Renal Failure

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/irnf20

High ultrafiltration rate induced intradialytic

hypotension is a predictor for cardiac remodeling:
a 5-year cohort study

Jinbo Yu, Xiaohong Chen, Yang Li, Yaqiong Wang, Zhonghua Liu, Bo Shen, Jie
Teng, Jianzhou Zou & Xiaoqiang Ding

To cite this article: Jinbo Yu, Xiaohong Chen, Yang Li, Yaqiong Wang, Zhonghua Liu, Bo Shen,
Jie Teng, Jianzhou Zou & Xiaoqiang Ding (2021) High ultrafiltration rate induced intradialytic
hypotension is a predictor for cardiac remodeling: a 5-year cohort study, Renal Failure, 43:1,
40-48, DOI: 10.1080/0886022X.2020.1853570

To link to this article: https://doi.org/10.1080/0886022X.2020.1853570

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RENAL FAILURE
2021, VOL. 43, NO. 1, 40–48
https://doi.org/10.1080/0886022X.2020.1853570

CLINICAL STUDY

High ultrafiltration rate induced intradialytic hypotension is a predictor for

cardiac remodeling: a 5-year cohort study
Jinbo Yu, a,b,c, Xiaohong Chena,c, Yang Lia,c, Yaqiong Wanga,c, Zhonghua Liua,c, Bo Shena,c,
Jie Tenga,c, Jianzhou Zoua,c and Xiaoqiang Dinga,c
a
Division of Nephrology, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, P. R. China; bShanghai Institute
of Kidney Disease and Dialysis, Shanghai, P. R. China;cShanghai Key Laboratory of Kidney and
Blood Purification, Shanghai, P. R. China

ABSTRACT ARTICLE HISTORY

Background: Intradialytic-hypotension (IDH) is a common complication of hemodialysis. High Received 10 August 2020
ultrafiltration rate (UFR) might lead to IDH. However, the relationships between UFR, IDH, and Revised 5 November 2020
cardiac remodeling among hemodialysis patients in the long-term have not been Accepted 6 November 2020
deeply explored.
KEYWORDS
Methods: This retrospective cohort study collected clinical and echocardiographic data. Patients Intradialytic hypotension;
were enrolled from 1 January 2014 to 31 March 2014 and were followed-up for 5-year. Those cardiac remodeling;
who suffered from more than four hypotensive events during three months (10% of dialysis ultrafiltration rate;
treatments) were defined as the IDH group. Subgroup analysis was done according to the UFR hemodialysis; left
of 10 ml/h/kg. Associations between UFR, IDH, and alterations of cardiac structure/function ventricular mass index
were analyzed.
Results: Among 209 patients, 96 were identified with IDH (45.9%). The survival rate of IDH
patients was lower than that of no-IDH patients (65.5% vs. 81.4%, p ¼ .005). In IDH group,
decreased ejection fraction (EF), larger left atrium diameter index (LADI), and left ventricular
mass index (LVMI) (p < .05) were observed at the end of the follow-up. In multivariate logistic
model, the interaction between UFR and IDH was notably associated with LVMI variation
(OR ¼ 1.37). After adjusting covariates, UFR was still an independent risk factor of LVMI variation
(OR ¼ 1.52) in IDH group. In subsequent analysis, we divided patients according to UFR 10 ml/h/
kg. For IDH-prone patients, decreased EF, larger LADI, and LVMI (p < .05) were observed at the
end of the study only in high-UFR group.
Conclusions: UFR and IDH have interactions on cardiac remodeling. High ultrafiltration rate
induced IDH is a predictor for cardiac remodeling in long-term follow-up.

Introduction response. Over ultrafiltration brings about the decrease

Intradialytic-hypotension (IDH) is reported to be one of of arterial blood volume, the decrease of cardiac filling
the most common complications of hemodialysis (HD), and cardiac output, and finally leads to hypotension.
occurring in between 10 and 70% of HD sessions Thus, IDH itself could suggest hemodynamic instability.
depending on different definitions used [1–3]. Many Studies have shown that cardiac structural alterations
studies have shown that IDH may be a potential factor have occurred at the early stage of renal insufficiency
for poor prognosis. For the short-term, IDH might result [6,7], and the alterations become worse after dialysis
in discomfort and inadequate dialysis, contributing to initiation [8]. The injuries of cardiovascular illnesses,
an early end of the dialysis session. While for the long- whether present before or after maintenance dialysis
term, IDH could lead to cardiovascular complications, initiation, and compensatory mechanisms, could trigger
more hospitalization, and all-cause mortality [4,5]. The the cardiac remodeling process. Furthermore, cardiac
possible mechanisms of IDH are excessive and rapid remodeling could contribute to hemodynamic instabil-
ultrafiltration and loss of cardiac compensatory ity. Over ultrafiltration leads to hemodynamic instability

CONTACT Jianzhou Zou [email protected]; Xiaoqiang Ding [email protected] Division of Nephrology, Zhongshan
Hospital, Shanghai Medical College, Fudan University, Shanghai 200032, P. R. China
Supplemental data for this article can be accessed here.
ß 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 RENAL FAILURE 41

as well. So cardiac remodeling and excessive ultrafiltra- Date collection and biochemical measurements
tion might be important determinants to IDH.
Patients’ attending physicians extracted information
However, the relationship between IDH and cardiac
like demographic data, comorbidity, biochemistry, and
remodeling has not yet been deeply explored. We pre-
antihypertensive drugs, from charts at the beginning of
sume that ultrafiltration rate (UFR), IDH, and cardiac
the recruitment period and the end of the study. In the
remodeling might have interaction. Our study aimed to
morning of 8–10 midweek non-dialysis day, blood sam-
assess the associations between UFR, IDH, and cardiac
structural/functional alterations among maintenance ples were taken after 30 min of rest in the semi- reclin-
hemodialysis (MHD) patients in long-term follow-up. ing position.

