Showing papers by "Csaba P. Kovesdy published in 2019"
TL;DR: Author(s): Saran, Rajiv; Robinson, Bruce; Abbott, Kevin C; Agodoa, Lawrence YC; Bragg-Gresham, Jennifer; Balkrishnan, Rajesh; Bhave, Nicole; Dietrich, Xue; Ding, Zhechen; Eggers; Gaipov, Abduzhappar; Gillen, Daniel; Gipson, Debbie; Gu, Haoyu; Guro, Paula; Haggerty, Diana
686 citations
Vanderbilt University Medical Center1, Vanderbilt University2, University of Pennsylvania3, National Institute for Health Research4, Queen Mary University of London5, Veterans Health Administration6, Emory University7, VA Boston Healthcare System8, University of Ioannina9, Imperial College London10, University of Leicester11, University of Bordeaux12, University of Michigan13, University of Cambridge14, McMaster University15, University of Dundee16, COMSATS Institute of Information Technology17, University of Newcastle18, Lund University19, Leiden University Medical Center20, University Medical Center Groningen21, University of Edinburgh22, Guy's and St Thomas' NHS Foundation Trust23, King's College London24, University of Texas Health Science Center at Houston25, University of Liverpool26, Broad Institute27, Boston University28, University of London29, University of Bristol30, Washington University in St. Louis31, university of lille32, Wellcome Trust Centre for Human Genetics33, University of Eastern Finland34, Wellcome Trust Sanger Institute35, National Institutes of Health36, Population Health Research Institute37, Brigham and Women's Hospital38, University of Sassari39, Wellcome Trust40, University of Oxford41, Harokopio University42, University of Washington43, Harvard University44, Stanford University45, VA Palo Alto Healthcare System46
TL;DR: Analysis of blood pressure data from the Million Veteran Program trans-ethnic cohort identifies common and rare variants, and genetically predicted gene expression across multiple tissues associated with systolic, diastolic and pulse pressure in over 775,000 individuals.
Abstract: In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.
310 citations
224 citations
TL;DR: The need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety is represented during the KDIGO conference.
213 citations
176 citations
Johns Hopkins University1, University Medical Center Groningen2, Karolinska Institutet3, Dalarna University4, University of Wisconsin-Madison5, University of Aberdeen6, University of Leicester7, University of Pennsylvania8, Brigham and Women's Hospital9, Tufts Medical Center10, United States Department of Veterans Affairs11, University of Minnesota12, Tohoku University13, University of California, San Diego14, Yamagata University15, Monash University16, Monash Medical Centre17, Levanger Hospital18, Norwegian University of Science and Technology19, University Hospital of North Norway20, University of Paris-Sud21, Versailles Saint-Quentin-en-Yvelines University22, French Institute of Health and Medical Research23, University of Calgary24, Dokkyo Medical University25, National Health Research Institutes26, China Medical University (Taiwan)27, Radboud University Nijmegen28, The George Institute for Global Health29, University of Tennessee Health Science Center30, Veterans Health Administration31, University of New South Wales32, Linköping University33
TL;DR: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change inalbuminuria as a surrogate endpoint for end-Stage kidney disease in clinical trials of progression of chronic kidneys disease in the setting of increased album inuria.
176 citations
University of Alberta1, University of British Columbia2, University of Calgary3, University of Ottawa4, University of Yaoundé I5, Saint Louis University6, University of Hassan II Casablanca7, University of Oxford8, Singapore General Hospital9, The George Institute for Global Health10, Manipal University11, University of California, Irvine12, University of California, Los Angeles13, Monash Medical Centre14, Monash University, Clayton campus15, University of Tennessee Health Science Center16, Veterans Health Administration17, Brigham and Women's Hospital18, University of Zurich19, University of Manchester20, Salford Royal NHS Foundation Trust21, Iran University of Medical Sciences22, University of Toronto23, St. Michael's Hospital24, University of Paris25, University of Melbourne26, Tbilisi State Medical University27, Charles University in Prague28, King Chulalongkorn Memorial Hospital29, Bezmialem Foundation University30, University of Hong Kong31, Memorial Hospital of South Bend32, Chang Gung University33, First Pavlov State Medical University of St. Peterburg34, Public Health Research Institute35, North Bristol NHS Trust36, University of Bristol37, University of Cape Town38, Pan American Health Organization39, University of Leicester40, University of Sydney41, University of Queensland42, Princess Alexandra Hospital43, Translational Research Institute44
TL;DR: These comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease and demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy.
