High cardiovascular event rates occur within the first weeks of starting hemodialysis

Early mortality is high in hemodialysis (HD) patients, but little is known about early cardiovascular event (CVE) rates after HD initiation. To study this we analyzed data in the AROii cohort of incident HD patients from over 300 European Fresenius Medical Care dialysis centers. Weekly rates of a composite of CVEs during the first year and monthly rates of the composite and its constituents (coronary artery, cerebrovascular, peripheral arterial, congestive heart failure, and sudden cardiac death) during the first 2 years after HD initiation were assessed. Of 6308 patients that started dialysis within 7 days, 1449 patients experienced 2405 CVEs over the next 2 years. The first-year CVE rate (30.2/100 person-years; 95% CI, 28.7-31.7) greatly exceeded the second-year rate (19.4/100; 95% CI, 18.1-20.8). Composite CVEs were highest during the first week with increased risk compared with the second year, persisting until the fifth month. Except for sudden cardiac death, temporal patterns of rates for all CVE categories were very similar, with highest rates during the first month and a high-risk period extending to 4 months. Higher or lower cumulative weekly dialysis dose, lower blood flow, and lower net ultrafiltration during dialysis were associated with CVE during the high-risk period, but not during the post high-risk period. Thus, the incidence of CVE in the first weeks after HD initiation is much higher than during subsequent periods which raises concerns that HD initiation may trigger CVEs. Early mortality is high in hemodialysis (HD) patients, but little is known about early cardiovascular event (CVE) rates after HD initiation. To study this we analyzed data in the AROii cohort of incident HD patients from over 300 European Fresenius Medical Care dialysis centers. Weekly rates of a composite of CVEs during the first year and monthly rates of the composite and its constituents (coronary artery, cerebrovascular, peripheral arterial, congestive heart failure, and sudden cardiac death) during the first 2 years after HD initiation were assessed. Of 6308 patients that started dialysis within 7 days, 1449 patients experienced 2405 CVEs over the next 2 years. The first-year CVE rate (30.2/100 person-years; 95% CI, 28.7-31.7) greatly exceeded the second-year rate (19.4/100; 95% CI, 18.1-20.8). Composite CVEs were highest during the first week with increased risk compared with the second year, persisting until the fifth month. Except for sudden cardiac death, temporal patterns of rates for all CVE categories were very similar, with highest rates during the first month and a high-risk period extending to 4 months. Higher or lower cumulative weekly dialysis dose, lower blood flow, and lower net ultrafiltration during dialysis were associated with CVE during the high-risk period, but not during the post high-risk period. Thus, the incidence of CVE in the first weeks after HD initiation is much higher than during subsequent periods which raises concerns that HD initiation may trigger CVEs. In patients with chronic kidney disease (CKD) the first months on hemodialysis (HD) have been identified as a high-risk period for patient survival.1.Noordzij M. Jager K.J. Increased mortality early after dialysis initiation: a universal phenomenon.Kidney Int. 2014; 85: 12-14Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar In both the US2.Soucie J.M. McClellan W.M. Early death in dialysis patients: risk factors and impact on incidence and mortality rates.J Am Soc Nephrol. 1996; 7: 2169-2175PubMed Google Scholar, 3.Bradbury B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar, 4.Collins A.J. Foley R.N. Gilbertson D.T. et al.The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis.Clin J Am Soc Nephrol. 2009; 4: S5-11Crossref PubMed Scopus (231) Google Scholar, 5.Chan K.E. Maddux F.W. Tolkoff-Rubin N. et al.Early outcomes among those initiating chronic dialysis in the United States.Clin J Am Soc Nephrol. 2011; 6: 2642-2649Crossref PubMed Scopus (97) Google Scholar, 6.Lukowsky L.R. Kheifets L. Arah O.A. et al.Patterns and predictors of early mortality in incident hemodialysis patients: new insights.Am J Nephrol. 2012; 35: 548-558Crossref PubMed Scopus (90) Google Scholar, 7.Robinson B.M. Zhang J. Morgenstern H. et al.Worldwide, mortality risk is high soon after initiation of hemodialysis.Kidney Int. 2014; 85: 158-165Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar and Europe,7.Robinson B.M. Zhang J. Morgenstern H. et al.Worldwide, mortality risk is high soon after initiation of hemodialysis.Kidney Int. 2014; 85: 158-165Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 8.Khan I.H. Catto G.R. Edward N. et al.Death during the first 90 days of dialysis: a case control study.Am J Kidney Dis. 1995; 25: 276-280Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 9.de Jager D.J. Grootendorst D.C. Jager K.J. et al.Cardiovascular and noncardiovascular mortality among patients starting dialysis.JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (525) Google Scholar increased mortality during the first 3 months after dialysis initiation, compared with subsequent periods, has been observed. The underlying reasons remain poorly understood. Early dialysis withdrawal may contribute to early