3%, p = 0.06) more frequently than those without insomnia. The scale of depression was correlated with NAS (r = -0.455, p < 0.001) and the serum albumin concentration was correlated with NAS (r = 0.337, p = 0.002). NAS, age, and serum albumin concentration were the major risk factors for insomnia in logistic regression analysis. CONCLUSION: The prevalence of insomnia in diabetic hemodialysis patients was 68.2%. Age, nutritional status, and depression were the major risk factors for sleep disturbance in diabetic patients.