Changes In Residual Renal Function Research Articles

#2752 Decline of residual renal function in peritoneal patients: in search of the lost kidney?

Abstract Background and Aims The latest (2020) recommendations of the International Society of Peritoneal Dialysis have proposed a new paradigm of adequacy. In this context, preserving residual renal function (RRF) is considered one of the most important therapeutic targets to reduce cardiovascular risk and mortality. Incremental peritoneal dialysis can contribute to preserving RRF. The goal of this study is to evaluate factors which are associated with a decline in RRF in APD patients. Method We conducted a retrospective study of incidental peritoneal dialysis patients between 2020 and 2022. We started considering 62 patients who underwent APD. 23 were excluded due to lack of data, follow-up of less than 1 year, need for haemodialysis sessions before or during follow-up, interfering surgery (bariatric surgery and nephrectomy) and treatment using the CAPD technique. We analyzed data from 39 APD patients (see Table 1) and classified them into two groups based on their RRF decline using the cut-off of 1 ml/min/year (calculated as the mean of urea and creatinine clearance). They were distinguished into slow progressors and fast progressors and we identified any differences in clinical and dialysis parameters at baseline and 12-month follow-up. We calculated dialytic, renal and total Kt/V in both groups and looked for possible predictors of faster RRF loss. For statistical analysis, we used ANOVA for continuous variables, Kruskal-Wallis for non-continuous variables and Fisher for qualitative variables. Finally, predictive data were extracted using logistic regression. Results We found 22 slow progressors and 17 fast progressors. A significant difference was found in the prevalence of cardiovascular disease (18.2% vs 47.1%, p 0.028), residual renal function (5.71 ml/min vs 6.85 ml/min, p 0,03) and dialysing solution volumes (13.2 L vs 14.1 L, p 0.05) between the two groups, with higher values in the fast progressors. In this group, more male patients were also observed (p 0.11), treated with 2 or more antihypertensive drugs (p 0.30) and exposed to higher weekly dialysate glucose (p 0.23) and daily ultrafiltration rates (p 0.23). At the 12-month follow-up, the mean decline in renal function was -1, 56 ml/min in the entire sample, -3.03 ml/min in the fast progressors group and -0.43 ml/min in the slow progressors group; the change in daily Uf inversely correlated with the change in RRF (p 0.025; r -0.35, Fig. 1). There was a mean reduction in ultrafiltrate volume (-22.7 ml vs +123.5 ml, p 0.028) and in the amount of glucose in the dialysing solutions (-138.6 g vs +100.5 g, p 0.007) compared to baseline values in patients who preserved RRF. In contrast, the difference between the two groups in the number of patients who started PD with<5 sessions per week is borderline (p 0.099). Weekly dialysis Kt/V is higher in fast-progressor patients (1 vs 0.88; p 0.205) with a total weekly Kt/V in both cases above the recommended target of 1.7. On multivariate regression analysis, baseline renal function and the presence of heart disease correlate with a more rapid decline in RRF (p 0.047; p 0.021 respectively). Conclusion With the limitations of low sample size and short follow-up time, we observed that ultrafiltration and peritoneal exposure to dialysate glucose may play a role in RRF loss, but more research is needed to confirm this. We found that patients with heart disease and higher baseline RRF were more likely to experience a faster decline in RRF. Overall findings suggest that maintaining RRF is crucial in APD patients, and incremental dialysis can help preserve it. We recommend further studies with longer follow-up times to better understand the relationship between RRF and APD.

