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Epigenetic alterations, such as those linked to DNA methylation, may potentially provide molecular explanations for complications associated with altered gene expression in illnesses, such as chronic kidney disease (CKD). Although both DNA hypo- and hypermethylation have been observed in the uremic milieu, this remains only a single aspect of the epigenetic landscape and, thus, of any biochemical dysregulation associated with CKD. Nevertheless, the role of uremia-promoting alterations on the epigenetic landscape regulating gene expression is still a novel and scarcely studied field. Although few studies have actually reported alterations of DNA methylation via methyl donor nutrient intake, emerging evidence indicates that nutritional modification of the microbiome can affect one-carbon metabolism and the capacity to methylate the genome in CKD. In this review, we discuss the nutritional modifications that may affect one-carbon metabolism and the possible impact of methyl donor nutrients on the microbiome, CKD, and its phenotype.

Health-related quality of life (HRQOL) is an important aspect of patients´ health that should be an integral part of the evaluation of patient-centered outcomes, not least because HRQOL associates with patients´ morbidity and mortality. This applies also to chronic kidney disease patients, including those dependent on renal replacement therapies, the type of which may influence patients´ perception of HRQOL. Several studies have addressed HRQOL in chronic kidney disease patients undergoing renal replacement therapies, especially transplanted patients and hemodialysis patients, while publications concerning peritoneal dialysis (PD) patients are scarcer. This review describes some of the methods used to assess HRQOL, factors influencing HRQOL in PD patients, HRQOL in PD vs hemodialysis, and the relation between HRQOL and patient outcomes. We conclude that assessment of HRQOL-often neglected at present-should be included as a standard measure of patient-centered outcomes and when monitoring the quality and effectiveness of renal care including PD treatment.

Peritoneal dialysis (PD) was introduced in China later than in most Western countries, and PD research activity was quite limited until the 1990s. However, in the 2000s, and even more so during the last decade, there has been an unsurpassed increase in the number of PD patients, paralleled by a substantial increase in PD research activity reflected by an increasing number of PD papers from China. In this brief review, we describe some of the factors that may explain the dramatic developments in PD research in mainland China, such as the focus on basic research using scientific approaches that subsequently could be applied also in clinical studies. Another important factor was the growing interactions with international PD research centers in Hong Kong and in Western countries. Thanks to strong support from Chinese national and regional funding sources, a growing number of young Chinese researchers went to key international PD centers to learn about novel advanced research techniques. This paved the way for long-lasting, productive collaborations with benefits also for the foreign host institutions. Finally, we present some current research projects, including basic research that may contribute to the understanding of mechanisms behind complications such as peritonitis, and clinical projects aiming at improving PD management guidelines and better understanding of the potential of PD in China. Because of the size of the PD population, now the largest in the world, and the increasing number, and quality, of researchers in the PD field, PD research in China is destined to be a major contributor to advancements in PD in the near future.

Introduction: Comparisons of survival between dialysis modalities is of great importance to patients with kidney failure, their families, and healthcare systems. Objective: This study’s objective was to compare mortality of patients on chronic hemodialysis (HD) or peritoneal dialysis (PD) and identify variables associated with mortality. Methods: This retrospective cohort study included adult incident patients with kidney failure treated with HD or PD by the Baxter Renal Care Services network in Colombia. The study was conducted between January 1, 2008, and December 31, 2013 (recruitment period), with follow-up until December 31, 2018. The outcome was the cumulative mortality rate at 1, 2, 3, 4, and 5 years. Propensity score matching (PSM) and the Gompertz parametric survival model were used to compare mortality in HD versus PD. Results: The analysis included 12,499 patients, of whom 57.4% were on PD at inception. The overall mortality rate was 14.0 events per 100 patient-years (95% confidence interval [CI], 13.61–14.42). Using an intention-to-treat approach, crude mortality rates were significantly lower in patients receiving HD (HD: 12.3 deaths per 100 patient-years [95% CI, 11.7–12.8] vs. PD: 15.5 [14.9–16.1], p < 0.01). Using a Gompertz parametric survival model, dialysis modality was not significantly associated with mortality (hazard ratio HD vs. PD 1.0, 95% CI, 0.9–1.1). After PSM, the mortality cumulative incidence functions between HD and PD were not statistically significantly different (p = 0.88). Conclusions: The present study in a large cohort of incident dialysis patients with at least 5 years follow-up and using PSM methods showed no differences in cumulative mortality between HD and PD patients. This evidence from a middle-income country may facilitate the process of dialysis modality selection globally.

Rationale & Objective: It is unknown whether initiating renin-angiotensin system (RAS) inhibitor therapy in patients with advanced chronic kidney disease (CKD) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs). We compared the risks for kidney replacement therapy (KRT), mortality, and major adverse cardiovascular events (MACE) in patients with advanced CKD in routine nephrology practice who were initiating either RAS inhibitor or CCB therapy.Study Design: Observational study in the Swedish Renal Registry, 2007 to 2017.Settings & Participants: 2,458 new users of RAS inhibitors and 2,345 CCB users with estimated glomerular filtration rates < 30 mL/min/1.73 m(2) (CKD G4-G5 without KRT) who were being followed up by a nephrologist. As a positive control cohort, new users of the same drugs with CKD G3 (estimated glomerular filtration rate, 30-60 mL/min/1.73 m(2)) were evaluated.Exposures: RAS inhibitor versus CCB therapy initiation.Outcome: Initiation of KRT (maintenance dialysis or transplantation), all-cause mortality, and MACE (composite of cardiovascular death, myocardial infarction, or stroke).Analytical Approach: HRs with 95% CIs were estimated using propensity score-weighted Cox proportional hazards regression adjusting for demographic, clinical, and laboratory covariates.Results: Median age was 74 years, 38% were women, and median follow-up was 4.1 years. After propensity score weighting, there was significantly lower risk for KRT after new use of RAS inhibitors compared with new use of CCBs (adjusted HR, 0.79 [95% CI, 0.69-0.89]) but similar risks for mortality (adjusted HR, 0.97 [95% CI, 0.88-1.07]) and MACE (adjusted HR, 1.00 [95% CI, 0.88-1.15]). Results were consistent across subgroups and in as-treated analyses. The positive control cohort of patients with CKD G3 showed similar KRT risk reduction (adjusted HR, 0.67 [95% CI, 0.56-0.80]) with RAS inhibitor therapy compared with CCBs.Limitations: Potential confounding by indication.Conclusions: Our findings provide evidence from real-world clinical practice that initiation of RAS inhibitor therapy compared with CCBs may confer kidney benefits among patients with advanced CKD, with similar cardiovascular protection.

Background and Aims In dialysis patients, urine volume is an easy-to-obtain marker of residual kidney function but information is lacking of its potential value as an estimate of the renal contribution to total clearance of small solutes. We explored whether correlations of urine volume with different estimations of the residual renal function for urea, creatinine, and phosphorus, could be used to assess renal solute clearances and renal mass removal for investigated solutes. Method In an observational study of 94 non-anuric (urine output ≥ 100 mL per 24 hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2) undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis (PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal clearances, ratio of urine solute to serum solute concentration, removed mass of each solute and the ratio of mass removed by urine (renal clearance) over total mass removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus were estimated from 24 h collections of urine and dialysate and determination of solute concentrations in serum, urine and dialysate. Statistical dependence between variables was tested using Spearman’s correlation coefficient (rho). Data are expressed as median with interquartile range. Results Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 – 1.7] g/week, respectively. The average contribution of residual renal removal to the total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively with urine volume (rho = -0.26, p < 0.05), but no such relationship was observed for urea and phosphorus. Only urine concentration of creatinine correlated weakly with urine volume with rho = -0.28 and p < 0.01. Urine concentration over plasma concentration did not correlate with urine volume for any solute. Renal urea clearance (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0 [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 - 32.9] L/week), (rho = 0.89, p < 0.001; Fig. 1A), while renal creatinine clearance correlated positively with phosphorus renal clearance (rho = 0.86, p Conclusion In PD patients, solute renal clearances and renal mass removal for urea, creatinine and phosphorus may be predicted from urine volume. Among renal clearances for urea, creatinine, and phosphorus two of them may be assessed based on measurements of the third one.