mortality,3.Bradbury B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar but withdrawal practice varies significantly across countries and overall accounts for a comparatively small proportion of early death.7.Robinson B.M. Zhang J. Morgenstern H. et al.Worldwide, mortality risk is high soon after initiation of hemodialysis.Kidney Int. 2014; 85: 158-165Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar Among other causes of death, up to 40% have been attributed to cardiovascular (CV) disease8.Khan I.H. Catto G.R. Edward N. et al.Death during the first 90 days of dialysis: a case control study.Am J Kidney Dis. 1995; 25: 276-280Abstract Full Text PDF PubMed Scopus (130) Google Scholar, 9.de Jager D.J. Grootendorst D.C. Jager K.J. et al.Cardiovascular and noncardiovascular mortality among patients starting dialysis.JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (525) Google Scholar and a large study found the greatest difference between mortality rates during the first 3 months and during the remainder of the first year on dialysis for CV-related deaths.3.Bradbury B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar Thus, study of CV events (CVE) after dialysis initiation should lead to a better understanding of the causes of early mortality, risk prediction, and preventive strategies in high-risk patients. However, there is a paucity of data on CVE rates following HD initiation. In particular, it is not known whether the time to event varies for specific CVE categories, whether CVE risk factors vary for different CVE categories, and whether CVE risk factors differ for early and subsequent periods on dialysis. The clinical circumstances of dialysis initiation vary, making analysis of the early time period after starting dialysis challenging. Although many patients will initiate HD in an outpatient setting, others will have their first dialysis during a hospitalization period and will be subsequently referred to dialysis centers after variable time periods. Thus, important clinical events may easily be missed in registries of chronic HD patients. In fact, because of these circumstances and additional administrative reasons, many large registries do not capture clinical data on the first months on HD.10.Foley R.N. Collins A.J. The USRDS: what you need to know about what it can and can't tell us about ESRD.Clin J Am Soc Nephrol. 2013; 8: 845-851Crossref PubMed Scopus (103) Google Scholar Smaller studies, on the other hand, may have been of insufficient size to provide reliable rate estimates for different CVEs,11.Rognant N. Alamartine E. Aldigier J.C. et al.Impact of prior CKD management in a renal on early outcomes in incident dialysis patients: a Nephrol. 2013; PubMed Scopus Google Scholar, J. et disease and outcomes in patients initiating dialysis: the for outcomes in for study.Am J Kidney Dis. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar have been important in early mortality after dialysis initiation. data as of the and CKD J. et and of a mortality risk from a European hemodialysis Int. Full Text Full Text PDF Scopus Google Scholar we the of CVE after dialysis initiation in a large cohort of incident HD patients over 300 Fresenius Medical Care dialysis in for the study were and different for patients initiating HD within and the were to capture early The AROii cohort incident patients to centers in European countries and HD on the of study or within a week of this HD an time and a small proportion time the of the study we to patients with a dialysis days and patients not initiate dialysis within days of to we patients with dialysis data or with a of kidney in a study cohort of 6308 patients. this study cohort patients dialysis within and the remainder dialysis with of 2405 CVEs were in 1449 patients of the study within 2 years after initiation of dialysis. The of the study cohort the of CVE in the study period in experienced events in the first 2 years after dialysis initiation to be and were or causes for their and this in their clinical with a of the CVE and observed. the of higher in those a were and patients were with to and of the study within 2 years of HD In a in a disease kidney disease kidney congestive heart composite cardiovascular peripheral sudden cardiac and in in a new congestive heart composite cardiovascular peripheral sudden cardiac and in The of patients starting dialysis in and those starting dialysis in the of higher proportion of in the for initiation and may in the were with Of the 1449 patients experienced a event during the study period. The of first events to all events (coronary peripheral congestive heart with the of sudden cardiac to the high mortality experienced this patient with of patients within 7 days of a first of sudden cardiac death compared with of patients other first The of events experienced the patients with events from 2 to but patients experienced 2 or 3 these the associated mortality with within 7 days of the subsequent events but subsequent events were associated with high mortality subsequent events within the event in but the in and both the in The time between a subsequent event and its days the subsequent event on the it a from the event in the in but the to the that a specific on 2 and second-year rates of composite CVE and different CVE categories for all study patients and for those initiating