Effect of Early Initiation of Dialysis on Cardiac Structure and Function: Results From the Echo Substudy of the IDEAL Trial

doi:10.1053/j.ajkd.2012.09.008

American Journal of Kidney Diseases

Volume 61, Issue 2, February 2013, Pages 262-270

https://doi.org/10.1053/j.ajkd.2012.09.008 Get rights and content

Background

Abnormalities of cardiac structure and function are common in patients undergoing dialysis, and cardiovascular disease is the major cause of mortality in this group. Heart failure is a common clinical manifestation of cardiovascular disease and is preceded by left ventricular hypertrophy (LVH). There are variable reports about the impact of dialysis on LVH, both deleterious and beneficial. Our study investigated whether the timing of the initiation of dialysis therapy had an impact on cardiac structure and function.

Study Design

Randomized controlled trial.

Setting & Participants

This is a cardiac substudy involving 182 patients with stage 5 chronic kidney disease in the IDEAL (Initiating Dialysis Early and Late) trial.

Intervention

The IDEAL trial randomly assigned patients on the basis of estimated glomerular filtration rate (eGFR), calculated using the Cockcroft-Gault equation, to start dialysis therapy early (GFR, 10-14 mL/min/1.73 m²), with the others starting late (GFR, 5-7 mL/min/1.73 m²).

Outcomes & Measurements

Echocardiograms were obtained at baseline and 12 months after randomization. Primary outcomes were change in left ventricular mass indexed for height (LVMi) between baseline and 12 months, left ventricular ejection fraction, left ventricular systolic annular velocity, ratio of mitral inflow velocity (E) to mitral annular velocity (Ea) (E/Ea), and left atrial volume indexed for height (LAVi).

Results

LVMi at baseline was elevated, but similar in both groups, with no significant change within or between groups at 12 months. E/Ea and LAVi were increased at baseline, consistent with significant diastolic dysfunction; there were no differences between groups at 12 months and no changes were observed for left ventricular volumes, left ventricular ejection fraction, stroke volume, and other echocardiographic parameters.

Limitations

Small multicenter study using echocardiography.

Conclusions

Advanced cardiac disease in these patients with stage 5 chronic kidney disease did not progress during the 12-month study period and planned early initiation of dialysis therapy did not result in differences in any echocardiographic variables of cardiac structure and function.

Section snippets

Study Design

This is a substudy of the IDEAL study, a randomized clinical trial that has been described previously.¹¹ Briefly, 32 centers in Australia and New Zealand recruited patients with progressive CKD and estimated glomerular filtration rate (eGFR) of 10-15 mL/min/1.73 m², which was determined using the Cockcroft-Gault equation and corrected for body surface area. The main IDEAL trial randomly assigned 828 adult patients to 2 groups: early or late initiation of renal dialysis therapy, with a median

Patient Characteristics

A total of 182 patients (21.9% of all randomly assigned IDEAL patients) consented to participate in the substudy between July 2002 and November 2008 and were followed up until November 2009. These patients were not different from those enrolled in the main IDEAL trial (Table 1) and represent on average 46% (range, 10%-80%) of all patients randomly assigned at those sites. Patients were recruited and randomly assigned as part of the main IDEAL study to receive either early- (n=91) or late-start

Discussion

Cardiovascular disease is a major cause of death in patients with CKD¹ and heart failure is one of the major contributors to this disease burden. The IDEAL trial¹² showed that early initiation of dialysis therapy (HD or PD) in patients with advanced CKD had no significant effect on all-cause mortality or cardiovascular events. The present study extends these findings by showing that planned early initiation of dialysis therapy did not result in differences in any echocardiographic variables of

Acknowledgements

A list of the IDEAL Echo Substudy Investigators follows. Echocardiography substudy principal investigators: J. Collins, B. Cooper, R.N. Doughty, T. Marwick, and G. Whalley. Echocardiography Core Laboratories: University of Auckland (R. Doughty, G. Gamble, H. Walsh, and G. Whalley) and University of Queensland (B. Haluska, T. Marwick, L. Short, and S. Wahi). IDEAL Study Coordinating Centre, University of Sydney: B. Cooper, A. Jackson, J. Kesselhut, and J. Murray. IDEAL Study Data Management

References (17)