#437 A multicenter, single-arm study of roxadustat in Chinese patients with chronic kidney disease-associated anemia receiving peritoneal dialysis

Abstract Background and Aims Anemia increases morbidity and mortality in patients with chronic kidney disease (CKD). Phase 3 studies have demonstrated the efficacy of roxadustat for anemia treatment in patients with CKD undergoing dialysis; however, data from Chinese patients undergoing peritoneal dialysis (PD) are limited. We evaluated the efficacy and safety of roxadustat in Chinese patients with CKD-anemia undergoing PD. Method In this phase 4, single-arm, multicenter study, we planned to enroll at least 150 Chinese patients with CKD-anemia undergoing PD (either erythropoiesis-stimulating agent [ESA]-treated or ESA-naïve at enrollment), including at least 50 patients with type 2 diabetes mellitus (T2DM) and 50 patients without diabetes mellitus (DM). Study visits occurred every 2 weeks until Week 8 and then every 4 weeks. All patients received oral roxadustat treatment three times per week for 24 weeks according to the approved product package insert. The primary efficacy endpoint was the proportion of patients with a mean hemoglobin (Hb) ≥100 g/L at Weeks 20–24. The secondary efficacy endpoints were subgroup analyses (T2DM vs. non-DM). The exploratory endpoints were the dose required to maintain Hb at ≥100 g/L over Weeks 20–24, the proportion of time when Hb was 100–130 g/L, changes in residual renal function (RRF), urea clearance index (Kt/V), and creatinine clearance (Ccr), amongst others. For the safety analyses, adverse events (AEs) were assessed during treatment and at 4 weeks after completion. Results Overall, 195 patients (116 male [59.5%]) with a mean (standard deviation [SD]) age of 46.3 (12.3) years were enrolled from 22 centers, and 172 (88.2%) completed the study (main reasons for discontinuation: withdrawal, 7 [3.6%]; AE, 5 [2.6%]; switched from PD to hemodialysis, 5 [2.6%]). Overall, 189 patients (96.9%) were ESA-treated and 43 (22.1%) had T2DM. The median (interquartile range) dialysis duration was 16.1 (5.2–43.2) months. The mean (SD) baseline Hb was 98.1 (10.7) g/L, and the ferritin level and transferrin saturation were 320.9 (287.5) μg/L and 35.5% (17.0%), respectively. The mean (SD) treatment duration was 154.3 (35.6) days, and the mean (SD) weekly dose was 244.9 (88.7) mg. The intention-to-treat (ITT) set and safety analysis set (SAF) included all 195 patients. In the ITT set, 85.1% (95% confidence interval [CI] 79.8%–90.5%) of patients had Hb ≥100 g/L over Weeks 20–24. According to the subgroup analysis, 89.2% (95% CI 78.5%–99.9%) of T2DM patients and 84.0% (95% CI 77.8%–90.1%) of non-DM patients had Hb ≥100 g/L over Weeks 20–24 (Fig. 1). The mean (SD) weekly dose required to maintain Hb at ≥100 g/L at Weeks 20–24 was 215.9 (100.0) mg, and the proportion of time that Hb was 100–130 g/L was 76.4% (23.2%). There was a slight decrease in RRF and Ccr. Table 1 shows the RRF, Kt/V, and Ccr results. Of the 195 SAF patients, 158 (81.0%) had ≥1 treatment-emergent AE (TEAE), 20 (10.3%) had drug-related TEAEs, 40 (20.5%) had treatment-emergent serious AEs, and 1 (0.5%) had a TEAE that led to death. The top three TEAEs were upper respiratory tract infection (25 [12.8%]), hypokalemia (17 [8.7%]), and hypoalbuminemia (15 [7.7%]). Conclusion Treatment with roxadustat for 24 weeks effectively corrected anemia in Chinese CKD patients undergoing PD and maintained Hb at ≥100 g/L in the majority of patients, irrespective of baseline T2DM. The AEs were consistent with the characteristics of patients with CKD undergoing PD and with the known safety profile of roxadustat.