Materials and methods Endpoint events

Patients The primary objective was to identify the association
End-stage kidney disease patients who started HD between IDH and the alterations in cardiac structure
before January 2014 in blood purification center, and function. The second objective was to evaluate the
Zhongshan Hospital, Fudan University, Shanghai, China, effect of UFR on cardiac structural and functional
were enrolled. Inclusion criteria were: ‹ Patients older alterations.
than eighteen, › undergoing dialysis three times a The alterations in cardiac structure and function
week, fi without cardiac dysfunction, fl on HD for were measured by echocardiography. An echocardio-
more than three months with acceptable dialysis effi- graphic machine (Philips IE33, Eindhoven, The
ciency. They were followed until 31 December 2019. Netherlands) with a 3.5-MHz multiphase array probe by
Dry weight was monitored and reevaluated every a single experienced cardiologist was used during a
month by designated physicians according to physical midweek non-dialysis day, and transthoracic echocar-
examinational findings, and NT-proBNP measured diographic examinations were conducted within two
monthly [9–11], to achieve an edema-free state. hours after blood sampling. The echocardiography was
done both at the run-in period and the end of the five-
IDH definition and patient group year follow-up. Cardiac structure was measured at the
end- diastolic phase according to the recommendations
Epidemiologic studies about IDH with outcomes are
of the Penn Convention. The left ventricular ejection
based merely on BP values [1]. But the IDH definition of
fraction (LVEF), used to evaluate the cardiac function,
nadir BP might exclude the effects of patients’ predialy-
was determined by two-dimensional echocardiography.
sis BP and volume status, which are the risk factors of
The left atrium diameter index (LADI) was calculated by
IDH and very important to patients’ prognosis. So, the
dividing the left atrium diastolic diameter (LADD) by
definition of IDH we used in our study was defined as a
body surface area (BSA). The Devereux formula was
sudden drop in systolic BP more than 20 mmHg or
used to calculate the LV mass. Left ventricular mass
mean artery pressure (MAP) more than 10 mmHg asso-
index (LVMI) was obtained by dividing LV mass by
ciated with clinical events and the need for interven-
height in meters rose to the power of 2.7. Left ventricu-
tions [2,3]. The intervention of IDH depends on the
rapid identification and intervention of nurses. Typical lar hypertrophy (LVH) was defined as LV mass/height2.7
interventions include repositioning the patient to  47 g/m2.7 in women and  50/m2.7 in men. LVMI vari-
improve hemoperfusion of vital organs (supine or ation was defined as the absolute percentage differ-
Trendelenburg posture), cessation of ultrafiltration, and ence of LVMI between the baseline and the end of the
fluid resuscitation with isotonic, hypertonic, or glucose study. The variation of LVMI over 50% was considered
solutions, and adjust dialysate temperature, as well as significant in the clinical base. Relative wall thickness
cessation of dialysis [12,13]. Blood pressures (BPs) were (RWT) was calculated as two  posterior wall thickness/
the average values of all the BPs taken hourly intradialy- LV internal linear dimension in diastole. Based on the
sis during the three-month recruitment phase. LVMI and RWT measurements [18], four geometric pat-
Patients who suffered from more than four hypoten- terns were described: ‹ normal (normal LVMI and nor-
sive events in three months (10% of HD treatments) mal RWT), › concentric remodeling (normal LVMI and
were defined as the IDH group [1,5,14,15]. Moreover, increased RWT), fi eccentric hypertrophy (abnormally
subgroups were defined according to the normalized increased LVMI and normal RWT), fl concentric hyper-
ultrafiltration rate of 10 mL/h/kg [15–17]. trophy (abnormally increased LVMI and increased RWT).
42 J. YU ET AL.

Statistical analysis cardiac structure (LADI; RWT; LVMI) and cardiac function
(LVEF) both at the beginning and the end of the study
Continuous variables were presented as mean ±
in different subgroups. We used univariate and multi-
Standard Deviation, while categorical variables were
variate logistic regression models to explore the inter-
expressed as numbers and percentages appropriately.
action between UFR and IDH on LVMI variation.
Student’s t-test was used to compare normal variables,
Covariates with p-values less than .05 in the univariate
whereas for categorical variables, chi-square tests were
analysis were included in the multivariate models. All
performed, respectively. Survival probability and
calculations were performed using SPSS version 24
median survival time are used to illustrate mortality in
(SPSS Inc., Chicago, IL). p < .05 was considered statistic-
IDH and no-IDH groups. The predictive effect of ultrafil-
ally significant.
tration on the onset of IDH was analyzed using univari-
ate and multivariate logistic regression models. A series
of models were conducted: (1) Model 1: adjusted for Results
demographic data (age, sex, and body mass index); (2)
Patient characteristics and the incidence of IDH
Model 2: adjusted for model 1 þ dialysis information
(interdialytic weight gain, residual renal function, dialy- A total of 209 patients (118 males and 91 females) with
sis vintage and single-pool Kt/V); (3) Model 3: adjusted an average age of 52.92 ± 18.68 (18–75) years were col-
for model 2 þ comorbid conditions (history of primary lected. 96 cases of IDH ( 4 hypotension events/
hypertension, coronary heart disease, and diabetes); (4) 3 months) and 113 cases without IDH (< 4 hypotension
Model 4: adjusted for model 3 þ biochemical data events/3 months). Table 1 showed demographic, clin-
(serum albumin, pre-albumin, creatinine and hemoglo- ical, and biochemical variables. IDH-prone patients were
bin); (5) Model 5: adjusted for model 4 þ cardiac condi- older, had higher BMI, interdialytic weight gain (IDWG)
tions (NT- proBNP, LV mass index, LVEF, and left atrium and ultrafiltration rate, lower predialysis and post-
diameter index); (6) Model 6: adjusted for model 5þ dialysis BP (p < .05). Compared with those with no-IDH,
predialysis BP (predialysis systolic BP and diastolic BP). there were more female patients and fewer patients
Paired t-test was used to evaluate the cardiac alteration with preserved residual kidney function in IDH group