dialysis within or The first-year rate of composite CVE and the second-year rate CVE rates were higher during the first year compared with the second In patients initiating HD the composite CVE rate difference in the and but the event rates of the other categories to be lower in those initiating of composite CVE and CVE constituents during the first and second year in patients overall as as in those initiating dialysis within Fresenius Medical Care dialysis centers in and of and congestive heart CI, composite cardiovascular Fresenius Medical Care dialysis centers in peripheral sudden cardiac and to the initiation of dialysis in a new congestive heart CI, composite cardiovascular Fresenius Medical Care dialysis centers in peripheral sudden cardiac and to the initiation of dialysis weekly composite CVE rates during the first year after HD initiation. The CVE rate during week it than higher than during week 2 and subsequently until week 4 to a during the remainder of the first rates for the composite CVE and the different CVE constituents in The temporal very for and all of which highest incidence rates during the first month. The event rate during month highest for and To periods of risk monthly event rates during year were to the event rate during year 2 Although the overall CVE high-risk period until month after dialysis initiation, the risk for and increased during the first but not the second the risk for increased during the first 2 and the risk for until month The event high for because the event rate during the second year lower than that for other CVEs. The risk for increased during months and In to other CVE categories, the incidence of a different with early and a compared with year 2 in month event rates for the composite cardiovascular events and periods for composite CVE and congestive heart composite cardiovascular peripheral sudden cardiac data the high-risk periods, during which the event rate significantly higher than the event rate of the second year in a new congestive heart composite cardiovascular peripheral sudden cardiac data the high-risk periods, during which the event rate significantly higher than the event rate of the second year 3 the of the between patient clinical and dialysis for the high-risk and post periods data in with we found between the of during the high-risk and the post high-risk period. that were associated with increased risk during both periods in of or as as and as underlying the other hand, dialysis were associated with increased or risk during the high-risk period, but not during the post high-risk period. weekly dialysis dose, blood and lower blood were associated with increased risk during the high-risk period and higher net ultrafiltration were associated with risk during the high-risk period The for the CVE were with the composite but with to with analysis the between patient and dialysis with CVE in the high-risk period data in or high cumulative weekly dialysis dose, high blood lower blood flow, and lower net ultrafiltration were associated with high early CVE CV risk factors and CVE were associated with CVE the high-risk associated with composite CVE in the high-risk and post high-risk periods data in high-risk of cardiovascular of cardiovascular of CKD of CKD of or lower cumulative weekly dialysis blood blood net chronic kidney cardiovascular event in a new were to whether the between dialysis and CVE in the high-risk period in patients initiating dialysis in or or of CVE patient were that these factors were not for with with we not have data on we on the of during the early dialysis period as a for a dialysis The proportion of patients an event lower among those patients initiating within in compared with those in this not the case a difference not found in patients initiating the monthly CVE in the and and patient similar, that a an in events soon after HD initiation. The of of with renal and is high in patients on Jager D.J. Grootendorst D.C. Jager K.J. et al.Cardiovascular and noncardiovascular mortality among patients starting dialysis.JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (525) Google Scholar, M. et of rate and with and cardiovascular mortality in a Kidney Full Text Full Text PDF PubMed Scopus Google Scholar, et al.Cardiovascular disease in chronic kidney clinical from Kidney Outcomes Int. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar The study that the period following dialysis initiation is a very high CV risk period, a much higher rate of CVE than the remainder of the first 2 years. rates that were and up to higher than during the second year on dialysis were found for events and peripheral as as heart during the first month on dialysis. of the composite CVE which a analysis of temporal in fact, that the first week of HD associated with CVE to have CVE rates after dialysis with that have an increased mortality during the first year on A.J. Foley R.N. Gilbertson D.T. et al.The state of chronic kidney disease, ESRD, and morbidity and mortality in the first year of dialysis.Clin J Am Soc Nephrol. 2009; 4: S5-11Crossref PubMed Scopus (231) Google Scholar, 9.de Jager D.J. Grootendorst D.C. Jager K.J. et al.Cardiovascular and noncardiovascular mortality among patients starting dialysis.JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (525) Google Scholar, et al.Early on renal the need for early 7: Google Scholar and in during the first J.M. McClellan W.M. Early death in dialysis patients: risk factors and impact on incidence and mortality rates.J Am Soc Nephrol. 