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      Interdialytic Weight Gain Effects on Hemoglobin Concentration and Cardiovascular Events

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          Abstract

          Introduction

          Although predialysis hemoglobin concentration is affected by interdialytic weight gain (IDWG), the interaction between these parameters is not well understood.

          Methods

          Using data from the Japanese Dialysis Outcomes and Practice Pattern Study phases 1–5, we analyzed patients who underwent maintenance hemodialysis. The exposure variable was hemoglobin concentration, and the effect modifier was IDWG at baseline. These 2 categorical variables were then combined and analyzed. The primary outcome was major adverse cardiovascular events (MACEs). Hazard ratios were estimated using a Cox model for the association between exposure and MACEs after adjusting for potential confounders. We examined additive interactions between hemoglobin concentration and IDWG by calculating the relative excess risk due to interaction, which is defined as a departure from the additivity of effects.

          Results

          A total of 8234 patients were enrolled. During a median follow-up of 2.1 years, 1062 (12.9%) patients developed MACEs. In IDWG categories of <6%, adjusted hazard ratios for MACEs tended to be lower as hemoglobin concentration increased. In IDWG categories of ≥6%, point estimation of MACEs with hemoglobin concentration of ≥11.0 g/dl–<12.0 g/dl was higher than that with hemoglobin concentration of ≥10.0 g/dl–<11.0 g/dl. The relative excess risk due to interaction was 0.22 (95% confidence interval 0.02–0.42) between IDWG category of ≥6% and hemoglobin categories of ≥11.0 g/dl–<12.0 g/dl, indicating a synergistic interaction.

          Conclusions

          The association between hemoglobin concentration and MACEs differed across IDWG. Consideration should be given to the upper limit of hemoglobin concentration in patients with high IDWG.

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          Most cited references 40

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          Correction of anemia with epoetin alfa in chronic kidney disease.

           Lynda Szczech,  ,  Shelly Sapp … (2006)
          Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P=0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.
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            Fluid retention is associated with cardiovascular mortality in patients undergoing long-term hemodialysis.

             Deborah Regidor,  Tamara B Horwich,  Suphamai Bunnapradist … (2009)
            Patients with chronic kidney disease (stage 5) who undergo hemodialysis treatment have similarities to heart failure patients in that both populations retain fluid frequently and have excessively high mortality. Volume overload in heart failure is associated with worse outcomes. We hypothesized that in hemodialysis patients, greater interdialytic fluid gain is associated with poor all-cause and cardiovascular survival. We examined 2-year (July 2001 to June 2003) mortality in 34,107 hemodialysis patients across the United States who had an average weight gain of at least 0.5 kg above their end-dialysis dry weight by the time the subsequent hemodialysis treatment started. The 3-month averaged interdialytic weight gain was divided into 8 categories of 0.5-kg increments (up to > or =4.0 kg). Eighty-six percent of patients gained >1.5 kg between 2 dialysis sessions. In unadjusted analyses, higher weight gain was associated with better nutritional status (higher protein intake, serum albumin, and body mass index) and tended to be linked to greater survival. However, after multivariate adjustment for demographics (case mix) and surrogates of malnutrition-inflammation complex, higher weight-gain increments were associated with increased risk of all-cause and cardiovascular death. The hazard ratios (95% confidence intervals) of cardiovascular death for weight gain or =4.0 kg (compared with 1.5 to 2.0 kg as the reference) were 0.67 (0.58 to 0.76) and 1.25 (1.12 to 1.39), respectively. In hemodialysis patients, greater fluid retention between 2 subsequent hemodialysis treatment sessions is associated with higher risk of all-cause and cardiovascular death. The mechanisms by which fluid retention influences cardiovascular survival in hemodialysis may be similar to those in patients with heart failure and warrant further research.
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              Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.

               E McCulloch,  Fang-Chi Hsu,  A Go … (2004)
              End-stage renal disease substantially increases the risks of death, cardiovascular disease, and use of specialized health care, but the effects of less severe kidney dysfunction on these outcomes are less well defined. We estimated the longitudinal glomerular filtration rate (GFR) among 1,120,295 adults within a large, integrated system of health care delivery in whom serum creatinine had been measured between 1996 and 2000 and who had not undergone dialysis or kidney transplantation. We examined the multivariable association between the estimated GFR and the risks of death, cardiovascular events, and hospitalization. The median follow-up was 2.84 years, the mean age was 52 years, and 55 percent of the group were women. After adjustment, the risk of death increased as the GFR decreased below 60 ml per minute per 1.73 m2 of body-surface area: the adjusted hazard ratio for death was 1.2 with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 (95 percent confidence interval, 1.1 to 1.2), 1.8 with an estimated GFR of 30 to 44 ml per minute per 1.73 m2 (95 percent confidence interval, 1.7 to 1.9), 3.2 with an estimated GFR of 15 to 29 ml per minute per 1.73 m2 (95 percent confidence interval, 3.1 to 3.4), and 5.9 with an estimated GFR of less than 15 ml per minute per 1.73 m2 (95 percent confidence interval, 5.4 to 6.5). The adjusted hazard ratio for cardiovascular events also increased inversely with the estimated GFR: 1.4 (95 percent confidence interval, 1.4 to 1.5), 2.0 (95 percent confidence interval, 1.9 to 2.1), 2.8 (95 percent confidence interval, 2.6 to 2.9), and 3.4 (95 percent confidence interval, 3.1 to 3.8), respectively. The adjusted risk of hospitalization with a reduced estimated GFR followed a similar pattern. An independent, graded association was observed between a reduced estimated GFR and the risk of death, cardiovascular events, and hospitalization in a large, community-based population. These findings highlight the clinical and public health importance of chronic renal insufficiency. Copyright 2004 Massachusetts Medical Society
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                Author and article information

                Contributors
                Yosuke Yamamoto
                Journal
                Journal ID (nlm-ta): Kidney Int Rep
                Journal ID (iso-abbrev): Kidney Int Rep
                Title: Kidney International Reports
                Publisher: Elsevier
                ISSN (Electronic): 2468-0249
                Publication date PMC-release: 27 July 2020
                Publication date Collection: October 2020
                Publication date (Electronic): 27 July 2020
                Volume: 5
                Issue: 10
                Pages: 1670-1678
                Affiliations
                [1 ]Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan
                [2 ]Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto, Japan
                [3 ]Division of Nephrology, Showa University School of Medicine, Tokyo, Japan
                [4 ]Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
                [5 ]Center for Innovative Research for Communities and Clinical Excellence, Fukushima Medical University, Fukushima, Japan
                [6 ]Shirakawa STAR for General Medicine, Fukushima Medical University, Fukushima, Japan
                Author notes
                [∗ ] Correspondence: Yosuke Yamamoto, Department of Healthcare Epidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. yamamoto.yosuke.5n@ 123456kyoto-u.ac.jp
                Article
                Publisher Item ID: S2468-0249(20)31426-1
                DOI: 10.1016/j.ekir.2020.07.027
                PMC ID: 7572305
                Copyright statement: © 2020 International Society of Nephrology. Published by Elsevier Inc.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Subject: Clinical Research

                Data availability:

                Keywords: major adverse cardiovascular events, predialysis, interaction, interdialytic weight gain, hemodialysis, hemoglobin

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