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Importance: More than 3.5 million people worldwide and 540 000 individuals in the US receive maintenance hemodialysis or peritoneal dialysis for the treatment of chronic kidney failure. The 5-year survival rate is approximately 40% after initiation of maintenance dialysis., Observations: Hemodialysis and peritoneal dialysis remove metabolic waste and excess body water and rebalance electrolytes to sustain life. There is no recommended estimated glomerular filtration rate (eGFR) threshold for initiating dialysis, and patient-clinician shared decision-making should help determine when to initiate dialysis. Persistent signs and symptoms of uremia (eg, nausea, fatigue) and volume overload (eg, dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia inform the timing of therapy initiation. A randomized clinical trial reported no mortality benefit to starting dialysis at higher eGFR (10-14 mL/min/1.73 m2) vs lower eGFR (5-7 mL/min/1.73 m2) levels. Observational data suggested no differences in 5-year mortality with use of hemodialysis vs peritoneal dialysis. Cardiovascular (eg, arrhythmias, cardiac arrest) and infection-related complications of maintenance dialysis are common. In the US, hemodialysis catheter-related bloodstream infections occur at a rate of 1.1 to 5.5 episodes per 1000 catheter-days and affect approximately 50% of patients within 6 months of catheter placement. Peritonitis occurs at a rate of 0.26 episodes per patient-year and affects about 30% of individuals in the first year of peritoneal dialysis therapy. Chronic kidney failure-related systemic complications, such as anemia, hyperphosphatemia, hypocalcemia, and hypertension, often require pharmacologic treatment. Hypotension during dialysis, refractory symptoms (eg, muscle cramps, itching), and malfunction of dialysis access can interfere with delivery of dialysis., Conclusions and Relevance: In 2021, more than 540 000 patients in the US received maintenance hemodialysis or peritoneal dialysis for treatment of chronic kidney failure. Five-year survival rate after initiation of maintenance dialysis is approximately 40%, and the mortality rate is similar with hemodialysis and peritoneal dialysis. Decisions about dialysis initiation timing and modality are influenced by patient symptoms, laboratory trajectories, patient preferences, and therapy cost and availability and should include shared decision-making.

Little is known about the prognostic value of left atrial strain by four-dimensional speckle-tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction. This prospective study collected clinical and echocardiographic data from 80 stable dialysis patients (mean age 57 ± 10 years; 62.5% men). All patients underwent the dedicated four-dimensional speckle-tracking echocardiography to measure LASr (peak longitudinal strain of reservoir function), LAScd (peak longitudinal strain of conduit function), LASct (peak longitudinal strain of contractile function), LASr&#95;c (peak circumferential strain of reservoir function), LAScd&#95;c (peak circumferential strain of conduit function) and LASct&#95;c (peak circumferential strain of contractile function). These patients were enrolled from August 2021 to August 2023 and followed-up for 19 months (interquartile-range 15 to 20 months). The primary outcome was a composite of all-cause mortality or major adverse cardiovascular events (MACEs). The study patients were classified into event (developed mortality or MACEs) and event-free group according to the primary outcome. Multivariate Cox regression analysis was used to investigate risk factors for all-cause mortality or MACEs. The event group had lower LASr (16.4% vs. 21.2%, P = 0.0003), LASct (8.2% vs. 11.2%, P = 0.01), LASr&#95;c (25.2% vs. 35.0%, P = 0.0004) and LASct&#95;c (14.9% vs. 20.9%, P = 0.001) than the event-free group. Using optimal cut-off value determined by ROC curve, the less LASr (LASr < 18.5%), LASct (LASct < 8.5%), LASr&#95;c (LASr&#95;c < 28.5%), and LASct&#95;c (LASct&#95;c < 17.5%) group had a higher mortality or MACEs rate. Multivariate cox regression analyses revealed that LASr (HR = 0.81, 95% CI [0.17; 0.91], P = 0.0005, per 1% increase) and LASr&#95;c (HR = 0.93, 95% CI [0.87; 0.98], P = 0.01, per 1% increase) were independent predictors of all-cause mortality or MACEs. Less peak longitudinal and circumferential strains of reservoir function are predictive of poor prognosis among end-stage renal disease patients with preserved left ventricular ejection fraction., (© 2024. The Author(s).)

The characteristics in dialyzer are associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. From the long-term nationwide population database. Prevalent HD patients during 2005-2012 were enrolled. Our main analysis to calculate the effect was cox regression multivariate model. Overall, the mean age of all population (N = 73 565) was 61.0 ± 13.6 years, the observation period is 2.46 years ±0.98 within 3 years and 64.6% used polysulfone (PS), polymethyl methacrylate (PMMA) (11.6%), polyethersulfone (11.4%), and cellulose triacetate (CTA) (10.7%), ethylene vinyl alcohol (EVAL) (hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.71-4.33) and CTA (HR 1.35, 95% CI 1.12-1.64) were associated with higher mortality than PS, but PMMA was not. EVAL and CTA adversely affected mortality and PMMA had no protective role. Further investigations on membrane characters on HD patients are warranted. Taipei Medical University (TMU) (TMU-JIRB (No. N201804051)., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal., (© 2021. The Author(s).)

