Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

RATIONALE & OBJECTIVE: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival. STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: Adult hemodialysis patients treated in hemodialysis 500 facilities participating in the Dialysis Outcomes Practice Patterns Study (DOPPS) between 1999 and 2015 in the US, Japan, and 4 four European countries: Germany, Italy, Spain, and UK. PREDICTORS: Four practice measures at each facility: the percentages of patients with Kt/V>1.2, interdialytic weight gain [IDWG]<5.7%, phosphorus<6 mg/dL, and using AV fistulae. OUTCOMES: Patient survival. ANALYTICAL APPROACH: Mediation analyses, adjusted for case mix, were conducted using 3-year study phase as the exposure and facility practice measures as potential mediators. RESULTS: In Europe, we observed a 13% improvement in overall case-mix adjusted survival per decade. Trends in facility practice measures, especially Kt/V and phosphorus, explained 10% improvement in case-mix survival per decade, representing 77% (10% explained of 13% improvement) of the observed improvement. In Japan, 73% of the observed 12%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially Kt/V and IDWG. In the US, 56% of the observed 47%/decade improvement in case-mix adjusted survival could be attributed to facility practices, especially AV fistula use and phosphorus control. LIMITATIONS: Unmeasured changes in the characteristics of the patient population over this period may confound the observed associations. CONCLUSION: The improvements in adjusted hemodialysis patient survival in Europe, Japan, and the US from 1999 to 2015 can be largely explained by improvements in specific facility practices. Future changes in patient survival may be responsive to further evolution in the implementation of common clinical practices.

Catheter Event Rates in Medical Compared to Surgical Peritoneal Dialysis Catheter Insertion.

Introduction: How patient, center, and insertion technique factors interact needs to be understood when designing peritoneal dialysis (PD) catheter insertion pathways. Methods: We undertook a prospective cohort study in 44 UK centers enrolling participants planned for first catheter insertion. Sequences of regressions were used to describe the associations linking patient and dialysis unit-level characteristics with catheter insertion technique and their impact on the occurrence of catheter-related events in the first year (catheter-related infection, hospitalization, and removal). Factors associated with catheter events were incorporated into a multistate model comparing the rates of catheter events between medical and surgical insertion alongside treatment modality transitions and mortality. Results: Of 784 first catheter insertions, 466 (59%) had a catheter event in the first year and 61.2% of transitions onto hemodialysis (HD) were immediately preceded by a catheter event. Catheter malfunction was less but infection was more common with surgical compared with medical insertions. Participants at centers with fewer late presenters and more new dialysis patients starting PD, had a lower probability of a catheter event. Adjusting for these factors, the hazard ratio for a catheter event following insertion (medical vs. surgical) was 0.70 (95% confidence interval [CI] 0.43 to 1.13), and once established on PD 0.77 (0.62 to 0.96). Conclusion: Offering both medical and surgical techniques is associated with lower catheter event rates and keeps people on PD for longer.

Clinical Outcomes in Patients on Hemodialysis with Congestive Heart Failure.