High-Salt Diet Accelerated the Decline of Residual Renal Function in Patients With Peritoneal Dialysis

Objective: This study aims to investigate the relationship between dietary salt intake and residual renal function in peritoneal dialysis (PD) patients.Methods: The daily salt intake of the patients was calculated based on a 3 day dietary record. Sixty-two patients were divided into three groups: 33 patients in the low salt intake group (salt intake <6.0 g/day), 17 in the medium salt intake group (salt intake 6.0 to <8.0 g/day), and 12 in the high salt intake group (salt intake ≥8.0 g/day). Regular follow-up was conducted every 3 months. Urine volume, peritoneal ultrafiltration volume, and other clinical indicators were recorded. Biochemical indexes were detected to evaluate the changes in residual renal function and peritoneal function during follow-up.Results: A positive correlation between dietary sodium intake and sodium excretion was found. During 12-month follow-up, a decrease of residual renal function showed a significant difference among the three groups (p = 0.041) (15.3 ± 27.5 vs. 12.5 ± 11.5 vs. 32.9 ± 18.4 L/W/1.73 m2 in the low-, medium-, and high salt intake groups, respectively). Consistently, a higher decline of residual renal function (adjusted β, 20.37; 95% CI, 2.83, 37.91) was found in participants with high salt intake (salt intake ≥8 g/day) compared with those in non-high salt intake.Conclusion: Our study showed that the sodium excretion by peritoneal dialysis was positively correlated with dietary sodium intake in PD patients. The high salt intake diet (salt intake ≥8 g/day) may lead to a faster decline of residual renal function in PD patients.

Relationship between trajectory of sleep quality and short-term changes in residual renal function in stage 3-5 chronic kidney disease patients.

Chronic kidney disease (CKD) is commonly associated with sleep disturbance. However, the relationship between the trajectory of sleep quality and short-term residual renal function is not clear. Thus, this study aimed to investigate such relationship. In total, 132 patients with CKD stage 3-5 were prospectively enrolled. All participants were followed-up for 6months. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to assess sleep quality. The longitudinal PSQI and estimated glomerular filtration rate (eGFR) were measured at baseline, the 3rd month and 6th month. The participants were stratified into three groups according to the PSQI trajectories. The primary outcome was set as the eGFR change among 6months less than the median. Sixty nine participants showed PSQI ≤ 5 at baseline and 15 patients had increased scores > 5 at 3rd month among them. 63 participants showed PSQI > 5 at baseline and 11 patients had decreased scores ≤ 5 at 3rd month. Only in patients whose baseline PSQI ≤ 5 but increased to > 5 at 3rd month presented a longitudinal decline in eGFR at both 3rd month and 6th month compared with baseline eGFR. Linear regression analysis for eGFR change showed no significant association between eGFR change and PSQI score. Logistic regression revealed worsen sleep quality will deteriorate renal function. A relationship was observed between worsening sleep quality and eGFR decline in non-dialysis CKD patients.

Associations between echocardiographic findings and prospective changes in residual renal function in patients new to peritoneal dialysis

Although echocardiograms are often performed when peritoneal dialysis is started, associations between commonly reported findings and prospective changes in renal function remain understudied. Ninety-nine of 101 patients in the Trio Trial had transthoracic echocardiograms within 6 months of dialysis initiation, and measurements of residual renal function every six weeks for up to two years. Generalized mixed modelling linear regression in STATA was used to examine associations between left atrial size, left ventricular hypertrophy, left ventricular ejection fraction, right ventricular systolic pressure, and left valvular calcification with subsequent slopes in renal function. After echocardiography (performed a median of 16 days following peritoneal dialysis initiation) right ventricular systolic pressure was associated with faster, while declining left ventricular ejection fraction and valvular calcification were associated with slower declines in residual renal function. Future studies could be conducted to confirm these findings, and identify pathophysiological mechanisms.

