FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1996384575> ?p ?o ?g. }

• W1996384575 endingPage "836" @default.
• W1996384575 startingPage "833" @default.
• W1996384575 abstract "Interventional trials indicate adverse outcomes when hemoglobin >13 g/dL is targeted in patients with chronic kidney disease (CKD) who receive erythropoiesis-stimulating agents (ESAs). It is not clear whether high-achieved hemoglobin with minimal to no ESA administration as observed in some patients with polycystic kidney disease (PKD) is also associated with poor outcomes. Survival models were examined to assess the association between hemoglobin increments and mortality in a 6-year cohort of 2,402 PKD and 110,875 non-PKD hemodialysis patients across infrequent versus frequent ESA therapy defined as ESA < 25% of cohort time versus otherwise, respectively. Mortality risk was estimated by Cox proportional regression [hazard ratio (HR) and 95% of confidence interval] analysis. Patients with PKD were aged 58 ± 13 years and included 46% women and 14% Blacks, respectively. Fully adjusted death HRs of time-averaged hemoglobin increments <11.0, 12.0 to <13.0, and ≥13.0 g/dL (reference: 11.0 to <12.0 g/dL) for frequent ESA therapy were 2.57 (1.48–4.48), 0.60 (0.43–0.82), and 0.81 (0.50–1.29), whereas for infrequent ESA therapy they were 1.33 (0.47–3.78), 0.28 (0.13–0.61), and 0.22(0.09–0.57), respectively. Hence, in patients with PKD who require infrequent ESA, incrementally higher achieved hemoglobin including >13.0 g/dL exhibits better survival; this incremental survival gain of higher hemoglobin is not observed in patients with PKD receiving frequent ESA administration, in whom hemoglobin concentration >13 exhibits increased mortality. Observational studies in patients with end-stage renal disease (ESRD) treated with hemodialysis and those with earlier stages of CKD have demonstrated a consistent association between anemia and subsequent morbidity and mortality [1-3]. However, controlled trials in patients with CKD have shown a higher risk for adverse cardiovascular events in patients targeted to achieve a higher hemoglobin level using ESAs [4-6]. However, a reanalysis of the Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR) trial showed that severe comorbidities may have confounded the associations between ESA use, hemoglobin, and outcomes [7]. Hence, it is not clear whether high hemoglobin level per se is a risk factor in patients with CKD or whether it is so only if ESA therapy is involved. Approximately 5% of patients with ESRD in the United States suffer from PKD [8]. Those patients with PKD who require maintenance hemodialysis (MHD) treatment seem to be different from other MHD patients: they report a better quality of life [9] and have greater survival than non-PKD patients, including other nondiabetic MHD patients [10]. These survival differences raise questions as to whether the aforementioned association between anemia and mortality in the general MHD population is also present in patients with PKD. There is a relative paucity of data for ESRD patients with PKD [11-13]. There are certain factors that may potentially affect the association between hemoglobin level and mortality in ESRD patients with PKD. In patients with PKD, plasma erythropoietin levels are roughly twice as high as those seen in other renal diseases for the reason that interstitial cells adjacent to the walls of proximal-type cysts can also produce erythropoietin [14]. Hence, as reported frequently, PKD may be associated with a modestly higher average hemoglobin concentration in patients with ESRD [11, 12]. Increased erythropoietin production may also occur early in the course, as ∼5% of nonazotemic men with PKD have a clearly elevated hemoglobin concentration (e.g., >18 g/dL) [13]. Given the greater survival, lower comorbidity burden and difference in erythropoietin production in patients with PKD when compared with other MHD patients, we hypothesized that a higher hemoglobin level would be associated with better survival in MHD patients with PKD, especially with minimal to no ESA therapy, but not in patients who routinely receive ESA. The baseline demographic, clinical, and laboratory characteristics of the 2,402 PKD and 110,875 non-PKD patients, divided into four subgroups based on hemoglobin categories, are summarized in Table 1. Patients with PKD were aged 58 ± 13 years and included 46% women and 14% Blacks, respectively. In the PKD population, higher hemoglobin level was associated with higher proportion of men, lower prevalence of diabetes, shorter time on dialysis, and higher serum albumin level (Table 1). The median follow-up time for the cohort was 788 days (interquartile range: 327–1190 days). We examined mortality predictability of time-averaged hemoglobin in patients with PKD. Subsequently, in time-averaged models, the survival analyses were decomposed based on two mutually exclusive subgroups of “regular” versus “infrequent” ESA therapy, if ESA was used >25% vs. <25% of the