Outcomes In End-stage Kidney Disease Research Articles

Frailty syndrome and end-stage kidney disease outcomes at a Latin American dialysis center.

Frailty syndrome generates a high risk of adverse outcomes and mortality, and its prevalence is elevated in patients with end-stage kidney disease. Few studies have reported the prevalence and outcomes of frailty in populations from less developed countries. To identify the clinical outcomes and factors associated with the frailty syndrome in patients with stage five chronic kidney disease who started renal replacement therapy - both hemodialysis and peritoneal dialysis- in a dialysis center in Bucaramanga, Colombia. This was a prospective study of patients with end-stage kidney disease who initiated dialysis at a center in Colombia and had a twelve-month follow-up. The overall frailty prevalence was 50.47% and two out of three patients older than 65 years had the syndrome. We found significantly higher followup mortality among patients with frailty: odds ratio of 2.95 (CI: 1.07- 8.13; p=0.036) in unadjusted analysis. Literature shows that compared to developed nations, Latin American adults are facing a higher prevalence of chronic diseases, and frailty syndrome is raising. In this study, according to the FRAIL scale, having a frailty syndrome predicts a higher mortality; hypoalbuminemia and low creatinine levels at the beginning of dialysis could act as predictors of its diagnosis.

Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease.

Background: We hypothesize that the poor survival outcomes of end-stage kidney disease (ESKD) patients undergoing hemodialysis are associated with a low filtering efficiency and selectivity. The current gold standard criteria using single or several markers show an inability to predict or disclose the treatment effect and disease progression accurately. Methods: We performed an integrated mass spectrometry-based metabolomic and proteomic workflow capable of detecting and quantifying circulating small molecules and proteins in the serum of ESKD patients. Markers linked to cardiovascular disease (CVD) were validated on human induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Results: We identified dozens of elevated molecules in the serum of patients compared with healthy controls. Surprisingly, many metabolites, including lipids, remained at an elevated blood concentration despite dialysis. These molecules and their associated physical interaction networks are correlated with clinical complications in chronic kidney disease. This study confirmed two uremic toxins associated with CVD, a major risk for patients with ESKD. Conclusion: The retained molecules and metabolite-protein interaction network address a knowledge gap of candidate uremic toxins associated with clinical complications in patients undergoing dialysis, providing mechanistic insights and potential drug discovery strategies for ESKD.

Racial Disparities in End-Stage Kidney Disease Outcomes among Asians and Native Hawaiians and Other Pacific Islanders across Geographic Residence

Introduction: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs). Materials and Methods: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000–December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves. Results: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66–0.67) and 0.72 (0.70–0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood. Conclusion: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.

Prevalence and outcomes of end-stage kidney disease in patients with systemic lupus erythematous: a population-based study.

This study aims to examine the prevalence and outcomes of end-stage kidney disease (ESKD) among systemic lupus erythematosus (SLE) patients. SLE patients identified from the national administrative datasets were linked to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to identify the ESKD cases. Period prevalence of ESKD among SLE patients was calculated. The risk of developing ESKD by ethnicity was explored with Cox Proportional Hazards model. The adjusted hazard ratio (HR) of all-cause mortality for Māori, Pacific, Asian compared to European/others was estimated. Of the 2837 SLE patients, 210 (7.4%) developed ESKD. The average period prevalence of ESKD among SLE patients was 5.7%. Men had twice the prevalence rate of ESKD than women (10.0% vs 5.2%). Māori and Pacific had higher prevalence rate than Asian and European/others (9.4%, 9.8% vs 4.4% and 3.8%). The adjusted HR of developing ESKD for men compared to women was 3.37 (95% CI 1.62-7.02). The adjusted HR of developing ESKD for Māori and Pacific compared to European/others was 4.63 (95% CI 1.61-13.29) and 4.66 (95% CI 1.67-13.00), respectively. Compared to European/others, Māori had an HR of 2.17 (95% CI 1.18-4.00) for all-cause mortality. SLE patients had a high prevalence rate of ESKD. Men, Māori, and Pacific patients with SLE were more likely to develop ESKD. Māori patients with ESKD had poorer survival than other patients. Interventions are needed to reduce the risk of ESKD and to improve the survival of ESKD patients for the disadvantaged groups.