Abstract: Objective To determine the global capacity (availability, accessibility, quality, and affordability) to deliver kidney replacement therapy (dialysis and transplantation) and conservative kidney management. Design International cross sectional survey. Setting International Society of Nephrology (ISN) survey of 182 countries from July to September 2018. Participants Key stakeholders identified by ISN's national and regional leaders. Main outcome measures Markers of national capacity to deliver core components of kidney replacement therapy and conservative kidney management. Results Responses were received from 160 (87.9%) of 182 countries, comprising 97.8% (7338.5 million of 7501.3 million) of the world's population. A wide variation was found in capacity and structures for kidney replacement therapy and conservative kidney management-namely, funding mechanisms, health workforce, service delivery, and available technologies. Information on the prevalence of treated end stage kidney disease was available in 91 (42%) of 218 countries worldwide. Estimates varied more than 800-fold from 4 to 3392 per million population. Rwanda was the only low income country to report data on the prevalence of treated disease; 5 (<10%) of 53 African countries reported these data. Of 159 countries, 102 (64%) provided public funding for kidney replacement therapy. Sixty eight (43%) of 159 countries charged no fees at the point of care delivery and 34 (21%) made some charge. Haemodialysis was reported as available in 156 (100%) of 156 countries, peritoneal dialysis in 119 (76%) of 156 countries, and kidney transplantation in 114 (74%) of 155 countries. Dialysis and kidney transplantation were available to more than 50% of patients in only 108 (70%) and 45 (29%) of 154 countries that offered these services, respectively. Conservative kidney management was available in 124 (81%) of 154 countries. Worldwide, the median number of nephrologists was 9.96 per million population, which varied with income level. Conclusions These comprehensive data show the capacity of countries (including low income countries) to provide optimal care for patients with end stage kidney disease. They demonstrate substantial variability in the burden of such disease and capacity for kidney replacement therapy and conservative kidney management, which have implications for policy.
111 citations
TL;DR: Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.
103 citations
Johns Hopkins University1, University of Wisconsin-Madison2, Mayo Clinic3, Karolinska Institutet4, Geisinger Health System5, Tufts Medical Center6, University of Auckland7, University of Tennessee Health Science Center8, Veterans Health Administration9, Kaiser Permanente10, University of British Columbia11, University of Toronto12, Cleveland Clinic Lerner Research Institute13, Case Western Reserve University14, Tel Aviv University15, Radboud University Nijmegen16, The George Institute for Global Health17, University Medical Center Groningen18
TL;DR: Slower decline in eG FR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.
Abstract: BACKGROUND: Decline in eGFR is a biologically plausible surrogate end point for the progression of CKD in clinical trials. However, it must first be tested to ensure strong associations with clinical outcomes in diverse populations, including patients with higher eGFR. METHODS: To investigate the association between 1-, 2-, and 3-year changes in eGFR (slope) with clinical outcomes over the long term, we conducted a random effects meta-analysis of 3,758,551 participants with baseline eGFR≥60 ml/min per 1.73 m2 and 122,664 participants with eGFR<60 ml/min per 1.73 m2 from 14 cohorts followed for an average of 4.2 years. RESULTS: Slower eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years was associated with lower risk of ESKD in participants with baseline eGFR≥60 ml/min per 1.73 m2 (adjusted hazard ratio, 0.70; 95% CI, 0.68 to 0.72) and eGFR<60 ml/min per 1.73 m2 (0.71; 95% CI, 0.68 to 0.74). The relationship was stronger with 3-year slope. For a rapidly progressing population with predicted 5-year risk of ESKD of 8.3%, an intervention that reduced eGFR decline by 0.75 ml/min per 1.73 m2 per year over 2 years would reduce the ESKD risk by 1.6%. For a hypothetical low-risk population with a predicted 5-year ESKD risk of 0.58%, the same intervention would reduce the risk by only 0.13%. CONCLUSIONS: Slower decline in eGFR was associated with lower risk of subsequent ESKD, even in participants with eGFR≥60 ml/min per 1.73 m2, but those with the highest risk would be expected to benefit the most.