Background and Aims Experimental studies and computational modeling show increased hydration of peritoneal tissue close to peritoneal surface after intraperitoneal (ip) administration of hypertonic dialysis fluid. This overhydration - due to fluid inflow from peritoneal cavity (driven by increased intraperitoneal pressure) and from blood (due to high interstitial concentration of osmotic agent diffusing from the cavity) - may lead to tissue swelling, as observed in experiments and in disturbed physiological conditions. We estimated the degree of swelling using linear poroelastic theory with fluid and solute transport parameters obtained from clinical studies. Method The spatially distributed model of peritoneal transport was extended by equations for tissue deformation and stress derived from linear poroelastic theory. The model describes also fluid and osmotic agent flows across tissue and capillary wall. We assumed that transport and deformation occur across a layer of tissue with initial intact width L0 and deformed width L; the deformation is described as the ratio L/L0. Transport parameters are assumed as average values estimated for intact tissue by Stachowska-Pietka (2019). As tissue stiffness (Lame coefficient) for muscle is not known, we examined stiffness ranging from 110 mmHg (connective tissue; interstitium) to 700 mmHg (solid tumor). We assumed that for initial periods of peritoneal dialysis when osmotic pressure of dialysis fluid is high: 1) osmotic pressure gradient across the capillary wall prevails over the combined Starling forces, 2) spatial profile of osmotic agent concentration in tissue (interstitial fluid) can be approximated by exponential function with the penetration depth ΛS. The model yields an equation for L/L0 to be solved numerically, but an approximated closed formula also works well for typical dialysis conditions. Results The model predicts that swelling of peritoneal tissue depends on factors such as tissue stiffness, tissue width, solute penetration depth, and transport parameters for tissue and capillary wall, and on the forces that induce fluid transport: intraperitoneal pressure and the increment of osmolality of dialysis fluid over plasma osmolality. Examples of L/L0 yielded by the model - with use of glucose 1.36% dialysis fluid and for two levels of ip hydrostatic pressure (Pip) - are shown. In Figure, left panel, for L0 = 1 cm representing human abdominal muscle, and solute diffusional penetration ΛS=ΛD=0.055 cm, or lower, as due to diffusion against fluid flow, ΛS=ΛD/2=0.027 cm, is plotted versus the tissue stiffness; the dialysis fluid with glucose 1.36% is applied (osmolality increment of 60 mmol/L at the beginning of peritoneal dwell, Waniewski et al, 1996) and Pip is 15 mmHg. As stiffness of abdominal and bowel muscles may be expected around 300 mm Hg, swelling might be up to 15%; it decreases with lower ip hydrostatic and osmotic pressures. Hypothetical dialysis at Pip = 0 (isobaric with interstitial fluid) would reduce swelling by factor 2, see Figure, right panel. The depth of osmotic agent penetration into the tissue impacts tissue hydration and swelling, see Figure 1 for L/L0 with twice reduced ΛS. The model and its approximation by the closed formula provide practically the same outcomes for clinical peritoneal dialysis, see Figure 1, but some discrepancy between them may occur for thin tissue, as rat abdominal wall. The approximate formula for L/L0 works well if ΛS is much shorter than L0. Nevertheless, for high degree of swelling a nonlinear theory should be constructed. Conclusion In peritoneal dialysis, exposure of peritoneal tissue to hypertonic dialysis fluid at increased hydrostatic pressure contributes to overhydration and swelling (by 5-15% after fluid infusion) of the tissue. The extent by which this swelling may contribute to changes in peritoneal tissue structure and function warrants further studies.

Background and Aims There is wide evidence that weak points of the care of end-stage Chronic kidney disease (CKD) patients in hemodialysis include three aspects that are suitable for intervention: exercise, nutrition and psychological support. Evidence shows that exercise for patients on hemodialysis results in increased functional capacity and strength and improved health-related quality of life and survival. Additionally, earlier studies have shown the benefits of psychological interventions and the positive effect of educational programs on nutritional status for patients on hemodialysis. Despite the well-known benefits of exercise, these programs are not being implemented in the routine clinical care of hemodialysis patients. Thus, the GoodRENal project aims to promote a healthy lifestyle among hemodialysis patients using a holistic pedagogical approach that, addressing adult learners, combines exercise, nutrition and psychological well-being as well as cognitive functioning. Method GoodRENal is a project funded by the European Community, Erasmus + program (336.327 euros). The project will last 3 years, from September 2020 to August 2023 and the Partners of the consortium include institutions from five European countries: Spain (Universidad CEU Cardenal Herrera, Hospital de Manises, Univesitat de Valéncia, Universitat Politécnica de Valéncia), Sweden (Skane University Hospital and Karolinska Institutet), Greece (Aristotles University of Thessaloniki) and Belgium (Katholieke Universiteit Leuven). Other supporting institutions are located in the UK, Chile and Brazil. Results The project will develop a virtual platform comprising three aspects of care: physical activity/exercise, nutrition, psychological well-being/cognition. In summary, the project outputs will be: 1. A didactic content on a modular platform with an educational program for integrated treatment in patients on hemodialysis; 2. A guideline to promote a healthy lifestyle among patients on hemodialysis for healthcare providers; 3. A guideline to promote a healthy lifestyle among patients on hemodialysis for patients, and their formal- and non-formal carers. At the present stage exploratory questionnaires regarding physical activity/exercise-nutrition-psychological well-being/cognition have been developed in consensus with all the partners. Data from this first exploratory study regarding needs and barriers of the stakeholders (patients, health professionals, carers) will be presented at the ERA-EDTA congress. Conclusion GoodRENal aims at improving the overall health, and thus the health-related quality of life, of patients on hemodialysis through a holistic and pedagogical approach that will target especially improvements of patient reported outcomes including quality of life.

Background and Aims Mortality in end stage renal disease is higher than in the general population. In addition, there is also an increase in mortality that cannot be explained by known risk factors. In this context, researchers have been determining on these additional risk factors for years. Although inflammation is a proven risk factor, further studies are still needed. In this study, we aimed to investigate the effect of membranes on the distribution of T cell subgroups in peripheral blood mononuclear cells (PBMC) that play an important role in inflammation. Method Twenty-five patients were enrolled in the study, and patients received hemodialysis treatment first with MCO membrane (MCO) for 3 months and then with high-flux membrane (HF) for another 3 months. Peripheral blood samples were taken from the patients just before the hemodialysis procedure at 0 (starting with MCO), 3rd (switching to HF) and 6th (end of study) months. PBMC’s were separated by ficoll density gradient centrifugation and stored in liquid nitrogen. Frozen cells were stained with fluorescently labeled monoclonal antibodies and were utilized with flow cytometry device. Data were analyzed using FlowJo7.6.5 programs. Results Proportions of helper T (CD3+CD4+), cytotoxic T (CD3+CD8+), and follicular helper T (CD3+CD4+ CXCR3-CXCR5+) cells were similar in both membranes. The use of MCO decreased the ratios of peripheral CD3+T (p=0.07) and Th1 (CD3+CD4+CXCR3+CCR6+) (p Conclusion : The results can be interpreted as the prevention of a Th1 dominant inflammation seen with HF. Therefore, it suggests that the use of MCO may reduce T cell based inflammation in peripheral blood.

Background and Aims Patients with end-stage renal disease (ESRD) have an increased risk of skeletal complications, including an increased fracture risk, which is only partially identified by determination of bone mineral density (BMD). Experimentally, the complex bone-and mineral disorders in ESRD cause disturbances of bone material properties, but these have not been studied in vivo. Determination of bone material strength index (BMSi) by reference point indentation (RPI) is a novel method to determine bone material quality in vivo and can identify patients at increased fracture risk, even in the presence of normal BMD. We determined BMSi in ESRD patients and investigated its association with BMD and serum markers of mineral metabolism. Method 15 Adult patients with ESRD, scheduled for a living-donor kidney transplantation, were included in this cross-sectional study. Laboratory analyses included calcium, phosphate, PTH 1-84 and alkaline phosphatase. BMSi was determined by RPI with the OsteoProbe RUO in the tibia. Bone mineral density was measured by dual X-ray absorptiometry. Results Patients with bone mineral strenght index above median had higher bone mineral density of the right hip and total body than patients below median (p = 0.04). Alkaline phosphatase was lower in patients with BMSi below the median (47 (35-71) U/L vs. 103 (53-318) U/L, p = 0.009). There was a trend towards a significant relationship between length and BMSi (p = 0.09). Conclusion We identified for the first time an association of BMSi with BMD and alkaline phosphatase in patients with ESRD. Our findings of an association of BMSi with BMD are in accordance with findings in other populations with increased fracture risk.

Background: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. Methods: Among 1580 patients participating in the Peridialysis study, a prospective study of causes and timing of DI, features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice were registered. Patients were followed for 12 months or until transplantation.Results: First-year mortality was 20.2%. In addition to age and comorbid factors, independent factors predicting death were: clinical contraindications to PD or HD, a rapidly falling eGFR before DI, suboptimal DI, acidosis, high C-reactive protein, signs of overhydration (pulmonary stasis) and cerebral symptoms at DI while eGFR at DI was not. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD.Conclusions: First-year mortality in incident dialysis patients was associated with high age, comorbidity, worsening of kidney failure and clinical symptoms, acidosis, inflammation, and suboptimal DI while eGFR at DI and dialysis modality did not appear as predictors. These findings support the view that choice of dialysis modality among patients who are able to make an informed decision can be based on patient preference.

Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI.Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality.First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD.First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

Objective Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS). Design and Methods We investigated 2 cohorts: MHDltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m2) and MHDBrazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m2), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition. Results Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHDItaly cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHDBrazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHDItaly: κ = 0.26, P = .003; MHDBrazil: κ = 0.22, P = .003) and between GLIM and MIS (MHDItaly: κ = 0.33, P Conclusion In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting.

