Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility.

INTRODUCTION: Preservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality. METHODS: We conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined. RESULTS: One hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (-28.0 ml/min per year; 95% CI: -60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (-291 ml/min per year; 95% CI: -550 to -32) while this was absent in biocompatible treatment. CONCLUSION: Despite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.

Long-term peritoneal dialysis treatment provokes activation of genes related to adaptive immunity.

Permanent irritation of the peritoneum during peritoneal dialysis (PD) treatment leads to local chronic inflammation and subsequently activation of processes driving fibrogenesis in the long-term. The aim of the study was to compare the peritoneal effluent transcriptome of 20 patients treated less and 13 patients treated more than 2 years using microarray analysis. An increased expression of genes associated with an immune response was observed in long-term treated patients with well preserved peritoneal function, when compared to patients treated less than 2 years. From 100 genes highly expressed in long-term patients, a significant up-regulation of six was found by RT-qPCR: LY9 (lymphocyte antigen 9), TNSFR4 (tumor necrosis factor receptor superfamily, member 4), CD 79A (CD79a molecule), CCR7 (chemokine C-C receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor alpha chain). Furthermore, the effluent cell population was analysed. A positive relationship between the number of granulocytes and NK cells on one hand, and duration of PD treatment on the other, was shown. We conclude, that the mechanisms of adaptive immunity promoting T helper 2 cells response are activated in the long-term before functional alterations develop. It consequently might trigger the fibrosis promoting processes.

The truth on current peritoneal dialysis: state of the art.

The share of peritoneal dialysis (PD) in the spectrum of chronic dialysis has decreased markedly in the Netherlands in the last 15 years. Consequently, the knowledge of nephrologists and nursing staff on PD has declined leading to a negative spiral in which loss of experience resulted in loss of enthusiasm to offer PD to patients and also in less interest in the new PD developments. All these changes took place while the results of PD improved and patient survival was at least similar to that on haemodialysis. The aim of this review is first to give a summary of the principles and practice of patient and staff education and to describe the role of the medical contribution in decision-making. On this basis, the second aim is to update internist-nephrologists on a number of issues that have been underexposed in the past. Recent patient and technique survival data of PD patients is reviewed, and also the new insights into dialysis adequacy. The presence of residual renal function is the main determinant of patient survival together with prevention of overhydration. Urea and creatinine removal are not important at all when patients are still passing urine. Many early problems with PD are due to the peritoneal catheter and suggestions are made for improvement of its function. The prevention and management of infections is reviewed, and also the regular assessment of peritoneal function. Free water transport is a predictor of encapsulating peritoneal sclerosis (EPS), which should be assessed regularly. The pathogenesis of EPS, treatment and the decreasing incidence are discussed.

Peritoneal dialysis and cardiovascular disease.

Cardiovascular (CV) death is the most frequent cause of dying in peritoneal dialysis (PD) patients. Risk factors include not only those that can be present in the general population, but also those related to the presence of end-stage renal disease (ESRD) and factors that are specific for PD modality. Hypertension is the most important general risk factor in PD patients, while obesity remains controversial. Inflammation, malnutrition, calcifications and probably endothelial dysfunction and oxidative stress are all CV risk factors present in ESRD that contribute to mortality in PD patients. Additional CV risk factors in PD are related to the glucose load, leading to increasing insulin resistance and a more atherogenic lipid profile. The presence of glucose degradation products in conventional dialysis solutions is mainly related to the development of peritoneal abnormalities, but not directly to cardiovascular disease. Loss of residual renal function and ultrafiltration failure promote overhydration, which is the most important PD-related risk factor for CV disease.

Prevalence of anemia and its impact on mortality and hospitalization rate in predialysis patients.

BACKGROUND/AIM: Anemia is associated with increased mortality and morbidity in both early and very late stages of chronic kidney disease (CKD). The aim of this study was to assess whether anemia is a risk factor for mortality or hospitalization in CKD stage 4-5 predialysis patients not yet on dialysis. METHODS: Incident predialysis patients were included between 1999 and 2001 and followed until January 2008 or death. Anemia was defined as mean hemoglobin (Hb) < or =11 g/dl in the 3 months before the start of predialysis. Associations were assessed by Cox regression, linear and logistic regression analysis. RESULTS: A total of 472 patients were included (median follow-up time 12 months, 11% died, 79% started dialysis). Mean Hb was 11.2 g/dl (minimum 7.6, maximum 16.9). Forty-eight percent of patients had anemia at the start of predialysis care. The adjusted mortality risk (hazard ratio, 95% confidence interval) for anemic compared to nonanemic patients was 1.92 (1.04, 3.52). Anemia tended to be related to all-cause but not to non-dialysis-related hospitalization risk. CONCLUSION: At the start of predialysis care, 48% of patients had anemia. Anemia as defined in guideline targets is not associated with an increase in hospitalizations not related to renal replacement therapy, but is likely an important risk factor for mortality in predialysis patients.

Effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with chronic kidney disease.