89 citations
Vanderbilt University Medical Center1, Vanderbilt University2, University of Pennsylvania3, Veterans Health Administration4, University of Utah5, University of Freiburg6, University Hospital Regensburg7, University of Regensburg8, Harvard University9, Broad Institute10, VA Boston Healthcare System11, Emory University12, VA Palo Alto Healthcare System13, Stanford University14, Brigham and Women's Hospital15, University of Tennessee Health Science Center16, Johns Hopkins University17
TL;DR: The authors reinterpret the genetic architecture of kidney function across ancestries, to identify not only genes, but the tissue and anatomical contexts of renal homeostasis and the clinical consequences of dysregulation.
Abstract: Chronic kidney disease (CKD), defined by low estimated glomerular filtration rate (eGFR), contributes to global morbidity and mortality. Here we conduct a transethnic Genome-Wide Association Study of eGFR in 280,722 participants of the Million Veteran Program (MVP), with replication in 765,289 participants from the Chronic Kidney Disease Genetics (CKDGen) Consortium. We identify 82 previously unreported variants, confirm 54 loci, and report interesting findings including association of the sickle cell allele of betaglobin among non-Hispanic blacks. Our transcriptome-wide association study of kidney function in healthy kidney tissue identifies 36 previously unreported and nine known genes, and maps gene expression to renal cell types. In a Phenome-Wide Association Study in 192,868 MVP participants using a weighted genetic score we detect associations with CKD stages and complications and kidney stones. This investigation reinterprets the genetic architecture of kidney function to identify the gene, tissue, and anatomical context of renal homeostasis and the clinical consequences of dysregulation. Persistently low levels of estimated glomerular filtration rate (eGFR) are a biomarker of chronic kidney disease. Here, the authors reinterpret the genetic architecture of kidney function across ancestries, to identify not only genes, but the tissue and anatomical contexts of renal homeostasis.
83 citations
TL;DR: Patiromer initiators receiving chronic hemodialysis had comparatively more severe, uncontrolled baseline hyperkalemia and medication order data show long-term patiromer use was associated with significantly reduced K+.
Fresenius Medical Care1, University of Utah2, University of Illinois at Chicago3, University of Tennessee Health Science Center4, Tufts Medical Center5, Cedars-Sinai Medical Center6, Harvard University7, Baylor College of Medicine8, University of Pennsylvania9, University of California, Los Angeles10, National Institutes of Health11
TL;DR: Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes, and more effective strategies are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.
Abstract: Background Data from clinical trials to inform practice in maintenance hemodialysis are limited. Incorporating randomized trials into dialysis clinical care delivery should help generate practice-guiding evidence, but the feasibility of this approach has not been established. Methods To develop approaches for embedding trials into routine delivery of maintenance hemodialysis, we performed a cluster-randomized, pragmatic trial demonstration project, the Time to Reduce Mortality in ESRD (TiME) trial, evaluating effects of session duration on mortality (primary outcome) and hospitalization rate. Dialysis facilities randomized to the intervention adopted a default session duration ≥4.25 hours (255 minutes) for incident patients; those randomized to usual care had no trial-driven approach to session duration. Implementation was highly centralized, with no on-site research personnel and complete reliance on clinically acquired data. We used multiple strategies to engage facility personnel and participating patients. Results The trial enrolled 7035 incident patients from 266 dialysis units. We discontinued the trial at a median follow-up of 1.1 years because of an inadequate between-group difference in session duration. For the primary analysis population (participants with estimated body water ≤42.5 L), mean session duration was 216 minutes for the intervention group and 207 minutes for the usual care group. We found no reduction in mortality or hospitalization rate for the intervention versus usual care. Conclusions Although a highly pragmatic design allowed efficient enrollment, data acquisition, and monitoring, intervention uptake was insufficient to determine whether longer hemodialysis sessions improve outcomes. More effective strategies for engaging clinical personnel and patients are likely required to evaluate clinical trial interventions that are fully embedded in care delivery.