time, respectively. Individuals with a hemoglobin concentration <11.0 g/dL had a higher risk for mortality (reference: 11.0 to <12.0 g/dL), the death risk was the lowest among those with an achieved hemoglobin concentration 12.0 to <13.0 g/dL, whereas death risk tend to increase with higher hemoglobin levels >13 g/dL (P <0.001 for the quadratic hemoglobin term in case-mix and MICS models). When time-dependent models were examined separately across the two ESA therapy frequencies in patients with PKD (Fig. 1), a significant effect modification by ESAs use was noticed (P-value for the interaction term <0.001) for the association of hemoglobin with mortality; a hemoglobin concentration >13 g/dL continued to confer greater survival in infrequent ESA dosing, whereas in regular ESA group, a hemoglobin concentration 12 to <13 g/dL had the greatest survival and not >13 g/dL. Fully adjusted death HRs (95% confidence interval) of time-averaged hemoglobin increments <11.0, 12.0 to <13.0, and ≥13.0 g/dL (reference: 11.0 to <12.0 g/dL) for regular ESA therapy were 2.57 (1.48–4.48), 0.60 (0.43–0.82), and 0.81 (0.50–1.29); and for infrequent ESA therapy were 1.33 (0.47–3.78), 0.28 (0.13–0.61), and 0.22 (0.09–0.57), respectively. The results were qualitatively the same when we adjusted for dose of iron supplementation and ESA dose (data not shown). Similar results were found when we restricted our population to those in the study at least three quarters as a sensitivity analysis (data not shown). In addition, the results were qualitatively the same when we defined the frequent (≥5,000 U/week) and infrequent (<5,000 U/week) ESA dose based on average administered ESA in our sensitivity analyses (data not shown). Hazard ratio (95% confidence intervals) of mortality across the hemoglobin categories using time-averaged Cox regression analyses in long-term hemodialysis patients with PKD on (A) ESA therapy and non-ESA therapy (B). Figure 2 shows pooled analyses comparing mortality predictability of hemoglobin increments in PKD versus non-PKD patients (hemoglobin reference: 11.0–12.0 g/dL in non-PKD patients). The fully adjusted death HR for time-averaged hemoglobin of 11.0 to <12.0 g/dL in patients with PKD were 0.85 (0.71–1.01), indicating 15% lower mortality in patients with PKD when compared with non-PKD patients with this hemoglobin level. However, the death HR was similar in PKD and non-PKD patients with low hemoglobin levels < 11.0 g/dL, whereas with higher hemoglobin levels, patients with PKD exhibited even greater survival advantages than non-PKD patients. Comparing mortality predictability of PKD versus non-PKD hemodialysis patients in fully (case mix and MICS) adjusted models time-averaged Cox regression analyses. This analysis of MHD patient data from a large and nationally representative contemporary cohort including 2,402 patients with PKD allows us to make several important observations. First, we confirm the previous findings of an association between lower achieved hemoglobin and higher risk for death in MHD patients using time-averaged Cox regression analysis. Second, despite a similar relationship between achieved hemoglobin and mortality in PKD and non-PKD MHD patients in lower hemoglobin ranges, patients with PKD had superior survival to non-PKD patients with higher hemoglobin levels. Third, in patients with PKD with infrequent ESA treatment, higher achieved hemoglobin levels, even above 13 g/dL, were associated with greater survival, whereas on regular ESA use, this high hemoglobin level showed an increased death risk when compared with hemoglobin in 12 to <13 g/dL range. This novel and differential finding suggests the putative role of ESA, or at least the ESA hyporesponsiveness, in causing the high mortality of hemoglobin above 13 g/dL. In our study, we found an association between lower hemoglobin level and higher death risk in patients with PKD. These findings are consistent with previous studies of hemodialysis and patients with CKD [1-3]. One of the first population studies in MHD patients reported a progressive increase in the risk of all-cause and cardiac death in patients with hemotocrit levels below the range of 33 to <36 percent [15]. Using a DaVita database, we have showed that a baseline hemoglobin level of 12 to 13 g/dL was associated with the highest 2-year survival in both MHD and peritoneal dialysis patients [3, 16]. Factors such as increased endogenous erythropoietin production [14] may have an effect on the association between hemoglobin level and mortality in MHD patients with PKD. Interestingly, we found, for the first time to our knowledge, that patients with PKD with infrequent ESA therapy, that is, <25% of the time, showed a different hemoglobin-mortality association in that the association was linear with a higher hemoglobin linked to better survival, whereas regular use of ESA therapy rendered a hemoglobin concentration >13 g/dL susceptible to higher death risk. This novel observation is similar to previous studies in some mainly