Patients with renal disease have increased rates of admission to the neurological intensive care unit related to overlapping risk factors for renal and cerebrovascular disease as well as unique risks associated with renal dysfunction alone. Management of acute neurological injury in these patients requires individualized attention to diagnostic and management factors as they relate to coagulopathy, disorders of immune function, encephalopathy and renal replacement modalities. Careful consideration of these brain-kidney interactions is necessary to optimize care for this special patient population and improve neurological and renal outcomes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alterations of fibroblast growth factor 23 (FGF-23) and Klotho levels are considered to be the earliest biochemical abnormality of chronic kidney disease - mineral and bone disease (CKDMBD) syndrome. Moreover, emerging data suggests that the dysregulated FGF-23 and Klotho axis has many effects on the cardiovascular (CV) system and contributes significantly to the increased CV morbidity and mortality rates of CKD patients. This review examines recent evidence on the role of FGF-23 and Klotho in the development and progression of CV complications of uremia namely cardiac hypertrophy, uremic cardiomyopathy, and atherosclerotic and arteriosclerotic vascular lesions. Moreover, the available evidence on their associations with adverse clinical outcomes are summarized. Undoubtedly, more studies are needed to further elucidate the effects of FGF-23 and Klotho on the heart and vessels and to gain insights into their prognostic value as CV risk factors. Finally, large prospective studies are required to test the hypothesis that modification of their levels would have a favourable impact on the unacceptably high mortality rates of these patient populations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Uremic toxins (UTs) generally accumulate in patients developing end-stage renal disease (ESRD). Although some kinds of UTs cause early death after starting hemodialysis (HD), it remains unknown whether the degree of excessive accumulation of various UTs is associated with worsening of prognosis. We retrospectively conducted this cohort study consisting of adult patients developing ESRD who initiated HD at the National Center for Global Health and Medicine from 2010 to 2019. We created a new uremic score, which was defined as the aggregate score of the following variables reflecting uremic state: elevated blood urea nitrogen, β2-microglobulin, and anion gap before starting HD. The primary outcome was early mortality within 1-year after HD commencement. The hazard ratio (HR) and 95% confidence interval (CI) for a one-point increase in uremic score was calculated with Cox proportional hazard models adjusted by baseline conditions. We included 230 participants, 16 of whom experienced the primary outcome of early mortality after HD commencement. Uremic score was significantly associated with the primary outcome (crude HR: 1.91, 95% CI 1.16-3.14; adjusted HR: 4.19, 95% CI 1.79-9.78). Our novel uremic score, reflecting accumulation of specific UTs, more precisely predicts early mortality after HD commencement.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failure results in disturbed renal metabolic activities with reduced renin, erythropoietin, and vitamin D production, which adversely affects the immune system. Decreased kidney function also leads to reduced glomerular filtration and the retention of uremic toxins. A large number of uremic toxins with detrimental effects on immune cells have been identified. Besides small water-soluble and protein-bound compounds originating from the intestinal microbiome, several molecules in the middle molecular range, e.g., immunoglobulin light chains, retinol-binding protein, the neuropeptides Met-enkephalin and neuropeptide Y, endothelin-1, and the adipokines leptin and resistin, adversely affect immune cells. Posttranslational modifications such as carbamoylation, advanced glycation products, and oxidative modifications contribute to uremic toxicity. Furthermore, high-density lipoprotein from uremic patients has an altered protein profile and thereby loses its anti-inflammatory properties., Competing Interests: The author declares no conflict of interest.

Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid ( p < 0.001), indoxyl sulfate ( p = 0.001), indole-3-acetic acid ( p = 0.024), p-cresyl glucuronide ( p = 0.004) and hippuric acid ( p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (-15.3 to 34.6) in patients treated with HDF and increased by 11.9% (-15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Chronic kidney disease is highly prevalent, affecting 10% to 15% of the adult population worldwide and is associated with increased cardiovascular morbidity and mortality. As chronic kidney disease worsens, a unique cardiovascular phenotype develops characterized by heart muscle disease, increased arterial stiffness, atherosclerosis, and hypertension. Cardiovascular risk is multifaceted, but most cardiovascular deaths in patients with advanced chronic kidney disease are caused by heart failure and sudden cardiac death. While the exact drivers of these deaths are unknown, they are believed to be caused by uremic cardiomyopathy: a specific pattern of myocardial hypertrophy, fibrosis, with both diastolic and systolic dysfunction. Although the pathogenesis of uremic cardiomyopathy is likely to be multifactorial, accumulating evidence suggests increased production of fibroblast growth factor-23 and αKlotho deficiency as potential major drivers of cardiac remodeling in patients with uremic cardiomyopathy. In this article we review the increasing understanding of the physiology and clinical aspects of uremic cardiomyopathy and the rapidly increasing knowledge of the biology of both fibroblast growth factor-23 and αKlotho. Finally, we discuss how dissection of these pathological processes is aiding the development of therapeutic options, including small molecules and antibodies, directly aimed at improving the cardiovascular outcomes of patients with chronic kidney disease and end-stage renal disease.

Chronic kidney disease (CKD) is associated with a high prevalence of cardiovascular diseases. During CKD, the uremic toxin indoxyl sulfate (IS)-derived from tryptophan metabolism-accumulates. IS is involved in the pathophysiology of cardiovascular complications. IS can be described as an endotheliotoxin: IS induces endothelial dysfunction implicated in cardiovascular morbidity and mortality during CKD. In this review, we describe clinical and experimental evidence for IS endothelial toxicity and focus on the various molecular pathways implicated. In patients with CKD, plasma concentrations of IS correlate with cardiovascular events and mortality, with vascular calcification and atherosclerotic markers. Moreover, IS induces a prothrombotic state and impaired neovascularization. IS reduction by AST-120 reverse these abnormalities. In vitro, IS induces endothelial aryl hydrocarbon receptor (AhR) activation and proinflammatory transcription factors as NF-κB or AP-1. IS has a prooxidant effect with reduction of nitric oxide (NO) bioavailability. Finally, IS alters endothelial cell and endothelial progenitor cell migration, regeneration and control vascular smooth muscle cells proliferation. Reducing IS endothelial toxicity appears to be necessary to improve cardiovascular health in CKD patients.

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)-kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23-klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.

3-Carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) is a metabolite of furan fatty acid and a marker of fish oil intake. CMPF is described as a protein-bound uremic toxin and interacts with free oxygen radicals, which can induce cell damages. However, the clinical consequences of CMPF accumulation in haemodialysis patients remain poorly documented. The aims of this study are to investigate potential association between CMPF levels and (i) biochemical and nutritional parameters; (ii) cardiovascular events and (iii) mortality. Two hundred and fifty-two patients undergoing maintenance haemodialysis were included. Routine clinical biochemistry tests and assay for CMPF by HPLC technique were performed at the inclusion. Body composition parameters were measured using a bioimpedance spectroscopy method. The enrolled patients were prospectively monitored for cardiovascular events and mortality. CMPF level was positively correlated with nutritional parameters and lean mass and is significantly higher in patients without protein-energy wasting. However, the multivariate linear regression analysis indicated that CMPF level was not independently associated with albumin, prealbumin, creatinemia and body mass index. Elevated serum CMPF was not associated with mortality and cardiovascular morbidity. Our results indicate that CMPF is not a relevant uremic toxin in haemodialysis and in contrast could be a marker of healthy diet and omega 3 intakes.