Introduction: Congestive heart failure (CHF) is one of the common complications in patients with end-stage kidney disease. In the general population, CHF increases the risk of the death. However, there is no well-designed relevant study in the Chinese hemodialysis (HD) population addressing the risks associated with CHF. The aim of this study was to explore the impact of CHF on clinical outcomes in HD patients. Methods: Data from a prospective cohort study, the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 (2012-2015), were analyzed. Demographic data, comorbidities, lab data, and death records were extracted. CHF was defined by the diagnosis records upon study inclusion. Our primary outcome was all-cause and cardiovascular (CV) mortality; secondary outcomes were all-cause and cause-specific hospitalization risk. Associations between CHF and outcomes were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were carried out. Results: Of 1,411 patients without missing CHF history information, 24.1% (340) had CHF diagnosis at enrollment. The overall mortality rates were 21.8% versus 12.0% (p < 0.001) in patients with and without CHF during follow-up, respectively. CHF was associated with higher all-cause mortality (adjusted HR: 1.72, 95% confidence interval [CI]: 1.17-2.53, p = 0.006), and the association with CV death was of similar magnitude (HR: 1.60, 95% CI: 0.91-2.81, p = 0.105). CHF patients had more episodes of hospitalization due to heart failure (HR: 2.93, 95% CI: 1.49-5.76, p < 0.01). However, compared with patients without CHF, the all-cause hospitalization risk was not much higher in CHF patients (HR: 1.09, 95% CI: 0.90-1.33, p = 0.39). Subgroup analysis found that the effect of CHF on all-cause mortality was stronger for male patients, patients with residual renal function, the elderly (≥60 years of age), patients with arteriovenous fistulae vascular accesses, nondiabetic patients, low-flux dialyzer users, and inadequately dialyzed patients (standardized Kt/V <2). Conclusion: In HD patients, CHF was found to be associated with a higher risk of all-cause mortality and cause-specific hospitalization risk. Further research is needed to identify opportunities to improve care for HD patients combined with CHF.

International practice patterns of dyslipidemia management in patients with chronic kidney disease under nephrology care: is it time to review guideline recommendations?

BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

HLA amino acid Mismatch-Based risk stratification of kidney allograft failure using a novel Machine learning algorithm.

OBJECTIVE: While associations between HLA antigen-level mismatches (Ag-MM) and kidney allograft failure are well established, HLA amino acid-level mismatches (AA-MM) have been less explored. Ag-MM fails to consider the substantial variability in the number of MMs at polymorphic amino acid (AA) sites within any given Ag-MM category, which may conceal variable impact on allorecognition. In this study we aim to develop a novel Feature Inclusion Bin Evolver for Risk Stratification (FIBERS) and apply it to automatically discover bins of HLA amino acid mismatches that stratify donor-recipient pairs into low versus high graft survival risk groups. METHODS: Using data from the Scientific Registry of Transplant Recipients, we applied FIBERS on a multiethnic population of 166,574 kidney transplants between 2000 and 2017. FIBERS was applied (1) across all HLA-A, B, C, DRB1, and DQB1 locus AA-MMs with comparison to 0-ABDR Ag-MM risk stratification, (2) on AA-MMs within each HLA locus individually, and (3) using cross validation to evaluate FIBERS generalizability. The predictive power of graft failure risk stratification was evaluated while adjusting for donor/recipient characteristics and HLA-A, B, C, DRB1, and DQB1 Ag-MMs as covariates. RESULTS: FIBERS's best-performing bin (on AA-MMs across all loci) added significant predictive power (hazard ratio = 1.10, Bonferroni adj. p < 0.001) in stratifying graft failure risk (where low-risk is defined as zero AA-MMs and high-risk is one or more AA-MMs) even after adjusting for Ag-MMs and donor/recipient covariates. The best bin also categorized more than twice as many patients to the low-risk category, compared to traditional 0-ABDR Ag mismatching (∼24.4% vs âˆ¼ 9.1%). When HLA loci were binned individually, the bin for DRB1 exhibited the strongest risk stratification; relative to zero AA-MM, one or more MMs in the bin yielded HR = 1.11, p < 0.005 in a fully adjusted Cox model. AA-MMs at HLA-DRB1 peptide contact sites contributed most to incremental risk of graft failure. Additionally, FIBERS points to possible risk associated with HLA-DQB1 AA-MMs at positions that determine specificity of peptide anchor residues and HLA-DQ heterodimer stability. CONCLUSION: FIBERS's performance suggests potential for discovery of HLA immunogenetics-based risk stratification of kidney graft failure that outperforms traditional assessment.

Patiromer utilization in patients with advanced chronic kidney disease under nephrology care in Germany.