Table 1. Demographic, clinical and biochemical data of the patients.

Characteristics Total (n ¼ 209) no-IDH (n ¼ 113) IDH (n ¼ 96) p value
Age, years 56.06 ± 13.87 52.63 ± 13.42 60.29 ± 13.31 <.001
Male 118 (60.2%) 81 (71.7%) 37 (44.6%) <.001
Normalized ultrafiltration rate, ml/h/kg 10.69 ± 4.14 9.65 ± 4.33 11.97 ± 3.50 <.001
IDWG, kg 3.85 ± 1.58 3.43 ± 1.65 4.35 ± 1.33 <.001
Preserved residual kidney function 41 (20.9%) 35 (31%) 6 (7.2%) <.001
Duration of dialysis, months 30.57 ± 38.25 30.69 ± 41.11 30.41 ± 34.20 .953
Dry weight, kg 58.67 ± 10.81 59.44 ± 10.16 57.73 ± 11.56 .259
spKt/Vurea 1.53 ± 0.63 1.57 ± 0.71 1.48 ± 0.53 .405
BMI, kg/m2 22.32 ± 4.01 21.67 ± 3.68 23.20 ± 4.29 .008
Serum albumin, g/L 39.14 ± 3.54 38.90 ± 3.78 39.42 ± 3.25 .342
Serum creatinine, lmol/L 995.30 ± 286.09 974.28 ± 298.93 1022.81 ± 267.71 .251
Hemoglobin, g/L 102 ± 25.24 99.28 ± 29.06 105.70 ± 18.39 .745
NT-proBNP, pg/mL 5051.94 ± 5472.11 4660.82 ± 5266.30 5547.72 ± 5721.52 .309
iPTH, ng/L 435.05 ± 462.15 393.52 ± 375.44 486.04 ± 548.57 .187
Serum b2MG, mg/L 29.36 ± 12.59 30.58 ± 11.96 27.88 ± 13.24 .176
hs CRP, mg/L 7.15 ± 12.26 7.62 ± 13.22 6.62 ± 11.15 .590
Predialysis-SBP, mmHg 136.63 ± 17.67 139.27 ± 13.19 133.52 ± 21.46 .019
Predialysis-DBP, mmHg 82.44 ± 10.81 84.47 ± 9.21 80.06 ± 12.05 .003
Postdialysis-SBP, mmHg 125.46 ± 19.26 133.3 ± 15.9 116.14 ± 18.81 <.001
Postdialysis-DBP, mmHg 78.45 ± 10.44 82.46 ± 8.37 73.68 ± 10.69 <.001
EF, % 63.18 ± 9.25 63.22 ± 7.69 63.13 ± 11.47 .962
LADI, mm/m2 24.91 ± 4.17 24.55 ± 4.32 25.49 ± 3.91 .238
RWT 0.46 ± 0.12 0.44 ± 0.80 0.49 ± 0.16 .057
LVMI, g/m2.7 47.33 ± 18.62 47.67 ± 16.07 46.92 ± 21.38 .798
Antihypertensive medication dosage, tablets 2.39 ± 1.80 2.32 ± 1.80 2.54 ± 1.84 .612
Antihypertensive medication type 1.98 ± 1.34 1.95 ± 1.34 2.04 ± 1.34 .778
Hypertension 129 (65.8%) 75 (66.4%) 54 (65.1%) .849
Diabetes mellitus 31 (15.8%) 15 (13.3%) 16 (19.3%) .257
Cardiovascular disease 18 (9.2%) 12 (10.6%) 6 (7.2%) .419
Cerebrovascular disease 3 (1.5%) 1 (0.9%) 2 (2.4%) .393
Values are mean (SD) for continuous variables and % (n) for categorical variables.
IDWG: interdialytic weight gain; BMI: body mass index; NT-proBNP: N-terminal pro-B-type natriuretic peptide; iPTH: intact parathyroid hormone; b2MG: b2-
microglobulin; hs-CRP: high-sensitive c-reactive protein; EF: ejection fraction; LADI: left atrium diameter index; RWT: relative wall thickness; LVMI: left ven-
tricular mass index; Preserved residual kidney function: 24 h urine output over 100 mL.
 RENAL FAILURE 43