A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients

Mineralocorticoid receptor antagonists have beneficial effects on left ventricular remodeling, cardiac fibrosis, and arrhythmia in heart failure, but efficacy and safety in dialysis patients is less clear. We evaluated the effect of spironolactone on left ventricular mass (LVM), an independent predictor of all-cause and cardiovascular mortality, in hemodialysis patients. In this placebo-controlled, parallel-group trial, 97 hemodialysis patients (23% female; mean age 60.3 years) were randomized to spironolactone 50 mg once daily (n=50) or placebo (n=47). The primary efficacy endpoint was change in LVM index (LVMi) from baseline to 40 weeks as determined by cardiac magnetic resonance imaging. Safety endpoints were development of hyperkalemia and change in residual renal function. There was no significant change in LVMi in participants randomized to spironolactone compared to placebo (-2.86±11.87 vs. 0.41±10.84 g/m2). There was also no difference in the secondary outcomes of mean 24-hour systolic or diastolic ambulatory blood pressure, left ventricular ejection fraction, 6-minute walk test distance, or New York Heart Association functional class. Moderate hyperkalemia (pre-dialysis potassium levels of 6.0-6.5 mmol/L) was more frequent with spironolactone treatment (155 vs. 80 events), but severe hyperkalemia (≥6.5 mmol/L) was not (14 vs. 24 events). Changes in residual urine volume and measured glomerular filtration rate did not differ between groups. There were no deaths in the spironolactone group and 4 deaths in the placebo group. Thus, treatment with 50 mg spironolactone did not change left ventricular mass index, cardiac function, or blood pressure in hemodialysis patients. Spironolactone increased the frequency of moderate hyperkalemia, but did not increase severe hyperkalemia.

Current Practice and Outcomes of Peritoneal Dialysis in the Nippon Medical School Musashi Kosugi Hospital.

Various innovations for preventing complications and improving a patient's quality of life have been implemented for peritoneal dialysis (PD), which was established in Japan approximately 35 years ago and introduced at our hospital in 1999. Herein, we investigate the outcomes of patients undergoing PD to identify approaches for improving their long-term prognosis. This retrospective study included 114 patients who underwent PD between September 1999 and August 2017 and included various parameters such as patient survival rate, technical survival rate, cause (s) of PD withdrawal, incidence of peritonitis, dialysis duration, and change in residual renal function (RRF). Furthermore, factors associated with PD withdrawal and duration, as well as risk factors for peritonitis, were examined. Mean (± standard deviation) PD duration was 35.62 (±29.88) months in all patients and 37.16 (±34.09) months in 58 patients who withdrew from treatment. Five-year continuance and survival rates were 40.41% and 55.74%, respectively (p=0.0061). However, in patients aged ≥65 years, the continuance and survival rates were not significantly different (p=0.1250). Furthermore, the continuance and survival rates in diabetic patients were not significantly different from those of non-diabetic patients (p=0.1334 and 0.7140, respectively). Comparison of changes in RRF in young and elderly patients revealed that it was not significantly sustained in elderly patients (p=0.0259). The Cox proportional hazards model revealed that age (p=0.0455) and total cholesterol levels (p=0.0494) were independent risk factors for PD withdrawal, and multiple regression analysis showed that the presence of peritonitis (p=0.0063) and low-density lipoprotein cholesterol (LDL-C) levels (p=0.0087) were significant factors for PD duration. Peritonitis incidence was 0.077 times per patient per year, and multivariate analysis identified PD duration (p=0.0009) and LDL-C levels (p=0.0054) as independent risk factors for peritonitis. The findings of this study revealed that assessment of the nutritional status of the patient and prevention of peritonitis are important for continuation of PD. PD is a safe treatment option that can maintain the quality of life in elderly patients. In a rapidly aging society, the need for PD-based medical care is expected to increase.

Measuring residual renal function in dialysis patients: can we dispense with 24-hour urine collections?

Residual renal function is associated with improved survival and quality of life for dialysis patients. Whereas residual renal function is monitored in peritoneal dialysis patients, many hemodialysis centers simply concentrate on achieving dialyzer urea clearance targets. Accurately quantifying residual renal function from urine collections is arduous. Thus, there is a clinical need to develop alternative methods of assessing residual renal function based on serum testing, especially for patients receiving less than thrice weekly dialysis.