Background: Hyperkalemia (HK) is a frequent condition in patients with chronic kidney disease (CKD) that is associated with high morbidity and mortality. Patiromer has recently been introduced as a potassium binder. Data on patiromer use in patients with CKD in the real-world setting in Europe are lacking. We describe time to discontinuation and changes in serum potassium levels among German CKD stage 3-5 patients starting patiromer. Methods: Duration of patiromer use was estimated by Kaplan-Meier curve, starting at patiromer initiation and censoring for death, dialysis, transplant or loss to follow-up. Serum potassium levels and renin-angiotensin-aldosterone system inhibitor (RAASi) use are described at baseline and during follow-up, restricted to patients remaining on patiromer. Results: We identified 140 patiromer users within our analysis sample [81% CKD stage 4/5, 83% receiving RAASi, and median K+ 5.7 (5.4, 6.3) mmol/L]. Thirty percent of patiromer users had prior history of polystyrene sulfonate use. Overall, 95% of patiromer users stayed on treatment past 1 month, with 53% continuing for over a year. Mean serum potassium levels decreased after patiromer initiation and remained stable under treatment during follow-up (up to 180 days). Among these patients, 73%-82% used RAASis during the time periods before and after patiromer initiation, with no obvious trend indicating discontinuation. Conclusion: Real-world evidence of patiromer use in Germany shows that, in line with what has been observed in clinical trials, patients on patiromer have a reduction in serum potassium when used long-term. Moreover, most patients on patiromer do not discontinue treatment prior to 1 year after initiation.

Optimized immunosuppression to prevent graft failure in renal transplant recipients with HLA antibodies (OuTSMART): a randomised controlled trial.

Background: 3% of kidney transplant recipients return to dialysis annually upon allograft failure. Development of antibodies (Ab) against human leukocyte antigens (HLA) is a validated prognostic biomarker of allograft failure. We tested whether screening for HLA Ab, combined with an intervention to improve adherence and optimization of immunosuppression could prevent allograft failure. Methods: Prospective, open-labelled randomised biomarker-based strategy (hybrid) trial in 13 UK transplant centres [EudraCT (2012-004308-36) and ISRCTN (46157828)]. Patients were randomly allocated (1:1) to unblinded or double-blinded arms and screened every 8 months. Unblinded HLA Ab+ patients were interviewed to encourage medication adherence and had tailored optimisation of Tacrolimus, Mycophenolate mofetil and Prednisolone. The primary outcome was time to graft failure in an intention to treat analysis. The trial had 80% power to detect a hazard ratio of 0.49 in donor specific antibody (DSA)+ patients. Findings: From 11/9/13 to 27/10/16, 5519 were screened for eligibility and 2037 randomised (1028 to unblinded care and 1009 to double blinded care). We identified 198 with DSA and 818 with non-DSA. Development of DSA, but not non-DSA was predictive of graft failure. HRs for graft failure in unblinded DSA+ and non-DSA+ groups were 1.54 (95% CI: 0.72 to 3.30) and 0.97 (0.54-1.74) respectively, providing no evidence of an intervention effect. Non-inferiority for the overall unblinded versus blinded comparison was not demonstrated as the upper confidence limit of the HR for graft failure exceeded 1.4 (1.02, 95% CI: 0.72 to 1.44). The only secondary endpoint reduced in the unblinded arm was biopsy-proven rejection. Interpretation: Intervention to improve adherence and optimize immunosuppression does not delay failure of renal transplants after development of DSA. Whilst DSA predicts increased risk of allograft failure, novel interventions are needed before screening can be used to direct therapy. Funding: The National Institute for Health Research Efficacy and Mechanism Evaluation programme grant (ref 11/100/34).

A different PET test: The relationship between pet ownership and peritonitis risk in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).

Pet ownership is common around the world, with pet ownership increasing in many countries. Current guidelines are not supportive of pet ownership for peritoneal dialysis (PD) patients. We examined the association between ownership of cats and dogs and the incidence of peritonitis among PD patients participating in the prospective, observational Peritoneal Dialysis Outcomes and Practice Patterns Study. A total of 3655 PD patients from eight different countries was included, with a median follow-up of 14 months and a total exposure time of 55,475 patient-months. There were 1347 peritonitis episodes with an overall peritonitis rate of 0.29 episodes per patient year. There was no significant increased risk of peritonitis with any type of pet ownership, adjusted hazard ratio (HR) of 1.09 (95% confidence interval (95% CI): 0.96-1.25). However, patients who owned both cats and dogs had an increased risk of peritonitis compared to patients without pets, HR = 1.45 (95% CI: 1.14-1.86). These results suggest that there is no increased risk of peritonitis with pet ownership except for those with both cats and dogs. This information should not prevent PD patients from owning pets but may be helpful for PD patients and their care team to direct training to minimise the risk of peritonitis.