Outcomes Among Undocumented Immigrant Kidney Transplant Recipients in California

There are over 2 million undocumented immigrants (UI) in California, where currently, all individuals regardless of immigration status have access to kidney transplant. There is a medical perception that UI face a higher risk of transplant failure due to language barriers and lack of access to immunosuppressive medication and health care when compared with US residents (UR). To elucidate the kidney transplant outcomes of UI at an academic medical center in California. A retrospective cohort study was conducted from a single transplant center during an 8-year study period. Patients who received a kidney transplant at the University of California, Irvine, between January 1, 2012, and September 1, 2019, were included in this study. Data were analyzed from October 2020 to August 2021. The primary exposure of this study was citizenship status. UI were defined as immigrants residing in the US without permission or legal documentation. The primary end point was all-cause graft loss defined as the return to dialysis, need for a second kidney transplant, or death. The secondary end points of this study were all-cause mortality and rejection. All-cause mortality between the 2 groups was compared using multiple Cox proportional hazard regression analysis. Other transplant outcomes, including all-cause graft loss and acute rejection, were examined by competing risks regressions with mortality and mortality plus graft loss serving as competing risks, respectively. Of all 446 consecutive kidney transplant recipients, the mean (SD) age was 47 (13) years; 261 patients (59%) were male, and 114 (26%) were UI. During a median (IQR) follow-up time of 3.39 (0.04-8.11) years, 6 UI and 48 UR experienced all-cause graft loss. UR had a 192% (hazard ratio, 2.92; 95% CI, 1.21-6.85; P = .01) and 343% (hazard ratio, 4.34; 95% CI, 1.05-18.69; P = .04) significantly increased unadjusted risk for all-cause graft loss and all-cause mortality, respectively. These results became nonsignificant and were mostly attenuated when adjusted for age and ethnicity. Finally, there was no difference in incidence rate of kidney allograft rejection between the 2 groups (UR, 3.5 per 100 person-years vs UI, 2.4 per 100 person-years; rate ratio, 1.45; 95% CI, 0.90-5.05; P = .08). This single-center cohort study found that kidney transplant outcomes of UI were not inferior to those of UR. Across the US, however, UI have consistently had unequal access to transplantation. These findings suggest that extending kidney transplants to UI is safe and does not portend worse outcomes. As a result, denying transplant according to immigration status not only results in higher costs but also worse end stage kidney disease outcomes for an already underserved population.

Supplementation with Folic Acid and Cardiovascular Outcomes in End-Stage Kidney Disease: A Multi-Institution Cohort Study.

Background: Folate is a water-soluble vitamin and is essential for maintaining cell functions. Dialysis removes folate, and folate deficiency is reported in patients with end-stage kidney disease (ESKD). However, there is no consensus as to the appropriate dosage of folate supplements and their advantages and disadvantages for patients with ESKD. Methods: This study was based on the electronic medical records of the Chang Gung Research Database (CGRD) of the Chang Gung Medical Foundation. We included patients who were diagnosed with ESKD, initiated hemodialysis, and were given folic acid supplements at any point from 1 January 2001 to 31 December 2019. The patients were divided into weekly and daily folic acid supplementation groups. We reduced the effects of confounding through the inverse probability of treatment weighting based on the propensity score. Results: We identified 2081 and 954 newly diagnosed patients with ESKD, who received daily and weekly folic acid supplements. The mean follow-up time was 5.8 years, and the event rates of arteriovenous access thrombosis were 17.0% and 23.6% in the daily and weekly folic acid supplementation groups (sub-distribution hazard ratio = 0.69, 95% confidence interval = 0.61 to 0.77), respectively. Neither group significantly differed in the occurrence of other clinical events, such as major cardiovascular cardiac events (e.g., myocardial infarction and ischemic stroke), all-cause mortality, cardiovascular death, infection death, malignancy, and adverse effects. Conclusion: a daily 5 mg folic acid supplementation might result in a lower event rate of arteriovenous access thrombosis in patients with ESKD than weekly folic acid supplementation. Further prospective studies are warranted to explore the preventive effect of folate on thrombosis.