Background: Conventional treatments for patients suffering with end-stage renal disease (ESRD) has several disadvantages, highlighting the importance of other reproducible modalities such as colonic dialysis (CD)., Objectives: The aim was to establish a CD model in uremic rats and evaluate the effect of two different peritoneal dialysis (PD) solutions., Methods: Thirty-two male Wistar rats were randomly divided into four groups. After right nephrectomy and left partial nephrectomy, a Malone antegrade continence enema (MACE) stoma was created. Seven days after the procedure, blood sampling was performed. In group I (N = 8) no postoperative intervention was performed. In group II (N = 8), CD was started through the MACE stoma by a low osmolar PD solution. Rats of group III (N = 8) underwent the same procedure with a high osmolar PD solution. Rats of group IV (N = 8) underwent CD without nephrectomy in order to evaluate the feasibility of this technique. Mannitol and activated charcoal were also added to both PD solutions. Weekly blood sampling was performed in order to evaluate the plasma creatinine and blood urea nitrogen (BUN) level., Results: In rats of the control group, the respective mean ± SD creatinine level was 1.5 ± 0.04 mg/dL, 7 days after the surgical procedure, but a lower creatinine level was found in groups II and III (0.8 ± 0.02 and 0.5 ± 0.03, respectively). Despite the fact that the creatinine level was in steady low states after regular CD in group II (1 ± 0.05) and group III (0.6 ± 0.02), it remained at higher levels in the control group (1.7 ± 0.08) 2 weeks postoperatively. Rats of group I did not survive until the third postoperative week, while the creatinine level was still lower in group III than in group II (0.6 ± 0.02 vs. 1.1 ± 0.03). Similar results were obtained for the BUN level at these timepoints. The mean ± SD survival period was 11 ± 2, 20 ± 3, and 33 ± 2 days in the animals of groups I, II, and III, respectively., Discussion: To the best of our knowledge, this is the first study of CD establishment in a rat model. Unfortunately, the amount of protein loss, elevation of blood glucose levels, and electrolyte disturbance were not evaluated in the current study because of the limited amount of blood samples. Disturbance of these factors might be a cause of mortality in experimental groups undergoing CD while a significant decrease in BUN and creatinine levels was obtained., Conclusion: CD with an efficient PD solution through a MACE stoma may be a valuable option when conventional methods are not available., (Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Previous studies show that serum bilirubin has potent antioxidant effect and is associated with protection from kidney damage and reduce cardiovascular events. The aim of this study was to examine the association of serum total bilirubin level and mortality in uremia patients who underwent hemodialysis., Methods: This is a nationwide retrospective long-term cohort study. Patients were registered in the Taiwan Renal Registry Data System (TWRDS) from 2005 to 2012. A total of 115,535 hemodialysis patients were surveyed and those with valid baseline total bilirubin (TB) data were enrolled. All-cause mortality was the primary outcome., Results: A total of 47,650 hemodialysis patients followed for 27.6 ± 12 months, were divided into 3 groups according to different baseline serum total bilirubin levels (0.1-0.3, 0.3-0.7, 0.7-1.2 mg/dL). Mean age was 61.4 ± 13.6 years, 50% were male, 13% were hepatitis B carriers, and 20% were hepatitis C carriers. Primary outcome was the 3-year mortality. The TB level 0.7-1.2 mg/dL group had high mortality, statistically significant hazard ratio of mortality was 1.14 (crude HR, 95% 1.07-1.20, p < 0.01), and adjusted HR was 1.18 (model 1, 95% CI 1.11-1.25), 1.21 (model 2, 95% CI 1.14-1.29, p < 0.01), 1.44 (model 3, 95% CI 1.06-1.96, p < 0.01), respectively. Sensitivity test showed that after excluding 14,899 patients with hepatitis B or C, or abnormal liver function, the highest level of TB associated with higher significant mortality was still robust., Conclusions: In our study, high TB level is associated with mortality in uremia patients undergoing long-term hemodialysis, but further studies of the different effects of unconjugated or conjugated bilirubin on hemodialysis patients are needed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Gastrointestinal bleeding remains the leading cause of morbidity and mortality for patients who need hemodialysis treatment. Our aim was to evaluate patients who needed hemodialysis and presented with bleeding during their hospital stay (uremic bleeding patients). Factors that increased the risk of bleeding and death were evaluated. Additionally, uremic bleeding patients were compared to non-uremic bleeding patients regarding gastrointestinal findings., Patients and Methods: Fifty-one uremic bleeding patients were compared to two control groups which included uremic (hemodialysis dependent and non-bleeding) and non-uremic (no renal insufficiency and bleeding) patients., Results: NSAIDs and anti-ulcer drug usage were more common in uremic bleeding and in uremic non-bleeding groups, respectively. Dialysis vintage was longer in uremic bleeding group. Comparison of uremic bleeding and non-bleeding uremic patients regarding the usage of ACEI or ARB drugs yielded non-significant results. Acute kidney injury, lower plasma albumin level and high CRP level were significantly increased the risk of mortality in uremic bleeding patients. Hospital stay more than 1 week was the only strong factor for mortality when multivariate analysis was performed. Gastroduodenal and duodenal ulcers were significantly detected in uremic bleeding and non-uremic bleeding patients; respectively., Conclusions: Hemodialysis patients presenting with gastrointestinal bleeding should be evaluated regarding use of prescriptions and efforts should be done in order to shorten their hospital stay and decrease their mortality. Effect of ACEI or ARB drugs should also be evaluated in future studies.

Background: Vascular access (VA) is the lifeline of hemodialysis patients. Although the autonomic nervous system might be associated with VA failure (VAF), it has never been addressed in previous studies. This study aimed to evaluate the predictive values of the heart rate variability (HRV) indices for long-term VA outcomes., Methods: This retrospective study was conducted using a prospectively established cohort enrolling 175 adult chronic hemodialysis patients (100 women, mean age 65.1 ± 12.9 years) from June 2010 to August 2010. Each participant received a series of HRV measurements at enrollment. After a 60-month follow-up period, we retrospectively reviewed all events and therapeutic procedures of the VAs which existed at the enrollment and during the follow-up period., Results: During the 60-month follow-up period, 37 (26.8%) had VAF but 138 (73.2%) didn't. The values of most HRV indices were statistically increased during hemodialysis since initiation in the non-VAF group, but not in the VAF group. Among all participants, the independent indicators for VAF included higher normalized high-frequency (nHF) activity [hazard ratio (HR) 1.04, p = 0.005], lower low-frequency/high-frequency (LF/HF) ratio (HR 0.80, p = 0.015), experience of urokinase therapy (HR 11.18, p = 0.002), percutaneous transluminal angioplasty (HR 2.88, p = 0.003) and surgical thrombectomy (HR 2.36, p = 0.035), as well as higher baseline serum creatinine (HR 1.07, p = 0.027) and potassium level (HR 1.58, p = 0.037). In subgroup analysis, a lower sympathetic activity indicated by lower LF/HF ratio was an independent indicator for VAF (HR 0.61, p = 0.03) for tunneled cuffed catheter, but conversely played a protective role against VAF (HR 1.27, p = 0.002) for arteriovenous fistula., Conclusions: HRV is a useful tool for predicting long-term VAF among hemodialysis patients.