(p < .01). There were no significant differences found in (serum albumin, pre-albumin, creatinine and hemoglo-
both the dosage and types of antihypertensive medica- bin), cardiac conditions (NT- proBNP, LV mass index,
tions, as well as comorbidities (e.g., cardiovascular dis- LVEF, and left atrium diameter index), and predialysis
ease and diabetes) between the two groups (p > .05). BP (predialysis systolic BP and diastolic BP), UFR was still
a predictor for IDH (p < .05) (Table 2).
IDH and prognosis
IDH and cardiac structural/functional alterations
Among 209 patients, 12 (5.7%) were excluded due to
kidney transplantation and transfer to other HD centers We compared cardiac structure and function at the
during the five-year observation period. The mortality recruitment time with those at the end of the 5-year
rate was 5.1/100-person-year, including 15 cardiovascu- study by echocardiography. In the IDH group, longer LV
lar events, 13 cerebrovascular events, nine severe infec- end-diastolic diameter, decreased LVEF, larger LADI as
tion deaths, eight sudden deaths, and five cancer well as larger LVMI (p < .05, p < .01) were observed at
deaths. The survival rate of IDH patients was lower than the end of the follow-up than at the recruitment time
that of patients with no-IDH (shown in Figure 1: 65.5% (Table 3). However, similar results were not found in the
vs. 81.4%, p ¼ .005). no-IDH group.

UFR and IDH Interactions between UFR and IDH on

cardiac remodeling
We constructed a series of logistic regression models to
test the predictive effects of UFR on the onset of IDH. As UFR is a risk factor of IDH, they might have inter-
After adjusting for confounding factors like demo- active effects on LVMI variation. We presumed that UFR
graphic data (age, sex, and body mass index), dialysis might have different prognostic effects on LVMI vari-
information (interdialytic weight gain, residual renal ation in IDH and no-IDH groups. We divided all of the
function, dialysis vintage and single-pool Kt/V), comor- patients into two groups according to LVMI variations
bid conditions (history of primary hypertension, coron- of 50% and constructed logistic regression models to
ary heart disease, and diabetes), biochemical data test the interaction effects of UFR and IDH on LVMI

Figure 1. Kaplan–Meier survival curves of patients with IDH and no-IDH.

44 J. YU ET AL.

variations. Crude model 1 showed that the interaction Furthermore, we divided IDH-prone patients into
of IDH and UFR had a significant association with LVMI two groups according to UFR 10 mL/h/kg [15–17]. We
variation (p ¼ .010) (Table 4). Subgroup analysis showed compared cardiac structure and function at the recruit-
that in IDH group, UFR was an independent risk factor ment time with those at the end of the study in both
of LVMI variation (OR ¼ 1.26, 95%CI 1.05–1.50), while in IDH-prone groups. During the 5-year follow-up, in the
the no-IDH group, such result was not found high-UFR group, longer aortic root inside diameter, LV
(OR ¼ 0.95, 95%CI 0.84–1.07). Besides, we created a end-diastolic diameter, LV end-systolic dimension, and
multivariate logistic regression model consisting of decreased EF, large LADI, as well as larger LVMI (p < .05)
demographic data (age, gender, and BMI) and cardiac were observed at the end of the follow-up. While there
conditions (cardiac comorbidity and ejection fraction), were no significant alterations in cardiac structure and
the interaction between UFR and IDH was notably asso- function in the low-UFR group throughout the study. In
ciated with LVMI variation (p ¼ .014). After adjusting the no-IDH group, no significant alterations were
these covariates in subgroups, UFR was still an inde- observed in cardiac structure and function with differ-
pendent risk factor of LVMI variation (OR ¼ 1.52, 95%CI ent levels of UFR (Table 5). For patients without primary
1.17–1.98) in the IDH group, while there were no such cardiac disease, abnormally increased LVMI, RWT and
findings (OR ¼ 0.95, 95%CI 0.81–1.10) in the no-
LADI were found in IDH patients. Similar results were
IDH group.
found in IDH patients with high-UFR (Supplemental
data). High ultrafiltration rate induced IDH is a deter-
Table 2. Logistic regression models of UFR on IDH. minant of cardiac remodeling.
Model HR 95%CI p value
Ultrafiltration (continuous variable, per 1ml/h/kg increase) Discussion
Unadjusted 1.16 1.08–1.26 <.001
Model 1 1.24 1.12–1.39 <.001 In order to explore the interactive effect of UFR and
Model 2 1.20 1.03–1.40 .017
Model 3 1.20 1.04–1.40 .016 IDH on cardiac remodeling, we conducted this retro-
Model 4 1.22 1.00–1.47 .042 spective cohort study. We found that the interaction
Model 5 1.65 1.05–2.61 .031
Model 6 2.37 1.21–4.62 .012 between UFR and IDH could predict cardiac remodeling
UFR: ultrafiltration rate; IDH: intradialytic-hypotension. in long-term follow-up. This finding was independent
Model 1: adjusted for demographic data (age, sex, and body mass index).
Model 2: adjusted for Model 1 þ dialysis information (interdialytic weight
of confounding risk factors. Furthermore, we found that
gain, residual renal function, dialysis vintage and single-pool Kt/V). for IDH-prone patients, high UFR would lead to cardiac
Model 3: adjusted for Model 2 þ comorbid conditions (history of primary
hypertension, coronary heart disease, and diabetes).
remodeling in long-term follow-up.
Model 4: adjusted for Model 3 þ biochemical data (serum albumin, pre- Cardiac remodeling found at the initiation of dialysis
albumin, creatinine and hemoglobin). may cause hemodynamic instability. In addition, the
Model 5: adjusted for Model 4 þ cardiac conditions (NT- proBNP, left ven-
tricular mass index, left ventricular ejection fraction, and left atrium diam- sequelae of cardiac remodeling may be a positive factor
eter index). of dialysis complications, especially IDH [19]. To some
Model 6: adjusted for Model 5þ predialysis blood pressure (predialysis
systolic blood pressure and diastolic blood pressure). extent, LVH lays the foundation for IDH occurrence
through LV stiffening [20] as well as myoischemia and

Table 3. IDH and cardiac structural/ functional alterations.

