Search

Purpose: Decreasing the risk of catheter related bloodstream infections (CRBSIs) remains a key focus for improving outcomes and reducing cost of care for hemodialysis (HD) patients. Recent studies demonstrate CRBSI rates can be improved by managing bacterial colonization at the catheter exit site. Herein we present the results of a study documenting the clinical performance of the NexSite HD catheter, a new tunneled central venous catheter which incorporates Exit Site Management (ESM) technology. Methods: We conducted an observational study using a prospective, multi-center registry of HD patients implanted with the NexSite HD catheter. The primary endpoint for the study was CRBSI rate for a period up to 180-days following catheter placement. Secondary endpoints included device placement success rate, exit site healing, development of an exit site or tunnel infection, and early or late non-infectious catheter-related complications. All reasons for early non-elective catheter removal were recorded. Results: A total of 115 HD patients at 6 sites were included in the final analysis. Cumulative catheter use was 10,924 days with a mean duration of 95 days. Seven patients experienced CRBSIs during the study period resulting in a CRBSI rate of 0.64 per 1,000 catheter-days. Seventy-four patients (64.3%) had either elective catheter removal (n = 56) or utilized the catheter for the entire 180-day observation period (n = 18). Thirty-five patients (30%) underwent non-elective device removal either due to CRBSI (n = 5), low flow (n = 16), exit site issues (n = 7), or for other causes (n = 7). Six patients died during the observation period with 1 death due to CRBSI-associated complications and the remaining 5 deaths attributed to non-device related causes. Conclusion: Our findings demonstrate that the NexSite HD catheter equipped with ESM technology can achieve a CRBSI rate in compliance with the NKF KDOQI (National Kidney Foundation Kidney Disease Outcome Quality Initiatives) Clinical Performance Guidelines stated goal of less than 1.0/1,000 catheter-days when used in hemodialysis patients using current standard of care nursing protocols. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Genotyping of HCV is crucial for successful therapy. To determine the HCV subgenotypes circulating in Palestine and to study the genetic variability of their core, we collected 84 serum samples which had tested positive for anti-HCV antibodies. Thirty-seven of these samples came from hemodialysis patients. Serum samples were subjected to viral RNA isolation and amplification of the HCV core gene. Thirty-three of the samples (39%) tested positive for HCV RNA. The HCV subgenotypes circulating in Palestine included 1a, 3a, and 4a, detected in 38%, 25%, and 22% of the samples, respectively. Furthermore, subgenotype 1b was present in three samples (9%), while the rare subgenotype 4v was present in two samples (6%). We identified a number of substitutions in the retrieved HCV core sequences, such as HCV 1b substitutions R70Q and M91L, which some studies have associated with hepatocellular carcinoma risk and poor virological response. In contrast to two previous studies reporting that HCV genotype 4 was predominant in the Gaza strip (present in just over 70% of samples), genotype 4 was detected in only 31% of the samples in our current study, whereas genotype 1 and 3 were present in 69% of samples. These differences may relate to the fact that many of our samples came from the West Bank and East Jerusalem. The co-circulation of different HCV genotypes and subgenotypes in Palestine suggests that subgenotyping prior to treatment is crucial in Palestinian patients. [ABSTRACT FROM AUTHOR]

CD34+ cells maintain vascular homeostasis and predict cardiovascular outcomes. We previously evaluated the association of CD34+ cells with cardiovascular disease (CVD) events over 23 months, but long-term CVD outcomes in relation to levels of CD34+ cells in patients on maintenance hemodialysis are unclear. Herein, we analyzed the long-term predictive potential levels of CD34+ cells for CVD outcomes and all-cause mortality. Between March 2005 and May 2005, we enrolled 215 patients on maintenance hemodialysis at Nagoya Kyoritsu Hospital and followed them up to 12.8 years. According to the CD34+ cell counts, patients were classified into the lowest, medium, and highest tertiles. Levels of CD34+ cells were analyzed in association with four-point major adverse CV events (MACEs), CVD death, and all-cause mortality. In univariate analysis age, smoking habit, lower geriatric nutrition risk index, lower calcium × phosphate product, and lower intact parathyroid hormone were significantly associated with the lowest tertile. Whereas, in multivariate analysis, age and smoking habit were significantly associated with the lowest tertile. Among 139 (64.7%) patients who died during a mean follow-up period of 8.0 years, 39 (28.1%) patients died from CVD. Patients in the lowest tertile had a significantly lower survival rate than those in the medium and highest tertiles (p ≤ 0.001). Using multivariable analyses, the lowest tertile was significantly associated with four-point MACEs (hazard ratio 1.80, p = 0.023) and CVD death (hazard ratio 2.50, p = 0.011). In conclusion, our long-term observational study revealed that a low level of CD34+ cells in the circulation predicts CVD outcomes among patients on maintenance hemodialysis. [ABSTRACT FROM AUTHOR]

Background and aims: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. Material and methods: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. Results: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. Conclusions: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials. [ABSTRACT FROM AUTHOR]

Aims: To explore actions and motivations for self-management practices of Pacific adults following diagnosis of end stage renal disease (ESRD). Methods: Focused ethnography using in-depth interviews with 16 Pacific people on haemodialysis for diabetic ESRD, in Auckland, New Zealand. Study participants were of Samoan, Cook Islander, Tongan, Niuean, or Tokelauan ethnicity and aged between 30 to 69 years old. Thematic analysis was used to code and identify emergent themes. Results: All participants assumed active responsibility for their self-management following their diagnosis of ESRD. They reported positive differences in their current self-management behaviours, compared to pre-ESRD diagnosis. In the face of their terminal diagnosis, participant’s motivations to self-manage their health were fuelled by hope; the hope to live long enough to change their family legacy of diabetes and ESRD. To achieve this, there was a dependency upon family members as a resource for self-management support. Yet at the same time, family members also had health concerns (including diabetes), and several participants themselves were carers for sick or elderly family members. Conclusion: The growing number of members (within family units) progressing from moderate to late-stage diabetes raises concerns about the sustainability of future family support in Pacific families in New Zealand with histories of diabetes, ESRD, and other chronic diseases. While the burden upon informal carers (family) has been well documented throughout the past few decades, the dynamics of bi-directional carer support between (two or more) sick family members and their families have had less exposure. This has potentially significant implications for Pacific peoples in New Zealand, considering the increases in diabetes prevalence within their families. [ABSTRACT FROM AUTHOR]

Objective: Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up. Methods: In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed. Results: Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (P<0.02). Kaplan–Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs (P<0.02). Cox regression analysis showed that the presence of TRFs (P<0.05; hazard ratio, 1.94; 95% CI: 1.07–3.56), but not early shunt occlusion, was associated with short patient survival. Conclusions: TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion. [ABSTRACT FROM AUTHOR]

Introduction: Integrated service delivery is considered to be an essential condition for improving the management and health outcomes of people with chronic kidney disease (CKD). However, research on the assessment of integrated care by patients and care providers is hindered by the absence of brief, reliable, and valid measurement tools. Objective: The aim of this study was to develop survey instruments for healthcare professionals and patients based on the Rainbow Model of Integrated Care (RMIC), and to evaluate their psychometric properties. Design: The development process was based on the US Food and Drug Administration guidelines. This included item generation from systematic reviews of existing tools and expert opinion on clarity and content validity, involving renal care providers and chronic kidney patients. A cross-sectional, multi-centre design was used to test for internal consistency and construct validity. Setting: Outpatient clinics in a large renal network. Participants: A sample of 30.788 CKD patients, and 8.914 renal care providers. Methods and analysis: Both survey instruments were developed using previous qualitative work and published literature. A multidisciplinary expert panel assessed the face and content validity of both instruments and following a pilot study, the psychometric properties of both instruments were explored. Exploratory factor analysis with principal axis factoring and with promax rotation was used to assess the underlying dimensions of both instruments; Cronbach’s alpha was used to determine the internal constancy reliability. Results: 17.512 patients (response rate: 56.9%) and 8.849 care providers (response rate: 69.5%) responded to the questionnaires. Factor analysis of the patient questionnaire yielded three internally consistent (Cronbach’s alpha > 0.7) factors: person-centeredness, clinical coordination, and professional coordination. Factor analysis of the provider questionnaire produced eight internally consistent (Cronbach’s alpha > 0.7) factors: person-centeredness, community centeredness, clinical coordination, professional coordination, organisational coordination, system coordination, technical and cultural competence. As hypothesised, care coordination patient and providers scores significantly correlated with questions about quality of care, treatment involvement, reported health, clinics’ organisational readiness, and external care coordination capacity. Conclusion: This study provides evidence for the reliability and validity of the RMIC patient and provider questionnaires as generic tools to assess the experience with or perception of integrated renal care delivery. The instruments are recommended in future applications testing test-retest reliability, convergent and predictive validity, and responsiveness. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is associated with substantial cardiovascular morbidity. Atrial fibrillation (AF) is a prevalent arrhythmia that increases the risk of both stroke and cardiovascular mortality. Information about the mortality risk among patients with advanced CKD and new-onset AF (NAF) in the presence and absence of dialysis is important. However, the association between advanced CKD and NAF in patients with and without dialysis is unclear. Objective: To investigate long-term outcomes of the association between advanced CKD and NAF in patients with and without dialysis. Methods: We conducted a nested case-control study based on the National Health Insurance Program in Taiwan. Each participant aged 20 years and older who had CKD with dialysis from 2000 to 2013 was assigned to the dialysis group, whereas sex-, age-, CKD duration-, and index date-matched participants without dialysis were randomly selected and assigned to the non-dialysis group. We used the Cox regression model to estimate the hazard ratio (HR) with the 95% confidence interval (CI) for mortality in CKD patients with combined dialysis and NAF. Patients with neither NAF nor dialysis served as the reference group. Results: We identified 3,673 dialysis cases and 7,346 Non-dialysis matched controls for enrolment in the study. The crude mortality rates were 3.3 (95% CI: 3.1–3.5), 10.98 (95% CI: 9.3–13.0), 9.2 (95% CI: 8.7–10.0), and 18.0 (95% CI: 15.4–21.2) in the [Non-dialysis, non-NAF], [Non-dialysis, NAF], [Dialysis, non-NAF], and [Dialysis, NAF] groups, respectively. After adjustment for age, gender, and co-morbidities, the aHRs were 2.0 (95% CI: 1.7–2.3), 2.7 (95% CI: 2.5–2.9), and 3.5 (95% CI: 2.9–4.1) in the [Non-Dialysis, NAF], [Dialysis, non-NAF], and [Dialysis, NAF] groups compared with the [Non-Dialysis, non-NAF] group, respectively. The Kaplan-Meier survival curves showed the highest mortality risk in the [Dialysis, NAF] group among the study groups. Patients with concurrent peritoneal dialysis and AF had the highest mortality risk: aHR = 4.3 (95% CI: 2.3–8.0). However, there was a relatively lower effect of NAF on mortality in patients on dialysis than in patients who were not. Conclusions: Patients with advanced CKD and NAF had a significantly increased risk of mortality. Dialysis is not risky for patients with concurrent CKD and NAF. Dialysis offers a sufficient survival benefit to be considered as a standard treatment, as indicated by the superior physical status of patients on dialysis. [ABSTRACT FROM AUTHOR]