The uremic solute indoxyl sulfate has been associated with increased mortality and other adverse outcomes in patients with chronic kidney disease. In a recent study published in Cell Host & Microbe, Devlin et al. describe a novel approach to alter the production of indoxyl sulfate through manipulation of the gut microbiota. Although this approach is far from clinical application, it may allow investigators to determine the contribution of uremic solutes to disease pathogenesis., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Haemodialysis is the only renal replacement therapy available in Cameroon; 95% of patients has received subsidies by the State since 2002 and the number of dialysis centers is growing. However, since the opening of the first center in 1990, there are no data on survival in chronic dialysis patients., Methods: We conducted a multicenter prospective cohort study of 15 months in order to assess mortality rates and factors that influence the survival of chronic hemodialysis patients in Cameroon., Résults: We followed 197 patients of whom 109 were incident patients. The average age was 47,97± 13.19 years and 55% were male. The mean duration of dialysis in prevalent patients was 12.5 months. The mortality rate was 57,58%, 50% of which occurred the first 3 months and abandonment rate was 8.6%. Uremia and catheter-related sepsis were the main causes of death. At a median follow up of 15 months, the overall survival was 30.77%, with an average duration of life of 8 months. Prevalent patients, patient's place of residence where the dialysis center is located, nonfamily management, predialysis follow up > 3 months, blood cholesterol when patient first started on dialysis> 1.5g/l, a mental test score > 25 were associated with a better survival., Conclusion: In Cameroon, mortality rate in hemodialysis patients is high, with a mean survival time of 8 months; most patients die within the first 3 months., Competing Interests: Les auteurs déclarent n'avoir aucun conflit d'intérêt.

Prevention of bone fractures is one goal of therapy for patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), as indicated by the Kidney Disease: Improving Global Outcomes guidelines. CKD patients, including those on hemodialysis, are at higher risk for fractures and fracture-related death compared to people with normal kidney function. However, few clinicians focus on this issue as it is very difficult to estimate bone fragility. Additionally, uremia-related bone fragility has a more complicated pathological process compared to osteoporosis. There are many uremia-associated factors that contribute to bone fragility, including severe secondary hyperparathyroidism, skeletal resistance to parathyroid hormone, and bone mineralization disorders. Uremia also aggravates bone volume loss, disarranges microarchitecture, and increases the deterioration of material properties of bone through abnormal bone cells or excess oxidative stress. In this review, we outline the prevalence of fractures, the interaction of CKD-MBD with osteoporosis in CKD patients, and discuss possible factors that exacerbate the mechanical properties of bone.

Background: Restless legs syndrome, also known as Willis/Ekbom disease (RLS/WED), is a sleep-related, sensorimotor disorder with a high prevalence among end-stage renal disease (ESRD) patients undergoing haemodialysis (HD) (about 15-40%). Whether RLS/WED in uremic patients influences cardiovascular morbidity and mortality remains a matter of controversy. The aim of this study was to evaluate the relationship of RLS/WED and mortality in a population of chronically dialyzed patients., Method: In 1996, we studied 128 patients with ESRD undergoing HD; 47 subjects (36.7%) complained RLS/WED symptoms. Fifteen years later we evaluated the mortality of this population. No clinical follow-up examination of the uremic population was made. The Kaplan-Maier curves in dialysis patients with or without RLS/WED (control group matched for age) were constructed for all-cause mortality and compared using log-rank test., Results: The Kaplan-Maier curves disclosed a lower mortality rate in the uremic patients with RLS/WED than in those without RLS/WED (p = 0.04). In our analysis, the mortality rate was not influenced by RLS/WED severity (p = 0.11) or gender (p = 0.15). No difference among the causes of death was found in the 2 groups., Conclusions: Our study suggests that mortality in ESRD patients is not influenced by concomitant RLS/WED. After a 15-year follow-up, survival rates in our cohort were significantly longer in uremic subjects with RLS/WED than in those without RLS/WED. Finally, we found no relationship between RLS/WED severity and mortality., (© 2017 S. Karger AG, Basel.)

Objective: To assess SV in our RRT population in the period 1976-2012 as well as the influence of technique transference (TT)., Material and Methods: The study included a retrospective cohort of 993 patients. Data were classified as transplant (Tx), change in technique, exitus or lost to follow-up. SV for TT was determined in patients with over 12 weeks of permanence., Results: The mortality risk adjusted for age, sex, dialysis technique or diabetes mellitus (DM) showed that the estimated risk of death increased by 4.8% per year increase (HR=1.048; 95% CI: 1.04-1.06; P<.001) and was 44% higher in diabetics compared to non-diabetics (HR=1.44; 95% CI 1.16-1.76; P<.01). Regarding SV for TT, patients who initiated HD had a shorter survival than those who initiated PD and transferred to HD (P=.00563)., Conclusion: In our experience, SV in RRT is dependent on age and coexistence of DM. It would be beneficial to reinstate the concept of "comprehensive care", in which RRT would start with PD and later transfer to HD., (Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Restless legs syndrome (RLS) affects almost one out of three end-stage renal disease patients. This review assesses the current treatment options for uremic RLS and the potential benefits of those treatments on quality of life parameters, cardiovascular mortality and survival. A systematic review was conducted searching PubMed and Scopus by using the Cochrane and PRISMA guidelines. Fourteen studies met the inclusion criteria in which the international RLS study group criteria were used as the primary diagnostic tool. Both pharmacological and non-pharmacological approaches were found to reduce the severity of uremic RLS symptoms. Only four studies reported changes on aspects related to quality of life while those changes were also associated with health benefits that resulted in reduced cardiovascular risk. The severity of uremic RLS symptoms can be ameliorated by using dopamine agonists and gabapentin, intravenous iron, exercise or supplementation with vitamins C and E, although some of those treatment benefits may be transient. There is a lack of strong evidence regarding the effects of the pharmacological approaches on quality of life and cardiovascular survival and mortality. In contrast exercise has been proven beneficial in both reducing the RLS symptoms' severity score and improving the quality of life., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: High urologic malignancy incidence has been reported in end-stage renal disease (ESRD) patients, especially of female sex. This study was undertaken to evaluate whether female recipients still carry an aggravated risk of this malignancy after kidney transplantation (KT)., Methods: The claims data from the Bureau of National Health Insurance of Taiwan were used for analysis. All KT recipients who developed urologic malignancy from January 1, 1999, to December 31, 2007 (n = 2,245) were enrolled in this study. By means of propensity score, a database of 1:4 ratio random incident ESRD patients with matched age, sex, comorbidity rates, and dialysis to index date was used as control (non-KT group, n = 8,980). The last observation period ended on December 31, 2008., Results: The cumulative urologic malignancy incidence rate was significantly higher in female recipients after KT than their female ESRD counterparts without KT (P < 0.001). This gap became more prominent approximately 2 years after transplantation. No similar trend was detected in male KT patients (P = 0.13). Incidence rate ratio of urologic malignancy was significantly higher in female recipients (incidence rate ratio, 2.13; 95% confidence interval [95% CI], 1.53-2.97) than in their male counterparts (incidence rate ratio, 1.43; 95% CI, 0.90-2.25). From multivariate Cox proportional hazard regression tests, female (hazards ratio, 2.10; 95% CI, 1.52-2.95) but not male sex (hazards ratio, 1.47; 95% CI, 0.93-2.32) was determined to be an independent factor for the development of urologic malignancy after KT. After acquiring this malignancy, KT recipients did not have any advantage in cumulative survival compared to ESRD patients without KT (P = 0.07)., Conclusion: Compared to males, female recipients tended to have a significantly higher urologic malignancy risk after KT.