Tufts Medical Center1, Johns Hopkins University2, University of Salerno3, Auckland City Hospital4, University Medical Center Groningen5, University of Alabama at Birmingham6, Osaka University7, Saarland University8, Jichi Medical University9, Yonsei University10, Innsbruck Medical University11, Clinical Trial Service Unit12, Shiga University of Medical Science13, Icahn School of Medicine at Mount Sinai14, University of California, San Francisco15, University of Ulm16, Charité17, Erasmus University Medical Center18, Peking University19, Utrecht University20, Norwegian University of Science and Technology21, University of Tennessee Health Science Center22, University of British Columbia23
TL;DR: Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities and hypertension, and knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.
01 Sep 2019
TL;DR: Current understanding of the potential pathophysiological mechanisms underlying the "gut-kidney-heart" axis in CKD is summarized to provide recent evidence on the associations between the gut microbiota, CKD, and CVD.
Abstract: The recent explosion of scientific interest in the gut microbiota has dramatically advanced our understanding of the complex pathophysiological interactions between the gut and multiple organs in h...
TL;DR: A ML-based method to accurately predict short-term postdialysis mortality in patients with incident ESRD could aid patients and clinicians in better decision making about the best course of action in patients approaching E SRD.
13 Mar 2019
TL;DR: Findings suggest that manipulating the endocannabinoid system may be an effective therapeutic strategy for the treatment of kidney disease and injury.
Abstract: Introduction: As the prevalence of kidney disease continues to rise worldwide, there is accumulating evidence that kidney injury and dysfunction, whether acute or chronic, is associated with major adverse outcomes, including mortality. Meanwhile, effective therapeutic options in the treatment of acute kidney injury (AKI) and chronic kidney disease (CKD) have been sparse. Many of the effective treatments that are routinely utilized for different pathologies in patients without kidney disease have failed to demonstrate efficacy in those with renal dysfunction. Hence, there is an urgent need for discovery of novel pathways that can be targeted for innovative and effective clinical therapies in renal disease states. Discussion: There is now accumulating evidence that the endocannabinoid (EC) system plays a prominent role in normal renal homeostasis and function. In addition, numerous recent studies have described mechanisms through which alteration in the EC system can contribute to kidney damage and disease. These include a potential role for cannabinoid receptors in tubulo-glomerular damage and fibrosis, which are common features of AKI, interstitial nephritis, glomerulopathy, and other conditions leading to AKI and CKD. Conclusion: These findings suggest that manipulating the EC system may be an effective therapeutic strategy for the treatment of kidney disease and injury. However, further mechanistic studies are needed to fully delineate the role of this system in various conditions affecting the kidneys. Furthermore, while most of the current literature is focused on the role of the EC system as a whole in renal pathophysiology, future studies will also need to clarify the contribution of each component of this system, including the EC mediators, in the pathogenesis of kidney disease and their potential role as part of a therapeutic strategy.
TL;DR: Higher RDW is associated with a higher risk of mortality and hospitalizations among incident PD patients, and these results were consistent across numerous sensitivity analyses.