Background: There are limited data on acute kidney injury (AKI) complicating acute myocardial infarction with cardiogenic shock (AMI-CS). This study sought to evaluate 15-year national prevalence, temporal trends and outcomes of AKI with no need for hemodialysis (AKI-ND) and requiring hemodialysis (AKI-D) following AMI-CS. Methods: This was a retrospective cohort study from 2000–2014 from the National Inpatient Sample (20% stratified sample of all community hospitals in the United States). Adult patients (>18 years) admitted with a primary diagnosis of AMI and secondary diagnosis of CS were included. The primary outcome was in-hospital mortality in cohorts with no AKI, AKI-ND, and AKI-D. Secondary outcomes included predictors, resource utilization and disposition. Results: During this 15-year period, 440,257 admissions for AMI-CS were included, with AKI in 155,610 (35.3%) and hemodialysis use in 14,950 (3.4%). Older age, black race, non-private insurance, higher comorbidity, organ failure, and use of cardiac and non-cardiac organ support were associated with the AKI development and hemodialysis use. There was a 2.6-fold higher adjusted risk of developing AKI in 2014 compared to 2000. Presence of AKI-ND and AKI-D was associated with a 1.3 and 1.7-fold higher adjusted risk of mortality. Compared to the cohort without AKI, AKI-ND and AKI-D were associated with longer length of stay (9±10, 12±13, and 18±19 days respectively; p<0.001) and higher hospitalization costs ($101,859±116,204, $159,804±190,766, and $265,875 ± 254,919 respectively; p<0.001). Conclusion: AKI-ND and AKI-D are associated with higher in-hospital mortality and resource utilization in AMI-CS. [ABSTRACT FROM AUTHOR]

Introduction: End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce. Methods: We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology. Results: In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter. Conclusions: Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation. [ABSTRACT FROM AUTHOR]

Background: The widespread use of central venous catheters (CVCs) has exposed patients to a high risk of catheter-related infection (CRI), which is linked to substantial morbidity and mortality. Several strategies for preventing CRI, including ethanol lock prophylaxis, have been explored. This study aimed to provide a comprehensive summary of randomized controlled trials (RCTs) assessing the efficacy and safety of ethanol locks for preventing CRI in patients with CVC. Methods: We searched six electronic databases, earlier relevant meta-analyses and the reference lists of the included studies for RCTs that assessed the effects of ethanol locks on CRI in patients with CVC versus a control group. Two authors independently assessed the methodological quality of the included studies using the Cochrane Risk of Bias tool and extracted relevant information according to a predesigned extraction form. Data were analyzed using the Cochrane Collaboration’s RevMan 5.3. Results: Nine studies involving 2451 patients were included. Although limited in power, the results of the meta-analysis indicated a positive effect of ethanol lock prophylaxis on reducing catheter-related bloodstream infection (CRBSI) compared to heparin alone [OR = 0.53, 95% CI 0.34, 0.82, P = 0.004]. The effects on other outcomes, such as exit site infection, catheter dysfunction, catheter removal, thrombosis and mortality, were not statistically significant (P > 0.05). Moreover, although the effect of ethanol on CRBSI was in the expected direction compared to 0.9% NaCl locks, this effect was not statistically significant (P > 0.05). Conclusions: The present data indicate that ethanol lock prophylaxis is a potential candidate for the prevention of CRBSI in patients with CVC. However, more attention should be paid to the uniform ethanol lock procedure and toxic effects after long-term ethanol lock exposure. [ABSTRACT FROM AUTHOR]

Purpose: Data for elucidating post-kidney transplantation (KT) acute pancreatitis (AP) risk are limited and no large-scale cohort study has investigated the impact of AP after KT. Method: Data from Taiwan National Health Insurance (NHI) Research Database (NHIRD) were calculated through the method of propensity score matching to compare the pancreatitis risk in patients with and without KT. Results: The overall pancreatitis incidence rates were 1.71 and 0.61 per 1,000 person-years in the KT and non-KT groups, respectively and corresponding adjusted HR (aHR [95% CI]) for pancreatitis was 2.48 (1.51–4.09) in the KT group. In the multivariable model, AP risk was higher in transplant patients with alcohol-related illnesses (aHR: 3.78, 95% CI: 1.32–10.8), gall stone disease (aHR: 3.53, 95% CI: 1.48–8.44), or past history of pancreatitis (aHR: 10.3, 95% CI: 5.08–20.8). Of note, recurrent AP risk was significantly higher in the KT group (aHR: 8.19, 95% CI: 2.89–23.2). Patients with post-KT AP demonstrated shorter patient and allograft survival than did those without (both P < 0.001, respectively). Conclusion: In conclusion, KT recipients are very likely to be associated with AP. Moreover, their inferior outcomes are strongly associated with post-KT AP. [ABSTRACT FROM AUTHOR]

Background: Chronic fluid overload is common in patients with chronic kidney disease (CKD) and can with time lead to poor prognosis regarding to the cardiovascular events. Serum NT-proBNP and OH/ECW might reflect fluid status of the patients, and the maximal tricuspid regurgitation velocity (TRVmax) could reflect systolic pulmonary artery pressure (SPAP). We investigated the relationship between markers of volume status and marker of pulmonary hypertension (PH) in non-dialysis CKD5 (CKD5-ND) patients. Methods: Bioimpedance spectroscopy (BIS), echocardiography, and measurement of serum NT-proBNP were performed in 137 consecutive patients on the same day. TRVmax greater than or equal to 2.9 m/s, corresponding to SPAP of approximately 36 mmHg, was used as a definition of the possibility of PH in the absence of left heart disease and chronic respiratory disease (PH group). Results: Patients with possibility of PH (TRVmax ≥ 2.9 m/s) was found in 27 (19.70%) . Among the values obtained from BIS, those reflecting the fluid balance (OH, OH/ECW, and E/I ratio) were significantly higher in the PH group. The OH/ECW in patients with PH were significantly higher than those patients without (26.76 ± 15.07 vs. 13.09 ± 15.05, P < 0.001). NT-proBNP was also significantly higher in PH group compared to the non-PH group (median = 10,112 pg/ml, IQR = 30,847 pg/ml vs. median = 1,973 pg/ml, IQR = 7,093 pg/ml, P < 0.001). OH/ECW was positively associated with TRVmax (r = 0.235, P = 0.006). Multivariate logistic regression revealed that increased OH/ECW and serum NT-proBNP were significantly associated with an increased risk of PH. Conclusions: A significant number of patients showed increased TRVmax, which was closely related to volume status in CKD5-ND patients. Echocardiography and BIS could be important players in a high possibility of PH detection and treatment in asymptomatic CKD patients. Therefore, these measures could be helpful to improve the cardiac outcomes after initiating renal replacement therapy. Further research may be needed to validate the consistency of this association across other stages of CKD. [ABSTRACT FROM AUTHOR]

Background: Clinical outcomes of patients with end-stage kidney disease (ESKD) secondary to membranous nephropathy (MN) have not been well described. This study aimed to evaluate patient and/or allograft outcomes of dialysis or kidney transplantation in patients with ESKD secondary to MN. Material and methods: All adult patients with ESKD commencing renal replacement therapy in Australia and New Zealand from January 1998 to December 2010 were extracted retrospectively from ANZDATA registry on 31st December 2013. Outcomes of MN were compared to other causes of ESKD. In a secondary analysis, outcomes of MN were compared to all patients with ESKD due to other forms of glomerulonephritis. Results: Of 32,788 included patients, 417 (1.3%) had MN. Compared to other causes of ESKD, MN experienced lower mortality on dialysis (adjusted hazard ratio [aHR] 0.79, 95% CI 0.68–0.92, p = 0.002) and following kidney transplantation (aHR 0.57, 95% CI 0.33–0.97, p = 0.04), had a higher risk of death-censored kidney allograft failure (aHR 1.55, 95% CI: 1.00–2.41, p = 0.05) but comparable risk of overall kidney allograft failure (aHR 1.35, 95% CI 0.91–2.01, p = 0.13). Similar results were obtained using competing-risk regression analyses. MN patients were significantly more likely to receive a kidney transplant (aHR 1.38, 95% CI 1.16–1.63, p<0.001) and to experience primary kidney disease recurrence in the allograft (aHR 4.92, 95% CI 3.02–8.01, p<0.001). Compared to other forms of glomerulonephritis, MN experienced comparable dialysis and transplant patient survival, but higher rates of kidney transplantation, primary renal disease recurrence and death-censored allograft failure. Conclusion: MN was associated with superior survival on dialysis and following kidney transplantation compared to patients with other causes of ESKD, and comparable patient survival compared to patients with other forms of glomerulonephritis. However, patients with MN exhibited a higher rate of death-censored allograft loss as a result of primary kidney disease recurrence. [ABSTRACT FROM AUTHOR]