Utility of Urinary Biomarkers in Predicting Loss of Residual Renal Function: The BAL Anz Trial

The ability of urinary biomarkers to predict residual renal function (RRF) decline in peritoneal dialysis (PD) patients has not been defined. The present study aimed to explore the utility of established biomarkers from kidney injury models for predicting loss of RRF in incident PD patients, and to evaluate the impact on RRF of using neutral-pH PD solution low in glucose degradation products. The study included 50 randomly selected participants from the balANZ trial who had completed 24 months of follow-up. A change in glomerular filtration rate (GFR) was used as the primary clinical outcome measure. In a mixed-effects general linear model, baseline measurements of 18 novel urinary biomarkers and albumin were used to predict GFR change. The model was further used to evaluate the impact of biocompatible PD solution on RRF, adjusted for each biomarker. Baseline albuminuria was not a useful predictor of change in RRF in PD patients (p = 0.84). Only clusterin was a significant predictor of GFR decline in the whole population (p = 0.04, adjusted for baseline GFR and albuminuria). However, the relationship was no longer apparent when albuminuria was removed from the model (p = 0.31). When the effect of the administered PD solutions was examined using a model adjusted for PD solution type, baseline albuminuria, and GFR, higher baseline urinary concentrations of trefoil factor 3 (TFF3, p = 0.02), kidney injury molecule 1 (KIM-1, p = 0.04), and interferon γ-induced protein 10 (IP-10, p = 0.03) were associated with more rapid decline of RRF in patients receiving conventional PD solution compared with biocompatible PD solution. Higher urinary levels of kidney injury biomarkers (TFF3, KIM-1, IP-10) at baseline predicted significantly slower RRF decline in patients receiving biocompatible PD solutions. Findings from the present investigation should help to guide future studies to validate the utility of urinary biomarkers as tools to predict RRF decline in PD patients.

Is hypoalbuminemia a prognostic risk factor for contrast-induced nephropathy in peritoneal dialysis patients?

ObjectiveResidual renal function (RRF) is an important predictor of outcome in peritoneal dialysis (PD) patients. Hypoalbuminemia was found to be an independent risk factor for the development of acute kidney injury. We investigated the possibility of an association between serum albumin levels and the development of iodine contrast media-induced nephropathy (CIN) in PD patients.MethodsA total of 103 PD patients who underwent invasive angiographies with exposure to iodine contrast media (ICM) were reviewed retrospectively. All patients received 0.9% saline intravenously at a rate of 75 mL per hour for 12 hours prior, during, and 12 hours after exposure to ICM. Acetylcysteine was given orally at a dose of 600 mg twice daily, on the day before and on the day of exposure to ICM. The nonionic, low-osmolar contrast agent iopromide was used at a mean dose of 75.0±15.2 mL. The changes in RRF from baseline to 1 week and 4 weeks after exposure to ICM were recorded. Outcomes of patients with serum albumin levels <3.8 g/dL and those with serum albumin levels ≥3.8 g/dL were compared. A reduction >30% in RRF at 7 days after exposure to ICM was considered CIN.ResultsCIN developed in 27.2% (28/103) of patients. Of the 103 patients, 59.2% (61) had serum albumin levels <3.8 g/dL. Of those, 37.7% (23/61) developed CIN, compared with 11.9% (5/42) of those with serum albumin levels ≥3.8 g/dL (P=0.004). After adjustment for all tested variables in a logistic regression with a stepwise selection model, serum albumin level at exposure to ICM was found to be the most powerful predictor of the development of CIN (odds ratio =4.5; confidence interval =1.5–13.0; P=0.006).ConclusionPD patients with serum albumin levels <3.8 g/dL should be monitored carefully when exposed to ICM. Serum albumin level may be considered a potential therapeutic target in the prevention of CIN and preservation of RRF in PD patients.