Background/aims: To evaluate the relationship between plasma hydrogen sulfide (H₂S) and cardiovascular risk markers, including pulse pressure (PP), left ventricular mass index (LVMI) and intima-media thickness (IMT), and mortality in chronic hemodialysis (CHD) patients and further investigate the underlying cardiovascular protection mechanism of H₂S., Methods: CHD patients, 113 of them, were studied. Plasma H₂S was measured through zinc acetate reaction. cPKCβII membrane translocation and phosphorylation of Akt were detected by western blot., Results: Lower plasma H₂S level in CHD patients was predictor of an increased PP, LVMI and IMT. Patients with lower H₂S had a lower survival at the end of the study. H₂S was an independent predictor of all-cause and cardiovascular mortality when adjusted for other risk factors. CHD patients with lower H₂S showed an increase of cPKCβII activation, but phosphorylation of Akt decreased. The level of VCAM-1 and ICAM-1 increased significantly., Conclusions: Lower plasma H₂S in CHD patients is associated with cardiovascular risk factors and mortality, which may be mediated by the cPKCβII/Akt pathway and further VCAM-1/ICAM-1 upregulation., (© 2015 S. Karger AG, Basel.)

Background: The marked excess in cardiovascular mortality that results from uremia remains poorly understood., Methods and Results: In 2 independent, nested case-control studies, we applied liquid chromatography-mass spectrometry-based metabolite profiling to plasma obtained from participants of a large cohort of incident hemodialysis patients. First, 100 individuals who died of a cardiovascular cause within 1 year of initiating hemodialysis (cases) were randomly selected along with 100 individuals who survived for at least 1 year (controls), matched for age, sex, and race. Four highly intercorrelated long-chain acylcarnitines achieved the significance threshold adjusted for multiple testing (P<0.0003). Oleoylcarnitine, the long-chain acylcarnitine with the strongest association with cardiovascular mortality in unadjusted analysis, remained associated with 1-year cardiovascular death after multivariable adjustment (odds ratio per SD 2.3 [95% confidence interval, 1.4 to 3.8]; P=0.001). The association between oleoylcarnitine and 1-year cardiovascular death was then replicated in an independent sample (n=300, odds ratio per SD 1.4 [95% confidence interval, 1.1 to 1.9]; P=0.008). Addition of oleoylcarnitine to clinical variables improved cardiovascular risk prediction using net reclassification (NRI, 0.38 [95% confidence interval, 0.20 to 0.56]; P<0.0001). In physiologic profiling studies, we demonstrate that the fold change in plasma acylcarnitine levels from the aorta to renal vein and from pre- to posthemodialysis samples exclude renal or dialytic clearance of long-chain acylcarnitines as confounders in our analysis., Conclusions: Our data highlight clinically meaningful alterations in acylcarnitine homeostasis at the time of dialysis initiation, which may represent an early marker, effector, or both of uremic cardiovascular risk.

Background: Uremic toxins are emerging as important, non-traditional cardiovascular risk factors in chronic kidney disease (CKD). P-cresol has been defined as a prototype protein-bound uremic toxin. Conjugation of p-cresol creates p-cresylsulfate (PCS) as the main metabolite and p-cresylglucuronide (PCG), at a markedly lower concentration. The objective of the present study was to evaluate serum PCG levels, determine the latter's association with mortality and establish whether the various protein-bound uremic toxins (i.e. PCS, PCG and indoxylsulfate (IS)) differed in their ability to predict mortality., Methodology/principal Findings: We studied 139 patients (mean ± SD age: 67±12; males: 60%) at different CKD stages (34.5% at CKD stages 2-3, 33.5% at stage 4-5 and 32% at stage 5D). A recently developed high-performance liquid chromatography method was used to assay PCG concentrations. Total and free PCG levels increased with the severity of CKD. During the study period (mean duration: 779±185 days), 38 patients died. High free and total PCG levels were correlated with overall and cardiovascular mortality independently of well-known predictors of survival, such as age, vascular calcification, anemia, inflammation and (in predialysis patients) the estimated glomerular filtration rate. In the same cohort, free PCS levels and free IS levels were both correlated with mortality. Furthermore, the respective predictive powers of three Cox multivariate models (free PCS+other risk factors, free IS+other risk factors and free PCS+other risk factors) were quite similar--suggesting that an elevated PCG concentration has much the same impact on mortality as other uremic toxins (such as PCS or IS) do., Conclusions: Although PCG is the minor metabolite of p-cresol, our study is the first to reveal its association with mortality. Furthermore, the free fraction of PCG appears to have much the same predictive power for mortality as PCS and IS do.