Some variables including age, comorbidity of diabetes, and so on at dialysis initiation are associated with patient prognosis. Cardiovascular (CV) events are a major cause of death, and adequate models that predict prognosis in dialysis patients are warranted. Therefore, we created models using some variables at dialysis initiation. We used a database of 1,520 consecutive dialysis patients (median age, 70 years; 492 women [32.4%]) from a multicenter prospective cohort study. We established the primary endpoint as a composite of the incidence of first CV events or all-cause death. A multivariable Cox proportional hazard regression model was used to construct a model. We considered a complex and a simple model. We used area under the receiver operating characteristic curve (AUROC) to assess and compare the predictive performances of the prediction models and evaluated the improvement in discrimination using the complex model versus the simple model using net reclassification improvement (NRI). We then assessed integrated discrimination improvement (IDI) to evaluate improvements in average sensitivity and specificity. Of 392 deaths, 152 were CV-related. Totally, 506 CV events occurred during the follow-up period (median 1,285 days). Finally, 692 patients reached the primary endpoint. Baseline data were set at dialysis initiation. AUROC for the primary endpoint was 0.737 (95% confidence interval [CI], 0.712–0.761) in the simple model and 0.765 (95% CI, 0.741–0.788) in the complex model. There were significant intergroup differences in NRI (0.44; 95% CI, 0.34–0.53; p < 0.001) and IDI (0.02; 95% CI, 0.02–0.03; p < 0.001). We prepared a Shiny R application for each model to automatically calculate the predicted occurrence probability (). The complex model made more accurate predictions than the simple model. However, the intergroup difference was not significant. Hence, the simple model was more useful than the complex model. The tool was useful in a real-world clinical setting because it required only routinely available variables. Moreover, we emphasized that the tool could predict the incidence of CV events or all-cause mortality for individual patients. In the future, we must confirm its external validity in other prospective cohorts. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to present average annual healthcare costs for Dutch renal replacement therapy (RRT) patients for 7 treatment modalities. Methods: Health insurance claims data from 2012–2014 were used. All patients with a 2014 claim for dialysis or kidney transplantation were selected. The RRT related and RRT unrelated average annual healthcare costs were analysed for 5 dialysis modalities (in-centre haemodialysis (CHD), home haemodialysis (HHD), continuous ambulatory peritoneal dialysis (CAPD), automated peritoneal dialysis (APD) and multiple dialysis modalities in a year (Mix group)) and 2 transplant modalities (kidney from living and deceased donor, respectively). Results: The total average annual healthcare costs in 2014 ranged from €77,566 (SD = €27,237) for CAPD patients to €105,833 (SD = €30,239) for patients in the Mix group. For all dialysis modalities, the vast majority (72–84%) of costs was RRT related. Patients on haemodialysis ≥4x/week had significantly higher average annual costs compared to those dialyzing 3x/week (Δ€19,122). Costs for kidney transplant recipients were €85,127 (SD = €39,679) in the year of transplantation and rapidly declined in the first and second year after successful transplantation (resp. €29,612 (SD = €34,099) and €15,018 (SD = €16,186)). Transplantation with a deceased donor kidney resulted in higher costs (€99,450, SD = €36,036)) in the year of transplantation compared to a living donor kidney transplantation (€73,376, SD = €38,666). Conclusions: CAPD patients have the lowest costs compared to other dialysis modalities. Costs in the year of transplantation are 25% lower for patients with kidneys from living vs. deceased donor. After successful transplantation, annual costs decline substantially to a level that is approximately 14–19% of annual dialysis costs. [ABSTRACT FROM AUTHOR]

Background and objective: Previous reports indicated that patients on thrice-weekly hemodialysis (HD) had higher mortality rates after the 3-day interdialytic interval. However, day-of-the-week patterns of emergency department (ED) visits and hospitalizations remain under-investigated. Methods: We conducted a retrospective cohort study of HD patients on thrice-weekly dialysis, using 2013 data from the United States Renal Data System (USRDS). We estimated crude incidence rates of ED visits and hospitalizations by day of the week and dialysis schedule (Monday, Wednesday, Friday or Tuesday, Thursday, Saturday). Using Poisson regression, we estimated case-mix adjusted rate ratios of all-cause ED visits and hospitalizations, and adjusted rates of cause-specific ED visits and hospitalizations. Results: We identified 241,093 eligible HD patients in 2013, who had 514,773 ED visits and 301,674 hospitalizations that year. Three distinct but related patterns of outcome events were observed. Crude and adjusted incidence rates of all-cause, cardiovascular, and infection-related ED visits and hospitalizations, but not vascular-access-related events, were higher on all three HD treatment days (“dialysis-day effect”). Rates for ED visits and hospitalizations were lower on weekends than weekdays, rising appreciably from Sunday to Monday for both dialysis schedules (“post-weekend effect”); and rates were highest after the long 3-day interval between dialysis sessions for both dialysis schedules (“interdialytic-gap effect”). In contrast, rates of hospitalizations not preceded by an ED visit were nearly the same Monday through Friday and lower on weekends for both dialysis schedules. Conclusions: Higher rates of ED visits and hospitalizations on the days of HD sessions and early in the week are a public-health concern that should stimulate research to explain these patterns and reduce the excessive morbidity and associated costs among patients on thrice-weekly HD, while improving quality of care and patient experience with dialysis. [ABSTRACT FROM AUTHOR]

Background: Relative blood volume (RBV) changes during hemodialysis (HD) are typically estimated based on online measurements of hematocrit, hemoglobin or total blood protein. The aim of this study was to assess changes in the above parameters during HD in order to compare the potential differences in the RBV changes estimated by individual methods. Methods: 25 anuric maintenance HD patients were monitored during a 1-week conventional HD treatment. Blood samples were collected from the arterial dialysis blood line at the beginning and at the end of each HD session. The analysis of blood samples was performed using the hematology analyzer Advia 2120 and clinical chemistry analyzer Advia 1800 (Siemens Healthcare). Results: During the analyzed 30 HD sessions with ultrafiltration in the range 0.7–4.0 L (2.5 ± 0.8 L) hematocrit (HCT) increased by 9.1 ± 7.0% (mean ± SD), hemoglobin (HGB) increased by 10.6 ± 6.3%, total plasma protein (TPP) increased by 15.6 ± 9.5%, total blood protein (TBP) increased by 10.4 ± 5.8%, red blood cell count (RBC) increased by 10.8 ± 7.1%, while mean corpuscular red cell volume (MCV) decreased by 1.5 ± 1.1% (all changes statistically significant, p < 0.001). HGB increased on average by 1.5% more than HCT (p < 0.001). The difference between HGB and TBP increase was insignificant (p = 0.16). Conclusions: Tracking HGB or TBP can be treated as equivalent for the purpose of estimating RBV changes during HD. Due to the reduction of MCV, the HCT-based estimate of RBV changes may underestimate the actual blood volume changes. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) related mortality and morbidity are high in end-stage renal disease (ESRD). The pathophysiology of CVD in ESRD may involve non-traditional CVD risk factors, such as accumulation of advanced glycation endproducts (AGEs), dicarbonyls, endothelial dysfunction (ED) and low-grade inflammation (LGI). However, detailed data on the relation of AGEs and dicarbonyls with ED and LGI in ESRD are limited. Methods: We examined cross-sectional Spearman’s rank correlations of AGEs and dicarbonyls with serum biomarkers of ED and LGI in 43 individuals with chronic kidney disease (CKD) stage 5 not on dialysis (CKD5-ND). Free and protein-bound serum AGEs (N∈-(carboxymethyl)lysine (CML), N∈-(carboxyethyl)lysine (CEL), Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)ornithine (MG-H1)) and serum dicarbonyls (glyoxal, methylglyoxal, 3-deoxyglucosone) were analyzed with tandem mass spectrometry, and tissue AGE accumulation was estimated by skin autofluorescence (SAF). Further, serum biomarkers of ED and LGI included sVCAM-1, sE-selectin, sP-selectin, sThrombomodulin, sICAM-1, sICAM-3, hs-CRP, SAA, IL-6, IL-8 and TNF-α. Results: After adjustment for age, sex and diabetes status, protein-bound CML was positively correlated with sVCAM-1; free CEL with sVCAM-1 and sThrombomodulin; glyoxal with sThrombomodulin; and methylglyoxal with sVCAM-1 (correlation coefficients ranged from 0.36 to 0.44). In addition, free CML was positively correlated with SAA; protein-bound CML with IL-6; free CEL with hs-CRP, SAA and IL-6; free MG-H1 with SAA; protein-bound MG-H1 with IL-6; and MGO with hs-CRP and IL-6 (correlation coefficients ranged from 0.33 to 0.38). Additional adjustment for eGFR attenuated partial correlations of serum AGEs and serum dicarbonyls with biomarkers of ED and LGI. Conclusions: In individuals with CKD5-ND, higher levels of serum AGEs and serum dicarbonyls were related to biomarkers of ED and LGI after adjustment for age, sex and diabetes mellitus. Correlations were attenuated by eGFR, suggesting that eGFR confounds and/or mediates the relation of serum AGEs and dicarbonyls with ED and LGI. [ABSTRACT FROM AUTHOR]