Pretransplant Psoas Muscle Cross-Sectional Area and Postkidney Transplant Outcomes

Sarcopenia is associated with adverse outcomes in end-stage kidney disease. We evaluated if pretransplant sarcopenia affects posttransplant outcomes in kidney transplant (KT) recipients. In this single-center retrospective study of adult patients with end-stage kidney disease, we analyzed the association between pre-KT psoas muscle cross-sectional area and critical posttransplant outcomes of decline in estimated glomerular filtration rate (eGFR), graft loss, rehospitalization, and mortality using Cox proportional hazard model adjusted for age, sex, and race. Pre-KT abdomen and pelvic computed tomography scans performed during evaluation for KT eligibility were available for 573 KT recipients. Of these, 465 KT recipients received kidney alone transplant, 71 received simultaneous liver kidney transplant (SLK), and 37 received simultaneous pancreas kidney transplant (SPK). Patients were 49 (SD, 13) years old, 16% Black, and 60% men. For kidney alone transplant recipients, a higher psoas muscle cross-sectional area was associated with a shorter length of hospitalization (β coefficient=-0.003; 95% CI, -0.005 to -0.0007). Conversely, pre-KT psoas muscle cross-sectional area did not predict decline in eGFR, graft loss, mortality, or early rehospitalization. For SLK recipients, psoas muscle cross-sectional area did not predict any of the priori outcomes. For SPK recipients, higher pretransplant psoas muscle cross-sectional area predicted a longer length of hospitalization (β coefficient=0.03; 95% CI, 0.01-0.05). There was no association between psoas muscle cross-sectional area and other outcomes assessed. Pretransplant psoas muscle cross-sectional areas are not predictive of post-transplant decline in eGFR, graft loss, rehospitalization or mortality in kidney alone, SPK, or SLK transplants.

On the importance of the interplay of residual renal function with clinical outcomes in end-stage kidney disease.

Chronic kidney disease (CKD) is one of the most important public health concerns of the century, and is associated with high rates of morbidity, mortality and social costs. CKD evolving towards end-stage kidney disease (ESKD) is on the rise resulting in a greater number of patients requiring peritoneal dialysis (PD) and hemodialysis (HD). The aim of this manuscript is to review the current literature on the interplay of residual renal function (RRF) with clinical outcomes in ESKD. The persistence of RRF is one of the most important predictors of decreased morbidity, mortality, and better quality of life in both PD and HD patients. RRF contributes to the well-being of ESKD patients through various mechanisms including higher clearance of solutes, maintenance of fluid balance, removal of uremic toxins and control of electrolytes. Furthermore, RRF has beneficial effects on inflammation, anemia, malnutrition, diabetes mellitus, obesity, changes in the microbiota, and cardiac diseases. Several strategies have been proposed to preserve RRF, such as blockade of the renin-angiotensin-aldosterone system, better blood pressure control, incremental PD and HD. Several clinical trials investigating the issue of preservation of RRF are ongoing. They are needed to broaden our understanding of the interplay of RRF with clinical outcomes in ESKD.