Abstract: Author(s): Soohoo, Melissa; Molnar, Miklos Z; Ujszaszi, Akos; Obi, Yoshitsugu; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar; Streja, Elani | Abstract: BackgroundRed blood cell distribution width (RDW) is found to be associated with different types of anemia and has recently been studied as a prognostic marker of mortality in hemodialysis patients. However, the relationship of RDW with mortality and hospitalization rate in peritoneal dialysis (PD) patients is less known.MethodsAmong 14 323 incident PD patients between 2007 and 2011 in the USA, we examined the relationship of baseline and time-varying RDW with the risk of mortality and time to first hospitalization using adjusted Cox models. In addition, we examined the relationship of baseline RDW and hospitalization rate using an adjusted negative-binomial regression model. Sensitivity analyses included competing risk models and subgroup analyses.ResultsThe study population comprised patients 56 ± 16 years of age, including 43% females, 23% African Americans and 62% diabetics, with a mean RDW of 15.3 ± 1.6%. In models adjusted for clinical characteristics and laboratory parameters, RDW exhibited an incremental relationship with the mortality risk, where RDW ≥16.5% had a 40% and 69% higher risk of death in baseline and time-varying analyses, respectively, compared with an RDW of 14.5-15.5%. Moreover, higher baseline RDW ≥16.5% was also associated with a higher risk of time to first hospitalization {hazard ratio 1.22 [95% confidence interval (CI) 1.14-1.29]} and a higher rate of hospitalizations [incidence rate ratio 1.16 (95% CI 1.09-1.23)]. These results were consistent across numerous sensitivity analyses.ConclusionsHigher RDW is associated with a higher risk of mortality and hospitalizations among incident PD patients. Further studies are needed to examine the mechanism behind RDW and adverse outcomes.
TL;DR: The relationship of higher TGs with mortality incrementally attenuated across worsening stages of CKD and attenuated to the null among patients with CKD stage 5/end-stage renal disease was observed.
TL;DR: Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L and when the odds of incident AKI were similar or lower in patients receiving vancomYcin compared to non-glycopeptide antibiotics as long as serum vancycin levels were ≤20mg/L.
Abstract: Background To determine the association of vancomycin with acute kidney injury (AKI) in relation to its serum concentration value and to examine the risk of AKI in patients treated with vancomycin when compared with a matched cohort of patients receiving non-glycopeptide antibiotics (linezolid/daptomycin). Methods From a cohort of > 3 million US veterans with baseline estimated glomerular filtration rate ≥60 mL/min/1.73 m2, we identified 33,527 patients who received either intravenous vancomycin (n = 22,057) or non-glycopeptide antibiotics (linezolid/daptomycin, n = 11,470). We examined the association of the serum trough vancomycin level recorded within the first 48 h of administration with subsequent AKI in all patients treated with vancomycin and association of vancomycin vs. non-glycopeptide antibiotics use with the risk of incident AKI. Results The overall multivariable adjusted ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptides were 1.1 (1.1-1.2), 1.2 (1-1.4), and 1.4 (1.1-1.7), respectively. When examined in strata divided by vancomycin trough level, the odds of AKI were similar or lower in patients receiving vancomycin compared to non-glycopeptide antibiotics as long as serum vancomycin levels were ≤20 mg/L. However, in patients with serum vancomycin levels > 20 mg/L, the ORs of AKI stages 1, 2, and 3 in patients on vancomycin vs. non-glycopeptide antibiotics were 1.5 (1.4-1.7), 1.9 (1.5-2.3), and 2.7 (2-3.5), respectively. Conclusions Vancomycin use is associated with a higher risk of AKI when serum levels exceed > 20 mg/L.
TL;DR: There is a dose-dependent relationship between higher pre- ESRD TSH levels >5.0 mIU/L and post-ESRD mortality and further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population of veterans.