Background: Sleep-disordered breathing (SDB) is common in patients with kidney disease; but often underdiagnosed as it is infrequently assessed in clinical practice. The objective of this study was to assess the risk factors of SDB in haemodialysis patients, and to identify useful assessment tools to detect SDB in this population. Methods: We used nocturnal oximetry, Epworth Sleepiness Scale (ESS) and STOPBANG questionnaire to screen for SDB in haemodialysis patients. Presence of SDB was defined by Oxygen desaturation index (ODI≥5/h), and further confirmed by apnoea-hypopnea index (AHI) from an in-laboratory polysomnography. Blood samples were collected prior to commencing a haemodialysis treatment. Results: SDB was detected in 70% of participants (N = 107, mean age 67 years). STOPBANG revealed that 89% of participants were at risk of SDB; however, only 17% reported daytime sleepiness on the ESS. Of the participants who underwent polysomnography (n = 36), obstructive sleep apnoea was identified in 86%, and median AHI was 34.5/h. Oximetry and AHI results were positively correlated (r = 0.62, P = 0.0001), as were oximetry and STOPBANG (r = 0.48; P<0.0001), but not ESS (r = 0.19; P = 0.08). Multivariate analysis showed that neck circumference (OR: 1.20; 95% CI: 1.07–1.34; P = 0.02) and haemoglobin (OR: 0.93; 95% CI: 0.88–0.97; P = 0.003) were independently associated with the presence of SDB. Conclusion: Dialysis patients with a large neck circumference and anaemia are at risk of SDB; using nocturnal oximetry is practical and reliable to screen for SDB and should be considered in routine management of dialysis patients, particularly for those who demonstrate risk factors. [ABSTRACT FROM AUTHOR]

Introduction: End-stage renal disease (ESRD) is increasing globally, and renal transplantation (RT) is the preferred renal replacement therapy to treat ESRD. Internationally, there are only a few countries with RT rates above 50 per million population (pmp), while most of the countries have RT rates between 30–40 pmp. The low- and middle-income countries (LMIC) makes up the majority for the RT rates below 20 pmp in which Malaysia belongs to despite its increasing ESRD rates. There is a need to explore the barriers to access RT with targeted solutions to improve the RT rates and service in LMIC. Thus, a qualitative study was undertaken in Malaysia to address this issue. Method: A qualitative methodological approach was performed between March-May 2018. Semi-structured interviews were used to explore current RT policy and service availability. Key-informants were identified from a detailed stakeholder analysis of RT system in Malaysia. Interviews were digitally audio-recorded, transcribed verbatim, coded with ATLAS.ti software and underwent thematic analysis thoroughly. Results: Eight key-informants participated in the study. Barriers and related solutions were classified using the socio-ecological model (SEM). As reported, the barriers and solutions of RT in Malaysia are the results of a complex interplay of personal, cultural, and environmental factors. Key barriers are linked to public’s attitude and perception towards RT and the unaccommodating practices in the healthcare fraternity for RT. Key-informants provided a systematic solution that shed light on how RT could be improved at each SEM level via effective communication, education and inter-agency collaboration. Conclusion: The SEM provided a framework to foster a better understanding of current practice, barriers, and solutions to RT in Malaysia. This study is the first to explore the barriers and related solutions to RT comprehensively as a whole. Implications of these findings could prompt a policy change for a better RT service delivery model not just for Malaysia but also for other LMIC. Further stakeholder engagement and evaluation of the systems are required to provide insight into best practices that will help to improve the RT rates and service in Malaysia. [ABSTRACT FROM AUTHOR]

The medium cut-off (MCO) dialyzer has shown good clearance of large middle molecules, but its long-term effects are unclear. We investigated whether MCO hemodialysis (HD) over one year could reduce middle molecule levels and cell-free hemoglobin (CFH), without albumin loss. A prospective cohort study in 57 hemodialysis patients was conducted. The patients were assigned to the MCO dialyzer group or the high-flux dialyzer group, according to the HD machine they used. The reduction ratio (RR) and one-year changes in small and middle molecules and CFH were analyzed. Over a 12-month follow-up, MCO HD did not reduce the serum levels of middle molecules (lambda free light chain [FLC], from 135.7 ± 39.9 to 132.0 ± 39.1 mg/L; kappa FLC, from 168.2 ± 58.5 to 167.7 ± 65.8 mg/L; β2-microglobulin, from 25.6 ± 9.6 to 28.4 ± 4.8 mg/L) or albumin (from 3.96 ± 0.31 to 3.94 ± 0.37 g/dL). MCO HD provided excellent RR of lambda FLC (49.3 ± 10.3%), kappa FLC (69.6 ± 10.4%) and β2-microglobulin (80.9 ± 7.3%), compared to high-flux HD. CFH was also removed well during an MCO HD session (RR of CPH, 85.5 [78.7–97.3] %), but long-term change was not significant (from 57.8 [46.2–79.1] to 62.0 [54.6–116.7] mg/L). The MCO dialyzer can be used effectively and safely in conventional HD settings, but long-term effects on large middle molecules and CFH were not significant. Further studies are needed to verify clinical benefits of the MCO dialyzer. [ABSTRACT FROM AUTHOR]

Hand function deterioration brings about inconvenience to the daily lives of the chronic kidney disease patients. However, a full spectrum of hand function examination is absent. Therefore, this study aimed to classify the hand sensorimotor functions of the chronic kidney disease patients using the novel sensorimotor assessment tools, manual tactile test (MTT) and pinch-holding-up activity (PHUA) test, and explore the feasibility in comparison with traditional evaluations in the clinical practice. 68 stage-5 chronic kidney disease patients and 50 healthy subjects were recruited in this study. A series of conventional evaluations and two novel hand function tools, manual tactile test and pinch-holding-up activity test were conducted from the perspective of hand dexterity, sensory input threshold, force generation and sensorimotor control. Independent t-test was used to find out group differences and the receiver operating characteristic curve was used to determine accuracy of the tests. In our results, significant reduction of hand dexterity, sensory input, force generation and sensorimotor control was found in patients from an overall perspective. This trend was discovered to be the same when dividing the subjects into the old and young age group. From the receiver operator characteristic curves, nearly all the areas under the curve of all tests were over 0.8. The novel evaluation tools, the manual tactile test and pinch-holding-up activity, were found to have comparable or even better accuracy than the traditional ones. The shape and weight subtests of the manual tactile test displayed the highest accuracy. To sum up, by incorporating the novel and conventional assessment tests, this study built up the fundamental understanding of the hand functions in multiple dimensions and consolidate the clinical merits of applying the two novel tools, manual tactile test and pinch-holding-up activity, on chronic kidney disease patients. [ABSTRACT FROM AUTHOR]

Background: Severe acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown. Objective: We hypothesized that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission. Design: Retrospective, propensity score matched cohort study. Participants: We identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI. Main Measures: The predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge. Results: AKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 [95% CI, 2.43–8.45]; p<0.0001) within 30 days following discharge. The association between AKI and subsequent infection remained significant at 31–60 days and 91 to 365 days but not during 61–90 days following discharge. Conclusion: Among patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge. [ABSTRACT FROM AUTHOR]