Association of Intraindividual Difference in Estimated Glomerular Filtration Rate by Creatinine vs Cystatin C and End-stage Kidney Disease and Mortality

As cystatin C is increasingly adopted to estimate glomerular filtration rate (eGFR), clinicians will encounter patients in whom cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) differ widely. The clinical implications of these differences, eGFRdiffcys-cr, are unknown. To evaluate the associations of eGFRdiffcys-cr with end-stage kidney disease (ESKD) and mortality among individuals with chronic kidney disease (CKD). This is a prospective cohort study of 4956 individuals with mild to moderate CKD from 7 clinical centers in the United States who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 to 2018. Statistical analyses were completed in December 2021. eGFRdiffcys-cr (eGFRcys - eGFRcr) was calculated at baseline and annually thereafter for 3 years. Because 15 mL/min/1.73 m2 represents a clinically meaningful difference in eGFR that also distinguishes CKD stages, eGFRdiffcys-cr was categorized as: less than -15 mL/min/1.73 m2, -15 to 15 mL/min/1.73 m2, and 15 mL/min/1.73 m2 or greater. The outcomes of ESKD, defined as initiation of maintenance dialysis or receipt of a kidney transplant, and all-cause mortality were adjudicated from study entry until administrative censoring in 2018. Among 4956 participants with mean (SD) age of 59.5 (10.5) years, 2152 (43.4%) were Black, 515 (10.4%) were Hispanic, and 2113 (42.6%) were White. There were 2156 (43.5%) women and 2800 (56.5%) men. At baseline, eGFRcys and eGFRcr values differed by more than 15 mL/min/1.73 m2 in one-third of participants (1638 participants [33.1%]). Compared with participants with similar baseline eGFRcys and eGFRcr (eGFRdiffcys-cr -15 to 15 mL/min/1.73 m2), those in whom eGFRcys was substantially lower than eGFRcr (eGFRdiffcys-cr < -15 mL/min/1.73 m2) had a higher risk of mortality (hazard ratio [HR], 1.86; 95% CI, 1.40-2.48) while those with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (subHR [SHR], 0.73; 95% CI, 0.59-0.89) and mortality (HR, 0.68; 95% CI, CI 0.58-0.81). In time-updated analyses, participants with eGFRdiffcys-cr less than -15 mL/min/1.73 m2 had higher risks of ESKD (SHR, 1.83; 95% CI, 1.10-3.04) and mortality (HR, 3.03; 95% CI, 2.19-4.19) compared with participants with similar eGFRcys and eGFRcr. Conversely, participants with eGFRdiffcys-cr of 15 mL/min/1.73 m2 or greater had lower risks of ESKD (SHR, 0.50; 95% CI, 0.35-0.71) and mortality (HR, 0.58; 95% CI, 0.45-0.75). Longitudinal changes in eGFRdiffcys-cr were associated with mortality risk. Compared with participants who had similar slopes by eGFRcys and eGFRcr, those with smaller eGFRcr declines had an 8-fold increased mortality risk (HR, 8.20; 95% CI, 6.37-10.56), and those with larger apparent declines by eGFRcr had a lower mortality risk (HR, 0.14; 95% CI, 0.08-0.24). These findings suggest that large differences between eGFRcys and eGFRcr were common in persons with CKD. These differences and their changes over time may be informative of ESKD and mortality risks, warranting monitoring of both eGFRcys and eGFRcr in this high-risk population.

Does delivering more dialysis improve clinical outcomes? What randomized controlled trials have shown.

Some randomized controlled trials (RCTs) have sought to determine whether different dialysis techniques, dialysis doses and frequencies of treatment are able to improve clinical outcomes in end-stage kidney disease (ESKD). Virtually all of these RCTs were enacted on the premise that 'more' haemodialysis might improve clinical outcomes compared to 'conventional' haemodialysis. Aim of the present narrative review was to analyse these landmark RCTs by posing the following question: were their intervention strategies (i.e., earlier dialysis start, higher haemodialysis dose, intensive haemodialysis, increase in convective transport, starting haemodialysis with three sessions per week) able to improve clinical outcomes? The answer is no. There are at least two main reasons why many RCTs have failed to demonstrate the expected benefits thus far: (1) in general, RCTs included relatively small cohorts and short follow-ups, thus producing low event rates and limited statistical power; (2) the designs of these studies did not take into account that ESKD does not result from a single disease entity: it is a collection of different diseases and subtypes of kidney dysfunction. Patients with advanced kidney failure requiring dialysis treatment differ on a multitude of levels including residual kidney function, biochemical parameters (e.g., acid base balance, serum electrolytes, mineral and bone disorder), and volume overload. In conclusion, the different intervention strategies of the RCTs herein reviewed were not able to improve clinical outcomes of ESKD patients. Higher quality studies are needed to guide patients and clinicians in the decision-making process. Future RCTs should account for the heterogeneity of patients when considering inclusion/exclusion criteria and study design, and should a priori consider subgroup analyses to highlight specific subgroups that can benefit most from a particular intervention.