Total no-IDH IDH
Mean ± SD Mean ± SD Mean ± SD
Echocardiography recruitment end of recruitment end of recruitment end of
parameters period the study p value period the study p value period the study p value
AORD, mm 32.71 ± 3.27 33.61 ± 5.07 .119 33.66 ± 3.37 34.36 ± 3.79 .271 31.45 ± 2.69 32.62 ± 6.30 .272
LAD, mm 39.95 ± 5.44 40.59 ± 7.61 .516 40.30 ± 6.39 41.27 ± 6.96 .446 39.48 ± 3.87 39.69 ± 8.40 .894
LVDD, mm 46.00 ± 6.52 50.37 ± 7.14 <.001 47.26 ± 5.94 50.59 ± 7.51 .013 44.30 ± 6.95 50.07 ± 6.68 .001
LVDS, mm 30.29 ± 5.38 31.36 ± 6.84 .256 31.20 ± 5.99 31.45 ± 6.00 .843 29.05 ± 4.19 31.24 ± 7.92 .127
IVST, mm 10.71 ± 1.83 11.00 ± 2.64 .376 10.72 ± 1.92 10.74 ± 2.06 .962 10.70 ± 1.74 11.35 ± 3.26 .272
LVPWT, mm 9.96 ± 1.51 10.53 ± 1.87 .018 9.98 ± 1.58 10.41 ± 1.71 .143 9.93 ± 1.42 10.70 ± 2.09 .062
LVEF, % 65.95 ± 7.41 63.89 ± 6.45 .068 65.47 ± 7.81 64.00 ± 6.82 .336 67.39 ± 5.72 63.55 ± 5.88 .010
LADI, mm/m2 24.53 ± 4.10 25.38 ± 4.70 .135 24.64 ± 4.13 24.26 ± 4.43 .623 24.74 ± 3.58 26.40 ± 5.32 .015
RWT 0.43 ± 0.09 0.45 ± 0.08 .128 0.43 ± 0.09 0.44 ± 0.08 .312 0.44 ± 0.10 0.47 ± 0.09 .257
LVMI, g/m2.7 45.21 ± 11.77 53.15 ± 19.89 .001 45.50 ± 11.88 49.28 ± 16.86 .173 44.77 ± 11.74 58.96 ± 22.75 <.001
Values are mean (SD) for continuous variables.
AoRD: aortic root inside diameter; LAD: left atrium diameter; LVDD: left ventricular end-diastolic diameter; LVDS: left ventricular end-systolic dimension;
IVST: interventricular septal thickness; LVPWT: left ventricular posterior wall thickness; LVEF: left ventricular ejection fraction; LADI: left atrium diameter
index; RWT: relative wall thickness; LVMI: left ventricular mass index.
 RENAL FAILURE 45

Table 4. Interactions between UFR and IDH on

LVEF: left ventricular ejection fraction; LADI: left atrium diameter index; RWT: relative wall thickness; LVMI: left ventricular mass index; AoRD: aortic root inside diameter; LAD: left atrium diameter; LVDD: left ven-
p-value
.135
.219
.034
.476

.001
.469
.398
.285
.063
.02
LVMI variation.
OR p value
Crude model 1 IDH 0.10 (0.01  1.32) .080

50.99 ± 15.09
34.94 ± 2.79
41.22 ± 6.19
50.30 ± 6.44
31.59 ± 5.06
11.06 ± 1.98
10.79 ± 1.67
64.64 ± 6.80
24.26 ± 3.72
0.44 ± 0.09
(0.84  1.07)

the study
UFR, ml/h/kg 0.95 .364

end of
IDH  UFR, ml/h/kg 1.33 (1.07  1.65) .010

Low-UFR
Adjusted model 2 IDH 0.07 (0.00  1.28) .072
UFR, ml/h/kg 0.99 (0.85  1.15) .875

Mean ± SD
IDH  UFR, ml/h/kg 1.37 (1.07  1.77) .014
IDH: intradialytic hypotension; UFR: ultrafiltration rate; LVMI: left ventricu-

45.16 ± 11.97
recruitment

33.75 ± 3.94
39.44 ± 5.34
47.15 ± 5.42
30.63 ± 5.18
10.15 ± 1.56
9.58 ± 1.23
65.82 ± 6.18
23.55 ± 3.62
0.42 ± 0.05
lar mass index model 2: adjusted for age, gender, body mass index, car-

period
diovascular comorbidity (coronary heart disease and arrhythmia),
ejection fraction.

no-IDH group
arrhythmia [21]. However, few researchers have

p-value
explored IDH and its effect on cardiac remodeling. In

.968
.956
.152
.764
.068
.206

.958
.027
.849
.52

tricular end-diastolic diameter; LVDS: left ventricular end-systolic dimension; IVST: interventricular septal thickness; LVPWT: left ventricular posterior wall thickness.
this study, we focused on the potential contribution of
IDH to the development of cardiac remodeling.