Background: Ramadan fasting is compulsory for all healthy adult Muslims. Although sick people are exempted from Ramadan fasting, some patients such as hemodialysis patients prefer to fast during Ramadan. The effect of Ramadan fasting on clinical outcomes and biochemical markers among hemodialysis patients is not clear. The aim of this study was to examine the effects of daily Ramadan fasting and partial Ramadan fasting on key biochemical and clinical markers among hemodialysis patients as compared to hemodialysis patients who chose not to fast during Ramadan. Methods: A prospective cohort study of 269 end stage renal disease patients were recruited from the hemodialysis unit in An-Najah National University Hospital, Nablus, Palestine. The participants were divided into three cohorts based on their plans for fasting during Ramadan in May 2018; Ramadan fasting group (RFG), Ramadan partial fasting group (RPFG) and Ramadan not-fasting group (RNFG). Key clinical and biochemical markers were measured before, during and after Ramadan. Results: After adjustment for diabetic and hypertension status and other sociodemographic variables, RFG had higher mean inter-dialytic weight gain (IDWG) by 0.62 kg than RNFG (95% confidence interval (CI) 0.26, 0.99). RPFG also had slight increase in mean IDWG than RNFG by 0.35 kg (95% CI 0.11, 0.60). Additionally, RFG and RPFG had significant increase in mean serum potassium as compared to RNFG. Diabetes was independently associated with increased IDWG by 0.48 kg (0.25, 0.72). Diabetes and hypertension were associated with some independent changes in biochemical markers, but these were clinically negligible. Conclusion: Our findings suggest that Ramadan fasting (fully or partially) is tolerable by hemodialysis patients and is not associated with important clinical complications. However, these patients should be made aware of the potential risk of fluid overload and hyperkalemia, if they decide to fast during Ramadan. Thus, they should be closely monitored and instructed to adhere to their dietary and fluid intake allowances. Further prospective cohort studies with comprehensive dietary measures and information on adverse clinical outcomes may provide more evidence about the tolerability and safety of Ramadan fasting by hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis. Methods: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults. We conducted cox regression analyses adjusted for demographic and clinical variables to evaluate the association with all-cause and cardiovascular mortality. Results: Overall, 4205 adults (mean age 61.6 ± 15.6 years) underwent oral mucosal examination with 40% affected by at least one lesion. The prevalence of oral lesions was (in order of frequency): oral herpes 0.5%, mucosal ulceration 1.7%, neoformation 2.0%, white lesion 3.5%, red lesion 4.0%, oral candidiasis 4.6%, geographical tongue 4.9%, petechial lesions 7.9%, and fissured tongue 10.7%. During median follow-up of 3.5 years, 2114 patients died (1013 due to cardiovascular disease). No association was observed between any individual oral lesion and all-cause or cardiovascular mortality when adjusted for comorbidities, except for oral candidiasis, which was associated with all-cause mortality (adjusted hazard ratio 1.37, 95% CI 1.00 to 1.86) and cardiovascular mortality (adjusted hazard ratio 1.64, 95% CI 1.09 to 2.46). Conclusion: Oral mucosal lesions are prevalent in haemodialysis patients. Oral candidiasis appears to be a risk factor for death due to cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to assess whether clusters of centers with similar peritoneal dialysis (PD) catheter related practices were associated with differences in the risk of technique failure. Methods: Patients on incident PD in French centers contributing to the French Language PD Registry from 2012 to 2016 were included in a retrospective analysis of prospectively collected data. Centers with similar catheter cares practices were gathered in clusters in a hierarchical analysis. Clusters of centers associated with technique failure were evaluated using Cox and Fine and Gray models. A mixed effect Cox model was used to assess the influence of a center effect, as explained by the clusters. Results: Data from 2727 catheters placed in 64 centers in France were analyzed. Five clusters of centers were identified. After adjustment for patient-level characteristics, the fourth cluster was associated with a lower risk of technique failure (cause specific-HR 0.70, 95%CI 0.54–0.90. The variance of the center effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and clusters of centers in the mixed effect Cox model. Favorable outcomes were observed in clusters with a greater proportion of community hospitals, where catheters were placed via open surgery, first dressing done 6 to 15 days after catheter placement, and local prophylactic antibiotics was applied on exit-site. Conclusion: Several patterns of PD catheter related practices have been identified in France, associated with differences in the risk of technique failure. Combinations of favorable practices are suggested in this study. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) is an easily implementable dialysis modality in end-stage renal disease (ESRD). PD may improve access to renal replacement therapy in low- and middle-income countries; however, these countries have a higher prevalence of protein-energy wasting in patients and poorer socioeconomic conditions. We evaluated the effects of HIV infection on serum albumin levels in ESRD patients starting continuous ambulatory PD (CAPD) and mortality outcomes. Methods: We conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa, from September 2012 to February 2015. Seventy HIV-negative and 70 HIV-positive ESRD patients were followed monthly for serum albumin levels and mortality events during the first 18 months of CAPD therapy. Results: The HIV-positive cohort recorded 28 deaths (40%) among patients with a functional CAPD catheter at 18 months and 13 deaths (18.6%) in the HIV-negative cohort (p = 0.005). The mean serum albumin levels were lower in the HIV-positive cohort than in the HIV-negative cohort during the 18-month follow-up. The mean difference in serum albumin levels between the two cohorts was 4.24 g/L (95% confidence interval [CI] 2.02–6.46, p<0.001) at baseline and 3.99 g/L (95% CI 1.19–6.79, p = 0.006) at 18 months. HIV-positive status (adjusted regression coefficient -2.84, CI -5.00–-0.67, p = 0.011), diabetes (adjusted coefficient -2.85; CI, -5.58–-0.12; p = 0.041), and serum C-reactive protein and blood hemoglobin levels were independent predictors of serum albumin levels on multivariable linear regression. Baseline serum albumin <25 g/L (subdistribution-hazard ratio [SHR] 13.06, 95% CI 3.09–55.14, p<0.001) and CD4+ cell count <200 cells/μL (SHR 3.2, CI 1.38–7.45, p = 0.007) were independent predictors of mortality in our competing risk model. Conclusions: HIV infection can adversely affect serum albumin levels in ESRD patients managed with CAPD, while low baseline serum albumin levels and impaired immunity reliably predict mortality. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) is increasingly used for long-term management of Cardiorenal Syndrome (CRS). We compared outcomes in incident PD patients according to their baseline heart failure status. Methods: This retrospective cohort study evaluated all-cause and cardiovascular mortality in incident PD patients with different heart failure status (non-CRS, acute heart failure [AHF], type II CRS, type IV CRS) who started PD between 2006 and 2016 in the Peking University Third Hospital. Results: Of 748 patients included in the study, there were 466 (62.3%), 214 (28.6%), 27 (3.6%), and 41 (5.5%) patients in the non-CRS, AHF, type II CRS and type IV CRS groups, respectively. Patients with CRS were older (p<0.001), with more diabetes mellitus (p<0.001), coronary heart history (p<0.001), higher estimated glomerular filtration rate (eGFR) (p<0.001), lower serum creatinine (p<0.001) and phosphorus levels (p = 0.003) compared to non-CRS patients. Respective all-cause survival rates for patients with non-CRS, AHF, type II CRS and type IV CRS were 90.6%, 87.1%, 85.2% and 84.8% at 1 year, and 63.1%, 47.7%, 27.3% and 35.1% at 5 years (p<0.001). The corresponding figures for cardiovascular survival were 93%, 92%, 84% and 81% at 1 year, and 67%, 59%, 55% and 54% at 5 years (p<0.001). However, after adjusting for confounding factors, the presence of CRS was not independently associated with all-cause mortality whereas type IV CRS (HR 2.10, 95% CI 1.03–4.28, p = 0.04) was associated with higher cardiovascular mortality as compared to without CRS. Conclusion: Incident PD patients with different types of CRS had higher rates of both all-cause and cardiovascular mortality compared with patients without CRS. However, these observed adverse outcomes may be related to associated older age and higher prevalence of comorbidities, rather than CRS per se, except for type IV CRS, treatment strategies to reduce high cardiovascular CVD mortality may needed. [ABSTRACT FROM AUTHOR]

Whether higher serum uric acid (UA) values comprise a risk factor for death and whether treatment for high UA is effective in patients undergoing hemodialysis (HD) are essentially unknown. To determine associations between UA and all-cause or cardiovascular (CV) mortality, interactions between UA or medication and effects on mortality, and significance of treatment for hyperuricemia in patients undergoing hemodialysis (HD). We collected the baseline data of 222,434 patients undergoing three HD sessions per week, extracted from a nationwide dialysis registry at the end of 2011 in Japan. Then we evaluated the interaction between serum uric acid level and all-cause and cardiovascular (CV) mortality by the end of 2012. Univariate and multivariate logistic regression and Cox regression analyses found higher all-cause and CV mortality rates among patients with lower, than higher UA values. Hazard ratios (HR) for all-cause and CV mortality were significantly lower in a group with, than without medication for hyperuricemia (HR, 0.837; 95% confidence interval (CI), 0.789–0.889 and HR, 0.830; 95%CI 0.758–0.909, respectively). Lower UA values remained associated with all-cause and CV mortality rates even when in patients taking medication for hyperuricemia. The chief interacting factors for higher mortality rates due to lower UA were higher BMI and diabetes mellitus. In conclusion, lower UA levels were independently associated with higher all-cause and CV mortality among Japanese patients undergoing HD. Intervention for hyperuricemia is considered to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the effect of cinacalcet use on all-cause and cause-specific hospitalization outcomes using a prospective cohort of maintenance hemodialysis patients. Methods: We used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism and examined baseline characteristics as well as longitudinal changes. All patients were cinacalcet-naïve at study enrollment. Further, we used a marginal structural model to account for time-varying confounders on cinacalcet initiation and hospitalization outcomes, and an Andersen-Gill–type recurrent event model to account for any recurring events of hospitalization in the outcome analysis using the weighted dataset. Results: Among the 3,276 patients, cinacalcet treatment was initiated in 1,384 patients during the entire follow-up. Cinacalcet users were slightly younger, included more patients with chronic glomerulonephritis and fewer patients with diabetes, were more likely to have a history of parathyroidectomy, and were more often used receiving vitamin D receptor activator, phosphate binders, and iron supplements. The overall hospitalization analysis yielded a hazard ratio (HR) of 0.97 (95% confidence interval [CI]: 0.80, 1.18). A trend toward a mild protective association was observed for cardiovascular-related hospitalizations (HR: 0.85; 95% CI: 0.64, 1.14). In the subgroup analysis, a protective association was seen due to cinacalcet use for infection-related hospitalizations in the lowest intact parathyroid hormone group (HR: 0.36; 95% CI: 0.14, 0.95). Conclusions: Cinacalcet initiation in patients on maintenance hemodialysis had no effect on all-cause and cause-specific hospitalizations. Although the overall association was statistically not significant, cinacalcet may have a protective association on cardiovascular-related hospitalization in all patients and infection-related hospitalization in patient with low intact parathyroid hormone. [ABSTRACT FROM AUTHOR]

Introduction: Few studies have linked high levels of plasma C-terminal fibroblast growth factor 23 (FGF23) with poor clinical outcomes in patients on maintenance haemodialysis (MHD), while the association between intact FGF23 and mortality in this group of patients remains inconclusive. Therefore, the aim of this study was to evaluate the association between plasma levels of intact FGF23 and mortality in dialysis patients. Methods: A prospective multicenter study involving patients undergoing dialysis at three dialysis centers in Johannesburg was undertaken between 1st October 2014 and 31st December 2017. Results: The study comprised 165 chronic dialysis patients (111 blacks, 54 whites) with a mean age of 46.6 ±14.2 years. During a three year follow up period, there were 46 deaths (1.03 per 100 person-years). The median plasma FGF 23 level was 382 pg/ml (interquartile range [IQR], 145–2977). In adjusted multivariable analyses, there was a non-statistically significant increase in the risk of mortality with higher quartiles of FGF 23 levels: the adjusted hazard ratios (HR) for the second, third and fourth quantiles were HR 3.20 (95% CI, 0.99–10.35; P = 0.052), HR 2.43(95% CI,0.65–9.09; P = 0.19), and HR 2.09 (95% CI, 0.66–7.32; P = 0.25),respectively. Corrected serum calcium 2.38–2.5 mmol/l [HR 2.98 (95% CI, 1.07–8.29; P = 0.04] and > 2.50 mmol/l [HR 5.50 (95% CI, 1.84–16.48; P = 0.002] were independently associated with increased risk of death. Likewise, patients with intact parathyroid hormone > 600 pg/ml had a 3.46-fold higher risk of death (HR 3.46, 95% CI, 1.22–9.82 P = 0.019). These findings persisted in time -dependent analyses. Conclusion: Higher levels of intact FGF 23 appear not to be independently associated with all-cause mortality in our dialysis patients, while hypercalcaemia and severe hyperparathyroidism were found to be independent predictors of mortality in this cohort of patients. [ABSTRACT FROM AUTHOR]