High rates of hospitalization in dialysis patients impose an increasing healthcare burden. We explored and compared hospital admission rates among patients starting hemodialysis (HD) and peritoneal dialysis (PD), and investigated causes of admission/readmission in search of potentially preventable risks.Observational study recruiting 8902 patients (3101 on PD) who started maintenance dialysis in Sweden between 2006 and 2016 and were followed-up for 2 years. We compared the Hazard Ratios (HR) for hospital admission and in-hospital death, and calculated the odds ratios (OR) of readmission within 30 days after discharge.Six thousand four hundred ninety-three (73%) patients were hospitalized at least once, and 246 admissions ended with in-hospital death. Compared with HD, patients on PD had a higher risk of hospitalization (HR 1.07; 95% CI 1.01-1.13), longer length of stay (mean difference of 2.06; 1.39-2.73 days), and higher risk of in-hospital death (HR 1.18; 1.03-1.37). Peritonitis and cardiovascular events were the most frequent causes of admission. Of 5810 patients discharged from the hospital, 1447 (25%) were readmitted and 124 (2%) died within 30 days. No differences in readmission risk were observed between dialysis modalities. There was frequently discordance between the cause of hospital admission and readmission, and we identified a consistent pattern of readmission attributed to complications from infections and their interplay with cardiovascular diseases.Our study illustrates a high burden of hospitalization in patients on dialysis, suggests the risk of longer hospitalizations for patients on PD, and identifies cardiovascular events and infections as complications that may benefit from closer post-discharge monitoring.

In patients with advanced chronic kidney disease (CKD), the accumulation of uremic toxins, caused by a combination of decreased excretion secondary to reduced kidney function and increased generation secondary to aberrant expression of metabolite genes, interferes with different biological functions of cells and organs, contributing to a state of chronic inflammation and other adverse biologic effects that may cause tissue damage. Several uremic toxins have been implicated in severe vascular smooth muscle cells (VSMCs) changes and other alterations leading to vascular calcification (VC) and early vascular ageing (EVA). The above mentioned are predominant clinical features of patients with CKD, contributing to their exceptionally high cardiovascular mortality. Herein, we present an update on pathophysiological processes and mediators underlying VC and EVA induced by uremic toxins. Moreover, we discuss their clinical impact, and possible therapeutic targets aiming at preventing or ameliorating the harmful effects of uremic toxins on the vasculature.

The transitory change of fluid and solute transport parameters occurring during the initial phase of a peritoneal dialysis dwell is a well-documented phenomenon; however, its physiological interpretation is rather hypothetical and has been disputed. Two different explanations were proposed: (1) the prevailing view—supported by several experimental and clinical studies—is that a vasodilatory effect of dialysis fluid affects the capillary surface area available for dialysis, and (2) a recently presented alternative explanation is that the molecular radius of glucose increases due to the high glucose concentration in fresh dialysis fluid and that this change affects peritoneal transport parameters. The experimental bases for both phenomena are discussed as well as the problem of the accuracy necessary for a satisfactory description of clinical data when the three-pore model of peritoneal transport is applied. We show that the correction for the change of transport parameters with dwell time provides a better fit with clinical data when applying the three-pore model. Our conclusion is in favor of the traditional interpretation namely that the transitory change of transport parameters with dwell time during peritoneal dialysis is primarily due to the vasodilatory effect of dialysis fluids.

In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p p p

Background The recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients. Methods This was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks. Results Among 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4). Conclusions Gradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.

Endothelins including its most abundant isoform, endothelin-1 (ET-1), are peptides acting as vasoconstrictors when binding to ETA and ETB receptors, and, in addition to their distinct roles in normal physiology, endothelins have a central role in the pathophysiology of many diseases including cardiovascular and renal diseases. Endothelin-1 (ET-1), the most potent vasoconstrictor in the cardiovascular system, regulates basal vascular tone and glomerular hemodynamics. ET-1 is involved also in vascular and cardiac hypertrophy, inflammation, and in the development and progression of cardiovascular diseases - e.g. essential hypertension, atherosclerosis, coronary artery disease, congestive heart failure, pulmonary arterial hypertension and cerebrovascular disease and renal diseases - e.g. acute renal failure, polycystic kidney disease and chronic kidney disease. Not surprisingly, the ET system has become a target for therapeutic interventions that now include a few already established and some new promising agents. In this narrative review, we summarize physiologic properties of the ET system, focusing especially on ET-1, and its role in the pathophysiology of ET system activated diseases, and discuss the potentials of therapeutic interventions targeting the ET system in cardiovascular and renal diseases. While ET receptor antagonists have already revolutionized the management of idiopathic pulmonary arterial hypertension, so far, this class of drugs have failed as medication for congestive heart failure. Clinical trials continue to explore new applications of endothelin receptor antagonists in treatment-resistant hypertension and chronic kidney disease and have shown some benefits in the latter group by reducing proteinuria; however, they have not been approved yet. We conclude that larger clinical trials are needed to validate the use of ET receptor antagonists in ET system activated diseases.

Background and Aims Transferrin saturation (TSAT) is an indicator of iron deficiency or overload, but its relationship with mortality in patients with different stages of chronic kidney disease (CKD) is unclear. We investigated the association of TSAT with mortality in CKD patients. Method In 479 CKD patients (97 CKD3-4 patients, 298 CKD5 non-dialysis patients and 84 peritoneal dialysis patients; median age 58 years, 67% males, 33% cardiovascular disease, CVD, and 29% diabetes), biomarkers of iron status (plasma iron, TSAT, transferrin and ferritin), systemic inflammation (high sensitivity C-reactive protein, hsCRP, and interleukin-6, IL-6) and nutritional status were assessed. During median follow-up of 35.6 months, 139 (29%) patients died, and 176 (37%) patients underwent renal transplantation. Patients were stratified into low (n=157) and high (n=322) TSAT tertile groups. All-cause and CVD mortality risk were analyzed with competing risk regression with renal transplantation as competing risk. Results TSAT [median 23% (IQR 17-30%)] was negatively associated with presence of DM and CVD, body mass index, hsCRP, IL-6, Framingham´s CVD risk score (FRS), erythropoietin resistance index (ERI) and iron supplementation, and positively associated with hemoglobin, ferritin and s-albumin. In competing risk analysis, low tertile of TSAT was independently associated with increased all-cause mortality risk (sHR=1.50, 95%CI 1.05-2.14) after adjusting for CKD stages, 1-SD of FRS, 1-SD of hemoglobin, 1-SD of hsCRP, 1-SD of ESA dose and iron supplementation (Figure 1). Conclusion TSAT was inversely associated with mortality risk in CKD patients. When evaluating clinical outcomes of CKD patients, iron status using TSAT as a predictive marker, should be considered.

Background and Aims Major osteoporotic fractures (MOF) are associated with increased morbidity and mortality in ESRD patients. We investigated incidence, predictors and clinical outcomes associated with first MOF (MOFfirst) following kidney transplantation (KT). Method In Swedish Renal Registry of 3992 first KT recipients (2005 -2016) (age 53 years, 65% men), we identified all MOFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MOFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MOFfirst using Cox proportional hazards models with fracture as time-varying exposure. Results During median follow-up of 4.8 years (IQR 2.2-7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MOFfirst (n=279) was 14/1000 patient-years and that of hip fractures (n=69) 3/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and two-fold increased among women. High age, female sex, previous history of MOF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MOFfirst, whereas pre-emptive KT was associated with lower risk of MOFfirst. Spline curves showed that impact of age in women on MOFfirst was markedly higher than in men. MOFfirst (including all cases) independently predicted increased all-cause mortality (hazard ratio, HR, 1.78(95%CI 1.35-2.36)). Among MOFfirst, hip fracture (HR, 4.68(95%CI 1.56-14.06)) and spine fracture (HR, 4.02(95%CI 1.19-13.54)) were significantly associated with increased all-cause mortality. Conclusion The initial six months following kidney transplantation is a high-risk period for major osteoporotic fractures, especially forearm fractures. MOFs, especially hip and spine fracture, are associated with increased mortality.