Peritoneal Dialysis-Associated Peritonitis Trends Using Medicare Claims Data, 2013-2017.

RATIONALE & OBJECTIVE: The occurrence and consequences of peritoneal dialysis (PD)-associated peritonitis limit its use in populations with kidney failure. Studies of large clinical populations may enhance our understanding of peritonitis. To facilitate these studies we developed an approach to measuring peritonitis rates using Medicare claims data to characterize peritonitis trends and identify its clinical risk factors. STUDY DESIGN: Retrospective cohort study of PD-associated peritonitis. SETTING & PARTICIPANTS: US Renal Data System standard analysis files were used for claims, eligibility, modality, and demographic information. The sample consisted of patients receiving PD treated at some time between 2013 and 2017 who were covered by Medicare fee-for-service (FFS) insurance with paid claims for dialysis or hospital services. EXPOSURES/PREDICTORS: Peritonitis risk was characterized by year, age, sex, race, ethnicity, vintage of kidney replacement therapy, cause of kidney failure, and prior peritonitis episodes. OUTCOME: The major outcome was peritonitis, identified using ICD-9 and ICD-10 diagnosis codes. Closely spaced peritonitis claims (30 days) were aggregated into 1 peritonitis episode. ANALYTICAL APPROACH: Patient-level risk factors for peritonitis were modeled using Poisson regression. RESULTS: We identified 70,271 peritonitis episodes from 396,289 peritonitis claims. Although various codes were used to record an episode of peritonitis, none was used predominantly. Peritonitis episodes were often identified by multiple aggregated claims, with the mean and median claims per episode being 5.6 and 2, respectively. We found 40% of episodes were exclusively outpatient, 9% exclusively inpatient, and 16% were exclusively based on codes that do not clearly distinguish peritonitis from catheter infections/inflammation ("catheter codes"). The overall peritonitis rate was 0.54 episodes per patient-year (EPPY). The rate was 0.45 EPPY after excluding catheter codes and 0.35 EPPY when limited to episodes that only included claims from nephrologists or dialysis providers. The peritonitis rate declined by 5%/year and varied by patient factors including age (lower rates at higher ages), race (Black > White>Asian), and prior peritonitis episodes (higher rate with each prior episode). LIMITATIONS: Coding heterogeneity indicates a lack of standardization. Episodes based exclusively on catheter codes could represent false positives. Peritonitis episodes were not validated against symptoms or microbiologic data. CONCLUSIONS: PD-associated peritonitis rates decline over time and were lower among older patients. A claims-based approach offers a promising framework for the study of PD-associated peritonitis.

International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique Survival.

Background: Icodextrin has been shown in randomized controlled trials to benefit fluid management in peritoneal dialysis (PD). We describe international icodextrin prescription practices and their relationship to clinical outcomes. Methods: We analyzed data from the prospective, international PDOPPS, from Australia/New Zealand, Canada, Japan, the United Kingdom, and the United States. Membrane function and 24-hour ultrafiltration according to icodextrin and glucose prescription was determined at baseline. Using an instrumental variable approach, Cox regression, stratified by country, was used to determine any association of icodextrin use to death and permanent transfer to hemodialysis (HDT), adjusted for demographics, comorbidities, serum albumin, urine volume, transplant waitlist status, PD modality, center size, and study phase. Results: Icodextrin was prescribed in 1986 (35%) of 5617 patients, >43% of patients in all countries, except in the United States, where it was only used in 17% and associated with a far greater use of hypertonic glucose. Patients on icodextrin had more coronary artery disease and diabetes, longer dialysis vintage, lower residual kidney function, faster peritoneal solute transfer rates, and lower ultrafiltration capacity. Prescriptions with or without icodextrin achieved equivalent ultrafiltration (median 750 ml/d [interquartile range 300-1345 ml/d] versus 765 ml/d [251-1345 ml/d]). Icodextrin use was not associated with mortality (HR=1.03; 95% CI, 0.72 to 1.48) or HDT (HR 1.2; 95% CI, 0.92 to 1.57). Conclusions: There are large national and center differences in icodextrin prescription, with the United States using significantly less. Icodextrin was associated with hypertonic glucose avoidance but equivalent ultrafiltration, which may affect any potential survival advantage or HDT.