46.93 ± 19.11
It is commonly recognized that the process of HD

33.58 ± 4.77
41.33 ± 8.02
50.96 ± 8.86
31.25 ± 7.18
10.32 ± 2.12
9.92 ± 1.66
63.16 ± 6.90
25.22 ± 5.27
0.47 ± 0.09
the study
end of
itself causes myocardial ischemia. IDH refers to intradia-

High-UFR
lytic hemodynamic instability, linked to episodic myo-

Mean ± SD
cardial stunning [22,23]. Repeated cardiac ischemia can
result in myocardial hypertrophy and fibrosis, reduce

45.96 ± 12.00
recruitment

33.54 ± 2.48
41.46 ± 7.53
47.40 ± 6.68
31.96 ± 6.96
11.48 ± 2.10
10.52 ± 1.85
65.00 ± 9.66
25.14 ± 4.66
0.41 ± 0.09
the response to filling pressure, and increase the risk of

period
hemodynamic compromise. Endothelial dysfunction,
impaired calcium regulation, and reperfusion after IDH
(the production of free radicals in the myocardium)

p-value
bring about this phenomenon [24]. Myocardial stunning

.453
.338
.575
.825
.700
.426
.667
.978
.659
.889
may cause LV dysfunction and structure alteration, lead-
ing to heart failure. In our study, we found no signifi-
29.89 ± 11.84
34.44 ± 13.31

27.78 ± 11.72

41.30 ± 11.89
cant difference of LVEF in both groups of patients at
47.00 ± 5.92

10.78 ± 2.39
10.56 ± 2.60
64.38 ± 4.81
24.36 ± 4.54
0.49 ± 0.11
the study
end of
Low-UFR

baseline, while decreased LVEF was observed in the IDH

group in long-term follow-up (p ¼ .010). Repetitive
Mean ± SD

ischemia episodes are cumulative, contributing to car-

Table 5. UFR and cardiac structural/ functional alterations in both groups.

diac fibrosis and cardiac hypertrophy, causing systolic

44.44 ± 10.08

40.62 ± 14.16
recruitment

33.11 ± 2.76
40.11 ± 4.62

28.78 ± 6.96
11.11 ± 1.54
9.67 ± 1.66
65.25 ± 5.09
24.35 ± 3.75
0.46 ± 0.10
period

LV dysfunction and LVH. So IDH could cause cardiac

dysfunction in the long term.
IDH group

Intermittent volume retention caused by IDH makes

patients suffer from chronic volume overload and,
p-value
.001
.167
<.001
.027
.205
.098
.010
.040
.283
<.001

eventually leads to myocardial remodeling. When BP

drops, LV diastolic function is crucial to sustain
adequate cardiac filling. LVH and significant diastolic
63.67 ± 22.75
33.36 ± 3.62
41.12 ± 6.03
50.88 ± 6.71
32.22 ± 6.41
11.50 ± 3.47
10.74 ± 1.97
63.28 ± 6.26
27.50 ± 5.43
0.46 ± 0.08
the study

dysfunction are common in HD patients, and they bear

end of
High-UFR

the burden of decreased myocardial compliance sec-

Values are mean (SD) for continuous variables.

ondary to increased fibrosis. The resulting increase in

Mean ± SD

LV stiffness resists chamber filling. In this case, the LV

45.87 ± 11.03

volume filling pressure curve is steep, and the rapid

recruitment

31.00 ± 2.52
39.30 ± 3.70
44.26 ± 6.07
29.13 ± 3.18
10.59 ± 1.79
10.00 ± 1.37
68.08 ± 5.84
25.28 ± 3.76
0.43 ± 0.10
period

reduction of LV volume will lead to a low output state,

such as IDH. The left atrium (LA) is considered to main-
tain LV diastole pressures, so LA structures and func-
tions are often marked as indirect indicators for
Echocardiography

diastolic function [25]. The left atrium dimension index

LADI, mm/m2

LVMI, g/m2.7
LVPWT, mm
parameters
AORD, mm

LVDD, mm

(LADI) is suggested to be used to evaluate the LV dia-

LVDS, mm
IVST, mm
LAD, mm

stolic function [26]. Previous studies [27,28] revealed

EF, %

RWT

that left atrium enlargement could predict IDH.