non-PKD cohorts; Goodkin et al. [17] reported that naturally occurring hemoglobin concentration >12 g/dL does not associate with increased mortality among hemodialysis patients. We found similar results to the study by Goodkin et al., where Hgb ≥ 12 g/dL was associated with lower mortality risk when compared with Hgb 11 to <12 g/dL subgroups. This study also reported that the likelihood of absence of ESA therapy is more than five times higher in patients with PKD than non-PKD patients [17]. A potential reason why the hemoglobin-mortality association is linear in patients with PKD with lower amounts of ESA therapy may be a lack of toxicity from high-dose ESA, which can also be associated with iron depletion [18-21] and subsequent thrombocytosis [22], whereas with the naturally occurring high hemoglobin levels in the healthiest subgroup of patients with PKD, this is not the case. Our study is notable for its large sample size. The detailed information on baseline covariates allowed us to control for a range of factors known to be related to the mortality of MHD patients. It is important to note that observational studies, such as ours, cannot prove causality. Moreover, unmeasured confounders might have an impact on our results. The information on comorbidities in our study was limited to that obtained from Medical Evidence Form 2728, a form in which comorbid conditions are underreported [23]. In addition, we do not have comorbidity data in the follow-up period. Additional potential limitation is the lack of information of endogenous erythropoietin level and several important comorbid conditions. Although a U-shaped association for hemoglobin-mortality is observed in that an achieved hemoglobin >13.0 g/dL is associated with higher mortality than a hemoglobin in 12 to <13 g/dL range in most MHD patients, in patients with PKD who required infrequent ESA therapy, the hemoglobin-mortality association is somewhat linear in that higher achieved hemoglobin levels even above 13 g/dL continue to be associated with greater survival. We extracted, refined, and examined data from all individuals with ESRD who underwent dialysis treatment from July 2001 through June 2006 in any one of the 580 outpatient dialysis facilities of DaVita, a large dialysis organization in the United States (prior to its acquisition of units owned by Gambro). Of the 164,789 cumulative patients treated in all DaVita units over the 5-year period, we excluded 13,312 patients without quarterly based data, 19,652 patients who were on peritoneal dialysis or in whom method of renal replacement therapy was unknown, and 802 patients aged >99 years or <18 years. From these 131,023 patients, 17,746 did not have hemoglobin data; therefore, our study population consisted of 2,402 MHD patients with PKD and 110,875 MHD patients without PKD at baseline. The study was approved by relevant Institutional Review Committees. The creation of the cohort has been described previously [24-29]. To minimize measurement variability, all repeated measures for each patient during any given calendar quarter, that is, over a 13-week interval, were averaged and the summary estimate was used in all models. Average hemoglobin values were obtained from up to 20 calendar quarters (q1 through q20). The first (baseline) studied quarter for each patient was the calendar quarter in which the patient's dialysis vintage was >90 days. The presence or absence of diabetes at baseline and history of tobacco smoking were obtained by linking the DaVita database to the data from Medical Evidence Form 2728 from the United States Renal Data System. The presence of preexisting comorbid conditions was similarly ascertained and grouped into 10 categories: ischemic heart disease, congestive heart failure, history of HIV infection, presence of AIDS, history of hypertension, history of other cardiac disease, cerebrovascular events, peripheral vascular disease, chronic obstructive pulmonary disease, and cancer [30]. Patients were followed for outcomes through June 30, 2007. Blood samples were drawn using uniform techniques in all dialysis clinics and were transported to the DaVita Laboratory in Deland, Florida, within 24 hr. All laboratory values, including hemoglobin, were measured by automated and standardized methods. Hemoglobin was measured at least monthly in virtually all patients. The 3-month-averaged hemoglobin for each quarter was used in our analyses. We divided hemoglobin a priori into four categories (<11.0, 11.0 to <12.0, 12.0 to <13.0, and ≥13.0 g/dL). “Regular” ESA therapy was defined as the administration of ESA for at least 25% of the time; otherwise it was called “infrequent” ESA therapy. The administration of ESA followed the guidelines of ESA treatment during the entire study period. Data were summarized using proportions and means (± standard deviation). The significance of difference between categorical variables was determined using the χ2 test and continuous variables using Student's t-test or ANOVA as appropriate. Survival