Hepatitis C Prevalence, Incidence, and Treatment in Chinese Hemodialysis Patients: Results From the Dialysis Outcomes and Practice Patterns Study-China (2019-21).

Background: Prior work from the Dialysis Outcomes and Practice Patterns Study (DOPPS) showed HCV prevalence in China in 2012-2015 being in the upper third and HCV incidence the 2nd highest among 15 different countries/regions investigated. The goal of the present investigation was to: (1) determine if HCV prevalence and incidence has changed, and (2) collect detailed data to understand how HCV is treated, monitored, and managed in Chinese HD facilities and non-dialysis chronic kidney disease (CKD) clinics. Data and Methods: Detailed data for 1,700 randomly selected HD patients were reported by 39 randomly selected HD facilities from Beijing, Shanghai, and Guangzhou participating in the DOPPS 7-China study from 2019 to 2021. The study site medical directors completed a survey regarding numerous aspects of HCV treatment and management in HD and ND-CKD patients. Results: In this 2019 to 2021 cohort, HCV prevalence was 7.4%, which was lower than the 14.8 and 11.5% HCV prevalence for the 2009-2011 and 2012-2015 cohorts, respectively. HCV incidence of 1.2 cases per 100 pt-yrs also was lower compared to the incidence of 2.1 for the 2012-2015 cohort. Although the great majority of study site medical directors indicated that all or nearly HCV+ patients should be treated for their HCV, very few HCV+ patients have been treated presumably due to substantial cost barriers for affording the new direct acting antivirals (DAAs). The randomly selected facilities in our DOPPS 7-China study appear to have excellent programs in place for frequent monitoring of patients and staff for HCV, education of staff, and referral of HCV cases to external infectious disease, gastroenterology, and liver disease specialists. Liver biopsies were not commonly performed in HCV+ HD patients. HCV genotyping also was rarely performed in participating units. Conclusions: Our study indicates a 50% decline in HCV prevalence and a >40% decline in HCV incidence in Chinese HD patients over the past 10-12 yrs. Chinese HD facilities and associated specialists appear to be well-equipped and organized for successfully treating and managing their HCV+ HD and CKD patients in order to achieve the WHO goal of eliminating HCV by 2030.

Variation in Peritoneal Dialysis Time on Therapy by Country: Results from the Peritoneal Dialysis Outcomes and Practice Patterns Study.

BACKGROUND AND OBJECTIVES: Quantifying contemporary peritoneal dialysis time on therapy is important for patients and providers. We describe time on peritoneal dialysis in the context of outcomes of hemodialysis transfer, death, and kidney transplantation on the basis of the multinational, observational Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) from 2014 to 2017. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 218 randomly selected peritoneal dialysis facilities (7121 patients) in the PDOPPS from Australia/New Zealand, Canada, Japan, Thailand, the United Kingdom, and the United States, we calculated the cumulative incidence from peritoneal dialysis start to hemodialysis transfer, death, or kidney transplantation over 5 years and adjusted hazard ratios for patient and facility factors associated with death and hemodialysis transfer. RESULTS: Median time on peritoneal dialysis ranged from 1.7 (interquartile range, 0.8-2.9; the United Kingdom) to 3.2 (interquartile range, 1.5-6.0; Japan) years and was longer with lower kidney transplantation rates (range: 32% [the United Kingdom] to 2% [Japan and Thailand] over 3 years). Adjusted hemodialysis transfer risk was lowest in Thailand, but death risk was higher in Thailand and the United States compared with most countries. Infection was the leading cause of hemodialysis transfer, with higher hemodialysis transfer risks seen in patients having psychiatric disorder history or elevated body mass index. The proportion of patients with total weekly Kt/V ≥1.7 at a facility was not associated with death or hemodialysis transfer. CONCLUSIONS: Countries in the PDOPPS with higher rates of kidney transplantation tended to have shorter median times on peritoneal dialysis. Identification of infection as a leading cause of hemodialysis transfer and patient and facility factors associated with the risk of hemodialysis transfer can facilitate interventions to reduce these events. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_05_31_CJN16341221.mp3.