Since about three decades, inhibitors of the renin-angiotensin system have been available in clinical practice. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) were primarily aimed at treatment of hypertension and heart failure, more of their positive effects were discovered later on. Patients with chronic kidney disease were recognised to profit the most from treatment with these agents; however some blind spots are still present. Patients with advanced renal failure are almost always excluded from the trials; patients with end-stage renal disease form the least studied population of all and outcomes of treatment with ACEi/ARB are still uncertain in these cohorts. The aim of this review is to summarise and update the evidence about effects of AII inhibitors in patients with chronic kidney disease with the specific emphasis on patients treated with dialysis. Lately a novel indication for ACEi/ARB administration, especially for peritoneal dialysis patients, has been proposed. It is based on the capacity of these drugs to inhibit the local tissue renin-angiotensin system, which results in less development of peritoneal fibrosis and a longer life for the peritoneal membrane. The most recent available data are presented in this review.

Glomerular filtration rate measurements by 125I-iothalamate should be corrected for inaccurate urine collections with 131I-hippuran.

BACKGROUND: Measuring GFR using exogenous markers without a bladder catheter, errors can be easily made due to incomplete urine collection. The aim was to quantify agreement for 125I-iothalamate GFR measurements with and without a correction for inaccurate urine collection using 131I-hippuran. METHODS: The last available GFR measurement of adult patients was included. GFR was measured in two subsequent clearance periods with 125I-iothalamate by the standard method with correction for inaccurate urine collections using 131I-hippuran. The uncorrected and corrected GFR measurements were compared within and between the time periods for each individual patient. To study the agreement between both methods, intraclass correlation coefficients (ICC) were calculated and Bland-Altman plots, with accompanying accuracies and precisions, were used. Cohen's kappa was calculated to analyze the agreement of both methods for classifying patients according to the stages of chronic kidney disease (CKD). RESULTS: For the 332 stable included patients, the mean GFR of the uncorrected measurements was 77.8 ml/min (34.7) and the mean GFR of the corrected measurements was 81.0 ml/min (34.9). The ICC was 0.80 for the uncorrected measurements with an accuracy of 7.3 ml/min and a precision of 21.7 ml/min. For the corrected GFR measurements the ICC was 0.98, with an accuracy of 2.1 ml/min and a precision of 6.5 ml/min. Comparison between the methods showed an ICC of 0.95, an accuracy of 3.2 and a precision of 11.0. In total, 86% of the patients were classified similarly into CKD stages with both methods, overall Cohen's kappa was 0.81. CONCLUSION: Agreement was better for GFR measurements corrected for inaccurate urine collections. Therefore, GFR measurements with 125I-iothalamate should be corrected for inaccurate urine collections using 131I-hippuran. Without such correction the GFR is easily underestimated which may lead to overtreatment.

Advances in peritoneal dialysis.

UNLABELLED: New peritoneal dialysis (PD) patients have a better survival than new haemodialysis (HD) patients in the first years on dialysis. During long-term treatment, this changes into a survival advantage for HD. The superior initial survival on PD is related to a better preservation of residual renal function of PD patients compared to HD. The importance of residual renal function is probably due to additional properties of native kidneys, such as a better removal of organic acids and low molecular weight proteins than occurs during dialysis. The magnitude of the residual glomerular filtration rate (rGFR) in PD patients is not only associated with better survival, but also with less uraemic symptoms, such as loss of appetite, and also with higher scores on quality of life tests. These relationships are absent for peritoneal clearance. Consequently measures to preserve rGFR are extremely important. Studies on an effect of peritoneal transport status on survival have given variable RESULTS: A large meta-analysis showed that fast transport patients have a 15% increased risk of death, but this is only the case for continous ambulatory peritoneal dialysis (CAPD) with conventional dialysis solutions. This suggests that the development of overhydration may be the link between transport status and mortality. A fast transport status can be inherent or acquired. The inherent form can either be due to an inflammatory state or to a large mesothelial cell mass. In both situations vasoactive mediators may be locally released. A permanent acquired fast transport status, leading to severe ultrafiltration failure develops in about one third of the patients. It is conceivable that the excess mortality in fast transport patients is caused by the types associated with an inflammatory status and with the acquired type of long-term PD. The latter, linked to morphological peritoneal alterations, is mainly caused by exposure to conventional dialysis solutions. An icodextrin based solution is especially indicated to treat ultrafiltration failure. The aim of the ''biocompatible'' solutions is to prevent the peritoneal changes. The results of animal and clinical studies are promising so far. The objective of modern PD is to extent its initial survival advantage to long-term treatment. Recent advances in knowledge of mechanisms and new dialysis solutions are likely to make this possible.

Ibuprofen-induced HUS.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a disease characterized by nonimmune hemolytic anemia, thrombocytopenia and renal impairment. There are many causes for HUS, but adverse reactions to drugs have been increasingly reported. Even the NSAIDs which have been reported as safe and effective painkillers are described as cause of recurrent HUS. PATIENT CASE: We describe a case of a 44-year-old woman who was admitted to our hospital because of thrombocytopenia and anemia after the use of 8 tablets of 400 mg ibuprofen (NSAIDs). The diagnosis HUS was made and she recovered completely after treatment with fresh-frozen plasma and seven plasma exchanges. CONCLUSION: No cause could be identified except the use of ibuprofen. Recognition of a drug-induced HUS is necessary to avoid reexposure and recurrent HUS.