Abstract: Author(s): You, Amy S; Sim, John J; Kovesdy, Csaba P; Streja, Elani; Nguyen, Danh V; Brent, Gregory A; Kalantar-Zadeh, Kamyar; Rhee, Connie M | Abstract: BackgroundAdvanced chronic kidney disease (CKD) patients, including those receiving dialysis, have a high prevalence of thyroid dysfunction. Although hypothyroidism is associated with higher death risk in end-stage renal disease (ESRD) patients, no studies have examined whether thyroid status in the pre-ESRD period impacts mortality after dialysis initiation.MethodsAmong US veterans with CKD identified from the national Veterans Affairs database that transitioned to dialysis over the period from October 2007 to September 2011, we examined the association of pre-ESRD serum thyrotropin (TSH) levels averaged over the 1-year pre-dialysis ('prelude') period with all-cause mortality in the first year following dialysis initiation.ResultsAmong 15 335 patients in the 1-year prelude cohort, TSH levels g5.0 mIU/L were associated with higher mortality in expanded case-mix Cox models (reference: TSH 0.5-5.0 mIU/L): adjusted hazard ratio (aHR) [95% confidence interval (CI) 1.20 (1.07-1.33). Similar findings were observed for TSH g5.0 mIU/L and mortality in the 2- and 5-year cohorts: aHRs (95% CI) 1.11 (1.02-1.21) and 1.15 (1.07-1.24), respectively. Analyses of finer gradations of TSH in the 1-year prelude cohort demonstrated that incrementally higher levels g5.0 mIU/L were associated with increasingly higher mortality in expanded case-mix models (reference: TSH 0.5-3.0 mIU/L): aHRs (95% CI) 1.18 (1.04-1.33) and 1.28 (1.03-1.59) for TSH levels g5.0-10.0 mIU/L and g10.0 mIU/L, respectively. In the 2- and 5-year cohorts, mortality associations persisted most strongly for those with TSH g10.0 mIU/L, particularly after laboratory covariate adjustment.ConclusionsAmong new ESRD patients, there is a dose-dependent relationship between higher pre-ESRD TSH levels g5.0 mIU/L and post-ESRD mortality. Further studies are needed to determine the impact of TSH reduction with thyroid hormone supplementation in this population.
TL;DR: Lower pre-ESRD serum albumin was associated with higher post-ES RD all-cause, cardiovascular, and infection-related mortalities and hospitalization rates and Declining serumalbumin levels in the pre- ESRD period were also associated with worse 12-month post-esRD mortality.
TL;DR: Higher UFR was associated with a rapid decline in RKF among conventional HD patients and KRU trajectories showed a greater KRU decline over time in higher UFR categories, indicating a greater decline in urine output after 1 year.
Abstract: Background: High ultrafiltration rate (UFR) has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of UFR on decline of residual kidney function (RKF) has not been elucidated among patients receiving conventional HD. Methods: We performed a retrospective cohort study of 7,753 patients who initiated conventional HD from 2007 to 2011 and survived the first year of dialysis with baseline UFR and renal urea clearance (KRU) data at baseline and 1 year (5th patient-quarter). The primary exposure was average UFR at the 1st patient-quarter from dialysis initiation (<4, 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg). Decline in RKF was defined as the percent change in KRU and decline in urine output during the first year after initiation of dialysis. We used a logistic regression model for rapid decline in RKF and a linear regression model for change in urine volume. Results: In our HD cohort, mean baseline UFR was 7.0 ± 3.1 mL/h/kg, and median (interquartile range) baseline KRU was 3.5 (2.1–5.3) mL/min/1.73 m2. There was a graded association between UFR and a rapid decline in RKF; the expanded case mix-adjusted ORs and 95% CIs were 1.21 (1.04–1.40), 1.34 (1.16–1.55), 1.73 (1.46–2.04), and 1.93 (1.48–2.52) for baseline UFR 4 to <6, 6 to <9, 9 to <13, and ≥13 mL/h/kg, respectively (reference: <4 mL/h/kg). KRU trajectories showed a greater KRU decline over time in higher UFR categories. Higher UFR was also associated with a greater decline in urine output after 1 year. Conclusion: Higher UFR was associated with a rapid decline in RKF among conventional HD patients. Further clinical trials are needed to elucidate a causal effect of UFR on RKF among HD patients.
TL;DR: Among an optimal start CKD cohort that transitioned to ESRD on an outpatient basis, there was no evidence of differences in early mortality between PD and HD.