To investigate how changes in eGFR can affect medical costs, a regional cohort of national health insurance beneficiaries in Japan was developed from a nationwide database system (Kokuho database, KDB), and non-individualized data were obtained. From 105,661 people, subjects on chronic dialysis and subjects without consecutive medical checkups were excluded. Finally, medical costs in the follow-up year categorized by annual changes in eGFR between baseline and the next year were longitudinally examined in 70,627 people ranging in age from 40 to 74 years. Global mean costs for subjects with a rapid decrease in eGFR (≤-30%/year) were the highest among all ΔeGFR categories. In men, the cost was 1.42 times that for a stable eGFR. A total of 6,268 (19.4%) men and 5,381 (14.0%) women with eGFR <60 ml/min/1.73 m2 were identified in the baseline year. The mean cost was higher with a low eGFR than without a low eGFR, and there were also higher proportions newly initiating dialysis in 2014 (low eGFR with rapid decrease in eGFR vs. with stable eGFR: 9.61% vs. 0.02% in women, P<0.001). Moreover, the costs for low eGFR subjects with a rapid decrease in eGFR were more than twice those of non-low eGFR subjects with a rapid decrease in eGFR and also compared to low eGFR subjects with a stable eGFR. Moreover, initiating chronic dialysis was considered one of the major causes of high medical costs in women with rapid eGFR decline. To the best of our knowledge, this is the first study of renal disease using a cohort developed from the KDB system recently established in Japan. [ABSTRACT FROM AUTHOR]

Background: Vancomycin is frequently used in hemodialysis (HD) and in hemodiafiltration (HDF) patients and is usually administered in the last 30 or 60 minutes of a dialysis session. Vancomycin pharmacokinetics are not well described in HDF patients. The aim of this study is to develop a population pharmacokinetic (PPK) model and dosing regimen for vancomycin in HDF patients and to evaluate its applicability in low-flux (LF-HD) patients. Methods: Two-compartment PPK models were developed using data from HDF patients (n = 17), and was parameterized as follows: non-renal clearance (CLm), renal clearance as a fraction of creatinine clearance (fr), central volume of distribution (V1), intercompartmental clearance (CL12), peripheral volume of distribution (V2) and extracorporeal extraction ratio (Eec). We evaluated the final model in a cohort of LF-HD patients (n = 21). Dosing schemes were developed for a vancomycin 24-h AUC of 400 mg*h/L. Results: Model parameters (± SD) were: CLm = 0.473 (0.271) L/h, fr = 0.1 (fixed value), V1 = 0.278 (0.092) L/kgLBMc, CL12 = 9.96 L/h (fixed value), V2 = 0.686 (0.335) L/kgLBMc and Eec = 0.212 (0.069). The model reliably predicted serum levels of vancomycin in both HDF and LF-HD patients during and between dialysis sessions. The median of the prediction error (MDPE) as a measure of bias is -0.7% (95% CI: -3.4%-1.7%) and the median of the absolute values of the prediction errors (MDAPE) as a measure of precision is 7.9% (95% CI: 6.0%-9.8%). In both HDF and LF-HD, the optimal vancomycin loading dose for a typical patient weighing 70 kg is 1700 mg when administered during the last 60 minutes of the hemodialysis session. Maintenance dose is 700 mg if administered during the last 30 or 60 minutes of the hemodialysis session. Conclusion: The developed PPK model for HDF is also capable of predicting serum levels of vancomycin in patients on LF-HD. A dosing regimen was developed for the use of vancomycin in HDF and LF-HD. [ABSTRACT FROM AUTHOR]

Background and aims: Malnutrition and inflammation are closely linked to vascular calcification (VC), the severity of which correlate with adverse outcome. However, there were few studies on the interplay between malnutrition, inflammation and VC progression, rather than VC presence per se. We aimed to determine the relationship of malnutrition, inflammation, abdominal aortic calcification (AAC) progression with survival in hemodialysis (HD) patients. Methods: Malnutrition and inflammation were defined as low serum albumin (< 40 g/L) and high hs-CRP (≥ 28.57 nmol/L), respectively. We defined AAC progression as an increase in AAC score using lateral lumbar radiography at both baseline and one year later. Patients were followed up to investigate the impact of AAC progression on all-cause and cardiovascular mortality. Results: AAC progressed in 54.6% of 97 patients (mean age 58.2±11.7 years, 41.2% men) at 1-year follow-up. Hypoalbuminemia (Odds ratio 3.296; 95% confidence interval 1.178–9.222), hs-CRP (1.561; 1.038–2.348), low LDL-cholesterol (0.976; 0.955–0.996), and the presence of baseline AAC (10.136; 3.173–32.386) were significant risk factors for AAC progression. During the mean follow-up period of 5.9 years, 38(39.2%) patients died and 27(71.0%) of them died of cardiovascular disease. Multivariate Cox regression analysis adjusted for old age, diabetes, cardiovascular history, and hypoalbuminemia determined that AAC progression was an independent predictor of all-cause mortality (2.294; 1.054–4.994). Conclusions: Malnutrition and inflammation were significantly associated with AAC progression. AAC progression is more informative than AAC presence at a given time-point as a predictor of all-cause mortality in patients on maintenance HD. [ABSTRACT FROM AUTHOR]

Purpose: End-stage renal disease (ESRD) patients exhibit silent white-matter alterations after long-term hemodialysis, which may be due to ESRD itself or the hemodialysis. The purpose of this study was to investigate the longitudinal white-matter alterations in the ESRD patients under 3-year long-term hemodialysis using voxel-wise analysis of diffusion tensor imaging (DTI). Materials and methods: 15 ESRD patients and 15 age-matched healthy controls participated in this study. Due to the development of abnormal brain lesions in some cases, 13 ESRD patients and 13 age-matched healthy controls were enrolled and underwent cognitive function assessment and DTI acquisition at two-time points separated by 3 years. Voxel-based analysis was performed to globally detect white-matter alterations between the two groups as well as between the two scans within the two groups. Results: In the ESRD patients, diffusivity indices were significantly increased and the fractional anisotropy was significantly decreased in both scans, as compared with healthy controls. Longitudinal comparisons showed significant white-matter alterations in healthy controls in three years, but little or no significant alterations were noted in the ESRD patients after additional 3-year hemodialysis. Conclusion: Poorer white matter integrity and cognitive function are noted in ESRD patients and the toxic effect of ESRD may be the major factor of white matter alterations. [ABSTRACT FROM AUTHOR]

Background: The hemodialysis regimen is an inevitable and mandatory treatment for patients with end-stage renal disease (ESRD). During the dialysis journey, patients may experience maladaptation in terms of sleep disturbances, depressive symptoms, and reduced health-related quality of life (HRQOL). Psychosocial resources such as social support may have beneficial influences on health outcomes, but studies have rarely analyzed the integrated relationships among risk factors which include pain, sleep disturbances, duration since diagnosis and various health outcomes in Taiwan. This study aimed to bridge this gap by investigating the relationships among related risk factors, social support, sleep disturbances, depressive symptoms, and HRQOL, which is composed of physical quality of life (PQOL) and mental quality of life (MQOL), in ESRD patients. Method: A correlational design was used, and 178 patients aged 20 years or older were recruited via convenience sample. The relationships among the risk factors, the mediators, depressive symptoms, PQOL, and MQOL were analyzed using structural equation modeling. Results: The findings showed that more than 70% of the participants reported poor sleep quality, and 32% reported depressive symptoms. When participants had greater pain and more sleep disorders, they were more likely to be depressed. When participants had more appraisal support; they had better PQOL and fewer depressive symptoms. Overall, the structural equation model explained 31.8% of the variance in self-reported depressive symptoms, 29.4% of the variance in PQOL, and 5.7% of the variance in MQOL. Moreover, appraisal support enhanced PQOL and reduced depressive symptoms by exerting its two mediating effects on sleep disturbances. Conclusion: Our findings indicate that patients with ESRD who have more social support have better PQOL and MQOL and fewer depressive symptoms than those with less social support. [ABSTRACT FROM AUTHOR]