R.N. Foley et al.
Clinical and echocardiographic disease in patients starting end-stage renal disease therapy
Kidney Int
(1995)
C. Zoccali et al.
Left ventricular mass monitoring in the follow-up of dialysis patients: prognostic value of left ventricular hypertrophy progression
Kidney Int
(2004)
J.S. Silberberg et al.
Impact of left ventricular hypertrophy on survival in end-stage renal disease
Kidney Int
(1989)
R.M. Lang et al.
Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology
J Am Soc Echocardiogr
(2005)
R.N. Foley et al.
Long-term evolution of cardiomyopathy in dialysis patients
Kidney Int
(1998)
G.A. Stewart et al.
Electrocardiographic abnormalities and uremic cardiomyopathy
Kidney Int
(2005)
C.W. McIntyre
Effects of hemodialysis on cardiac function
Kidney Int
(2009)
C.W. McIntryre
Effects of hemodialysis on cardiac function
Kidney Int
(2009)

There are more references available in the full text version of this article.

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Decisions regarding the initiation of renal replacement therapy (RRT)—whether hemodialysis (HD), peritoneal dialysis, kidney transplantation, or palliative care is chosen—are critical when considering combined efforts among nephrologists, patients, family members, and nonphysician health care personnel. The transition from management of progressive chronic kidney disease (CKD) to that of end-stage renal disease (ESRD) requires the nephrologist to have a clear understanding of the disease trajectory in the individual patient and to function as a teacher for the patient and members of the patient's family, as well as for their professional and social networks. These functions involve an understanding of the patient both as an individual and as a member of a social milieu and require an appreciation of the patient's culture, spirit, and belief systems. Although all therapeutic choices facing patients with advanced CKD have advantages and disadvantages, many of the steps in the transition to ESRD care are common to all the choices. In particular, recent advances in clinical science (based on evidence derived from observational studies and clinical trials) allow the nephrologist to advise patients regarding appropriate timing of initiation of RRT and factors related to successful creation of vascular access, which will promote the best health outcomes. The nephrologist, while delivering complex care at the time of a crucial transition, plays a key role in determining whether the start of RRT with HD will be characterized by a “smooth landing” or a “crash landing,” ultimately by serving as a coordinator of education and multidisciplinary consultation.
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Summary: Heart failure (HF) is a major comorbidity in patients with end-stage kidney disease (ESKD). The pathogenesis of HF in patients on renal replacement therapy represents the confluence of several traditional and nontraditional vascular risk factors, unique to the milieu of chronic kidney disease and the dialysis modality. The diagnosis of HF with ESKD is complicated by the background of frequent inevitable fluid shifts superimposed on underlying myocardial pump abnormalities and dialysis-induced myocardial stunning. A careful temporal assessment of symptoms and physical findings, cardiac imaging, hemodynamic data, and biomarkers help establish an accurate diagnosis of HF in ESKD. Accurate volume assessment and its tight management remains the cornerstone of treatment in HF in patients on dialysis. A multidisciplinary approach between the cardiologist and nephrologist in optimizing pharmacologic strategies for HF in this population, and dialysis-based options such as frequent dialysis, may help reduce the burden of HF in this vulnerable population. Finally, including patients with ESKD in clinical trials for HF therapies, and designing pragmatic trials that bring targeted strategies for HF into the daily clinical practice of dialysis, will shed light on the optimal management of the dual burden of cardiomyopathy and advanced kidney disease.
Left Atrial Volume as a Biomarker of Target Organ Damage in Cardionephrology: A Study in a Wide Range of Renal Function
2018, Chest
Citation Excerpt :
Cardiac chambers, compared one with another, respond differently to renal dysfunction. LA volume has been shown to increase markedly in patients with severe renal dysfunction.4,13 Mechanisms that might be responsible for the LA enlargement include fluid overload,4 inflammation,14 and LV diastolic dysfunction.15
Cardiac chamber size was previously studied by echocardiography, among patients with progressive kidney disease only. We aimed to explore the relations between all heart chamber volumes as assessed by CT pulmonary angiography and renal function, throughout all ranges.
Using a novel technology for automatic four-chamber volumetric analysis, we analyzed CT pulmonary angiography results for 748 consecutive patients (between January 1 and December 31, 2014) without pulmonary embolism, and correlated the chamber volumes, indexed to body surface area, with the estimated glomerular filtration rates (eGFRs).