analysis was performed using time-dependent and time-averaged analysis to examine whether hemoglobin predicted survival in patients with PKD. The primary analysis examined the association between time-dependent or time-averaged hemoglobin with mortality. We prefer time-averaged models that examine the cumulative association of low or high hemoglobin with mortality over long periods of time, whereas time-dependent models have also been examined for comparative purposes (not shown). The presence of nonlinearity in the survival association was tested by adding the quadratic term of hemoglobin to the models already containing the linear term. Additional subgroups analyses were performed in patients receiving or not receiving ESAs therapy. For each analysis, including subgroup analyses, three models were examined: Model I: Unadjusted or minimally adjusted models included hemoglobin categories and change of hemoglobin categories and entry calendar quarter (q1 through q20). Model II: Case-mix-adjusted models that included hemoglobin categories and change of hemoglobin categories and entry calendar quarter plus age, gender, presence of diabetes, race/ethnicity (African Americans and other self-categorized Blacks, Non-Hispanic Caucasians, Asians, Hispanics, and others), categories of dialysis vintage (<6 months, 6–12 months, 12–24 months, and ≥2 years), primary insurance (Medicare, Medicaid, and others), and marital status (married, single, divorced, and widowed), type of vascular access (catheter, AVF, and graft), dialysis dose as indicated by Kt/V (single pool), 10 preexisting comorbid conditions, history of tobacco smoking. Model III: Case-mix plus malnutrition-inflammation complex syndrome-adjusted models included all of the covariates in the case-mix model as well as body mass index, and eight laboratory surrogates with known association with clinical outcomes in hemodialysis patients including serum levels of albumin, total iron-binding capacity, creatinine, calcium, bicarbonate, nPCR as an indicator of daily protein intake, also known as the normalized protein nitrogen appearance, white blood cell count (WBC), and lymphocyte percentage. In sensitivity analyses we reexamined survival models in “regular” and “infrequent” ESA therapy groups after the population was restricted to those who had been in the study at least three quarters (data not shown). For all analysis, two-sided P-values are reported, and results were considered statistically significant if P < 0.05. All statistical analyses were carried out with the SAS, version 9.1 (SAS Institute, Cary, NC). The authors thank DaVita Clinical Research for providing the clinical data. This study was supported by a philanthropic grant from Mr. Harold Simmons. Author Contributions: Anuja Shah contributed to analyzing and interpretation of data and writing the manuscript; Miklos Z. Molnar contributed to analyzing and interpretation of data and writing the manuscript; Lilia R. Lukowsky contributed to analyzing and interpretation of data and writing the manuscript; Joshua J. Zaritsky contributed to analyzing and interpretation of data and writing the manuscript; Csaba P. Kovesdy contributed to analyzing and interpretation of data and writing the manuscript; Kamyar Kalantar-Zadeh designed, organized, and coordinated the study, managed data entry, contributed to data analysis and interpretation of data, and wrote the manuscript. Anuja Shah*, Miklos Z. Molnar , Lilia R. Lukowsky §, Joshua J. Zaritsky¶, Csaba P. Kovesdy** , Kamyar Kalantar-Zadeh* § ¶, * Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor, UCLA Medical Center, Torrance, California, Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor, UCLA, Torrance, California, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary, § Department of Epidemiology, UCLA School of Public Health, Los Angeles, California, ¶ David Geffen School of Medicine at UCLA, Los Angeles, California, ** Division of Nephrology, University of Virginia, Charlottesville, Virginia, Division of Nephrology, Salem VA Medical Center, Salem, Virginia." @default.
• W1996384575 created "2016-06-24" @default.
• W1996384575 creator A5028345951 @default.
• W1996384575 creator A5037829607 @default.
• W1996384575 creator A5047313234 @default.
• W1996384575 creator A5057684886 @default.
• W1996384575 creator A5072778477 @default.
• W1996384575 creator A5074587712 @default.
• W1996384575 date "2012-05-28" @default.
• W1996384575 modified "2023-09-24" @default.
• W1996384575 title "Hemoglobin level and survival in hemodialysis patients with polycystic kidney disease and the role of administered erythropoietin" @default.
• W1996384575 cites W1987603059 @default.
• W1996384575 cites W1993518728 @default.
• W1996384575 cites W1998943227 @default.
• W1996384575 cites W2003784194 @default.
• W1996384575 cites W2015972217 @default.
• W1996384575 cites W2038327657 @default.
• W1996384575 cites W2040029744 @default.
• W1996384575 cites W2049258517 @default.
• W1996384575 cites W2054827204 @default.