Background: Regional anticoagulation with citrate during renal replacement therapy (RRT) reduces the risk of bleeding, extends dialyzer lifespan and is cost-effective. Therefore, current guidelines recommend its use if patients are not anticoagulated for another reason and if there are no contraindications against citrate. RRT with regional citrate anticoagulation has been established in critically ill patients as continuous veno-venous hemodialysis (CVVHD) to reduce citrate load. However, CVVHD is inferior regarding middle molecule clearance compared to continuous veno-venous hemofiltration (CVVH). The use of a high cut-off dialyzer in CVVHD may thus present an option for middle molecule clearance similar to CVVH. This may allow combining the advantages of both techniques. Methods: In this prospective, randomized, single-blinded single-center-trial, sixty patients with acute renal failure and established indication for renal replacement therapy were randomized 1:1 into two groups. The control group was put on CVVHD using regional citrate anticoagulation and a high-flux dialyzer, while the intervention group was on CVVHD using regional citrate anticoagulation and a high-cut-off dialyzer. The concentrations of urea, creatinine, β2-microglobulin, myoglobin, interleukin 6 and albumin were measured pre- and post-dialyzer 1, 6, 12, 24 and 48 hours after initiating CVVHD. Results: Mean plasma clearance for β2-microglobulin was 19.6±5.8 ml/min in the intervention group vs. 12.2±3.6 ml/min in the control group (p<0.001). For myoglobin (8.0±4.5 ml/min vs. 0.2±3.6 ml/min, p<0.001) and IL-6 (1.5±4.3 vs. -2.5±3.5 ml/min, p = 0.002) a higher mean plasma clearance using high-cut-off dialyzer could be detected too, but no difference for urea, creatinine and albumin could be observed concerning this parameter between the two groups. Conclusion: CVVHD using a high cut-off dialyzer results in more effective middle molecule clearance than that with high-flux dialyzer. Trial registration: German Clinical Trials Register (, registered 26th November 2013) [ABSTRACT FROM AUTHOR]

Background: Calcium oxalate (CaOx) deposition in the kidney may lead to loss of native renal function but little is known about the prevalence and role of CaOx deposition in transplanted kidneys. Methods: In patients transplanted in 2014 and 2015, all for-cause renal allograft biopsies obtained within 3 months post-transplantation were retrospectively investigated for CaOx deposition. Additionally, all preimplantation renal biopsies obtained in 2000 and 2001 were studied. Results: In 2014 and 2015, 388 patients were transplanted, of whom 149 had at least one for-cause renal biopsy. Twenty-six (17%) patients had CaOx deposition. In the population with CaOx deposition: Patients had significantly more often been treated with dialysis before transplantation (89 vs. 64%; p = 0.011); delayed graft function occurred more frequently (42 vs. 23%; p = 0.038); and the eGFR at the time of first biopsy was significantly worse (21 vs. 29 ml/min/1.73m2; p = 0.037). In a multivariate logistic regression analysis, eGFR at the time of first biopsy (OR 0.958, 95%-Cl: 0.924–0.993, p = 0.019), dialysis before transplantation (OR 4.868, 95%-Cl: 1.128–21.003, p = 0.034) and the time of first biopsy after transplantation (OR 1.037, 95%-Cl: 1.013–1.062, p = 0.002) were independently associated with CaOx deposition. Graft survival censored for death was significantly worse in patients with CaOx deposition (p = 0.018). In only 1 of 106 preimplantation biopsies CaOx deposition was found (0.94%). Conclusion: CaOx deposition appears to be primarily recipient-derived and is frequently observed in for-cause renal allograft biopsies obtained within 3 months post-transplantation. It is associated with inferior renal function at the time of biopsy and worse graft survival. [ABSTRACT FROM AUTHOR]

Improvement in Home Dialysis (HoD) utilizations as a mean to improve the patient reported and health services outcomes, has been a long-held goal of the providers and healthcare system in United States. However, measures to improve HoD rates have yielded limited success so far. Lack of patient awareness of chronic kidney disease (CKD) and its management options, is one of the important barriers against patient adoption of HoD. Despite ample evidence that Comprehensive pre-ESERD Patient Education (CPE) improves patient awareness and informed HoD choice, use of CPE among US advanced CKD patients is low. Need for significant resources, lack of validated data showing unequivocal and reproducible benefits, and the lack of validated CPE protocols proven to have consistent efficacy in improving not only patient awareness but also HoD rates in US population, are major limitations deterring adoption of CPE in routine clinical practice. We recently demonstrated that if a structured, protocol based CPE is integrated within the routine nephrology care for patients with advanced CKD, it substantially improves informed HoD choice and utilizations. However, this requires establishing CPE resources within each nephrology practice. Efficacy of a stand-alone CPE model, independent of clinical care, has not been examined till date. In this report we report the efficacy of our structured CPE protocol, delivered outside the realm of routine nephrology care—as a stand-alone patient education program, in a geographically distant region, and show that: when provided opportunity for informed dialysis choice, a majority of advanced CKD patients in US would prefer HoD. We also show that initiating CPE leads to accelerated growth in HoD utilizations and reduces disparities in HoD utilizations, goals for system improvements. Finally, the reproducibility of our structured CPE protocol with consistent efficacy data suggest that initiating such programs at institutional levels has the potential to improve informed dialysis selection and HoD rates across any similar large healthcare institute within US. [ABSTRACT FROM AUTHOR]

This study evaluated the combined effect of recipient-to-donor weight and sex mismatch after deceased-donor renal transplantation in a German transplant cohort and the evolution of recipient-to-donor weight difference over a 13-year observation period. The association of absolute weight and sex difference with graft failure was explored in an outpatient cohort of deceased-donor transplant recipients who underwent kidney transplantation between 2000 and 2012. Graft failure was defined as repeated need for dialysis or death with a functioning graft. Recipient and donor sex pairings were classified as sex concordant (MDMR/FDFR) or discordant (MDFR/FDMR). These classes were further stratified into four groups according to recipient-to-donor weight mismatch ≥10 kg (recipient > donor) or <10 kg (recipient < donor). Multivariable Cox proportional hazards models were applied to evaluate the time to graft loss adjusting for donor, immunologic, surgical, organizational, and recipient predictors. Sex-concordant transplant pairings <10 kg weight difference served as the reference group. Among 826 transplant recipients, 154 developed graft failure (18.6%). Median graft survival time was 3.9 years; first quartile (0.2–1.2), second quartile (1.2–2.9), third quartile (2.9–5.8), and fourth quartile (5.8–12.4). After multivariable adjustment, the highest relative hazard for graft failure was observed for sex-discordant transplant pairings with a ≥10 kg weight difference between recipient and donor (compared to the reference group MDMR/FDFR with weight difference <10 kg, MDMR/FDFR with weight difference ≥10 kg, hazard ratio 1.86, 95% confidence interval 1.07–3.32—p = 0.029; MDFR/FDMR with weight difference <10 kg, hazard ratio 1.14, 95% confidence interval 0.78–1.68—p = 0.507, and MDFR/FDMR with weight difference ≥10 kg, hazard ratio 2.00, 95% confidence interval 1.15–3.48—p = 0.014). A recipient-to-donor weight mismatch of ≥10 kg was associated with an increased risk of graft loss or recipient death with a functioning graft. Concurrent sex discordance seemed to enhance this effect as indicated by an increase in the hazard ratio. We detected no significant tendency for increasing recipient-to-donor weight differences from 2000 to 2012. [ABSTRACT FROM AUTHOR]

Background: Protein energy wasting (PEW) is a risk factor for death. However, the cutoff vales for PEW are not optimized for early identification of hemodialysis patients with malnutrition. We evaluated the prognosis of Japanese maintenance hemodialysis patients using nutritional indices optimized for them. Materials and methods: We analyzed data from a nation-wide prospective cohort study of the Japanese Society for Dialysis Therapy Renal Data Registry to develop and validate a nutritional risk index (n = 48349, 48349, respectively). The association of nutritional factors with one-year death was tested using Cox proportional hazards models. Their cutoff levels were determined from the hazard ratios or receiver operating characteristic curves. Then, risk index was developed using scoring models. Results: Male was 61.4%; average age, 65.7±12.2 years; and diabetes mellitus, 32.8%. Four clinical factors were retained in the final model: low BMI (<20kg/m2), yes = 3, no = 0; low serum albumin level (young <3.7g/dL; old <3.5g/dL), yes = 4, no = 0; abnormal serum total cholesterol level, low (<130mg/dL) = 1, high (220≥mg/dL) = 2, no = 0; low serum creatinine level (young female, <9.7mg/dL; old female, <8.0mg/dL; young male, <11.6mg/dL; old male, <9.7mg/dL), yes = 4, no = 0. In the validation dataset, medium- and high-risk groups (total score 8 to 10; 11 or more) showed a higher risk of all-cause death than the low-risk group (0 to 7): medium-risk group (10.5%), hazard ratio adjusted for baseline characteristics 1.96 (95% confidence interval 1.77, 2.16); high-risk group (8.2%), 3.91 (3.57, 4.29). The medium- and high-risk groups also showed a higher risk of cardiovascular disease- and infection-caused deaths than the low-risk group. Conclusion: We developed a new nutritional risk index for hemodialysis patients, which may detect patients with malnutrition with a high-risk of death. [ABSTRACT FROM AUTHOR]

In chronic kidney disease both renal insufficiency and chronic inflammation trigger elevated hepcidin levels, which impairs iron uptake, availability. and erythropoiesis. Here we report the two first-in-human phase 1 trials of PRS-080#22, a novel, rationally engineered Anticalin protein that targets and antagonizes hepcidin. A single intravenous infusion of placebo or PRS-080#22 was administered to 48 healthy volunteers (phase 1a) and 24 patients with end stage chronic kidney disease (CKD) on hemodialysis (phase 1b) at different doses (0.08-16mg/kg for the phase 1a study and 2-8mg/kg for the phase 1b study) in successive dosing cohorts. The primary endpoint for both randomized, double-blind, phase 1 trials was safety and tolerability. Following treatment, all subjects were evaluable, with none experiencing dose limiting toxicities. Most adverse events were mild. One serious adverse event occurred in the phase 1b (CKD patient) study. There were no clinically significant changes in safety laboratory values or vital signs. PRS-080#22 showed dose-proportional pharmacokinetics (PK), with a terminal half-life of approximately three days in healthy volunteers and 10 to 12 days in CKD patients. Serum hepcidin levels were suppressed in a dose dependent manner and remained low for up to 48 hours after dosing. PRS-080#22 dose-dependently mobilized serum iron with increases in both serum iron concentration and transferrin saturation. No consistent changes were observed with regard to ferritin, reticulocytes, hemoglobin, and reticulocyte hemoglobin. Low titer anti-drug-antibodies were detected in five healthy volunteers but in none of the CKD patients. PRS-080#22, a novel Anticalin protein with picomolar affinity for hepcidin, was safe and well-tolerated when administered to healthy volunteers and CKD patients at all doses tested. The drug exhibited linear pharmacokinetics, longer half-life in CKD patients in comparison to healthy volunteers as well as expected pharmacodynamic effects which hold promise for further clinical studies. [ABSTRACT FROM AUTHOR]