Background and Aims Vitamin K is a potential protective factor against premature vascular aging and vascular calcification (VC). Whether vitamin K supplement could halt VC progression in patients with end-stage renal disease (ESRD) is not clear, partially due to the heterogeneity of measurements of VC in different vascular sites. Here we investigated the associations between non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP), a circulating marker of vitamin K insufficiency, and premature vascular aging phenotypes evaluated by coronary artery calcium (CAC) scoring, aortic valve calcium (AVC) scoring, and histology scoring of presence of media calcification in vascular biopsies in patients with ESRD. Method In this observational cohort study, 223 ESRD patients (median age 54 years, 68% males) comprising non-dialysis patients (n=109), prevalent peritoneal dialysis (PD, n=80, median dialysis vintage 11.6 months) and prevalent hemodialysis patients (HD, n=34, median dialysis vintage 12.0 months) underwent baseline measurements of plasma dp-ucMGP and scoring of CAC and AVC by computed tomography scan. Framingham risk score (FRS), inflammation and other relevant clinical and biochemical data were determined at baseline. In a sub-group of patients (n=94), scoring of media calcification by histology in epigastric artery biopsies was also performed. Results Plasma dp-ucMGP levels (median 1568 pmol/L) significantly correlated with age (rho=0.38), presence of cardiovascular disease (CVD, rho=0.16), triglycerides (rho=0.19), FRS (rho=0.33), high-sensitivity C-reactive protein (hsCRP; rho=0.35), CAC score (rho=0.30) and AVC score (rho=0.24) but did not differ with regards to treatment modality (i.e. non-dialysis, PD and HD). In multivariate regression analyses, with adjustment for presence of CVD, FRS, hsCRP and triglycerides, increased dp-ucMGP levels were independently associated with increased CAC score (coefficients 0.12, p=0.04), but not with AVC score nor presence of media calcification in epigastric arteries. Conclusion Our data suggest that vitamin K insufficiency as indicated by increased dp-ucMGP levels associates with premature vascular calcification evaluated by CAC but not with AVC or media calcification assessed by histology. This discrepancy warrants further studies to explore the pathophysiological background between vitamin K metabolism and susceptibility of calcification in different vascular sites as well as the pattern of VC (i.e. intima and media calcification) within sites.

Background and Aims Bone loss is associated with progression of cardiac calcification and increased mortality in end stage renal disease (ESRD) patients but the relations and underlying causes are unclear. We investigated factors associated with changes of bone mineral density (BMD) during the first year after initiation of dialysis and the association between BMD changes and subsequent mortality in ESRD patients. Method In a prospective study of 242 ESRD patients (median age 55 years, 61% men) starting dialysis, total BMD and BMD at specific bone sites (including seven subregions: head, arms, legs, trunk, hip, pelvis and spine) was assessed by whole body dual-energy X-ray absorptiometry (DXA) at baseline and one year after dialysis start. Framingham cardiovascular disease (CVD) risk score, body composition, nutritional status, handgrip strength, various biochemical biomarkers (white blood cell, hemoglobin, albumin, creatinine, calcium, phosphate, intact parathyroid hormone, triglyceride, cholesterol, HDL cholesterol and high-sensitivity C-reactive protein) were recorded. We used multivariate linear regression analysis for BMD change analysis. We followed patients from 12 months after initiating of dialysis until renal transplantation, death or end of 60 months follow-up. During follow-up, 59 patients (24%) died due to CVD (n=33) or other causes (n=26) and 95 patients (39%) underwent renal transplantation. Fine and Gray competing risk analysis was used to ascertain associations of BMD changes with all-cause and CVD-related mortality. Results From baseline to one year after initiation of dialysis, there was a significant decrease of BMDtotal and BMDleg, trunk, rib, pelvis and spine in hemodialysis (HD) patients, whereas no difference was seen in peritoneal dialysis (PD) patients. In multivariate linear regression analysis adjusting for several confounders, HD therapy - compared to PD therapy - was significantly associated with negative changes in BMDtotal (β=-0.15), BMDhead (β=-0.14), BMDleg (β=-0.18) and BMDtrunk (β=-0.16). The direction and extent of changes in BMD, i.e. increase of BMD, associated with statistically significant lower all-cause mortality risk for BMDtotal (sHR, 0.91), BMDhead (sHR 0.91) and BMDleg (sHR 0.92), while for CVD-mortality a significant association with BMD changes was found only for changes in BMDhead (sHR 0.92). Conclusion In patients starting on dialysis, PD therapy appeared to have a beneficial effect on BMD changes as compared to HD during the first year of dialysis therapy. This difference may have implications for clinical outcomes as the degree of bone loss was associated with subsequent mortality. Changes towards increased BMDtotal, BMDhead and BMDleg associated with lower all-cause mortality. For head region – which is known as a cortical bone rich site – positive BMD change associated also with lower CVD mortality suggesting that increase or maintenance of BMD of cortical bone rich sites may have stronger association with clinical outcome in ESRD than BMD of trabecular bone.

Background and Aims Patients with chronic kidney disease (CKD) are at high risk of cardiovascular disease (CVD) due to complex processes in the uremic milieu linked to CKD - mineral and bone disorders (CKD-MBD). These processes alter structure and function of heart and vasculature e.g. by causing ectopic calcification that makes vessels stiffer thus affecting pulse (pressure) wave profiles. Our study aimed to derive patient-specific parameters using pulse wave propagation model including arterial stiffness and compare those parameters with cardiovascular status including biopsy proven severity of vascular calcification. Method In a group of 81 CKD (stage 5) patients undergoing living donor kidney transplantation, the degree of medial calcification in epigastric artery was histologically graded as 0 (n=22), 1 (n=31), 2 (n=21) and 3 (n=7) representing no, minimal, moderate and extensive signs of vascular calcification, respectively. Concomitantly 82 features were determined including demographic and anthropometric features, blood biomarkers related to CKD - MBD and other measurements. Pressure profiles (circles in Fig. 1) in radial artery were recorded using applanation tonometer (SphygmoCor, AtCor Medical, Australia) and used to derive patient-specific parameters from a mathematical model describing blood flow and pressure in 55 major arteries. Results The model was able to reproduce all recorded pressure profiles with high accuracy with average relative error less than 8% (compare solid line and circles in Fig. 1). Vascular stiffness, derived from the model, in arterial branches located in the area of artery for which calcification was histologically quantified, was significantly higher for higher calcification score (p-value < 0.001). The estimated stiffness correlated with the level of troponin T (rho=0.65**), advanced glycation end-products (by skin autofluorescence, rho=0.55*), osteoprotegerin (rho=0.44**), hepcidin 25 (rho=0.32*, interleukin 6 (rho=0.29*) and choline (rho=0.28**), (‘**’ and ‘*’ denote p-value < 0.01 and 0.05, respectively). Stiffer arteries were found in patients with diagnosed CVD (p-value < 0.01). Conclusion We demonstrate that a mathematical model based on a single peripheral recording of pulse pressure profile has the potential to provide information about cardiovascular status in the individual patient. Also, the estimated stiffness correlates well with several well-established CVD risk factors. Our mathematical model of the arterial tree, if validated in larger cohorts of patients, may be used as computational tool to predict vascular stiffness without need of arterial biopsy.

Background and Aims The incidence of fractures is markedly higher in dialysis patients than in pre-dialysis patients, but it is not clear to what extent the initiation of dialysis as such is associated with accelerated fracture incidence or if fracture rates are already increasing prior to dialysis start among incident dialysis patients. Here we investigated the temporal pattern of occurrence of a first major osteoporotic fracture (MOF) among incident dialysis patients in the pre-dialysis period and in the period following dialysis initiation. Method We analyzed data from Swedish Renal Registry (SRR) and identified 9041 incident dialysis patients (2005 -2015; age 67 years, 67% men). We identified all first MOF (MOFfirst) in hip, spine, humerus and forearm during 12 months before and after dialysis initiation. Using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death and renal transplantation, we estimated adjusted fracture incidence rates and predictors of MOFfirst. Results During the whole follow-up period, there were 361 fractures including 196 hip fractures. The crude incidence rate of MOFfirst (n=157) before dialysis initiation was 17/1000 patient-years and after initiation of dialysis the incidence rate of MOFfirst increased to 24/1000 patient-years. Overall the adjusted MOFfirst incidence rates increased from 6 months before initiation of dialysis, fluctuated, and stabilized at a higher rate than that of the baseline rate after 12 months. The adjusted hip fracture rate rose steeply 3 months before dialysis initiation, declined 3 months after dialysis initiation, fluctuated, and then became stabilized. On the contrary, the adjusted incidence rates of other fractures, i.e., non-hip fractures, appeared to be stable all the time, before as well as after initiation of dialysis. Female gender, higher age and previous history of MOF had a negative impact on fracture incidence rates before and after dialysis initiation. Conclusion We conclude that the incidence of MOFfirst is increasing already from 6 months prior to dialysis initiation among incident dialysis patients, and that there is a further increase following dialysis initiation. For hip fracture, which was the most common MOF, the temporal pattern of incidence rates was compressed to a high risk period lasting from 3 months before to 3 months after dialysis initiation, underlining the need of increased attention to prevent hip fractures in incident dialysis patients during this critical period.