An investigation into possible sex differences in Association of Haemoglobin with survival among Haemodialysis patients in the J-DOPPS cohort.

AIMS: Lower haemoglobin levels are common among females without kidney diseases. However, little is known about the sex-specific management of anaemia in haemodialysis patients. METHODS: This prospective cohort study investigated the role of sex differences in the association between categorical baseline or time-varying haemoglobin levels and all-cause mortality via cox regression using data from 6890 patients in the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS, 2005-2015). Likelihood ratio tests were used to evaluate the effect modification of sex on the relationship between haemoglobin and mortality. RESULTS: A total of 781 patients died during the median follow-up of 31 months. Mortality risk, adjusted for case mix, varied between five haemoglobin categories, with the highest category (≥12 g/dL) having a hazard ratio of 0.73 (0.41-1.29) for females and 2.02 (1.03-3.95) for males versus 10-10.9 g/dL. Despite this difference, the p-value comparing the overall among males versus females was.35. Similar associations were observed in models stratified by patient age (<75 years), time on dialysis (≤1 year), and models lagging the haemoglobin exposure. CONCLUSION: The results based on this sample of Japanese haemodialysis patients did not support the hypothesis that the association between haemoglobin and survival differed by sex. We also could not conclude that the association was identical, as the parameter estimates are consistent with male patients having a relatively greater mortality risk than female patients at higher haemoglobin levels. More detailed investigations into the effects of higher haemoglobin levels by sex might help better understand strategies for anaemia management.

Potential Surrogate Outcomes for Kidney Failure in Advanced CKD: Evaluation of Power and Predictive Ability in CKDopps.

RATIONALE & OBJECTIVE: Potential surrogate end points for kidney failure have been proposed in chronic kidney disease (CKD); however, they must be evaluated to ensure accurate, powerful, and harmonized research, particularly among patients with advanced CKD. The aim of the current study was to investigate the power and predictive ability of surrogate kidney failure end points in a population with moderate-to-advanced CKD. STUDY DESIGN: Analysis of longitudinal data of a large multinational CKD observational study (Chronic Kidney Disease Outcomes and Practice Patterns Study). SETTING & PARTICIPANTS: CKD stage 3-5 patients from Brazil, France, Germany, and the United States. OUTCOMES: Reaching an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2 or eGFR decline of ≥40%, and composite end points of these individual end points. ANALYTICAL APPROACH: Each end point was used as a time-varying indicator in the Cox model to predict the time to kidney replacement therapy (KRT; dialysis or transplant) and was compared by the number of events and prediction accuracy. RESULTS: 8,211 patients had a median baseline eGFR of 27 mL/min/1.73 m2 (interquartile range, 21-36 mL/min/1.73 m2) and 1,448 KRT events over a median follow-up of 2.7 years (interquartile range, 1.2-3.0 years). Among CKD stage 4 patients, the eGFR < 15 mL/min/1.73 m2 end point had higher prognostic ability than 40% eGFR decline, but the end points were similar for CKD stage 3 patients. The combination of eGFR < 15 mL/min/1.73 m2 and 40% eGFR decline had the highest prognostic ability for predicting KRT, regardless of the CKD stage. Including KRT in the composite can increase the number of events and, therefore, the power. LIMITATIONS: Variable visit frequency resulted in variable eGFR measurement frequency. CONCLUSIONS: The composite end point can be useful for CKD progression studies among patients with advanced CKD. Harmonized use of this approach has the potential to accelerate the translation of new discoveries to clinical practice by identifying risk factors and treatments for kidney failure.