TL;DR: Pneumococcal vaccination was cost-effective among adults aged 50 to 64 years with CKD even when assuming the lowest vaccine efficacy or 50% higher vaccine costs, and the cost-effectiveness of expanding its indication to younger adults with CKd less severe than kidney failure or nephrotic syndrome is suggested.
TL;DR: Among veterans with non–dialysis‐dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end‐stage renal disease is associated with favorable early end‐ stage renal disease outcomes.
Abstract: Background Although studies have shown that statin therapy in patients with non-dialysis-dependent chronic kidney disease was associated with a lower risk of death, this was not observed in dialysis patients newly initiated on statins. It is unclear if statin therapy benefits administered during the predialysis period persist after transitioning to end-stage renal disease. Methods and Results In 47 720 veterans who transitioned to end-stage renal disease during 2007 to 2014, we examined the association of statin therapy use 1 year before transition with posttransition all-cause and cardiovascular mortality and hospitalization incidence rates over the first 12 months of follow-up. Associations were examined using multivariable adjusted Cox proportional hazard models and negative binomial regressions. Sensitivity analyses included propensity score and subgroup analyses. The cohort's mean± SD age was 71±11 years, and the cohort included 4% women, 23% blacks, and 66% diabetics. Over 12 months of follow-up, there were 13 411 deaths, with an incidence rate of 35.3 (95% CI , 34.7-35.8) deaths per 100 person-years. In adjusted models, statin therapy compared with no statin therapy was associated with lower risks of 12-month all-cause (hazard ratio [95% CI], 0.79 [0.76-0.82]) and cardiovascular (hazard ratio [95% CI ], 0.83 [0.78-0.88]) mortality, as well as with a lower rate of hospitalizations (incidence rate ratio [95% CI ], 0.89 [0.87-0.92]) after initiating dialysis. These lower outcome risks persisted across strata of clinical characteristics, and in propensity score analyses. Conclusions Among veterans with non-dialysis-dependent chronic kidney disease, treatment with statin therapy within the 1 year before transitioning to end-stage renal disease is associated with favorable early end-stage renal disease outcomes.
TL;DR: The adoption of novel clinical trial design elements characteristic of pragmatic clinical trials and platform trials could help improve both the internal and external validity of RCTs in ESRD, ultimately resulting in the adoption of therapeutic interventions that can be rapidly translated to clinical practice.
Abstract: Patients with end-stage renal disease (ESRD) experience extremely high morbidity and mortality and there are virtually no therapeutic interventions besides dialysis treatment that are proven in properly designed randomized controlled trials (RCTs) to improve patients' outcomes. Historically, the number of RCTs performed in the ESRD population has been very low compared with other medical subspecialties, and several of the few large RCTs have yielded inconclusive or negative results, dampening enthusiasm for future investment in similar trials. Recent initiatives promoting a focus on patient-centered outcomes and more active patient and caregiver involvement in the planning and conduct of clinical trials may result in more clinically relevant RCTs and broader participation from patients representing the diversity of the ESRD population. The adoption of novel clinical trial design elements characteristic of pragmatic clinical trials and platform trials could help improve both the internal and external validity of RCTs in ESRD, ultimately resulting in the adoption of therapeutic interventions that can be rapidly translated to clinical practice.
TL;DR: In this large retrospective analysis of an unselected nationwide cohort of patients hospitalized for AF, obese patients demonstrated lower risk-adjusted odds of in-hospital mortality and stroke events, consistent with an "obesity paradox."