The clinical application of frailty in nephrology and transplantation.

Clinicians treating end-stage kidney disease (ESKD) and kidney transplant patients face unique challenges in their care because of the high burden of frailty in these patients. Frailty has gained significant attention by medical and surgical specialties for risk stratification in the past decades. This review highlights the importance of measuring frailty in kidney transplant candidates and recipients. Emerging data support that frailty is present even at younger ages among patients undergoing dialysis, transplant evaluation, or transplantation. It is estimated that 18.8% of younger (18-64 years) candidates, 25.2% of older (≥65 years) candidates, 14.3% of younger recipients, and 20.8% of older recipients are frail. Additionally, frailty is dynamic and subject to change pretransplantation and posttransplantation. Although many patients and clinicians are aware of the importance of measuring frailty, further studies addressing the need for interventions to reduce frailty burden are needed. Frailty is independently associated with many adverse outcomes in ESKD and kidney transplant populations. Given the growing number of ESKD and kidney transplant patients, it is pivotal to expand the utility of frailty measurement in clinical practice, recognize the burden of frailty, and identify appropriate interventions to mitigate the adverse effects of frailty.

Chronic kidney disease progression and mortality risk profiles in Germany: results from the Chronic Kidney Disease Outcomes and Practice Patterns Study.

BackgroundChronic kidney disease (CKD) progression among German patients in a representative setting has not been described previously. The Verband Deutsche Nierenzentren and Chronic Kidney Disease Outcomes and Practice Patterns Study established a longitudinal observational cohort among German CKD patients to research variations in patient care and outcomes in real-world nephrology practices.MethodsA cohort of CKD Stages 3 (25%) and 4 (75%) patients was established from German nephrologist-run CKD clinics in 2013–16. Linear models were used to determine the estimated glomerular filtration rate (eGFR) slope during follow-up and Cox models were used to assess outcomes of end-stage kidney disease (ESKD) and death.ResultsA total of 1834 patients (median age 75 years, 58% male, 42% diabetics, median baseline eGFR 25 mL/min/1.73 m2) were followed for a median of 29 months. More than 50% had slow or no decline and 17% declined ≥5 mL/min/1.73 m2/year. After 4.5 years, the incidence of ESKD was 8% and of deaths without ESKD 16% among patients with eGFR ≥30 mL/min/1.73 m2 and 37% and 19% for eGFR <30 mL/min/1.73 m2. Adjusted models showed higher risks of ESKD or death for patients with worse kidney function at baseline, male sex, diabetes and higher blood pressure; a higher risk of ESKD with higher albuminuria; and a higher risk of death with older age or cardiovascular comorbidity.ConclusionsRoutine nephrology care of patients in Germany comprises mostly elderly patients, many with slow CKD progression. Identification of risk factors for CKD progression and mortality may help guide resources by closer follow-up of high-risk patients.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

