Predialysis End-stage Renal Disease Research Articles

The Effects of Hemodialysis and Peritoneal Dialysis on the Gut Microbiota of End-Stage Renal Disease Patients, and the Relationship Between Gut Microbiota and Patient Prognoses.

Gut microbiota alterations occur in end-stage renal disease (ESRD) patients with or without dialysis. However, it remains unclear whether changes in gut microbiota of dialysis ESRD patients result from dialysis or ESRD, or both. Similarly, there is a dearth of information on the relationship between gut microbiota and ESRD prognoses. We collected fecal samples and tracked clinical outcomes from 73 ESRD patients, including 33 pre-dialysis ESRD patients, 19 peritoneal dialysis (PD) patients, and 21 hemodialysis (HD) patients. 16S rRNA sequencing and bioinformatics tools were used to analyze the gut microbiota of ESRD patients and healthy controls. Gut microbiota diversity was different before and after dialysis. Bacteroidetes were significantly deceased in HD patients. Twelve bacterial genera exhibited statistically significant differences, due to dialysis (all P < 0.05, FDR corrected). HD reversed abnormal changes in Oscillospira and SMB53 in pre-dialysis patients. Functional predictions of microbial communities showed that PD and HD altered signal transduction and metabolic pathways in ESRD patients. Furthermore, Bacteroides and Phascolarctobacterium were associated with cardiovascular mortality. Dorea, Clostridium, and SMB53 were related to peritonitis in PD patients. This study not only demonstrated differences in gut microbiota between pre-dialysis and dialysis ESRD patients, but also firstly proposed gut bacteria may exert an impact on patient prognosis.

CD28null and Regulatory T Cells Are Substantially Disrupted in Patients with End-Stage Renal Disease Due to Diabetes Mellitus.

Background: End-stage renal disease (ESRD) is associated with alterations in T-cell immunity, including increased CD28null and reduced regulatory T cells (Tregs). However, whether immune disturbances are due to ESRD or primary disease is not yet clear. As diabetes mellitus is the leading cause of ESRD, we evaluated its impact on the immune profile of ESRD patients. Methods: CD28null, Tregs, and natural killer cells were initially analyzed by flow cytometry in 30 predialysis ESRD patients due to diabetes (DM), 30 non-DM (NDM), and 25 healthy controls. Measurements were repeated after 6 months on hemodialysis (HD) or peritoneal dialysis (CAPD). Results: The percentage of CD4 + CD28null cells, CD8 + CD28null cells, and Tregs showed significant differences in DM, NDM, and controls; mean rank 33.71 vs. 25.68 vs. 18.88, p = 0.006, 37.79 vs. 28.82 vs. 17.08, p = 0.008, and 20.79 vs. 26.12 vs. 41.33, p = 0.001, respectively. DM vs. NDM had increased CD4 + CD28null and CD8 + CD28null cells, 11.5% (1.5%–24%) vs. 4.1% (0–42.3%), p = 0.02 and 61.3% (24%–76%) vs. 43% (5.7%–85%), p = 0.04, respectively. After 6 months on HD but not CAPD, DM showed a significant further increase in CD4 + CD28null cells, from 30 (14–100) to 52.7 (15–203), p = 0.02; and CD8 + CD28null cells, from 137 (56–275) to 266 (103–456), p = 0.01. Conclusions: Diabetes mellitus affects T-cell subtypes even at predialysis stage, though changes become more prominent after commencement on HD.

Estimation of population-based utility weights for health states of chronic kidney disease, dialysis and kidney transplantation.

This study aimed to determine the utility of chronic kidney disease (CKD)-related health states in the Korean general population by using the standard gamble (SG) method. Seven hypothetical CKD-related health states were developed and revised based on previous publications. Data from 242 individuals from the Korean general population were obtained via computer-assisted personal interviews and used to evaluate the CKD-related health states by using the visual analogue scale (VAS) and SG methods. Mean and median utility values were calculated for each health state. To assess the reliability of the valuation, some samples were retested and evaluated using intraclass correlation coefficients (ICC). In all health states, the utility weights from SG were higher than those from VAS. The difference in utility values between the two valuation methods ranged from 0.258 to 0.308. The utility value of CKD grade 3 was the highest and that of peritoneal dialysis (PD) was the lowest. The utility weights tended to decrease in accordance with the progression of CKD. CKD grade 3 was assigned a SG utility value of 0.878, whereas PD was assigned 0.507. The SG utility values of predialysis end-stage renal disease, haemodialysis, kidney transplantation (KT), and post-KT recovery states were 0.666, 0.547, 0.748 and 0.827, respectively. The mean ICC (SD) at the individual level was 0.746 (0.281) for the SG scores. Our results could be used to measure the burden of kidney disease or to evaluate the economic efficiency of CKD-related interventions.

Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation.