46 J. YU ET AL.

Volume-dependent (preload) factors, such as salt and This study comprehensively assesses the risk factors
volume overload, lead to cardiomyocyte lengthening (including UFR and IDH) for cardiac remodeling in MHD
and eccentric remodeling. Stress-dependent (afterload) patients. We firstly testified the contribution of IDH to
factors such as aortic stiffness and hypertension predis- cardiac remodeling in the clinical base. Another is the
position toward cell thickening and concentric remodel- consideration of ultrafiltration, which is relevant both to
ing. On the contrary, those with eccentric hypertrophy IDH and cardiac remodeling. Furthermore, we have a
are accompanied by coronary artery diseases, leading long-term follow-up period.
to LV dilatation and systolic dysfunction in the long- However, our study has several limitations. First, the
term [29]. Eccentric LV hypertrophy is related to mean sample size was rather small. The results might not be
peripheral resistance, but a high cardiac index is con- validated in other populations. Nevertheless, patients of
sistent with excessive circulating blood volume [18]. So the study were free of cardiac dysfunction, and we did
LVH sets the background for IDH development. In our not have enough information on diastolic function (e.g.,
study, LADI and LVMI were used to evaluate left atrial e/e’ or E/A). Further research might target whether our
enlargement and LVH. We found that the frequent study results could be testified in MHD patients with
onset of IDH might predict cardiac remodeling, includ- various comorbidities. An additional limitation is that
ing LA dilatation, eccentric LV hypertrophy, and LVH, in the effect of varied vascular accesses on hemodynamic
long-term follow-up. stability was not assessed. Fourth, we did not use
IDH occurs when dialysis ultrafiltration exceeds the objective methods (e.g., bio-impedance) to assess fluid
plasma reperfusion rate of standard physiologic com- status, which is more objective and accurate to deter-
pensatory mechanisms. UFR and total volume removal mine volume status. The last important limitation is
are risk factors of IDH [13,14]. Nevertheless, we also that we did not have information about specific inter-
found that UFR was an independent risk factor for IDH ventions and adjustments of antihypertensive medica-
in a series of models. Studies suggested that UFR tions (e.g., angiotensin converting enzyme inhibitors
>10 mL/h/kg was related to a higher risk of mortality and b-receptor blockers) that may confound and mod-
and a higher risk of IDH [16,17,30]. So, we use UFR ify our associations.
10 mL/h/kg to evaluate the impact of different volume
status on cardiac alterations. We found that in the IDH
group with high UFR, decreased LVEF, larger LADI, and Conclusions
LVMI were shown at the end of the study. So high UFR
would cause cardiac remodeling only in IDH- IDH and myocardial remodeling, especially LVH, are
prone patients. closely related to each other. On the one hand, LVH is
IDH might cause coronary hypoperfusion, myocardial an important determinant and etiology of IDH, because
stunning [22], and RAAS dysregulation [31–33], contri- LVH paves the way for the frequent occurrence of IDH,
buting to LVH. This study divided all of the patients and actively promotes the BP drop during dialysis
into two groups according to the LVMI variation of 50% through mechanisms including arrhythmia and myocar-
and constructed logistic regression models to test the dial ischemia. On the other hand, IDH might predict car-
interaction effects of UFR and IDH on LVMI variations. diac remodeling due to long-term over-ultrafiltration.
Both univariate and multivariate regression models sug- Excessive ultrafiltration might not induce cardiac
gested that the interaction between UFR and IDH was remodeling in patients with better compensatory
notably associated with LVMI variation. Subgroup ana- mechanisms. However, over ultrafiltration for IDH-prone
lysis showed that after adjusting for the demographic patients causes decreased cardiac output in the long-
data (age, gender, and BMI) and cardiac conditions (car- term, contributing to cardiac dysfunction and remodel-
diac comorbidity and ejection fraction), UFR was still an ing. Strategies, including proper ultrafiltration setting,
independent risk factor of variation of LVMI (OR ¼ 1.52) should be taken to maintain hemodynamic stability,
in the IDH group. At the same time, there were no such especially in IDH-prone patients.
findings (OR ¼ 0.95) in the no-IDH group. Thus, we pre-
sume that long-term over ultrafiltration for some of the
IDH-prone patients infers cardiac overload, leading to Acknowledgements
cardiac dysfunction and LVH in long-term follow-up. The authors are grateful to all participating patients and dia-
IDH and over ultrafiltration might have a synergistic lysis staff of Blood Purification Center, Division of
effect on cardiac remodeling. Nephrology, Zhongshan Hospital, Fudan University.
 RENAL FAILURE 47