End-Stage Kidney Disease From Scleroderma in the United States, 1996 to 2012

IntroductionAlthough the management of scleroderma continues to evolve, it is unknown whether the burden of end-stage kidney disease (ESKD) treated with maintenance renal replacement therapy from SD has changed.MethodsWe examined United States Renal Data System data (n = 1,677,303) for the years 1996 to 2012 to quantify the incidence and outcomes of ESKD from scleroderma treated with renal replacement therapy (n = 2398). Outcomes assessed through demography-matched scleroderma-positive/scleroderma-negative comparisons included recovery of kidney function, mortality, listing for transplant, renal transplantations, and graft failure.ResultsOverall ESKD rates from scleroderma were 0.5 per million per year. Adjusted incidence ratios fell over time, to 0.42 in 2012 (vs. 1996, 95% confidence interval [CI] = 0.32−0.54, P < 0.001). Adjusted incidence ratios for ESKD from scleroderma fell over time in both sexes, all age, race, and ethnicity categories except age < 20 years and Asian race, and in all regions of the United States. After initiating renal replacement therapy, patients with scleroderma had a greater likelihood of recovery of kidney function (hazards ratio [HR] = 2.67, 95% CI = 1.90−3.76, P < 0.001) and death (HR = 1.44, 95% CI = 1.34−1.54, P < 0.001) and a lower likelihood of transplantation (HR = 0.51, 95% CI = 0.44−0.59, P < 0.001) than demography-matched patients without scleroderma.ConclusionThe incidence of ESKD from scleroderma appears to have declined in the United States since 1996. ESKD from scleroderma is associated with an enhanced likelihood of recovery of kidney function and death, a reduced likelihood of transplantation, and similar outcomes after transplantation.

Long-term outcomes of end-stage kidney disease for patients with lupus nephritis

Patient outcomes in end-stage kidney disease (ESKD) secondary to lupus nephritis have not been well described. To help define this we compared dialysis and transplant outcomes of patients with ESKD due to lupus nephritis to all other causes. All patients diagnosed with ESKD who commenced renal replacement therapy in Australia and New Zealand (1963-2012) were included. Clinical outcomes were evaluated in both a contemporary cohort (1998-2012) and the entire 50-year cohort. Of 64,160 included patients, 744 had lupus nephritis as the primary renal disease. Forthe contemporary cohort of 425 patients with lupus nephritis, the 5-year dialysis patient survival rate was 69%. Of 176 contemporary patients with lupus nephritis who received their first renal allograft, the 5-year patient, overall renal allograft, and death-censored renal allograft survival rates were 95%, 88%, and 93%, respectively. Patients withlupus nephritis had worse dialysis patient survival (adjusted hazard ratio 1.33, 95% confidence interval 1.12-1.58) and renal transplant patient survival (adjusted hazard ratio 1.87, 95% confidence interval 1.18-2.98), but comparable overall renal allograft survival (adjusted hazard ratio 1.19, 95% confidence interval 0.84-1.68) and death-censored renal allograft survival (adjusted hazard ratio 1.05, 95% confidence interval 0.68-1.62) compared with ESKD controls. Similar results were found in the entire cohort and when using competing-risks analysis. Thus, the ESKD of lupus nephritis was associated with worse dialysis and transplant patient survival but comparable renal allograft survival compared with other causes of ESKD.

Anaemia and early phase cardiovascular events on haemodialysis.

Although the mechanism of the cardio-renal anaemia syndrome (CRAS) has been elucidated in considerable detail over the past decade, cardiovascular disease (CVD) remains a leading cause of death among patients with end-stage kidney disease (ESKD) undergoing haemodialysis, and these patients' cardiovascular mortality is greater than that of the general population. Recent studies have reported that the CVD risk increases with advancing chronic kidney disease (CKD) stage. Furthermore, the incidence of cardiovascular events is highest during the first week after dialysis initiation, with increased risk in incident haemodialysis patients. This accumulated evidence demonstrates that how patients are managed during the pre-dialysis phase may have important implications on long-term outcomes in ESKD. Anaemia, a non-traditional risk factor for CVD, advances exponentially along with declining kidney function due to insufficient erythropoietin production. Anaemia causes functional abnormalities of the heart, as represented by cardiac hypertrophy, which results from increased cardiac workload induced by an increased preload. Left ventricular hypertrophy (LVH), a traditional risk factor for CVD, is especially associated with advanced CKD stage and could be a major risk factor for cardiovascular complications such as ischaemic heart disease, heart failure, and sudden cardiac death. In ESKD, anaemia develops more severely and requires a higher amount of erythropoiesis-stimulating agent (ESA) therapy before dialysis initiation. This suggests that improvement in anaemia management during the pre-dialysis phase may have a beneficial effect on cardiac hypertrophy and contribute to reducing the CVD risk after initiating haemodialysis.