BackgroundNative arteriovenous fistula (AVF) is the most appropriate type of vascular access for chronic dialysis. Its patency rates depend on vascular wall characteristics. Ketoacid analogues of essential amino acids (KA/EAA) are prescribed in end-stage renal disease (ESRD) pre-dialysis patients to lower toxic metabolic products generation and improve nutritional status. We hypothesized that very-low protein diet (VLPD) supplemented with KA/EAA may influence arterial wall stiffness and affect AVF maturation rates and duration in pre-dialysis ESRD patients.MethodsIn a prospective, cohort, 3 years study we enrolled 67 consecutive non-diabetic early referral ESRD patients that underwent AVF creation in our hospital. Patients were divided in two groups based on their regimen 12 months prior to surgery: a VLPD supplemented with KA/EAA study group versus a low protein diet non-KA/EAA-supplemented control group. For each patient we performed serum analysis for the parameters of bone mineral disease, inflammation and nutritional status, one pulse wave velocity (PWV) measurement and one Doppler ultrasound (US) determination prior the surgery, followed by consequent Doppler US assessments at 4, 6, 8 and 12 weeks after it. Rates and duration of mature AVF achievement were noted. We used logistic regression to analyze the association between AVF maturation and KA/EAA administration, by comparing rates and durations between groups, unadjusted and adjusted for systolic blood pressure, C-reactive protein, PWV, phosphorus values. All parameters in the logistic model were transformed in binary variables. A p-value < α = 0.05 was considered significant; data were processed using SPSS 16 software and Excel.ResultsIn the study group (n = 28, aged 57 ± 12.35, 13 females) we registered better serum phosphate (p = 0.022) and C-reactive protein control (p = 0.021), lower PWV (p = 0.007) and a higher percent of AVF creation success (33.3 % versus 17.8 %, p < 0.05). AVF maturation duration was lower in study group (5.91 versus 7.15 weeks, p < 0.001).ConclusionsVLPD supplemented with KA/EAA appear to improve the native AVF primary outcome, decreasing the initial vascular stiffness, possible by preserving vascular wall quality in CKD patients through a better serum phosphate levels control and the limitation of inflammatory response.

Proactive Surveillance Approach to Guarantee a Functional Arteriovenous Fistula at First Dialysis is Worth

To evaluate the impact of a proactive surveillance program on functional access rate at the time of first dialysis. In January 2010, a proactive surveillance program to intercept failures to mature was set up at the University Hospitals Leuven. Patients receiving an arteriovenous fistula (AVF) for pre-dialysis end-stage renal disease between January 2010 and May 2013 were retrospectively analyzed. The primary end-point was a functional AVF at first dialysis. Also, AVF- associated complications and reinterventions were analyzed. Furthermore, primary, assisted primary and secondary patency rates were estimated using Kaplan-Meier survival curves. One hundred sixty-four patients were included in the study. Patients were followed until first dialysis. Median follow-up time was 287 days (interquartile range, 108-551 days). During follow-up, 40 patients (24.4%) needed one or more additional interventions, resulting in 60 reinterventions. Ten patients needed dialysis within the minimal accepted maturation period of the AVF (4 weeks). Of the 154 patients who could await the maturation period of the AVF, 145 (94.2%) appeared ready for use at the time of dialysis or at the end of the study period. In 34 of them (22%), this was thanks to one or more interventions during follow-up. A dedicated surveillance program of patients with AVFs in the pre-dialysis stadium detects failure to mature. Close coaching and proactive intervention can aid the patient in his own "fistula first" project.

Improvement of gastric motility by hemodialysis in patients with chronic renal failure

Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). We have previously demonstrated that patients with predialysis end-stage renal disease showed a high prevalence of GI symptoms and gastric hypomotility, and that gastric hypomotility appears to be an important factor in generating GI symptoms. However, it is not clear whether impaired gastric motor function would improve after hemodialytic treatment. To examine the relationship between gastric motor function and GI symptoms in CRF patients on hemodialysis. The study was performed in 19 patients with CRF treated with hemodialysis for more than six months and in 12 matched healthy controls. GI symptom severity was quantified in all patients. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi-solid meals using the (13)C-acetic acid breath test. Six patients had no symptoms, and 11 had slight GI symptoms with a total symptom score of less than 5. Compared with controls, CRF patients revealed no differences in gastric motility parameters, with the exception of a lower percentage of normogastria in EGG at fasting state. Eleven patients had normal gastric motor function (Group A), and eight showed abnormalities of either gastric myoelectrical activity or gastric emptying (Group B). There was no difference in symptom score between Group A and Group B. More than half of the patients with CRF on hemodialysis demonstrated normal gastric motility, and no or slight GI symptoms. Hemodialytic treatment may improve impaired gastric motility and reduce GI symptoms in patients with CRF.