Background and Aim: The clinical aspects of patients with hepatocellular carcinoma (HCC) undergoing maintenance dialysis are largely unknown. We aimed to investigate the long-term survival and prognostic determinants of dialysis patients with HCC., Methods: A total of 2502 HCC patients, including 30 dialysis patients and 90 age, sex, and treatment-matched controls were retrospectively analyzed., Results: Dialysis patients more often had dual viral hepatitis B and C, lower serum α-fetoprotein level, worse performance status, higher model for end-stage liver disease (MELD) score than non-dialysis patients and matched controls (P all < 0.05). There was no significant difference in long-term survival between dialysis and non-dialysis patients and matched controls (P = 0.684 and 0.373, respectively). In the Cox proportional hazards model, duration of dialysis < 40 months (hazard ratio [HR]: 6.67, P = 0.019) and ascites (HR: 5.275, P = 0.019) were independent predictors of poor prognosis for dialysis patients with HCC. Survival analysis disclosed that the Child-Turcotte-Pugh (CTP) provided a better prognostic ability than the MELD system. Among the four currently used staging systems, the Japan Integrated Scoring (JIS) system was a more accurate prognostic model for dialysis patients; a JIS score ≥ 2 significantly predicted a worse survival (P = 0.024)., Conclusions: Patients with HCC undergoing maintenance dialysis do not have a worse long-term survival. A longer duration of dialysis and absence of ascites formation are associated with a better outcome in dialysis patients. The CTP classification is a more feasible prognostic marker to indicate the severity of cirrhosis, and the JIS system may be a better staging model for outcome prediction., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Objectives: Uremic metabolic acidosis is only partially corrected in many hemodialysis patients, and low serum bicarbonate predicts higher death risk. This study determined the comparative efficacy of peritoneal dialysis in correcting uremic metabolic acidosis and the association of serum bicarbonate and death risk with the two therapies., Design, Setting, Participants, & Measurements: Data were obtained from 121,351 prevalent ESRD patients (peritoneal dialysis, 10,400; hemodialysis, 110,951) treated in DaVita facilities between July 1, 2001 and June 30, 2006, with follow-up through June of 2007., Results: Serum bicarbonate was <22 mEq/L in 25% and 40% of peritoneal dialysis and hemodialysis patients, respectively. Thus, peritoneal dialysis patients were substantially less likely to have lower serum bicarbonate (adjusted odds ratio<20 mEq/L, 0.45 [0.42, 0.49]; <22 mEq/L, 0.41 [0.39, 0.43]). Time-averaged serum bicarbonate<19 mEq/L was associated with an 18% and 25% higher risk for all-cause and cardiovascular mortality, respectively, in prevalent peritoneal dialysis patients (reference group: serum bicarbonate between 24 and <25 mEq/L). In analyses using the entire cohort of peritoneal dialysis and hemodialysis patients, the adjusted risk for all-cause mortality was higher in most subgroups with serum bicarbonate<22 mEq/L, irrespective of dialysis modality., Conclusions: The measured bicarbonate is significantly higher in peritoneal dialysis patients, suggesting that the therapy provides a more complete correction of metabolic acidosis than intermittent hemodialysis. Survival data suggest maintaining serum bicarbonate>22 mEq/L for all ESRD patients, irrespective of dialysis modality.

Background: Serum indoxyl sulfate (IS) is a uremic toxin that accelerates the progression of chronic kidney disease (CKD). The aim of this study was to determine whether serum IS is associated with hemodynamic parameters or cardiac events in patients with nonischemic dilated cardiomyopathy (DCM)., Methods and Results: The 76 patients with DCM had their serum IS and plasma brain natriuretic peptide (BNP) levels measured, and underwent echocardiographic examination. Mean (± standard deviation) left ventricular ejection fraction (LVEF) and BNP levels in the patients were 32.5 ± 10.7% and 204 ± 219 pg/ml, respectively. Patients were divided into 2 groups, low IS (<0.9 µg/ml) and high IS (≥ 0.9 µg/ml), based on the median value of serum IS. Although there were no significant differences in LVEF and BNP between the groups, E/e' was significantly greater in the high IS group than in the low IS group. Furthermore, E/e' was an independent determinant of serum IS level. The risk of a cardiac event was significantly higher in the high IS group than in the low IS group (P=0.014). Moreover, serum IS was a significant predictor of cardiac events even after adjustment for BNP., Conclusions: Cardiac dysfunction is associated with the serum IS level, which might serve as a new prognostic marker in DCM patients with normal renal function or mild to moderate CKD.

Since beta-2 microglobulin (B2M) is a surrogate marker for middle molecular weight uremic toxins and the major protein component in dialysis-related amyloidosis, it has been frequently studied in dialysis patients. It is not known, however, whether B2M has an impact in patients with chronic kidney disease (CKD) not yet on dialysis. Here we studied the relationship of plasma B2M levels to clinical and cardiovascular outcomes in 142 patients (mean age of 67 years) at different stages of CKD. B2M levels increased with CKD stage and thus were highest in hemodialysis patients. Baseline B2M levels were associated with vascular calcification but not with arterial stiffness or bone density. During a mean follow-up of 969 days, 44 patients died and 49 suffered a cardiovascular event. Higher B2M levels were independently associated with overall and cardiovascular mortality and cardiovascular events in the whole cohort and with cardiovascular events in the predialysis cohort. Moreover, B2M appeared to be a better predictor than well-established factors associated with outcomes in this population, such as estimated glomerular filtration rate ((eGFR), only for predialysis patients), inflammation biomarkers, and other factors included in a propensity score. Thus, we confirm the strong relationship between B2M levels and eGFR and confirm the power of B2M to predict overall and cardiovascular mortality and cardiovascular events in patients at different stages of CKD.

Aim: Long term dialysis is life-saving for patients with end stage renal disease (ESRD). However, in ESRD patients with multiple comorbid conditions, dialysis may actually be futile, and conservative management is advisable. We studied the life expectancy of Chinese ESRD patients treated conservatively., Methods: We reviewed 63 consecutive ESRD patients who were treated conservatively in our centre. Duration of survival was calculated from the date of initial assessment for dialysis, as well as the expected date of needing dialysis based on previous trend of renal function decline., Results: At the end of the observation period, 55 patients died. Twelve patients died before the expected date of needing dialysis because of unrelated reasons, while 36 deaths were directly attributed to uraemia. The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months). The median overall survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) from the theoretical date of needing dialysis. The survival from the theoretical date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function., Conclusions: In Chinese ESRD patients treated conservatively, the median survival is around 6 months after the theoretical date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Background and Objectives: Follistatin mediates muscle growth and bone mineralization. At present, it is unknown whether circulating follistatin levels are altered in chronic kidney disease (CKD) or links to CKD risk factors and outcomes., Design, Setting, Participants, & Measurements: Plasma follistatin levels were cross-sectionally analyzed in relation to protein-energy wasting (PEW), handgrip strength (HGS), bone mineral density (BMD), and inflammatory markers in 280 CKD stage 5 patients, 32 CKD stage 4 patients, 16 CKD stage 3 patients, and 32 control subjects. In CKD stage 5 patients survival was prospectively investigated during a follow-up period of up to 5 years., Results: The plasma follistatin concentration was not higher in CKD stage 5 patients than in other CKD stages or controls. In CKD stage 5 patients, circulating follistatin positively correlated with age, high-sensitivity C-reactive protein (hsCRP), and IL-6; negatively correlated with HGS, serum creatinine, and BMD; and was increased in patients with PEW. In a multivariate logistic regression model, lower HGS, lower BMD, and higher hsCRP independently correlated with higher follistatin levels. In a Cox regression model, follistatin levels were not associated with all-cause mortality., Conclusions: Circulating follistatin levels were neither elevated nor predicted outcome in patients with CKD. However, increased follistatin levels occurred together with increased inflammation, reduced muscle strength, and low BMD, suggesting an involvement of a mechanism including follistatin in the uremic wasting process., (Copyright © 2011 by the American Society of Nephrology)