After adjustment for age, all cardiac chamber volumes aside from that of the left ventricle inversely correlated with the eGFR. For every 10-unit decrease in eGFR, the volume indices of the left atrium, right atrium, and right ventricle were larger by 3.1%, 2.3%, and 1.5% (P < .001, P = .003, P = .007), respectively. There was a significant correlation between left atrial volume index and eGFR (r = −0.43; P < .001). In a categorical comparison, patients with even minimal renal dysfunction (eGFR, 60 to 90 mL/min/1.73 m²) had a 10.3% larger left atrial volume index (95% CI, 3.1-17.9; P = .004) compared to patients with an eGFR > 90 mL/min/1.73 m².
A simple concomitant volumetric analysis of all four cardiac chambers by CT pulmonary angiography demonstrated that differences in volume correlate with renal function even within the normal range spectrum. The difference was most evident in the left atrium. This finding may be the first clue to evolving cardiorenal syndrome and may serve as a target for early therapeutic interventions.
ClinicalTrials.gov; Clinical Trials registration number (Helsinki Committee): 0603-15-TLV; URL: www.clinicaltrials.gov.
Evolution of Echocardiographic Measures of Cardiac Disease From CKD to ESRD and Risk of All-Cause Mortality: Findings From the CRIC Study
2018, American Journal of Kidney Diseases
Citation Excerpt :
Our findings differ from the single-center Hong Kong CASCADE (A Study of Longitudinal ChAngeS of CArdiac Structure and Function in Chronic KiDney DisEase) Study of patients with stages 3 to 5 CKD, which found that LVMI, left atrial volume, and diastolic dysfunction worsened over 1 year, particularly in participants at more advanced stages of CKD (140 CASCADE enrollees had CKD stages 4 and 5).32 In contrast, in the IDEAL trial conducted in Australia and New Zealand, a subset of 182 participants had serial echocardiograms obtained 12 months apart11 and there was no change in LVMI, left atrial volume, diastolic dysfunction, or LVEF (97% of participants had started dialysis therapy by the second echocardiogram).11 Important differences between our study and the CASCADE Study and IDEAL trial are: (1) our study was a multicenter study that consisted of a diverse US patient population that is larger in size (thus, there may be greater power to detect differences) and focused exclusively on patients who transitioned to ESRD; (2) 40% of patients in IDEAL initiated PD (vs HD) therapy, which may have affected volume and blood pressure and thus echocardiographic measures; and (3) most patients in CASCADE did not initiate dialysis therapy during the course of the study.
Abnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality.
Prospective study.
We studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD.
We measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD.
All-cause mortality after dialysis therapy initiation.
Cox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality.
Over a mean of 2.9 years between pre- and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P < 0.001) and LVESV (18.6 to 20.2 mL/m^2.7; P < 0.001). During this time, there was improvement in left ventricular mass index (60.4 to 58.4 g/m^2.7; P = 0.005) and diastolic relaxation (11.11% to 4.94% with moderately/severely abnormal; P = 0.02). Changes in left atrial volume (4.09 to 4.15 mL/m²; P = 0.08) or LVEDV (38.6 to 38.4 mL/m^2.7; P = 0.8) were not significant. Worsening from CKD to ESRD of LVEF (adjusted HR for every 1% decline in LVEF, 1.03; 95% CI, 1.00-1.06) and LVESV (adjusted HR for every 1 mL/m^2.7 increase, 1.04; 95% CI, 1.02-1.07) were independently associated with greater risk for postdialysis mortality.
Some missing or technically inadequate echocardiograms.
In a longitudinal study of patients with CKD who subsequently initiated dialysis therapy, LVEF and LVESV worsened and were significantly associated with greater risk for postdialysis mortality. There may be opportunities for intervention during this transition period to improve outcomes.

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: Originally published online November 16, 2012.

^⁎: A list of the IDEAL Echo Substudy Investigators appears in the Acknowledgements.

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Original InvestigationDialysisEffect of Early Initiation of Dialysis on Cardiac Structure and Function: Results From the Echo Substudy of the IDEAL Trial

Background

Study Design

Setting & Participants

Intervention

Outcomes & Measurements

Results

Limitations

Conclusions

Section snippets

Study Design

Patient Characteristics

Discussion

Acknowledgements

Kidney Int

Kidney Int

Kidney Int

J Am Soc Echocardiogr

Kidney Int

Kidney Int

Kidney Int

Effects of hemodialysis on cardiac function

Kidney Int

Original Investigation
Dialysis
Effect of Early Initiation of Dialysis on Cardiac Structure and Function: Results From the Echo Substudy of the IDEAL Trial