Background: Arteriovenous fistulas (AVF) for haemodialysis often experience early thrombosis and maturation failure requiring intervention and/or central venous catheter (CVC) placement. This secondary and exploratory analysis of the FAVOURED study determined whether omega-3 fatty acids (fish oils) or aspirin affected AVF usability, intervention rates and CVC requirements. Methods: In 567 adult participants planned for AVF creation, all were randomised to fish oil (4g/d) or placebo, and 406 to aspirin (100mg/d) or placebo, starting one day pre-surgery and continued for three months. Outcomes evaluated within 12 months included AVF intervention rates, CVC exposure, late dialysis suitability failure, and times to primary patency loss, abandonment and successful cannulation. Results: Final analyses included 536 participants randomised to fish oil or placebo (mean age 55 years, 64% male, 45% diabetic) and 388 randomised to aspirin or placebo. Compared with placebo, fish oil reduced intervention rates (0.82 vs 1.14/1000 patient-days, incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.54–0.97), particularly interventions for acute thrombosis (0.09 vs 0.17/1000 patient-days, IRR 0.53, 95% CI 0.34–0.84). Aspirin significantly reduced rescue intervention rates (IRR 0.45, 95% CI 0.27–0.78). Neither agent significantly affected CVC exposure, late dialysis suitability failure or time to primary patency loss, AVF abandonment or successful cannulation. Conclusion: Although fish oil and low-dose aspirin given for 3 months reduced intervention rates in newly created AVF, they had no significant effects on CVC exposure, AVF usability and time to primary patency loss or access abandonment. Reduction in access interventions benefits patients, reduces costs and warrants further study. [ABSTRACT FROM AUTHOR]

Background: Assessment of infection-related mortality remains inadequate in patients undergoing peritoneal dialysis. This study was performed to develop a risk model for predicting the 2-year infection-related mortality risk in patients undergoing peritoneal dialysis. Methods: The study cohort comprised 606 patients who started and continued peritoneal dialysis for 90 at least days and was drawn from the Fukuoka Peritoneal Dialysis Database Registry Study in Japan. The patients were registered from 1 January 2006 to 31 December 2016 and followed up until 31 December 2017. To generate a prediction rule, the score for each variable was weighted by the regression coefficients calculated using a Cox proportional hazard model adjusted by risk factors for infection-related mortality, including patient characteristics, comorbidities, and laboratory data. Results: During the follow-up period (median, 2.2 years), 138 patients died; 58 of them of infectious disease. The final model for infection-related mortality comprises six factors: age, sex, serum albumin, serum creatinine, total cholesterol, and weekly renal Kt/V. The incidence of infection-related mortality increased linearly with increasing total risk score (P for trend <0.001). Furthermore, the prediction model showed adequate discrimination (c-statistic = 0.79 [0.72–0.86]) and calibration (Hosmer–Lemeshow test, P = 0.47). Conclusion: In this study, we developed a new model using clinical measures for predicting infection-related mortality in patients undergoing peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Background: Early markers to predict delayed kidney graft function (DGF) may support clinical management. We studied the ability of four biomarkers (neutrophil gelatinase associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), cystatin C, and YKL-40) to predict DGF after deceased donor transplantation, and their association with early graft function and GFR at three and twelve months. Methods: 225 deceased donor kidney transplant recipients were included. Biomarkers were measured using automated assays or ELISA. We calculated their ability to predict the need for dialysis post-transplant and correlated with the estimated time to a 50% reduction in plasma creatinine (tCr50), measured glomerular filtration rate (mGFR) and estimated GFR (eGFR). Results: All biomarkers measured at Day 1, except urinary L-FABP, significantly correlated with tCr50 and mGFR at Day 5. Plasma NGAL at Day 1 and a timed urine output predicted DGF (AUC = 0.91 and AUC 0.98). Nil or only weak correlations were identified between early biomarker levels and mGFR or eGFR at three or twelve months. Conclusion: High plasma NGAL at Day 1 predicts DGF and is associated with initial graft function, but may not prove better than P-creatinine or a timed urine output. Early biomarker levels do not correlate with one-year graft function. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Some clinicians keep patients in stage 5 chronic kidney disease (CKD) without hemodialysis for a while. This study investigated whether previously-initiated hemodialysis in stage 5 CKD patients may become a prognostic factor for in-hospital mortality due to pneumonia. Methods: Patient data were obtained from the multi-institutional diagnosis procedure combination database between April 1, 2012 and March 31, 2016. The patients had records of pneumonia as both trigger and major diagnoses and records of end stage renal disease (ESRD) or stage 5 CKD as a comorbidity or other diagnoses on admission and aged 18 years or older. The following factors were adjusted: age, sex, body mass index, Barthel index, orientation disturbance, arterial oxygen saturation, systolic blood pressure, C-reactive protein level or the extent of consolidation on chest radiography, ambulance use, hospitalization within 90 days, and comorbidities upon admission. The primary outcome measure was all-cause in-hospital mortality obtained via multivariable logistic regression analysis using four Models. Model 1 involved complete case analysis with overlapping; one hospitalization per patient was counted as one. Model 2 involved a complete case analysis without overlapping; only the first hospitalization per patient was counted. Model 3 involved multilevel analysis clustered by hospital codes. Model 4 was created after multiple imputation for lacking adjusted factors. Results: A total of 907 hospitals and 7,726 patients were identified. Hemodialysis was significantly associated with lower in-hospital mortality in all models (odds ratio [OR] = 0.68, 95% confidence interval [CI]: 0.54–0.87 in Model 1; OR = 0.71, 95% CI: 0.55–0.91 in Model 2; OR = 0.67, 95% CI: 0.52–0.86 in Model 3; and OR = 0.68, 95% CI: 0.54–0.87 in Model 4). Conclusion: Previously-initiated hemodialysis may be an independent prognostic factor for in-hospital mortality in pneumonia patients with end-stage renal disease. This should be borne in mind when considering the time of initiation of dialysis. [ABSTRACT FROM AUTHOR]

Avascular osteonecrosis (AVN) is a bone complication that indicates poor functional prognosis. Modern immunosuppressive and steroid-sparing drugs have significantly lowered the occurrence of AVN after kidney transplantation (KT). However, recent data on its incidence rates and risk factors are lacking. Using a large, recent cohort, we sought to investigate AVN incidence and risk factors, with a special focus on mineral and bone disorders. We conducted a cohort study in 805 patients who underwent KT between 2004 and 2014. AVN was identified in 32 patients (4%): before KT in 15 (1.8%) and after KT in 18 (2.2%) cases, including one patient with both. In the group with post-KT AVN, the median time intervals from KT to 1) first symptoms and 2) AVN diagnosis were 12 months [1–99] and 20 months [4–100], respectively. Being overweight/obese, having pre-transplant diabetes or hyperparathyroidism at transplantation, developing acute rejection, and receiving higher cumulative corticosteroid doses were associated with AVN occurrence. Multivariate analysis revealed that BMI ≥ 26 kg/m2 and higher cumulative corticosteroid doses were predictive of AVN. In conclusion, overweight/obesity is a strong risk factor for AVN. Despite a low maintenance dose, the use of corticosteroids—mostly for treatment of acute rejection—remains an independent risk factor. [ABSTRACT FROM AUTHOR]

Background: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). Methods: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. Results: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). Conclusions: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF. [ABSTRACT FROM AUTHOR]

Background: Ilio-psoas hematoma is a potentially lethal condition that can arise during hospital stay. However, neither the incidence nor the prognosis of patients whose stay in intensive care units (ICU) is complicated by a iatrogenic ilio-psoas hematoma is known. Methods: A bicentric retrospective study was conducted to compile the patients who developed an ilio-psoas hematoma while they were hospitalized in ICU between January 2009 and December 2016. Their biometric characteristics, pre-existing conditions, the circumstances in which the hematoma was diagnosed, the treatments they received and their prognosis were recorded. Results: Forty patients were diagnosed with an ilio-psoas hematoma during their ICU stay. The incidence of this complication was 3.8 cases for 1000 admissions, taking into account only patients who stayed more than three days in ICU. The median age of patients was 74 years old and the median time between admission and the diagnosis of ilio-psoas hematoma was 12.6 days. A large proportion of them was obese (42.5%) and/or under dialysis (50%) prior to developing their hematoma. Ninety-five percent of the patients had heparin at prophylactic or therapeutic doses. Only 10% of them were above the therapeutic range of anticoagulation. The ICU mortality rate was of 50% following this complication (versus a general mortality rate of 22% for the patients without IPH over the same period of time). Patients with IPH that were complicated by disseminated intravascular coagulopathy had a significantly higher mortality rate than those with IPH and no disseminated intravascular coagulopathy (OR 6.91, 95% CI [1.28; 58.8], p = 0.04). Conclusion: Age, anticoagulation, a high body mass index and dialysis seem to be risk factors of developing an ilio-psoas hematoma in ICU. Iatrogenic ilio-psoas hematomas complicated by disseminated intravascular coagulopathies are more at risk of leading to death. It is noteworthy that activated partial thromboplastin time above the therapeutic range was not a good predictor of developing a hematoma for patients who received unfractioned heparin therapy. [ABSTRACT FROM AUTHOR]