Background and Aims Home dialysis with peritoneal dialysis (PD) or home hemodialysis (HD) has medical and socioeconomic benefits but home dialysis is generally underutilized. While many factors determine choice of initial dialysis modality, starting patients on home dialysis requires timely planning, educational activities and an active program to promote home dialysis. Here we investigated factors including patient suitability, pre-dialysis preparations and institutional factors determining choice of dialysis modality among patients initiating dialysis. Method Choice of dialysis modality was investigated in 1588 consecutive patients (age 63.8 ±15.3 years. 35.8% female; diabetic nephropathy 24.4%) participating in the Peridialysis study, a multinational multi-centre prospective study of causes and timing of planned and unplanned dialysis initiation (DI) over a 3-year period in 15 Nordic and Baltic nephrology departments. All dialysis modalities were available and free of charge to patients. All centres offered pre-dialysis education programs to patients with timely referral. Clinical and biochemical data during the pre-dialytic period, centre data, and reasons for DI and choice of dialysis modality were registered. Results: 516 (32.4%) patients were not offered home dialysis because they were judged to be unsuitable (384; 24%): PD was contraindicated in 338 (21.2%) patients - for physical (142; 8.9%), mental (80, 5.0%) or abdominal (116; 7.3%) reasons and HD was contraindicated in 46 (2.9%) patients. In addition, 106 (6.7%) were not offered home dialysis for various reasons; and deaths before modality choice occurred in 26 (1.6%) patients. Factors associated with unsuitability were high age, comorbidity, late referral (risk ratio, RR, 1.9), inflammation (C-reactive protein >50 mg/L (RR 2.6) and rapid loss of renal function (RR 2.0). Patients who were not assessed for home dialysis comprised mainly patients with late referral (RR 5.8) and/or unplanned DI (RR 9.6). Of the remaining 1072 (67.6%) patients, who had a free choice of modality, 700 (65.3%) chose home dialysis, either PD (661; 61.7%) or home HD ( 39 3.6%) while 372 (34.7%) patients chose centre HD. Factors associated with choice of centre dialysis were late referral (RR 1.8), suboptimal DI (RR 2.0), symptomatic uraemia (RR 1.6) and p-urea >30 mM (2.6). Somatic differences between patients choosing home dialysis and centre dialysis were minor. Independent institutional factors reducing information about home dialysis were treatment at a university hospital (RR 4.3) and absence of an active preference for home dialysis, “home dialysis first” policy (RR 3.0). Conclusion The results of the Peridialysis study indicate that the incidence of home dialysis could be increased by a “home dialysis first” department policy and by efforts to reduce the incidence of late referrals and unplanned DI. Acutely ill patients and patients with unplanned DI may be candidates for home dialysis if assessment of home dialysis suitability and dialysis educational program are performed after their clinical condition has improved. Given a free choice, most patients (65%) choose home dialysis.

Background and Aims Preventing hyperkalemia - a potentially fatal complication in advanced CKD - by prescribing diets low in K (=limited intake of healthy components such as vegetables, fruits, whole grains and nuts) leads to poor dietary quality. K-restricted unhealthy diets may affect quality of life, patient satisfaction with treatment, achievement of nutritional targets, and increase risk of obstipation, gut dysbiosis and progression of CKD. We designed a feasibility study to test if a low-protein healthy K-rich diet with fruits, vegetables, whole grains and nuts with concomitant use of new potassium binder (SZC) can be safely prescribed to patients with CKD stages 4 and 5 with hyperkalemia. Method A feasibility descriptive single arm open-label interventional trial lasting 6 weeks will enroll 36 CKD patients at the outpatient clinic with: age 18 - 85 years; glomerular filtration rate < 29 ml/min/1.73 m2 and not on dialysis; serum K > 5.1 mmol/L or in previous use of sodium polystyrene sulfonate (SPS) to decrease serum K levels, and who develops hyperkalemia after SPS is ceased. Patients with serum K > 6.5 mmol/L and those likely to start dialysis within 2 months, with inflammatory bowel syndrome or with a history of hypokalemia ( Results NA Conclusion This interventional feasibility pilot study will test the hypothesis that - with precautions aiming at reducing risk of hyperkalemia - a K-rich healthy diet in patients with CKD stage 4 may improve patient satisfaction with treatment and patient symptoms. Depending on the results, a larger randomized controlled longitudinal trial will be considered to investigate if K-rich diet in CKD stage 4-5 patients is safe and beneficial.

Background and Aims Community-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk are conflicting. In this large Swedish population-based cohort, we explore the links between kidney function, kidney function decline and dementia incidence. Method In the Stockholm CREAtinine Measurements (SCREAM) project, we studied the association of baseline eGFR with the risk of incident dementia among 329,822 residents of Stockholm who accessed healthcare, were ≥65 years and had no previous history of dementia. We estimated the rate of eGFR decline among the 205,622 residents with repeated eGFR measurements during the first year and investigated its association with dementia risk. The primary outcome was dementia incidence based on ICD-10 codes or use of anti-dementia drugs. Secondary outcomes were incidence of the dementia subtypes Alzheimer’s and vascular dementia. Results 18,983 cases of dementia (5.8% of participants) were detected throughout 1,185,304 person-years. Dementia incidence rates (IR) were progressively higher with lower eGFR: from 6.56/1000 person-years in persons with eGFR 90-104 ml/min to 30.28/1000 person-years in those with eGFR Conclusion In the general population, both low kidney function and faster kidney function decline are associated with increased risk of developing dementia, particularly vascular dementia.

Background and Aims The width of the peritoneum (composed mainly of connective tissue and relatively free of vasculature) is increased in patients on peritoneal dialysis compared to healthy subjects. We investigated to what extent increased intraperitoneal (ip) hydrostatic and osmotic pressures following the infusion of dialysis fluid will change hydration status and width of the peritoneum. Method Using linear theory of poroelasticty, clinical data on transport parameters and experimental data on elastic characteristics of the interstitium, the relative change of the width of the poroelastic layer subject to the combined effect of external hydrostatic and effective osmotic pressures (that is, ideal osmotic pressure multiplied by reflection coefficient for osmotic agent) can be described as a function of effective pressure and elastic modulus of the layer: Lmod/L0 = 1/(1-deltaP*/lambda*), where L0 is initial thickness of the tissue, Lmod is modified thickness of the layer, deltaP* is change in effective combined pressure, and lambda* is the elastic modulus of the poroelastic material. The same formula describes also the change in fractional free fluid volume ratio, thetaF. The elastic modulus of the connective tissue was assumed to be 110 mmHg, as measured for the subcutaneous layer of the tip of mouse tail by Swartz et al (J Biomech, 1999), and reflection coefficient for glucose in the interstitium of 0.0035 as estimated by Stachowska-Pietka et al (NDT, 2019) from clinical data for patients on peritoneal dialysis. Results The ip hydrostatic pressure increases by 2-3 mmHg to 15 mmHg at rest depending on infused volume of dialysis fluid (and posture, body weight and location in abdominal cavity), and may increase to 100 mmHg during activities as coughing, whereas the osmotic pressure of glucose 3.86% dialysis fluid is around 400 mmHg above the osmotic pressure of plasma and interstitial fluid (in equilibrium with plasma). However, due to the low reflection coefficient of interstitium, the effective osmotic pressure of dialysis fluid minus the physiological value of interstitial osmotic pressure is only 1.4 mmHg, and is quickly decreasing with dwell time. Therefore, hydrostatic pressure is the dominant factor for interstitial hydration. Assuming ip pressure of 15 mmHg, the stretch of the peritoneum increases its equilibrium width (at 0 mmHg and isotonic interstitial fluid) by 15%. During physical activities peritoneum may transiently thicken even more. Conclusion The peritoneum becomes overhydrated after infusion of dialysis fluid, which increases interstitial hydrostatic pressure; the thickness and fractional free fluid volume of the peritoneum increase by 15% although transiently higher increases may occur following activities that increase intraperitoneal pressure. The mechanical changes in the peritoneum may contribute to the biological changes in cells present there, as fibroblasts and mesothelial cells. The swelling of the peritoneum is in agreement with the increase in the fractional free fluid volume of the intramuscular interstitium behind the peritoneum as reported by Zakaria et al (Am J Physiol Heart Circ Physiol, 1999).

Background and Aims Major osteoporotic fractures (MOF) are common in dialysis patients. We investigated incidence, predictors and clinical outcomes associated with first MOF occurring after initiation of dialysis (MOFfirst). Method In Swedish Renal Registry of 9714 incident (2005 -2016) dialysis patients (median age 68 years, 67% men), we identified all MOFfirst in hip, spine, humerus and forearm. Using flexible parametric hazard models and Fine-Gray analysis, we estimated incidence, mortality rates and predictors of MOFfirst, and, in time-dependent analysis, risk of all-cause and cardiovascular disease (CVD) mortality following MOFfirst. Results During median follow-up of 2.2 years, the crude incidence rate of MOFfirst (n=835) was 24/1000 patient-years (pt-yrs) and that of hip fractures (n=470) 13/1000 pt-yrs. The multivariate-adjusted fracture incidence rates increased gradually after dialysis initiation and were 47% higher among women. Female sex, higher age, presence of comorbidities, and previous history of MOF (MOFprevious) were associated with increased risk for MOFfirst, whereas peritoneal dialysis as compared to hemodialysis was associated with decreased fracture risk. The adjusted fracture incidence rate of MOFfirst during the first 90 days following dialysis initiation was higher in patients with MOFprevious than in those without MOFprevious. MOFfirst independently predicted increased all-cause mortality (sub-distribution hazard ratio, sHR, 1.67(95%CI 1.47-1.91) and CVD-related mortality (sHR 1.49 (95%CI 1.22-1.84). Adjusted mortality rate following hip fractures was higher than for other types of MOF. Spline curves showed that mortality following MOFfirst was highest during the first 6 months of follow-up. Conclusion Major osteoporotic fractures are common and associated with increased mortality in incident dialysis patients.