Objective: To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion (HP) could improve the clearance rate of middle and large molecule uremic toxins so as to improve the quality of life of MHD patients and reduce their mortality rate., Methods: This study was a prospective, randomized, controlled clinical trial. 100 MHD patients were selected and then randomly divided into two groups after four weeks of run-in period. Group 1 received HD alone 2 times a week and the combined treatment of HD with HP (HD+HP) once a week, whereas Group 2 was given HD alone 3 times a week. This study was followed up for a mean of 2 years. The primary outcome was the death of patients. Secondary end points included normal clinical data, leptin, high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), ß(2) microglobulin (ß(2)-MG), immunoreactive parathyroid hormone (iPTH), tumor necrosis factor-α (TNF-α) and the index of dimensions of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 Chinese Edition )., Results: At the end of the two-year observation, the serum concentration of leptin, hsCRP, iPTH, IL-6, ß(2)-MG and TNF-α, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), cardiothoracic ratio, left ventricular mass index (LVMI), the EPO doses and the types of antihypertensive drugs used were lower with Group 1 than with Group 2 (p<0.05); Group 1 had higher hemoglobin (Hb), ejection fraction (EF), and body mass index (BMI) (p<0.05). No statistical difference between the two groups was observed in terms of serum albumin, serum iron (SI), total iron binding capacity (TIBC), cardiac output (CO), Kt/V, early/atrial mitral inflow velocities (E/A) (p>0.05). Besides, the SF-36 indicated that the total score of overall dimentions of Group 1 was higher than Group 2 (p<0.05) and the quality of life of Group 1 was evidently better than Group 2. The Kaplan-Meier Survival Curves for the 2-year observation period showed that patients in Group 1 had obvious survival advantage while Log-rank test results showed p<0.05. No serious adverse incidents occurred during the HD+HP treatment., Conclusions: HD+HP was superior to HD in regularly eliminating middle and large molecule uremic toxins accumulated in the body. These findings suggest a potential role for HD+HP in the treatment to improve the quality of life and survival rate of MHD patients.

Background and Objectives: Premature cardiovascular (CV) events, especially sudden cardiac death, are common in ESRD patients and associated with uremic cardiomyopathy. Identification of high-risk patients is difficult. Microvolt T-wave alternans (MTWA) is a noninvasive method of detecting variability in electrocardiogram (ECG) T-wave morphology and is a promising technique for identifying patients at high risk of ventricular tachyarrhythmias. MTWA results of ESRD and hypertensive left ventricular hypertrophy (LVH) patients were assessed to determine the prevalence of abnormal results and associations with uremic cardiomyopathy., Design, Setting, Participants, & Measurements: In this single-center observational study, 200 ESRD and 30 LVH patients underwent assessment including CV history, ECG, cardiac magnetic resonance imaging, and an MTWA exercise test. MTWA results were classified as "negative" or "abnormal" on the basis of previously published reports., Results: An abnormal MTWA result was more common in ESRD compared with LVH patients (57.5% versus 26.7%, respectively; P = 0.002). In ESRD patients, MTWA was significantly associated with uremic cardiomyopathy, clinical history of atherosclerosis (coronary, cerebral, peripheral) and diabetes mellitus, older age, and hemodialysis therapy. Independent associations with an abnormal MTWA result were older age, macrovascular disease, increased left ventricle (LV) mass, and LV dilation., Conclusions: Features of uremic cardiomyopathy are associated with an abnormal MTWA result.

The golden target for dialysis therapy should be to guarantee longer survival and to give a higher quality of life without dialysis-related complications. In order to achieve this target, the choice of dialysis modality and membrane is essential but we have not yet established what the best choice for a dialysis modality and membrane are. Generally, we choose a dialysis modality for better solute removal and better biocompatibility. In this issue we would like to propose that the patients' preference for dialysis therapy is a useful parameter in prescribing the dialysis modality. In our recent experience, chronic dialysis patients have had preferences on a dialysis modality and membrane, those being PMMA, EVAL, AN-69 and pre-dilution online HDF. These modalities could relieve them of uncomfortable dialysis-related symptoms such as insomnia, itchiness, irritability, and so on. Other characteristics of these modalities are of a nutritional advantage, a broad removal pattern of uremic toxins including low-molecular-weight protein and protein-bound uremic toxins, and good biocompatibility free from chemical components of dialysis membrane. In conclusion, patients' symptoms could be a useful parameter to choose a dialysis modality and membrane., (Copyright © 2011 S. Karger AG, Basel.)

Background: Calcific uremic arteriolopathy (CUA) is a rare complication in end stage renal disease with high mortality. Numerous case reports and one case series of 3 patients report the benefit of sodium thiosulfate (STS) for treatment of CUA. The purpose of this evaluation was to examine the response to a STS-based treatment approach in patients with CUA with 1 year follow up., Methods: A retrospective case series of 6 consecutive patients from Manitoba, Canada who met predefined diagnostic criteria for CUA and received STS between 2006 and 2008 were included. STS responders were defined as improvement in at least one of the following three parameters: pain severity, wound size and diagnostic imaging/radiography. Mortality, STS dose, duration, adverse events and cost were also collected., Results: Four patients were classified as responders. The 2 responders who survived at 1 year of follow-up demonstrated an improvement in all 3 parameters examined including an improvement in their follow-up diagnostic imaging results within the first 4 - 6 weeks of STS treatment. At 1 year of follow-up, 3 patients died., Conclusion: Using an STS-based multifaceted treatment approach for CUA, 4 patients responded but 3 of 6 patients died within 1 year. Further larger prospective studies are needed to delineate STS responders from non-responders.

Background: Dialysis patients with uremic pruritus have worse outcomes. However, the pathophysiology of the high mortality in these patients remains inconclusive except for links with calcium/phosphate imbalance and sleep disturbance. Whether inflammation, an outcome predictor in dialysis patients, plays a role is unknown., Methods: This prospective study included 321 chronic hemodialysis (HD) patients (>3 months) for survival analysis. A visual analog scale (VAS) was used to measure the severity of itching, and the patients were divided into four groups: no pruritus (VAS = 0, N = 118), mild (VAS 1-3, N = 76), moderate (VAS 4-7, N = 89) and severe pruritus (VAS 8-10, N = 38). The Pittsburgh Sleep Quality Index (PSQI) was used to define sleep disturbance, while high-sensitive C-reactive protein (hs-CRP) and tumor necrosis factor α (TNF-α) were used to evaluate inflammation. The patients were followed-up for 30 months., Results: Patients with moderate/severe pruritus had higher hs-CRP, but similar TNF-α levels; they also had a worse survival rate (P = 0.0197, log rank test). By stratifying hs-CRP levels, those with higher hs-CRP had worse survival regardless of the severity of uremic pruritus. In a Cox proportional hazard model, hs-CRP levels and moderate/severe uremic pruritus were independent predictors of mortality after adjusting for age, poor sleeper (PSQI > 5), diabetes, albumin, phosphate, hemoglobin and parathyroid hormone levels and (hs-CRP) × (moderate/severe uremic pruritus) (all P < 0.05)., Conclusion: In moderate/severe pruritic HD patients, those with higher hs-CRP suffer from worse overall mortality. Inflammation may bridge uremic pruritus to high mortality, and elevated hs-CRP predicts a worse outcome in this population.