Extracellular volume expansion, measured by multifrequency bioimpedance, does not help preserve residual renal function in peritoneal dialysis patients

Residual renal function is a major survival determinant for peritoneal dialysis patients. Hypovolemia can cause acute kidney injury and loss of residual renal function, and it has been suggested that patients receiving peritoneal dialysis should preferably be maintained hypervolemic to preserve residual renal function. Here we determined whether hydration status predicted long-term changes in residual renal function. Changes in residual renal function and extracellular water (ECW) to total body water (TBW) measured by multifrequency bioimpedance in 237 adult patients who had paired baseline and serial 12 monthly measurements were examined. Baseline hydration status (ECW/TBW) was not significantly associated with preservation of residual renal function, unlike baseline and follow-up mean arterial blood pressure. When the cohort was split into tertiles according to baseline hydration status, there was no significant correlation seen between change in hydration status and subsequent loss in residual renal function. Increased ECW/TBW in peritoneal dialysis patients was not associated with preservation of residual renal function. Similarly, increments and decrements in ECW/TBW were not associated with preservation or reduction in residual renal function. Thus, our study does not support the view that overhydration preserves residual renal function and such a policy risks the consequences of persistent hypervolemia.

Lean Body Mass Predicts Long-Term Survival in Chinese Patients on Peritoneal Dialysis

BackgroundReduced lean body mass (LBM) is one of the main indicators in malnutrition inflammation syndrome among patients on dialysis. However, the influence of LBM on peritoneal dialysis (PD) patients’ outcomes and the factors related to increasing LBM are seldom reported.MethodsWe enrolled 103 incident PD patients between 2002 and 2003, and followed them until December 2011. Clinical characteristics, PD-associated parameters, residual renal function, and serum chemistry profiles of each patient were collected at 1 month and 1 year after initiating PD. LBM was estimated using creatinine index corrected with body weight. Multiple linear regression analysis, Kaplan–Meier survival analysis, and Cox regression proportional hazard analysis were used to define independent variables and compare survival between groups.ResultsUsing the median LBM value (70% for men and 64% for women), patients were divided into group 1 (n = 52; low LBM) and group 2 (n = 51; high LBM). Group 1 patients had higher rates of peritonitis (1.6 vs. 1.1/100 patient months; p<0.05) and hospitalization (14.6 vs. 9.7/100 patient months; p<0.05). Group 1 patients also had shorter overall survival and technique survival (p<0.01). Each percentage point increase in LBM reduced the hazard ratio for mortality by 8% after adjustment for diabetes, age, sex, and body mass index (BMI). Changes in residual renal function and protein catabolic rate were independently associated with changes in LBM in the first year of PD.ConclusionsLBM serves as a good parameter in addition to BMI to predict the survival of patients on PD. Preserving residual renal function and increasing protein intake can increase LBM.

A Combination of Biocompatible Peritoneal Dialysis Solutions and Residual Renal Function, Peritoneal Transport, and Inflammation Markers: A Randomized Clinical Trial

The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. Prospective, randomized, controlled, open-label study. Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. RRF, daily urine volume, serum and dialysate cytokine levels. RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. Unblinded, relatively short follow-up; no formal sample-size calculations. Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Blood volume-monitored regulation of ultrafiltration in fluid-overloaded hemodialysis patients: study protocol for a randomized controlled trial.

BackgroundData generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients.Methods/designBCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters).DiscussionPatients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients.Trial registrationClinicalTrials.gov, NCT01416753

Left Atrial Enlargement Is Associated with a Rapid Decline in Residual Renal Function in ESRD Patients on Peritoneal Dialysis

Left atrial (LA) volume index (LAVI) has been considered a stable indicator of diastolic dysfunction and an independent predictor of mortality in patients with end-stage renal disease. To date, however, little is known about the relationship between LA enlargement and the changes in residual renal function (RRF). This study was undertaken to investigate the association between LA enlargement and the decline in RRF in 121 incident peritoneal dialysis patients. Within 2 months after the initiation of peritoneal dialysis, LA enlargement was determined by echocardiography and RRF by 24-hour urine collection. Subsequently, RRF was measured every 6 months. The rates of decline in RRF were significantly greater in patients with LA enlargement (LAVI > 32mL/m(2)) compared with those without LA enlargement (-0.17 ± 0.18 vs -0.07 ± 0.16 mL/min/month/1.73 m(2), P=.002). In a linear mixed model, there was a significant difference in the rates of RRF decline over time between patients with and without LA enlargement (P < .001). Pearson's correlation analysis revealed that there were significant inverse correlations between the rates of the decline in RRF and LAVI (r= -0.22, P= .018). In multiple linear regression analysis adjusted for other risk factors, LAVI was found to be an independent determinant of the rates of decline in RRF (β= -0.026, P= .018). This study shows that a higher LAVI is independently associated with a more rapid decline in RRF in patients with end-stage renal disease on peritoneal dialysis.