The Relationship between Kt/VUrea and Npna in Anuric Peritoneal Dialysis Patients: A Comparison with Predialysis Patients

It is unknown whether a given level of urea clearance by the native kidneys provides better or similar control of uremia than the same level of urea clearance by continuous peritoneal dialysis (PD). More insight into possible differences between renal and peritoneal urea clearances is warranted. Therefore, we investigated the relationship between Kt/V(urea) and protein equivalent of total nitrogen appearance normalized to body weight (nPNA), the relationship between urea clearance and creatinine appearance, and other nutritional parameters in PD patients without residual renal function, and in predialysis end-stage renal disease patients. All patients participated in the Netherlands Cooperative Study on the Adequacy of Dialysis. This is a prospective cohort study of incident dialysis patients, in whom regular assessments of renal function are done. A group of 75 PD patients was identified at the first follow-up assessment in which their urine production was less than 100 mL/day. These patients were considered the anuric group. This group was compared with a control group of 97 predialysis patients studied 0-4 weeks before the start of dialysis treatment. Linear relationships were present between Kt/V(urea) and nPNA, in both the predialysis patients and the anuric PD patients. A significant difference was present between the slopes of the two regression lines (0.40 vs 0.18, p = 0.007). When Kt/V(urea) exceeded 1.3/week, a given level of Kt/V(urea) was associated with a higher nPNA in predialysis than in anuric PD patients. Similar relationships were found between Kt(urea) and PNA. Kt(urea) was also significantly related to urine or dialysate creatinine appearance. A significant difference existed between the slopes of the regression lines in the two groups of patients (p < 0.001). A weekly Kt(urea) of 70 L was associated with a urine creatinine appearance of 11.0 mmol/day and a dialysate creatinine appearance of 8.4 mmol/day. Nutritional status measured with creatinine appearance and Subjective Global Assessment was better in the predialysis population, despite much lower values for Kt/V(urea) in these patients. The relationship between Kt/V(urea) and nPNA in anuric PD patients is different from that in a predialysis population. It follows from our results that, when Kt/V(urea) is above 1.3/week, a given level of Kt/V(urea) is associated with a higher nPNA in predialysis than in anuric PD patients. This challenges the concept of equivalency between renal and peritoneal Kt/V(urea) with respect to control of uremic morbidity.

Quality of Life in Predialysis End-Stage Renal Disease Patients at the Initiation of Dialysis Therapy

To assess health-related quality of life (QL) in a group of Dutch predialysis end-stage renal disease (ESRD) patients prior to the initiation of dialysis, and to compare QL between patients with different intended initial dialysis treatments. In a prospective cohort study, demographic, clinical, and QL data were obtained from Dutch adult patients who were consecutively enrolled from 27 different centers 0 - 4 weeks prior to the beginning of their chronic dialysis treatment. Of the 301 patients who completed the QL questionnaires (of a possible 337 enrolled patients), 152 intended to start with hemodialysis (pre-HD) and 149 patients with peritoneal dialysis (pre-PD). Perceived QL of pre-HD and pre-PD patients. Quality of life was assessed with two generic health assessment instruments: the SF-36 and the EuroQol. After correction for group differences, pre-HD patients scored consistently, but not significantly, lower for all separate dimensions of the SF-36 and the overall health score of the EuroQol compared to pre-PD patients. However, analyzing the dimensions of the SF-36 together, adjusted for case-mix, pre-HD patients scored significantly lower than pre-PD patients. Mean difference was 6.5 points (p = 0.04). Multivariate adjustment for known case-mix differences at the start of dialysis therapy was not sufficient to adjust for all patient selection effects on QL. Consequently, published QL comparisons between HD and PD in nonrandomized cohort studies should be interpreted with caution. Assessment of QL just before start of dialysis therapy and subsequent adjustment for baseline values may be the only valid alternative for randomized studies.

Pharmacokinetic study of recombinant human erythropoietin treatment in pre-dialysis end stage renal disease patients.

We treated pre-dialysis ESRD patients with recombinant human erythropoietin (rHuEPO) by either the subcutaneous (s.c.) or intravenous (i.v.) route, and investigated the pharmacokinetics of rHuEPO. Twenty patients were divided equally into two groups by the difference in route, and rHuEPO was administered once per week for 8 weeks. The dose was 3,000 and 6,000 IU in the s.c. group and 3,000, 6,000 and 9,000 IU in the i.v. group. Although anemia was corrected significantly in both groups, residual renal function was not affected significantly. Pharmacokinetic study revealed that none of the parameters changed between the initial and final treatments in any of the groups. Area under the curve (AUC) and maximum concentration (Cmax) was consistently smaller in the s.c. --than in the i.v.--treated group. Mean residence time (MRT) was 3 times longer in the s.c. group than in the i.v. group. Bioavailability of rHuEPO in the s.c. group was around 35%, and mean absorption time (MAT) was around 25 hours. Though the s.c. route has been reported to be more effective for correcting anemia with rHuEPO than the i.v. route when rHuEPO was administered either twice or three times per week, our study demonstrated that the effect of rHuEPO was almost equal between the s.c.-treated and i.v.-treated groups when rHuEPO was administered once per week. We assume that this equivalent degree of efficacy in the s.c. group in spite of low values of AUC and Cmax might be derived by the longer MRT. Thus, we consider that MRT is an important factor and the efficacy of rHuEPO should be investigated with evaluation of MRT when the administration route is different.

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. Three year retrospective study. Subregional nephrology service serving a mixed urban and rural population of 800,000. 60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.