• W1996384575 cites W2068087609 @default.
• W1996384575 cites W2071119045 @default.
• W1996384575 cites W2084100872 @default.
• W1996384575 cites W2090046834 @default.
• W1996384575 cites W2092213978 @default.
• W1996384575 cites W2103528057 @default.
• W1996384575 cites W2105642896 @default.
• W1996384575 cites W2107215009 @default.
• W1996384575 cites W2111999751 @default.
• W1996384575 cites W2116763351 @default.
• W1996384575 cites W2120939456 @default.
• W1996384575 cites W2129162902 @default.
• W1996384575 cites W2131136483 @default.
• W1996384575 cites W2135233650 @default.
• W1996384575 cites W2146958531 @default.
• W1996384575 cites W2156905902 @default.
• W1996384575 cites W2160663184 @default.
• W1996384575 cites W2162195477 @default.
• W1996384575 cites W2213612481 @default.
• W1996384575 doi "https://doi.org/10.1002/ajh.23255" @default.
• W1996384575 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22641426" @default.
• W1996384575 hasPublicationYear "2012" @default.
• W1996384575 type Work @default.
• W1996384575 sameAs 1996384575 @default.
• W1996384575 citedByCount "13" @default.
• W1996384575 countsByYear W19963845752013 @default.
• W1996384575 countsByYear W19963845752014 @default.
• W1996384575 countsByYear W19963845752015 @default.
• W1996384575 countsByYear W19963845752016 @default.
• W1996384575 countsByYear W19963845752017 @default.
• W1996384575 countsByYear W19963845752018 @default.
• W1996384575 countsByYear W19963845752022 @default.
• W1996384575 crossrefType "journal-article" @default.
• W1996384575 hasAuthorship W1996384575A5028345951 @default.
• W1996384575 hasAuthorship W1996384575A5037829607 @default.
• W1996384575 hasAuthorship W1996384575A5047313234 @default.
• W1996384575 hasAuthorship W1996384575A5057684886 @default.
• W1996384575 hasAuthorship W1996384575A5072778477 @default.
• W1996384575 hasAuthorship W1996384575A5074587712 @default.
• W1996384575 hasBestOaLocation W19963845752 @default.
• W1996384575 hasConcept C126322002 @default.
• W1996384575 hasConcept C177713679 @default.
• W1996384575 hasConcept C2778063415 @default.
• W1996384575 hasConcept C2778534260 @default.
• W1996384575 hasConcept C2778653478 @default.
• W1996384575 hasConcept C2778917026 @default.
• W1996384575 hasConcept C2779134260 @default.
• W1996384575 hasConcept C2780145431 @default.
• W1996384575 hasConcept C71924100 @default.
• W1996384575 hasConceptScore W1996384575C126322002 @default.
• W1996384575 hasConceptScore W1996384575C177713679 @default.
• W1996384575 hasConceptScore W1996384575C2778063415 @default.
• W1996384575 hasConceptScore W1996384575C2778534260 @default.
• W1996384575 hasConceptScore W1996384575C2778653478 @default.
• W1996384575 hasConceptScore W1996384575C2778917026 @default.
• W1996384575 hasConceptScore W1996384575C2779134260 @default.
• W1996384575 hasConceptScore W1996384575C2780145431 @default.
• W1996384575 hasConceptScore W1996384575C71924100 @default.
• W1996384575 hasIssue "8" @default.
• W1996384575 hasLocation W19963845751 @default.
• W1996384575 hasLocation W19963845752 @default.
• W1996384575 hasLocation W19963845753 @default.
• W1996384575 hasOpenAccess W1996384575 @default.
• W1996384575 hasPrimaryLocation W19963845751 @default.
• W1996384575 hasRelatedWork W2372141393 @default.
• W1996384575 hasRelatedWork W2390387684 @default.
• W1996384575 hasRelatedWork W2413363211 @default.
• W1996384575 hasRelatedWork W2414888762 @default.
• W1996384575 hasRelatedWork W2470369214 @default.
• W1996384575 hasRelatedWork W2805683016 @default.
• W1996384575 hasRelatedWork W2885191723 @default.
• W1996384575 hasRelatedWork W3154212710 @default.
• W1996384575 hasRelatedWork W3198719624 @default.
• W1996384575 hasRelatedWork W4312983352 @default.
• W1996384575 hasVolume "87" @default.
• W1996384575 isParatext "false" @default.
• W1996384575 isRetracted "false" @default.
• W1996384575 magId "1996384575" @default.

• next