Routinely measured cardiac troponin I and N-terminal pro-B-type natriuretic peptide as predictors of mortality in haemodialysis patients.

AIMS: Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) are elevated in haemodialysis (HD) patients, and this elevation is associated with HD-induced myocardial stunning/myocardial strain. However, studies using data from the international Dialysis Outcomes and Practice Patterns Study (DOPPS) have shown that these cardiac biomarkers are measured in <2% of HD patients in real-world practice. This study aimed to examine whether routinely measured N-terminal pro-BNP (NT-proBNP) and cTnI (contemporary assay) are more appropriate than clinical models for reclassifying the risk of HD patients who have the highest risk of death. METHODS AND RESULTS: Pre-dialysis levels of cTnI and NT-proBNP at study enrolment were measured in 1152 HD patients (Japan DOPPS Phase 5). The patients were prospectively followed for 3 years. Cox regression was used to test the associations of cardiac biomarkers with all-cause mortality, adjusting for potential confounders. Subgroup analyses were performed to assess potential effect modification of clinical characteristics, such as age, systolic blood pressure, HD vintage, diabetes mellitus, coronary artery disease, and a history of congestive heart failure. At baseline, 337 (29%) patients had elevated cTnI (99th percentile of a healthy population: >0.04 ng/mL) with a median (inter-quartile range) level of 0.020 (0.005-0.041) ng/mL, and 1140 (99%) patients had elevated NT-proBNP (cut-off for heart failure: >125 pg/mL) with a median level of 3658 (1689-9356) pg/mL. There were 167 deaths during a median follow-up of 2.8 (2.2-2.8) years. Higher levels of both cardiac biomarkers were incrementally associated with mortality after adjustment for potential confounders. Even after adjustment for alternative cardiac biomarkers, the overall P value for the association was <0.01 for both biomarkers. However, the prognostic significance of NT-proBNP was moderately diminished when cTnI was added to the model. The hazard ratios of mortality for cTnI > 0.04 ng/mL (vs. cTnI < 0.006 ng/mL) and NT-proBNP > 8000 pg/mL (vs. NT-proBNP < 2000 pg/mL) were 2.56 (95% confidence interval: 1.37-4.81) and 1.90 (95% confidence interval: 0.95-3.79), respectively. Subgroup analyses showed that the associations of both cardiac biomarkers with mortality were generally consistent between stratified groups. CONCLUSIONS: Routinely measured NT-proBNP and cTnI levels are strongly associated with mortality among prevalent HD patients. These associations remain robust, even after adjustment for alternative biomarkers, suggesting that cTnI and NT-proBNP have identical prognostic significance and may reflect different pathological aspects of cardiac abnormalities.

Thrombocytopenia predicts mortality in Chinese hemodialysis patients- an analysis of the China DOPPS.