Haemodiafiltration and mortality in end-stage kidney disease patients: a pooled individual participant data analysis from four randomized controlled trials.

Mortality rates remain high for haemodialysis (HD) patients and simply increasing the HD dose to remove more small solutes does not improve survival. Online haemodiafiltration (HDF) provides additional clearance of larger toxins compared with standard HD. Randomized controlled trials (RCTs) comparing HDF with conventional HD on all-cause and cause-specific mortality in end-stage kidney disease (ESKD) patients reported inconsistent results and were at high risk of bias. We conducted a pooled individual participant data analysis of RCTs to provide the most reliable evidence to date on the effects of HDF on mortality outcomes in ESKD patients. Individual participant data were used from four trials that compared online HDF with HD and were designed to examine the effects of HDF on mortality endpoints. Bias by informative censoring of patients was resolved. Hazard ratios (HRs) and 95% confidence intervals (95% CI) comparing the effect of online HDF versus HD on all-cause and cause-specific mortality were calculated using the Cox proportional hazard regression models. The relationship between convection volume and the study outcomes was examined by delivered convection volume standardized to body surface area. After a median follow-up of 2.5 years (Q1-Q3: 1.9-3.0), 769 of the 2793 participants had died (292 cardiovascular deaths). Online HDF reduced the risk of all-cause mortality by 14% (95% CI: 1%; 25%) and cardiovascular mortality by 23% (95% CI: 3%; 39%). There was no evidence for a differential effect in subgroups. The largest survival benefit was for patients receiving the highest delivered convection volume [>23 L per 1.73 m(2) body surface area (BSA) per session], with a multivariable-adjusted HR of 0.78 (95% CI: 0.62; 0.98) for all-cause mortality and 0.69 (95% CI: 0.47; 1.00) for cardiovascular disease mortality. This pooled individual participant analysis on the effects of online HDF compared with conventional HD indicates that online HDF reduces the risk of mortality in ESKD patients. This effect holds across a variety of important clinical subgroups of patients and is most pronounced for those receiving a higher convection volume normalized to BSA.

Resistin and all-cause and cardiovascular mortality: effect modification by adiponectin in end-stage kidney disease patients

Resistin is a major adipose tissue cytokine implicated in insulin resistance, inflammation and vascular damage. This cytokine is raised in patients with end-stage kidney disease (ESKD) but the relationship between resistin and major clinical outcomes has not been investigated in this population. We studied the mutual relationship between resistin and the two major adipokines (adiponectin and leptin) and the interaction between resistin and adiponectin (ADPN) and all-cause and cardiovascular (CV) mortality in a cohort of 231 haemodialysis patients followed up for 57 ± 44 months. Plasma resistin was substantially raised in ESKD patients when compared with healthy subjects (P < 0.001). On univariate analysis, resistin was related inversely to ADPN (r = -0.14, P = 0.04) and directly to C-reactive protein (r = 0.15, P = 0.03), but was largely independent of leptin (r = 0.08, P = 0.24) and the HOMA-IR index (r = -0.04, P = 0.51). During the follow-up, 165 patients died (96 for CV causes). On both univariate (all-cause mortality: P = 0.004; CV mortality P < 0.001) and multivariate (all-cause mortality: P = 0.01; CV mortality P < 0.001) Cox regression analyses, the effect of resistin on study outcomes was closely dependent on ADPN levels. There was a consistent excess risk for all-cause (P = 0.002) and CV mortality (P = 0.003) by plasma resistin (20 ng/mL) in patients in the first ADPN tertile, but no risk excess for these outcomes was apparent in patients in the third tertile. This study indicates that resistin predicts death and fatal CV events depending on plasma ADPN levels. These findings underscore the importance of the interaction among adipokines for the prediction of adverse clinical outcomes in ESKD.