Loss of Residual Renal Function was Not Associated with Glycemic Control in Patients on Peritoneal Dialysis

Better glycemic control has been reported to slow the progression of nephropathy in predialysis diabetic patients. However, the relationship between glycemic control and residual renal function (RRF) in patients on peritoneal dialysis (PD) is uncertain. 89 incident diabetic patients on PD were recruited from 5 centers. We measured glomerular filtration rate (GFR) and hemoglobin A1c (HbA1c) within 2 months (baseline) after the start of PD and at 6 and 12 months. GFR was calculated as the average of renal creatinine and urea clearances. We analyzed whether mean HbA1c was associated with change in GFR (ΔGFR) over 1 year. During the first year of PD, ΔGFR was -1.7 ± 3.4 mL/min/1.73 m² and was not affected by mean HbA1c. Acute hemodialysis before starting PD and mean arterial diastolic pressure were related to the decline of GFR in a multivariate analysis. Glycemic control was not associated with change in RRF in diabetic patients during the first year after starting PD.

Changes in the human peritoneal mesothelial cells during aging

The number of older patients admitted to peritoneal dialysis (PD) programmes is growing. At the same time, there is increasing data about the role of mesothelial cells in determining the functional alteration of the peritoneum during PD. However, little is known about the functional changes accompanying the ageing process in mesothelial cells. We aimed to evaluate whether the aging process is accompanied by changes in some functional characteristic of the human peritoneal mesothelial cells (HPMC), which could account for the poor prognosis observed in old patients with PD. HPMCs were isolated from patients undergoing a nonurgent, nonseptic abdominal surgical procedure, without renal, vascular or inflammatory disease. Cytokine levels (by enzyme-linked immunosorbent assay (ELISA)), nitrates+nitrites, and cyclooxygenase (COX) activity (by a chemiluminescence assay), cytokines, COX, nitric oxide synthase (NOS), and nuclear factor (NF)-kappaB1, two messenger ribonucleic acid (mRNA) gene expressions (by reverse transcriptase (RT)-Multiplex PCR), COX, and NOS promoter gene activities, and NF-kappaB-dependent transcription (by transient transfection assays) were determined. Our data show a significant increase in cytokines, COX, and NOS activities, and mRNA expression of cytokines, COX-2, inducible nitric oxide synthase (iNOS) and precursors of NF-kappaB in HPMCs from old people. This was also the case for COX-2 and iNOS promoter gene activities and NF-kappaB-dependent transcription. There was a positive correlation between the age of the donor's cell and the proinflammatory profile of the HPMCs. Such age-dependent increase (around two-three times) is partially abolished by different antioxidant or free-radical scavengers. Thus, aging is accompanied by the presence of an inflammatory state in HPMCs, which involves the participation of different reactive oxygen species.

Long-term use of 1.1% amino acid dialysis solution in hypoalbuminemic continuous ambulatory peritoneal dialysis patients.