1996; 7: 2169-2175PubMed Google Scholar, I.H. et on renal in is there a 1996; PubMed Scopus Google Scholar or B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar, 7.Robinson B.M. Zhang J. Morgenstern H. et al.Worldwide, mortality risk is high soon after initiation of hemodialysis.Kidney Int. 2014; 85: 158-165Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar Although data on mortality rates large cohort study of over patients highest mortality rates within the first 2 K.E. Maddux F.W. Tolkoff-Rubin N. et al.Early outcomes among those initiating chronic dialysis in the United States.Clin J Am Soc Nephrol. 2011; 6: 2642-2649Crossref PubMed Scopus (97) Google Scholar which of an early high-risk period. causes may contribute to early mortality on but the of CV B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar, 6.Lukowsky L.R. Kheifets L. Arah O.A. et al.Patterns and predictors of early mortality in incident hemodialysis patients: new insights.Am J Nephrol. 2012; 35: 548-558Crossref PubMed Scopus (90) Google Scholar which is with of CVE rates after dialysis initiation. risk which we found to be associated with CVE in the early after dialysis initiation, as and CVE were identified to be associated with early mortality in HD J.M. McClellan W.M. Early death in dialysis patients: risk factors and impact on incidence and mortality rates.J Am Soc Nephrol. 1996; 7: 2169-2175PubMed Google Scholar, 3.Bradbury B.D. Fissell R.B. Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar Although we a overall mortality rate of within week following a the of CVEs were not a in morbidity early after dialysis initiation. different reasons may the increased rate of CVE following the of dialysis. of renal the and in a to initiate dialysis may be of the subsequent for but is for as or The second and be that the initiation of dialysis In fact, the HD has been to and et cardiac is associated with an in and blood J Am Soc Nephrol. PubMed Scopus Google Scholar, The of cardiac in J Kidney Dis. 2013; Full Text Full Text PDF PubMed Scopus Google Scholar et in the blood of the Int. 2014; PubMed Scopus Google Scholar J. E. et of initiation of hemodialysis on of and Int. Full Text Full Text PDF PubMed Scopus Google Scholar and in renal have we in PubMed Scopus Google Scholar events a temporal of CVE with the dialysis Thus, about of all in dialysis patients were found to during or after HD J. et disease and outcomes in patients initiating dialysis: the for outcomes in for study.Am J Kidney Dis. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar, et in patients on a study.Am J Kidney Dis. Full Text Full Text PDF PubMed Scopus Google Scholar rates and CVE rates in a large US study of dialysis patients were found to be associated with the dialysis with highest rates on the following the R.N. Gilbertson D.T. et and mortality among patients J 2011; PubMed Scopus Google Scholar of what causes temporal between dialysis and additional factors a that the during the first weeks and months of dialysis. Although a in mortality rates may be the that high-risk patients early and patients do not the incidence rates for a of different CVEs in over The of between risk factors and CVE were for the high-risk and the post high-risk period, and we found little for factors that associated with CVE during the high-risk period. of and specific of kidney disease, analysis during the early high-risk period, and it is that these factors their with In to an early for other CVE the of event that a different with in incidence rates during the first 2 years. this difference but it is important to that the of is to be lower than that for other et al.Cardiovascular disease in chronic kidney clinical from Kidney Outcomes Int. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar study has overall event rates were lower in patients initiating of The reasons for this difference remain that many events within the first week after dialysis initiation, it is that and events in patients initiating HD prior to capture in the in a to patient and be this we to analysis with the study than those patients initiating within that this may lead to an of event the of initiating within or that the of these patients a impact on risk CVEs were on the of and were not In particular, between heart and is do not have data on that may have for the of first to the of renal dialysis initiation, the specific for starting or renal N. M. Early mortality in dialysis and of renal the is than we Int. 2014; Full Text Full Text PDF PubMed Scopus Google Scholar patients were to a dialysis we to event rates after dialysis initiation with event rates during the period. 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Albert J.M. et al.Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).Clin J Am Soc Nephrol. 2007; 2: 89-99Crossref PubMed Scopus (375) Google Scholar, 6.Lukowsky L.R. Kheifets L. Arah O.A. et al.Patterns and predictors of early mortality in incident hemodialysis patients: new insights.Am J Nephrol. 2012; 35: 548-558Crossref PubMed Scopus (90) Google Scholar large of associated mortality is to A.J. 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