BACKGROUND: Hemodialysis (HD) patients have a higher mortality rate compared with general population. Our previous study revealed that platelet counts might be a potential risk factor. The role of platelets in HD patients has rarely been studied. The aim of this study is to examine if there is an association of thrombocytopenia (TP) with elevated risk of all-cause mortality and cardiovascular (CV) death in Chinese HD patients. METHODS: Data from a prospective cohort study, China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5, were analyzed. Demographic data, comorbidities, platelet counts and other lab data, and death records which extracted from the medical record were analyzed. TP was defined as the platelet count below the lower normal limit (< 100*109/L). Associations between platelet counts and all-cause and CV mortality were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the independent associated factors, and subgroup analyses were also carried out. RESULTS: Of 1369 patients, 11.2% (154) had TP at enrollment. The all-cause mortality rates were 26.0% vs. 13.3% (p < 0.001) in patients with and without TP. TP was associated with higher all-cause mortality after adjusted for covariates (HR:1.73,95%CI:1.11,2.71), but was not associated with CV death after fully adjusted (HR:1.71,95%CI:0.88,3.33). Multivariate logistic regression showed that urine output < 200 ml/day, cerebrovascular disease, hepatitis (B or C), and white blood cells were independent impact factors (P < 0.05). Subgroup analysis found that the effect of TP on all-cause mortality was more prominent in patients with diabetes or hypertension, who on dialysis thrice a week, with lower ALB (< 4 g/dl) or higher hemoglobin, and patients without congestive heart failure, cerebrovascular disease, or hepatitis (P < 0.05). CONCLUSION: In Chinese HD patients, TP is associated with higher risk of all-cause mortality, but not cardiovascular mortality. Platelet counts may be a useful prognostic marker for clinical outcomes among HD patients, though additional study is needed.

Mortality, hospitalization and transfer to haemodialysis and hybrid therapy, in Japanese peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES: Survival of peritoneal dialysis (PD) patients in Japan is high, but few reports exist on cause-specific mortality, transfer to haemodialysis (HD) or hybrid dialysis and hospitalisation risks. We aimed to identify reasons for transfer to HD, hybrid dialysis and hospitalisation in the Japan Peritoneal Dialysis and Outcomes Practice Patterns Study. METHODS: This observational study included 808 adult PD patients across 31 facilities in Japan in 2014-2017. Information on all-cause and cause-specific mortality and hospitalisation and permanent transfer to HD and PD/HD hybrid therapy were prospectively collected and rates calculated. RESULTS: Median follow-up time was 1.66 years where 162 patients transferred to HD, 79 transferred to hybrid dialysis and 74 patients died. All-cause and cardiovascular disease (CVD)-related mortality rates were 5.1 and 1.7 deaths/100 patient-years, respectively. Rates of transfer to HD and hybrid therapy were 11.2 and 5.5 transfers/100 patient-years, respectively. Among HD transfers, 40% were due to infection (including peritonitis), while 20% were due to inadequate solute/water clearance. Eighty-one percent of hybrid dialysis transfers were due to inadequate solute/water clearance. All--cause, peritonitis-related and CVD-related hospitalisation rates were 120.4, 21.1 and 15.6/100 patient-years, respectively. Median hospital length of stay was 19 days. CONCLUSIONS: Mortality, hospitalisation and transfer to HD/hybrid dialysis rates are relatively low in Japan compared to many other countries with hybrid transfers, accounting for one-third of dialysis transfers from PD. Further study is needed to explain the high inter-facility variation in hospitalisation rates and how to further reduce hospitalisation rates for Japanese PD patients.

Blood flow rate: An independent risk factor of mortality in Chinese hemodialysis patients.

BACKGROUND: Studies suggested the association between blood flow rate (BFR) and mortality might be beyond dialysis adequacy. This study aimed to explore if BFR is an independent predictor of clinical outcomes in Chinese hemodialysis (HD) patients. METHODS: This study included data from patients in China Dialysis Outcomes and Practice Patterns Study (DOPPS) Phase 5. Patients with a record of BFR were included, and demographic data, comorbidities, hospitalization, and death records were collected. Associations between BFR and all-cause mortality and hospitalization were analyzed using Cox regression models. RESULTS: One thousand four hundred twelve (98.9%) patients were included. Most patients were with BFR < 300 ml/min. After full adjustment, each 10-ml/min increase of BFR was associated with a 6.4% decrease in all-cause mortality risk (HR: 0.936, 95% CI: 0.880-0.996) but not first hospitalization (HR: 0.987, 95% CI: 0.949-1.027). The impact of BFR on mortality may be more prominent in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl. CONCLUSION: Increased BFR is independently associated with a lower risk of all-cause mortality within the range of BFR 200-300 ml/min. And this effect is more pronounced in patients who were male gender, nondiabetic, albumin < 4.0 g/dl, and hemoglobin ≥ 9.0 g/dl.