Association of serum fetuin-A levels with mortality in dialysis patients.

Calcifying atherosclerosis is an active process, which is controlled by calcification inhibitors and inducers. Fetuin-A, an acute phase glycoprotein, is one of the more powerful circulating inhibitors of hydroxyapatite formation. A prospective multicenter cohort study was initiated to include both hemodialysis (HD) and peritoneal dialysis (PD) patients in an evaluation of the association of serum fetuin-A levels with both cardiovascular (CV) and non-CV mortality. An increase in the serum fetuin-A concentration of 0.1 g/l was associated with a significant reduction in all-cause mortality of 13%. There was a significant 17% reduction in non-CV mortality and a near significant reduction in CV mortality. This association of fetuin-A and mortality rates was comparable in both HD and PD patients even when corrected for factors, including but not limited to age, gender, primary kidney disease, C-reactive protein levels, and nutritional status. We conclude that serum fetuin-A concentrations may be a general predictor of mortality in dialysis patients.

Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure.

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

[Malnutrition, inflammation and atherosclerosis (MIA-syndrome) in dialysis patients]. / Malnutritie, inflammatie en atherosclerose (MIA-syndroom) bij dialysepatiënten.

Malnutrition and chronic inflammation are frequently-occurring complications in dialysis patients. These conditions are associated with cardiovascular diseases and predict hospitalisation and mortality. There is assumed to be a pathophysiologic association between malnutrition, inflammation and atherosclerosis in this patient population. Indeed, chronic inflammation can induce an atherogenic and catabolic state, while a low food intake can lead to malnutrition and inflammation, but can also result from it. These complex associations constitute the basis for 'malnutrition, inflammation and atherosclerosis (MIA syndrome)'. Inflammation and malnutrition associated atherosclerosis may explain a large part of the high mortality in dialysis patients. An integrated approach is needed to treat this multifactorial complication. Randomised clinical trials on this subject are lacking as yet.

Children with chronic renal failure have reduced numbers of memory B cells.

Reduced serum IgG and subclass levels have been demonstrated in children with chronic renal failure. To study possible causes of this reduction, we analysed B cell subset composition, T helper cell frequencies and immunoglobulin (Ig) production capacity in vitro in children with chronic renal failure, with or without dialysis treatment. B cell subsets were characterized by determining CD27, IgM, IgD and CD5 expression within the CD19(+) population. Intracellular expression of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 in PMA/ionomycin-stimulated peripheral blood mononuclear cells (PBMC) was used to evaluate T helper frequencies. The capacity of B cells to secrete Ig in vitro was determined by measuring IgG(1), IgG(2) and IgM in culture supernatants of anti-CD2/CD28 monoclonal antibody (MoAb)- or SAC/IL-2-stimulated PBMC. Memory B cell numbers (identified as percentage or absolute number of CD19(+) IgM-IgD- or CD19(+)CD27(+) lymphocytes) were lower in children treated with haemodialysis (HD), peritoneal dialysis (PD) and children with chronic renal failure before starting dialysis treatment (CRF) compared to healthy controls (HC) (P < 0.05). Compared with HC, CD5(+) (naive) B cells were reduced in HD-treated patients but not for PD or for children with chronic renal failure before starting dialysis treatment (CRF). No significant differences in CD4(+) T helper cell subsets were found between the groups. However, CRF children had a higher percentage of IFN-gamma producing CD8(+) T lymphocytes compared to HC (P = 0.02). Finally, IgG(1), IgG(2) and IgM production in vitro was similar in the four groups. In conclusion, significantly lower numbers of memory type B cells were found in children with chronic renal failure compared to healthy controls. This reduction may contribute to the low Ig levels found in these children.

Validation of the KDQOL-SF: a dialysis-targeted health measure.

BACKGROUND: In evaluations of dialysis therapy, an assessment of health-related quality of life (HRQOL) is often important. The aim of this study was to determine the basic psychometric properties, reliability and validity of the short form of the KDQOL i.e. the KDQOL-SF, a dialysis-targeted instrument, and to assess its ability to detect changes over time. METHODS: In a prospective cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), all new adult ESRD patients in 32 different Dutch centers were consecutively enrolled. Demographic, clinical and HRQOL data were obtained 3 and 12 months after the start of chronic dialysis therapy. RESULTS: The reliability of the KDQOL-SF was supported by test results that were above the recommended minimal values. Validity of KDQOL-SF was confirmed by the hypothesized positive correlations of the overall health rating and renal function, and by the negative correlations between the number of comorbidities and dialysis dose. Moreover, dialysis-targeted dimensions were more sensitive in detecting relevant differences pertaining to kidney diseases than generic dimensions. The KDQOL-SF was able to detect clinical changes over time. CONCLUSIONS: The psychometric properties of the KDQOL-SF were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SF in studies evaluating dialysis therapy.