Background and Aims There is a lack of data that could help to guide the choice of antihypertensive agents in patients with advanced chronic kidney disease (CKD). We evaluated whether initiating treatment with a renin-angiotensin system inhibitor (RASi) is superior to calcium channel blockers (CCB) in preventing mortality, major adverse cardiovascular events (MACE) or kidney replacement therapy (KRT) in patients with advanced CKD. Method Observational study from the Swedish Renal Register, 2007-2017. We identified all nephrologist-referred patients in Sweden who initiated RASi or CCB treatment and had non-dialysis dependent advanced CKD (eGFR Results The propensity-score weighted cohort included 2479 RASi and 2327 CCB initiators who were well-matched for baseline confounders (all standardized differences Conclusion Compared with CCB, initiation of RASi in patients with advanced CKD was associated with a lower risk of KRT, but no different risk of mortality or MACE.

Background and Aims The recent years have witnessed several therapeutic improvements regarding both peritoneal dialysis (PD) treatment itself and the prevention and management of complications. We evaluated trends in implementation of therapeutic improvements and their relationship with survival and other relevant clinical outcomes in PD patients from Sweden. Method Using the Swedish Renal Registry (SRR), clinical data from all patients initiating PD in Sweden between 2006 and 2015 were linked to other national healthcare registries to obtain information on vital status, hospitalization and diagnoses during in and out-patient care, along with information on all dispensed drugs, from inclusion to the end of 2017. We first evaluated trends in the use of PD-related treatments and of selected key medications within 2-year blocks. We then evaluated the incidence of death, major cardiovascular events (MACE), technique failure, transplantation and peritonitis episodes within one and two years from PD initiation using standardized incidence rates via logistic regression to account for differences in patient characteristics over time. In subsequent Cox regression models, we studied whether adjustment for implementation of these therapeutic changes modified observed trends in clinical outcomes. Finally, patient survival was compared against the age-sex matched general Swedish population using standardized incidence ratios (SIR). Results 3,312 patients (mean age 63±15 years; 34% women) initiated PD in Sweden during the study period. Across 2-year time blocks, there was no difference over time in the distribution of age, sex or comorbidities with the exception of an increased proportion of patients with chronic pulmonary disease. The proportion of patients undergoing automated peritoneal dialysis and using icodextrin increased over time, while mean standard Kt/V and weekly creatinine clearance did not change. The use of non-calcium phosphate binders, cinacalcet and calcium-channel blockers increased, and the use of angiotensin-converting enzyme inhibitors /angiotensin receptor blockers, erythropoietin, iron, and calcium supplements showed decreasing trends. After standardization for differences in demography and comorbidities, the one-year incidence of peritonitis decreased by 13% and the rate of kidney transplantation increased by 52% in 2014/15 compared to 2006/07. The rates of death, MACE or technique failure did not show differences over time. Similar results were observed with 2-years of follow up and when applying Cox models; Per 2-year period, the risk of peritonitis within one year decreased by 8% (HR 0.92, 95% CI 0.87-0.98) regardless of age, sex, comorbidity and the abovementioned therapeutic changes. The risk of death for PD patients was in 2006/2007 4 times higher [SIR 4.08 (3.15–5.29)] and in 2014/15 3.7 times higher [SIR 3.65 (2.70–4.94)] than the general population, corresponding to a reduction of SIR by 11%. Conclusion During the last 10 years, there has been a gradual implementation of new and established evidence-based treatments in patients starting PD in Sweden. Although survival rates are improving compared to the general population, there were no clear differences in the rates of technique failure, MACE or death across PD patients over time. We observed, however, consistent improvements in peritonitis frequency and access to transplantation.

Background and Aims While chronological age associates with increased risk of death, there is a quest for markers of biological age in chronic kidney disease (CKD) that better reflect accumulation of tissue and cellular damage, which could contribute to shorter life span. Skin autofluorescence (SAF) is a biomarker for accumulation of advanced glycation end products in skin that associate with chronological age and with factors that may increase mortality risk. However, the predictive capacity of SAF for mortality has not been fully elucidated in CKD. We have investigated the relationship between biological age calculated by SAF, chronological age and all-cause mortality in patients with CKD stage 5. Method In a cohort of 199 CKD5 patients (non-dialysis CKD5, n=100, hemodialysis, n=27 and peritoneal dialysis, n=72; median age 66 years, 34% females, 21% diabetes (DM), 20% cardiovascular disease (CVD), and 34% malnourished), we calculated biological age by a formula based on SAF measurements using the AGE Reader. Framingham risk score, coronary artery calcium score, the heart rate-corrected augmentation index, body composition, nutritional status, handgrip strength, and various biochemical markers (hemoglobin, albumin, creatinine, intact-parathyroid hormone, triglyceride, cholesterol, HDL-cholesterol, high-sensitivity C-reactive protein (hsCRP), and interleukin (IL)-6) were recorded at baseline. During median follow-up of 38 months, 34 patients died, and 51 patients underwent renal transplantation. We analyzed spline curves showing sub-distribution hazard risk (sHR) for all-cause mortality with biological age calculated by SAF and chronological age by the Fine and Gray competing risk analysis. Results There was a significant association between biological age calculated by SAF and chronological age (rho=0.48; p Conclusion All-cause mortality risk increased linearly with higher chronological age and SAF-estimated biological age - and with similar magnitude of sHR for the two - suggesting that prediction of mortality risk based on SAF is not superior compared to chronological age in CKD. We conclude that biological age calculated by SAF and chronological age are equally robust predictors of clinical outcomes in CKD; however, both indices are influenced by the inflammatory status.

Background and Aims Ageing represents the greatest risk factor contributing to increased morbidity and mortality in most chronic diseases; it encompasses numerous biological changes resulting in declining physiological function and increasing burden of disease. Whether new biomarkers of ageing and risk scores for predicting physiological outcomes, including mortality, are applicable and more accurate than chronological age in patients with chronic kidney disease (CKD) is not clear. So far, the DNA methylation (DNAm) PhenoAge biomarker of ageing (Levine et al. Aging 2018) has not been tested in CKD. While we had no access to DNAm data, we applied the phenotypic age estimate proposed by Levine et al., which was included in their calculations of DNAm PhenoAge, and tested the relationship between estimated phenotypic age (ePhenoAge) and chronological age, respectively, with all-cause mortality in patients with CKD. Method In a cohort of 333 CKD patients (stage 1, n=78; stage 3-4, n=64; and stage 5, n=191) with median age 56 years, 43% females, 24% diabetes (DM), 25% cardiovascular disease (CVD), and 22% malnourished, we estimated age by ePhenoAge, using a formula with calculations based on nine biomarkers and chronological age, and compared this age index with chronological age. Framingham risk score, body composition, nutritional status, handgrip strength, and various biochemical markers (white blood cells, mean cell volume, hemoglobin, albumin, creatinine, glucose, calcium, alkaline phosphatase, intact-parathyroid hormone, triglyceride, cholesterol, HDL-cholesterol, high-sensitivity C-reactive protein (hsCRP), and interleukin (IL)-6) were recorded. During a median follow-up period of 52 months, 65 patients died, and 111 patients underwent renal transplantation. We used spline curve to illustrate sub-distribution hazard risk (sHR) for all-cause mortality versus increasing ePhenoAge and chronological age respectively as obtained by the Fine and Gray competing risk analysis. Results In univariate analyses, IL-6 (rho=0.49, p Conclusion All-cause mortality risk was associated with increasing chronological age in competing risk analysis with adjustments of confounders. A similar trend was observed for ePhenoAge, a finding which to a large extent may be explained by the inflammatory status of the study subjects. However, contrary to expectations, ePhenoAge was not as powerful as chronological age in predicting mortality, underlining that our knowledge about factors influencing phenotypic age in CKD patients is still limited. This should motivate further study of the potential role of other estimates of biological age in CKD.