Disclosure statement [11] Agarwal R, Andersen MJ, Pratt JH. On the importance
of pedal edema in hemodialysis patients. Clin J Am
None of the authors has any competing interests to declare, Soc Nephrol. 2008;3(1):153–158.
financial or otherwise. [12] Assimon MM, Flythe JE. Intradialytic blood pressure
abnormalities: the highs, the lows and all that lies
between. Am J Nephrol. 2015;42(5):337–350.
Ethical statement [13] Sands JJ, Usvyat LA, Sullivan T, et al. Intradialytic hypo-
All procedures performed in studies involving human partici- tension: frequency, sources of variation and correlation
pants were in accordance with the ethical standards of with clinical outcome. Hemodial Int. 2014;18(2):415–422.
Zhongshan Hospital, Fudan University, at which the studies [14] Tisler A, Akocsi K, Borbas B, et al. The effect of fre-
were conducted (IRB approval number B2013-139) and with quent or occasional dialysis-associated hypotension
the 1964 Helsinki declaration and its later amendments or on survival of patients on maintenance haemodialysis.
comparable ethical standards. Each participant signed an Nephrol Dial Transplant. 2003;18(12):2601–2605.
informed consent form before entering the study. [15] Chou JA, Streja E, Nguyen DV, et al. Intradialytic hypo-
tension, blood pressure changes and mortality risk in
incident hemodialysis patients. Nephrol Dial
Funding Transplant. 2018;33(1):149–159.
[16] Flythe JE, Kimmel SE, Brunelli SM. Rapid fluid removal
This study is supported by the National Natural Science during dialysis is associated with cardiovascular mor-
Foundation of China [Grant No.81903969], the Youth bidity and mortality. Kidney Int. 2011;79(2):250–257.
Foundation of Zhongshan Hospital [Grant No.2019ZSQN22], [17] Mactier R, Nic H, Breen C. Renal association clinical
Shanghai “science and technology innovation plan” technical practice guideline on haemodialysis. Nephron Clin
standard project [No. 19DZ2205600], as well as by the Pract. 2011;118(s1):c241–86.
Natural Science Foundation of China [No.81800677]. [18] Lang RM, Bierig M, Devereux RB, European Association
of Echocardiography, et al. Recommendations for cham-
ber quantification: a report from the American Society
References of Echocardiography’s Guidelines and Standards
[1] Flythe JE, Xue H, Lynch KE, et al. Association of mor- Committee and the Chamber Quantification Writing
tality risk with various definitions of intradialytic hypo- Group, developed in conjunction with the European
tension. JASN. 2015;26(3):724–734. Association of Echocardiography, a branch of the
[2] National Kidney Foundation: KDOQI clinical practice European Society of Cardiology. J Am Soc Echocardiogr.
guidelines on hypertension and antihypertensive 2005;18(12):1440–1463.
agents in chronic kidney disease. 2012. Available [19] Chao C-T, Huang J-W, Yen C-J. Intradialytic hypoten-
from: http://www.kidney.org/professionals/kdoqi/ sion and cardiac remodeling: a vicious cycle. Biomed
guidelines_bp. Res Int. 2015;2015(undefined):724147.
[3] Kooman J, Basci A, Pizzarelli F, et al. EBPG guideline [20] Shah Anoop SV, Chin Calvin WL, Vassiliou V, et al. Left
on haemodynamic instability. Nephrol Dial Transplant. ventricular hypertrophy with strain and aortic stenosis.
2007; 22(Supplement 2):ii22–44. Circulation. 2014;130(18):1607–1616.
[4] Inrig JK, Oddone EZ, Hasselblad V, et al. Association of [21] Kozhevnikov D, Caref Edward B, El-Sherif N.
intradialytic blood pressure changes with hospitaliza- Mechanisms of enhanced arrhythmogenicity of
tion and mortality rates in prevalent ESRD patients. regional ischemia in the hypertrophied heart. Heart
Kidney Int. 2007;71(5):454–461. Rhythm. 2009;6(4):522–527.
[5] Yu J, Liu Z, Shen B, et al. Intradialytic hypotension as [22] Burton JO, Jefferies HJ, Selby NM, et al. Hemodialysis-
an independent risk factor for long-term mortality in induced cardiac injury: determinants and associated
maintaining hemodialysis patients: a 5-year follow-up outcomes. CJASN. 2009;4(5):914–920.
cohort study. Blood Purif. 2018;45(4):320–326. [23] Burton JO, Jefferies HJ, Selby NM, et al. Hemodialysis-
[6] Foley RN, Parfrey PS, Harnett JD, et al. Clinical and induced repetitive myocardial injury results in global
echocardiographic disease in patients starting end- and segmental reduction in systolic cardiac function.
stage renal disease therapy. Kidney Int. 1995;47(1): CJASN. 2009;4(12):1925–1931.
186–192. [24] Zuidema MY, Dellsperger KC. Myocardial stunning
[7] Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology with hemodialysis: clinical challenges of the cardiore-
of cardiovascular disease in chronic renal disease. Am nal patient. Cardiorenal Med. 2012;2(2):125–133.
J Kidney Dis. 1998;32(5 Suppl 3):S112–S9. [25] Miyoshi H, Oishi Y, Mizuguchi Y, et al. Early predictors
[8] Glassock RJ, Pecoits-Filho R, Barberato SH. Left ven- of alterations in left atrial structure and function
tricular mass in chronic kidney disease and ESRD. related to left ventricular dysfunction in asymptomatic
CJASN. 2009;4(Supplement 1):S79–S91. patients with hypertension. J Am Soc Hypertens.
[9] National Kidney F. KDOQI Clinical Practice Guideline 2013;7(3):206–215.
for Hemodialysis Adequacy: 2015 update. Am J Kidney [26] Tsang Teresa SM, Barnes Marion E, Gersh Bernard J,
Diseases. 2015;66(5):884–930. et al. Left atrial volume as a morphophysiologic
[10] Frank Peacock W, Soto KM. Current technique of fluid expression of left ventricular diastolic dysfunction and
status assessment. Congest Heart Fail. 2010;16 Suppl relation to cardiovascular risk burden. Am J Cardiol.
1 (Suppl 1):S45–S51. 2002;90(12):1284–1289.
48 J. YU ET AL.

[27] Barberato SH, Misocami M, Pecoits-Filho R. Association hemodialysis: associations with reduced mortality in
between left atrium enlargement and intradialytic the DOPPS. Kidney Int. 2006;69(7):1222–1228.
hypotension: role of diastolic dysfunction in the [31] Ritz E. Left ventricular hypertrophy in renal disease:
hemodynamic complications during hemodialysis. beyond preload and afterload. Kidney Int. 2009;75(8):
Echocardiography. 2009;26(7):767–771. 771–773.
[28] Tripepi G, Mattace-Raso F, Mallamaci F, et al. [32] Graziani G, Finazzi S, Mangiarotti R, et al. Different car-
Biomarkers of left atrial volume: a longitudinal study diovascular responses to hemodialysis-induced fluid
in patients with end stage renal disease. depletion and blood pressure compliance. J Nephrol.
Hypertension. 2009;54(4):818–824. 2010;23(1):55–61.
[29] Levy D, Larson MG, Vasan RS, et al. The progression [33] Schunkert H, Sadoshima J, Cornelius T, et al.
from hypertension to congestive heart failure. J Am Angiotensin II induced growth responses in isolated
Med Assoc. 1996;275(20):1557–1562. adult rat hearts: evidence for load-independent induc-
[30] Saran R, Bragg-Gresham JL, Levin NW, et al. Longer tion of cardiac protein synthesis by angiotensin II. Circ
treatment time and slower ultrafiltration in Res. 1995;76(3):489–497.