Purpose of Review: Convective treatments are characterized by enhanced removal of middle and large molecular weight solutes, important in the genesis of many complications of hemodialysis, compared with conventional low-flux hemodialysis. The availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of hemodialysis patients. In this study we will critically review the most important published studies evaluating the impact of convective treatments on dialysis outcomes., Recent Findings: The Hemodialysis (HEMO) study showed that greater urea removal nonsignificantly reduces the relative risk of mortality and that also high-flux hemodialysis was associated with a nonsignificant reduction, although a secondary analysis pointed to an advantage for high-flux membranes in subgroups of patients. More recently, the Membrane Permeability Outcome (MPO) study found that survival could be improved by use of high-flux membranes compared with low-flux dialysis in high-risk patients as identified by serum albumin < or =4 g/dl as well as in people with diabetes. In an observational study, hemodiafiltration with large reinfusion volume has been associated with a lower relative risk of mortality, compared with low-flux hemodialysis., Summary: The biologic plausibility of advantages of convective treatments and the results of the MPO and Dialysis Outcomes and Practice Patterns (DOPPS) studies are supporting rationales for the use of convective treatments to improve survival and delay long-term complications of hemodialysis patients.

Most epidemiologic data, thus far, have focused on short-term outcomes of acute kidney injury (AKI). Lo et al. correlate AKI with long-term outcomes. The concept of 'uremic memory' sheds light on the importance of AKI and its permanent imprint. The focus of research should be on prevention of an episode of AKI, when possible.

Background: It has been reported that more than 30% of patients present with congestive heart failure at the initiation of renal replacement therapy (RRT). We followed up a cohort of patients with refractory congestive heart failure (RCHF) who started dialysis between 2005 and 2006 and conducted an observational cohort study in order to evaluate the clinical features at the time RRT was started, and the survival rate of patients with RCHF METHODS: Data were collected on 33 uremic subjects (24 male) with RCHF, referred by cardiologists, who started dialysis between 2005 and 2006 and were followed-up for 42 months. The following parameters were derived from clinical records: age, sex, history of ischemic heart disease (IHD), cerebrovascular disease (CVD), peripheral vascular disease (PVD), diabetes, smoking, hypertension, myeloma or malignancies, the cause for dialysis and procedure used to initiate treatment., Results: RCHF was the cause of initial RRT in 15 patients in 2005 and in 18 the following year with an incidence of 27 out of 100 patients per year. Diabetes was diagnosed in 51% (n = 17) of cases. More than 80% of patients with RCHF had histories of hypertension and smoking. IHD, CVD and PVD were present in 66%, 30% and 54% of cases, respectively. Cancers were recorded in 36% of subjects. Fluid overload was the cause of urgent dialysis in 73% of cases; a central venous catheter (CVC) was placed in 75% of patients. Mean survival of patients with RCHF was 23 months. Eighteen patients died because of cardiovascular events after a mean follow-up of 365 +/- 387 days; they had higher prevalence of a smoking history (100% vs. 73%, p = 0.02) and CVD (44% vs. 13%, p = 0.05) than the survivors., Conclusions: In uremic patients starting dialysis, RCHF appears to be a frequent condition, comorbidity is high and they require urgent treatment by CVC because of fluid overload. Since RCHF is time- and resource-consuming, nephrologists need to ameliorate its management.

Standard hemodialysis is a far from ideal treatment for uremia since the morbidity and mortality of patients on hemodialysis are still significantly higher than those of non-hemodialyzed subjects with similar demographic characteristics. Because it has been suggested that the cause could lie in the inadequate removal of ''middle molecules'' by standard hemodialyis, two alternative treatments have been proposed: high-efficiency hemodialyis and high-flux hemodialyis. The 2002 results of the HEMO study showed that both these treatments are associated with a non-significant reduction in the relative risk of death (4% and 8%, respectively). The MPO study, which - unlike the HEMO study - enrolled only incident cases and not did not allow reuse of dialyzers, evaluated the mortality rate with high-flux and low-flux hemodialysis in a sicker population, i.e., patients with hypoalbuminemia, and showed a significant reduction in the relative risk of death especially in patients with diabetes. In an attempt to define the clinical impact of hemodiafiltration, some of the efficacy data from clinical studies are reviewed in light of a number of factors that may be related to the high mortality among hemodialysis patients. The current state of affairs suggests it is reasonable to prefer high-flux hemodialysis in sicker patients, especially diabetics. Moreover, the use of ultrapure dialysis fluid is recommended to reduce chronic inflammation and its consequences.

The population of elderly patients entering chronic dialysis programmes is increasing. Elderly patients are susceptible to malnutrition and have multiple complicating disorders in addition to uraemia. Selecting appropriate dialysis modality is particularly critical in elderly patients. Continuous ambulatory peritoneal dialysis (CAPD) has many advantages to elderly patients; however, the clinical outcome varies for elderly CAPD patients. In comparison with Westerners, Southeast Asians have a small body mass index and may be more suited to CAPD therapy. To identify the prognostic predictors in elderly Southeast Asian patients, this historical cohort study analysed 144 patients aged > or = 65 years at initiation of CAPD. A group of haemodialysis (HD) patients aged > or = 65 years was utilised as the control group. Survival curves for patient and technique were derived from Kaplan-Meier analysis and were further analysed by Cox-Mantel log-rank test. To elucidate the impact of individual factors on patient survival, various significant univariables were further subjected to multivariate analysis. No significant increase existed for relative risk of technique failure in elderly patients compared with younger patients. This analytical data indicates that CAPD was as good as HD for elderly uraemic patients regarding to the patient survival. Diabetes, dependent patients, low albumin levels and previous HD history were significant poor prognostic factors for survival of elderly CAPD patients. In conclusion, CAPD is an effective modality of renal replacement therapy for Southeast Asian elderly patients. The technique survival was not affected by patient age.