Background and Aims Home dialysis with peritoneal dialysis (PD) or home hemodialysis (HD) has medical and socioeconomic benefits but home dialysis is generally underutilized. While many factors determine choice of initial dialysis modality, starting patients on home dialysis requires timely planning, educational activities and an active program to promote home dialysis. Here we investigated factors including patient suitability, pre-dialysis preparations and institutional factors determining choice of dialysis modality among patients initiating dialysis. Method Choice of dialysis modality was investigated in 1588 consecutive patients (age 63.8 ±15.3 years. 35.8% female; diabetic nephropathy 24.4%) participating in the Peridialysis study, a multinational multi-centre prospective study of causes and timing of planned and unplanned dialysis initiation (DI) over a 3-year period in 15 Nordic and Baltic nephrology departments. All dialysis modalities were available and free of charge to patients. All centres offered pre-dialysis education programs to patients with timely referral. Clinical and biochemical data during the pre-dialytic period, centre data, and reasons for DI and choice of dialysis modality were registered. Results: 516 (32.4%) patients were not offered home dialysis because they were judged to be unsuitable (384; 24%): PD was contraindicated in 338 (21.2%) patients - for physical (142; 8.9%), mental (80, 5.0%) or abdominal (116; 7.3%) reasons and HD was contraindicated in 46 (2.9%) patients. In addition, 106 (6.7%) were not offered home dialysis for various reasons; and deaths before modality choice occurred in 26 (1.6%) patients. Factors associated with unsuitability were high age, comorbidity, late referral (risk ratio, RR, 1.9), inflammation (C-reactive protein >50 mg/L (RR 2.6) and rapid loss of renal function (RR 2.0). Patients who were not assessed for home dialysis comprised mainly patients with late referral (RR 5.8) and/or unplanned DI (RR 9.6). Of the remaining 1072 (67.6%) patients, who had a free choice of modality, 700 (65.3%) chose home dialysis, either PD (661; 61.7%) or home HD ( 39 3.6%) while 372 (34.7%) patients chose centre HD. Factors associated with choice of centre dialysis were late referral (RR 1.8), suboptimal DI (RR 2.0), symptomatic uraemia (RR 1.6) and p-urea >30 mM (2.6). Somatic differences between patients choosing home dialysis and centre dialysis were minor. Independent institutional factors reducing information about home dialysis were treatment at a university hospital (RR 4.3) and absence of an active preference for home dialysis, “home dialysis first” policy (RR 3.0). Conclusion The results of the Peridialysis study indicate that the incidence of home dialysis could be increased by a “home dialysis first” department policy and by efforts to reduce the incidence of late referrals and unplanned DI. Acutely ill patients and patients with unplanned DI may be candidates for home dialysis if assessment of home dialysis suitability and dialysis educational program are performed after their clinical condition has improved. Given a free choice, most patients (65%) choose home dialysis.

Background: Kidney fibrosis is the ultimate consequence of advanced stages of chronic kidney disease (CKD); however, there are currently no reliable biomarkers or noninvasive diagnostic tests available for the detection of kidney fibrosis. Lysyl oxidase (LOX) promotes collagen cross-linking, and serum LOX levels have been shown to be elevated in patients with fibrosis of the heart, lungs, and liver. However, serum LOX levels have not been reported in patients with kidney fibrosis. We explored whether serum LOX levels are associated with kidney fibrosis. Method: Overall, 202 patients with kidney disease underwent renal biopsy, scoring of kidney fibrosis, and determination of the area of kidney fibrosis. LOX levels were measured in serum and in kidney tissues. We analyzed the association of circulating LOX and tissue LOX levels with the scores and areas of kidney fibrosis. LOX expression was also investigated with in vitro and in vivo kidney fibrosis models. Results: Serum LOX levels were higher in patients with kidney fibrosis than in those without kidney fibrosis (p < 0.001) and higher in patients with moderate-severe kidney fibrosis than in patients with mild kidney fibrosis (p < 0.001). Both serum LOX and renal tissue LOX levels correlated with the area of kidney fibrosis (r = 0.748, p < 0.001; r = 0.899, p < 0.001, respectively). Receiver operating characteristic curve analysis of serum LOX levels showed an area under the curve of 0.80 (95% CI: 0.74–0.86). The optimal serum LOX level cutoff point was 253.34 pg/mL for the prediction of kidney fibrosis and 306.56 pg/mL for the prediction of moderate-severe kidney fibrosis. LOX expression levels were significantly upregulated (2.3–2.6 and 6-fold, respectively) in in vitro and in vivo interstitial fibrosis models. Conclusions: Both serum LOX and tissue LOX levels correlated with the presence and degree of kidney fibrosis in patients with CKD. These results suggest that serum LOX levels could potentially serve as a noninvasive diagnostic biomarker for kidney fibrosis and may further potentially serve as a stratified biomarker for the identification of mild and moderate-severe kidney fibrosis.

Background: Transferrin saturation (TSAT) is an indicator of iron deficiency or overload, but its relationship with mortality in patients with different stages of chronic kidney disease (CKD) is unclear. We investigated the association of TSAT with mortality in CKD patients. Methods: In 479 CKD patients (97 CKD3-4 patients, 298 CKD5 non-dialysis patients and 84 peritoneal dialysis patients; median age 58 years, 67% males, 33% cardiovascular disease, CVD, and 29% diabetes), biomarkers of iron status (plasma iron, TSAT, transferrin and ferritin), systemic inflammation (high sensitivity C-reactive protein, hsCRP, and interleukin-6, IL-6) and nutritional status were assessed. During median follow-up of 35.6 months, 139 (29%) patients died, and 176 (37%) patients underwent renal transplantation. Patients were stratified into Low (n=157) and Middle and high (n=322) TSAT tertile groups. All-cause and CVD mortality risk were analyzed by competing risk regression with renal transplantation as competing risk. Results: TSAT (median 23%; interquartile range, 17-30%) was negatively associated with presence of diabetes and CVD, body mass index, hsCRP, IL-6, erythropoiesis stimulating agent (ESA) dose, erythropoietin resistance index (ERI) and iron supplementation, and positively associated with hemoglobin, ferritin and s-albumin. In competing risk analysis, low tertile of TSAT was independently associated with increased all-cause mortality risk (sHR=1.74, 95%CI 1.30-2.54) and CVD mortality risk (sHR=1.80, 95%CI 1.02-3.16) after fully adjusting for 1-standard deviation (SD) of age, sex, CKD stages, 1-SD of hemoglobin, 1-SD of ferritin, 1-SD of hsCRP, 1-SD of ESA dose and iron supplementation. Conclusions: Lower TSAT indicating iron deficiency was independently associated with increased mortality risk in CKD patients, underlining that iron status should be considered when evaluating clinical outcomes of CKD patients.

Background Major fractures (MF) are associated with increased mortality in the general population and represent an even higher risk in patients with chronic kidney disease. We investigated incidence, predictors and clinical outcomes associated with first MF (MFfirst) following kidney transplantation (KT). Methods We used the Swedish National Renal Registry of 3992 first KT recipients (2005–2016) (median age 53 years, 65% men) and identified all MFfirst in hip, spine, humerus and forearm following KT. We estimated incidence rates and predictors of MFfirst using flexible parametric hazard models and Fine-Gray analysis accounting for competing risk of death, and risk of all-cause mortality following MFfirst using Cox proportional hazards models with fracture as time-varying exposure. Results During median follow-up of 4.8 years (IQR 2.2–7.9 years), there were 279 fractures of which 139 were forearm fractures. The crude incidence rate of MFfirst (n = 279) was 13.5/1000 patient-years and that of hip fractures (n = 69) 3.4/1000 patient-years. The multivariate-adjusted fracture incidence rates were highest during the first 6 months following KT, and 86% higher in women than in men. High age, female sex, previous history of MF, diabetes nephropathy, pretransplant dialysis therapy and acute rejection were associated with increased risk for MFfirst, whereas pre-emptive KT was associated with lower risk of MFfirst. Spline curves showed markedly higher impact of higher age on risk of MFfirst in women than in men. MFfirst (n = 279) independently predicted increased all-cause mortality risk (hazard ratio, HR, 1.78(95%CI 1.35–2.36)). Among MFfirst, with humerus fracture as reference, hip fracture (HR, 4.68(95%CI 1.56–14.06)) and spine fracture (HR, 4.02(95%CI 1.19–13.54)), but not forearm fracture (HR, 1.17 (95%CI 0.38–3.53)), were associated with increased all-cause mortality risk. Conclusions The initial 6 months following kidney transplantation is a high-risk period for MF. Among MF, hip fracture and spine fracture associate with substantially increased all-cause mortality risk.

AIM To evaluate possible associations between estimated glomerular filtration rate (eGFR) and hypoglycaemia in adults with diabetes. METHODS We conducted an observational study in adults with diabetes from the Stockholm Creatinine Measurement (SCREAM) project, a Swedish healthcare utilization cohort during 2007 to 2011. We evaluated diagnoses and outpatient glucose tests for incidence rate ratios (IRRs) of hypoglycaemia (overall and by severity) in outpatient care by eGFR strata using zero-inflated negative binomial regression. We identified clinical predictors through ordinal logistic regression and assessed 7-day and 30-day mortality from hypoglycaemia in relation to eGFR with Cox proportional hazard models. RESULTS We identified 29 434 people with diabetes (13% with type 1 diabetes). Their mean age was 66 years, 43% were women and the median eGFR was 80 mL/min/1.73 m2 . During 2 years of follow-up, 1812 patients (6.2%) had hypoglycaemia registered at least once. The risk of hypoglycaemia increased linearly with lower eGFR, with an IRR of 1.2 (95% confidence interval [CI] 1.0-1.4) for eGFR 60-89 mL/min/1.73 m2 and 5.8 (95% CI 3.8-9.0) for eGFR