Abstract: Obesity has been linked with increased incidence of atrial fibrillation (AF), but impact of presence of obesity on outcomes of hospitalizations for AF has not been investigated. We used the National Inpatient Sample database 2010 to 2014 to identify all adult hospitalizations aged >= 18 years with a primary diagnosis of AF. Obese patients were identified using the co-morbidity variable for obesity, as defined in National Inpatient Sample databases. Multivariable logistic regression was used to compare in-hospital outcomes (mortality, acute stroke events) between obese and non-obese patients with AF. Of 431, 734 hospitalizations for AF, 66,138 (15.3%) were obese. Obese patients were younger and more likely to be African-Americans compared with non-obese patients. Despite being younger, obese patients had significantly higher prevalence of cardiovascular co-morbidities such - as hypertension, diabetes mellitus, dyslipidemia, smoking, heart failure, and chronic renal failure (p <0.001 for all). After multivariate risk-adjustment, obese patients had a lower observed in-hospital mortality (0.5% vs 1.0%; unadjusted odds ratio = 0.52, 95% confidence interval [CI] 0.46 to 0.58, p <0.001; adjusted odds ratio = 0.83, 95% CI 0.73 to 0.94, p <0.001) and acute stroke events (0.4% vs 0.7%, unadjusted odds ratio = 0. 65, 95% CI 0.57 to 0.73, p < 0.001; adjusted odds ratio = 0.82, 95% CI 0.72 to 0.94) compared with non-obese patients. In conclusion, in this large retrospective analysis of an unselected nationwide cohort of patients hospitalized for AF, obese patients demonstrated lower risk-adjusted odds of in-hospital mortality and stroke events, consistent with an "obesity paradox."
TL;DR: Cardiovascular death is the leading cause of mortality in patients undergoing hemodialysis, however, traditional risk factors, such as diabetes, hypertension, and other comorbidities, do not fully account for this excess risk.
Abstract: Cardiovascular death is the leading cause of mortality in patients undergoing hemodialysis. However, traditional risk factors, such as diabetes, hypertension, and other comorbidities, do not fully account for this excess risk. Uremic toxins, substances that accumulate in patients with kidney failure
TL;DR: Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABGs should be considered in this vulnerable population when deciding on the optimal revascularization strategy.
Abstract: Author(s): Gaipov, Abduzhappar; Molnar, Miklos Z; Potukuchi, Praveen K; Sumida, Keiichi; Szabo, Zoltan; Akbilgic, Oguz; Streja, Elani; Rhee, Connie M; Koshy, Santhosh KG; Canada, Robert B; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P | Abstract: BackgroundPrevious studies reported that compared with percutaneous coronary interventions (PCIs), coronary artery bypass grafting (CABG) is associated with a reduced risk of mortality and repeat revascularization in patients with mild to moderate chronic kidney disease (CKD) and end-stage renal disease (ESRD). Information about outcomes associated with CABG versus PCI in patients with advanced stages of CKD is limited. We evaluated the incidence and relative risk of acute kidney injury (AKI) associated with CABG versus PCI in patients with advanced CKD.MethodsWe examined 730 US veterans with incident ESRD who underwent a first CABG or PCI up to 5 years prior to dialysis initiation. The association of CABG versus PCI with AKI was examined in multivariable adjusted logistic regression analyses.ResultsA total of 466 patients underwent CABG and 264 patients underwent PCI. The mean age was 64 ± 8 years, 99% were male, 20% were African American and 84% were diabetic. The incidence of AKI in the CABG versus PCI group was 67% versus 31%, respectively (P l 0.001). The incidence of all stages of AKI were higher after CABG compared with PCI. CABG was associated with a 4.5-fold higher crude risk of AKI {odds ratio [OR] 4.53 [95% confidence interval (CI) 3.28-6.27]; P l 0.001}, which remained significant after multivariable adjustments [OR 3.50 (95% CI 2.03-6.02); P l 0.001].ConclusionCABG was associated with a 4.5-fold higher risk of AKI compared with PCI in patients with advanced CKD. Despite other benefits of CABG over PCI, the extremely high risk of AKI associated with CABG should be considered in this vulnerable population when deciding on the optimal revascularization strategy.
TL;DR: Among very-elderly incident hemodialysis patients, Dialysis therapy withdrawal exhibits wide variations across age, race and ethnicity, regions, cognitive status, dialysis vascular access, and nutritional status.