Malnutrition is a common problem in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Hypoalbuminemia in CAPD patients is an independent risk factor for death and is associated with malnutrition. Previous short-term studies have examined the use of amino acid based PD solutions in terms of albumin levels and anthropometric changes, but not clinical outcome. We report on the extended use of 1.1% amino acid based peritoneal dialysis solution (Nutrineal) and have assessed clinical utility in terms of nutrition, biochemical indices, dialysis adequacy and clinical outcomes. The effect of Nutrineal was studied retrospectively in 22 patients during the past 30 months. All patients had an albumin level of < 35 g/l prior to commencing Nutrineal, and had either a protein intake < 1.2 g/kg or weight loss of > 5% in the previous 3 months. 19 of the 22 patients underwent an 8-week trial of oral nutritional supplements with no improvement in serum albumin level. Albumin level, normalized protein catabolic rate, weight, Kt/V and creatinine clearance were assessed for all patients prior to Nutrineal and at the end of the study period. The mean time on Nutrineal therapy was 13.6 months (range 6-26 months). There were no reported side effects of the treatment. There was an average of 1 episode of peritonitis per 23 treatment months, and only 1 patient died (4% annually adjusted mortality cf 8.9% on the peritoneal dialysis program as a whole). There was a significant increase in albumin level from 22.45 +/- 0.97 range 14-33 g/l to 25.68 +/- 1.159 range 16-35 g/l (p = 0.0036). Normalized protein catabolic rate increased significantly, from 0.898 +/- 0.053 to 1.085 +/- 0.056 g/kg/day (p = 0.0057). Weight decreased slightly although this did not reach statistical significance. Kt/V and creatinine clearance both decreased significantly, but remained within the adequate range in > 80% of the patients. There was no significant change in residual renal function (mean residual creatinine clearance 3.8 +/- 0.59 ml/min at the start of the study period, cf 3.4 +/- 0.61 ml/min at the end). These data suggest that Nutrineal can be used safely and effectively for an extended period of time. Such use is associated with a low mortality rate and a low peritonitis rate, although dialysis adequacy is compromised to a degree.

Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis.

Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients' first year on PD and declining RRF may be linked with inflammation. A total of 76 PD patients (40 males, mean age 56.8+/-14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4-h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups. Initially, group I had a lower proportion of high transporters and more often high serum C-reactive protein (sCRP, > or =10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF < or =1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=-0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF. Our preliminary short-term study suggests that changes in peritoneal transport rate during patients' first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.

Impact of Residual Renal Function on Dialysis Adequacy in Paediatric CAPD Patients

This study was designed to determine the impact of residual renal function (RRF) on dialysis adequacy indices and clinical outcome parameters in paediatric CAPD patients. Seventeen children on CAPD were included. Residual renal function was described by residual diuresis (UO: urine output), residual renal solute clearances [RR.KT/V (residual renal KT/V), RR.Ccr (residual renal creatinine clearance) and GFR (glomerular filtration rate)]. Pearson's correlation coefficients and multiple linear regression analysis were used in statistical analysis. Mean W.KT/V (weekly KT/V) vas 1.97±0.6 and mean T.Ccr (total Ccr) was 56±32 L/week/1.73 m2. Both of these indices were found to be strongly correlated with RRF (GFR, UO, RR.KT/V and RR.Ccr) (p<0.001), but not with peritoneal solute clearances. W.KT/V was found to be influenced essentially by RR.KT/V (p<0.001) and also dialysate fill volume (DV) (p<0.01). T.Ccr was influenced primarily by RR.Ccr (p<0.001) and serum cr levels (p<0.05). In addition significant positive correlations were detected between serum albumin, haemoglobin (Hb), haematocrit (Htc) levels and residual diuresis (p<0.05) and a significant negative correlation was found between mean blood pressure and residual diuresis (p<0.05). It was concluded that the mean values of W.KT/V and T.Ccr were heavily influenced by RRF. Almost all variations in W.KT/V and T.Ccr represented changes in RRF. In addition, anaemia, hypertension and hypoalbuminaemia, which are known as clinical criteria of inadequate dialysis, were found to be influenced by residual diuresis. Thus one of the goals of paediatric nephrologists must be the preservation of renal reserve. Since the rate of decline in RRF was significantly lower in CAPD, it should be the first choice of long-term maintenance dialytic therapy for children who have residual renal reserve.