Summary Background & aims Chronic kidney disease (CKD) patients have numerous complications associated with inflammation, which is a potential driver for cardiovascular disease. Curcumin, a compound of the curcuminoid class produced by the Curcuma longa, has been reported to activate nuclear factor erythroid factor 2-related (Nrf2) and inhibit nuclear factor kappa-B (NF-kB). Our aim was to evaluate the effects of curcumin juice on the expression of inflammatory transcription factors in hemodialysis (HD) patients. Methods and results This double-blind randomized pilot study included 31 HD patients divided into two groups: curcumin group (receiving 100 mL of orange juice with 12 g of carrot and 2.5 g of turmeric after each dialysis session/week for 3 months) and control group (receiving the same juice without curcumin); 14 patients in each arm completed the study. The mRNA expression of Nrf2, NF-kB, NLRP3 inflammasome and IL-1β in peripheral blood mononuclear cells (PBMC; using real-time quantitative polymerase chain reaction, qPCR) and routine biochemistries, food intake and anthropometrics were analyzed. After three months of supplementation, the curcumin group showed a significant decrease in NF-kB mRNA expression (AU) [from 1.08 (0.77–1.38) to 0.52 (0.32–0.95),p = 0.02] and in plasma high sensitivity C-reactive protein (hsCRP) levels [from 3.8 (2.5–6.8) to 2.0 (1.1–3.8) mg/L, p = 0.04]. There was no change in the other evaluated markers. Conclusion Three months treatment with curcumin in CKD patients undergoing HD resulted in decreased markers of inflammation, NF-kB mRNA expression and hsCRP, suggesting that oral supplementation of curcumin may have an anti-inflammatory effect in this patient group. Trial registration Approved by the Ethics Committee of the Faculty of Medicine/UFF, number: 2.346.933. This study was registered within ClinicalTrials.gov under the number NCT 03475017.

International audience; Inflammatory and innate immune responses triggered by pathogen-associated and other danger-associated signals emerging during infections, results in the activation of cytosolic inflammasomes. The nod-like receptor pyrin domain containing 3 (NLRP3) is one of the inflammasomes mediating such responses through the activation of caspase-1, which increases the production and release of pro-inflammatory cytokines, such as IL-1β and IL-18 and induces programmed cell death through pyroptosis. NLRP3 is thought to play a crucial role in the underlying inflammatory responses in many lifestyles related chronic diseases. Consequently, research on the NLRP3 inflammasome has expanded dramatically in recent years. Although several studies have investigated the role of NLRP3 activation in chronic kidney disease (CKD), few studies have evaluated strategies to modulate its activation by means of interventions using non-pharmacological strategies. This review discusses some nutritional strategies (bioactive compounds, probiotics and caloric restriction) that have been shown to influence NLRP3 in experimental models of renal disease, and in CKD. It discusses how nutritional interventions could potentially dampen NLRP3 associated inflammatory burden, as part of nutritional strategies to prevent and treat CKD and its complications.

BackgroundUltrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overall peritoneal transport characteristics in UFF patients in relation to corresponding local alterations of peritoneal tissue and capillary wall transport properties.MethodsSix-hour dwell studies using 3.86% glucose solutions and radioisotopically labelled serum albumin added to dialysate as a volume marker were analysed in 31 continuous ambulatory PD patients, 20 with normal ultrafiltration (NUF) and 11 with UFF. For each patient, the physiologically based parameters were evaluated for both transport barriers using the spatially distributed approach based on the individual intraperitoneal profiles of volume and concentrations of glucose, sodium, urea and creatinine.ResultsUFF patients as compared with NUF patients had increased solute diffusivity in both barriers, peritoneal tissue and capillary wall, decreased tissue hydraulic conductivity and increased local lymphatic absorption and functional decrease in the fraction of the ultra-small pores. This resulted in altered distribution of fluid and solutes in the peritoneal tissue, and decreased penetration depths of fluid and solutes into the tissue in UFF patients.ConclusionsMathematical modelling using a spatially distributed approach for the description of clinical data suggests that alterations both in the capillary wall and in the tissue barrier contribute to UFF through their effect on transport and distribution of solutes and fluid within the tissue.

Under normal conditions, inflammation is a protective and physiological response to various harmful stimuli. However, in several chronic debilitating disorders, such as chronic kidney disease, inflammation becomes maladaptive, uncontrolled and persistent. Systemic persistent inflammation has, for almost 20 years, been recognized as a major contributor to the uraemic phenotype (such as cardiovascular disease, protein energy wasting, depression, osteoporosis and frailty), and a predictor of cardiovascular and total mortality. Since inflammation is mechanistically related to several ageing processes (inflammageing), it may be a major driver of a progeric phenotype in the uraemic milieu. Inflammation is likely the consequence of a multifactorial aetiology and interacts with a number of factors that emerge when uraemic toxins accumulate. Beside interventions aiming to decrease the production of inflammatory molecules in the uraemic milieu, novel strategies to increase the removal of large middle molecules, such as expanded haemodialysis, may be an opportunity to decrease the inflammatory allostatic load associated with retention of middle molecular weight uraemic toxins.

Antibiotic resistance is a major global health threat. High prevalences of colonization and infection with multi-drug resistance organisms (MDROs) have been reported in patients undergoing dialysis. It is unknown if this finding extends to patients with mild and moderate/severe kidney disease. An observational study included all adult incident patients hospitalized with a discharge diagnosis of infection in four hospitals from Guangzhou, China. Inclusion criteria: Serum creatinine measurement at admission together with microbial culture confirmed infections. Exclusion criterion: Undergoing renal replacement therapy. Four categories of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) were compared: eGFR ≥ 105, 60–104 (reference), 30–59, and 2. The odds ratio of MDROs, defined as specific pathogens (Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp.) resistant to three or more antibiotic classes, were calculated using a multivariable logistic regression model across eGFR strata. Of 94,445 total microbial culture records, 7,288 first positive cultures matched to infection diagnosis were selected. Among them, 5,028 (68.9%) were potential MDROs. The odds of infections by MDROs was 19% and 41% higher in those with eGFR between 30–59 ml/min/1.73 m2 (Adjusted odds ratio, AOR): 1.19, 95% CI:1.02–1.38, P = 0.022) and eGFR 2 (AOR: 1.41, 95% CI:1.12–1.78, P = 0.004), respectively. Patients with impaired renal function have a higher risk of infections by MDROs. Kidney dysfunction at admission may be an indicator for need of closer attention to microbial culture results requiring subsequent change of antibiotics.

Probiotics may mitigate the generation of uremic toxins and inflammatory biomarkers. The aim of this study was to evaluate the effects of probiotics on uremic toxins and inflammatory biomarkers in CKD. In this randomized, double-blind, placebo-controlled trial, 30 patients (63.8 ± 7.5 years, 14 men, mean BMI of 27.2 ± 3.8 kg/m2) were assigned to receive one of two treatments: probiotics (n = 15; Streptococcus thermophilus, Lactobacillus acidophilus and Bifidobacteria longum-90 billion CFU per day) or placebo (n = 15) daily for three months. Plasma uremic toxins were measured using reversed-phase liquid-chromatography (RP-HPLC); choline, betaine and trimethylamine-N-oxide (TMAO) were measured using liquid chromatography–mass spectrometry (LC-MS/MS); and inflammatory biomarkers were measured using ELISA. Uremic toxins were not influenced by the probiotics; however, IL-6 levels increased significantly from 15.6 (14.8–20.8) pg/mL to 23.0 (17.6–29.6) pg/mL, p = 0.01. There was a positive correlation between the levels of p-cresyl sulfate and urea (r = 0.55; p = 0.02) and between TMAO and CRP (r = 0.46; p = 0.05) at baseline. These data suggest that probiotic supplementation did not result in expected benefits for non-dialysis CKD patients.

Low serum albumin (S-Alb) is a frequent feature of end-stage renal disease (ESRD) that independently predicts mortality. Serum albumin has mainly been considered a biomarker of visceral protein and immunocompetence status, fundamental to nutritional assessment. However, low S-albumin level is associated with persistent systemic inflammation and many bodies of evidence show that S-Alb has a limited role as a marker of nutritional status. We reported that a low S-Alb concentration was an independent risk factor for poor outcome in ESRD only in the presence of systemic inflammation. Moreover, the relationships between inflammatory biomarkers and outcome are confounded also by alterations in body composition (such as obese sarcopenia) and oxidative stress. Taken together, S-Alb alone should not be used as a proxy of the nutritional status in a dialysis patient. Its association with dietary intake is poor and low S-Alb values are most often non-nutritional in origin. When analyzing S-Alb to predict mortality risk in ESRD, it should always be combined with measurement of hsCRP.

Açai (Euterpe oleracea Mart.) fruit from the Amazon region in Brazil contains bioactive compounds such as α-tocopherol, anthocyanins (cyanidin 3-glycoside and cyanidin 3-rutinoside), and other flavonoids with antioxidant and anti-inflammatory properties. Moreover, the prebiotic activity of anthocyanins in modulating the composition of gut microbiota has emerged as an additional mechanism by which anthocyanins exert health-promoting effects. Açai consumption may be a nutritional therapeutic strategy for chronic kidney disease (CKD) patients since these patients present with oxidative stress, inflammation, and dysbiosis. However, the ability of açai to modulate these conditions has not been studied in CKD, and this review presents recent information about açai and its possible therapeutic effects in CKD.