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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 20  |  Issue : 3  |  Page : 165-172

Effect of improving dialysis adequacy on the right ventricular functions


1 Department of Internal Medicine & Nephrology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
2 Assistant Specialist of Internal Medicine, Tala General Hospital

Date of Submission06-Dec-2019
Date of Acceptance15-Feb-2020
Date of Web Publication17-Jul-2020

Correspondence Address:
Dr. Elshahat A Yousef
Lecturer of Internal Medicine and Nephrology, Internal Medicine Department, Faculty of Medicine, Mansoura University
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_43_19

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  Abstract 


Background Right ventricular dysfunction (RVD) is a common finding in hemodialysis (HD) patients especially those who are inadequately dialyzed. The aim of this study is to evaluate the effect of improving dialysis adequacy, anemia, and hypertension treatment on the RV function in a cohort of HD patients.
Patients and methods The study included 60 HD patients admitted in Mansoura University Hospital, Nephrology Unit. Assessment of patients included complete clinical evaluation, estimation of Kt/V, urea reduction rate, and RV function assessed by echocardiography; all were done at the beginning of the study and 6 months after initiation of protocols of therapy needed for improvement of dialysis adequacy, anemia, and hypertension. Tissue Doppler imaging-derived myocardial performance index was used as the main index of RVD.
Results The study results revealed an increased prevalence of RVD in maintenance HD patients. Moreover, this study showed a significant improvement of the mean tissue Doppler-derived myocardial performance index in the studied patients at the end of the study (after improvement of Kt/V, anemia, and hypertension), compared with initial values at the start of the study, from 0.54±0.03 to 0.48±0.02, respectively, with significant P value of 0.001.
Conclusion RVD is common among HD patients, but improving dialysis adequacy together with proper management of hypertension and anemia plays an essential role in the improvement of RVD.

Keywords: chronic kidney disease, hemodialysis, myocardial performance index, right ventricle, tissue Doppler


How to cite this article:
Sabry A, Bahy A, Atta M, Yousef EA. Effect of improving dialysis adequacy on the right ventricular functions. J Egypt Soc Nephrol Transplant 2020;20:165-72

How to cite this URL:
Sabry A, Bahy A, Atta M, Yousef EA. Effect of improving dialysis adequacy on the right ventricular functions. J Egypt Soc Nephrol Transplant [serial online] 2020 [cited 2020 Aug 13];20:165-72. Available from: http://www.jesnt.eg.net/text.asp?2020/20/3/165/290014




  Introduction Top


Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence, prevalence, poor outcomes, and high cost. Cardiovascular death risk is higher in patients with end-stage renal disease (ESRD). Left ventricular abnormalities are present at the initiation of dialysis in ∼80% of dialysis patients. The associations between many classical risk factors like hyperlipidemia, smoking, hypertension, and cardiac outcomes in ESRD are inconsistent, and other many factors unique to ESRD and its therapy may be important [1].

Adequacy of dialysis should be assessed in all patients at least monthly, as the clinically based assessment has been proven to be reliable. Adequate dialysis should always include careful blood pressure control and extracellular fluid volume management with the regular re-evaluation of ideal dry weight, salt intake, and a review of the ultrafiltration rate. Adequacy of dialysis can be assessed in several ways; the most common acceptable methods are formal urea-kinetic Kt/V, urea reduction rate (URR), and natural log Kt/V by Daugirdas second-generation formula [2]. The minimum achieved single pool Kt/V should be 1.2 (URR=65%). To consistently achieve this in at least 80% of patients, it is recommended that the target single pool Kt/V should be 1.4 (URR=70%) [3].

Hemodialysis (HD) which is usually carried out via a surgically created native arteriovenous fistula (AVF) has been associated with an increased risk of pulmonary hypertension (PHT), a condition reported as a predictor of mortality in these patients [4]. Although patients undergoing chronic dialysis exhibit an increased prevalence of PHT, mostly owing to AVF, data on the development of right ventricular dysfunction (RVD) are lacking [5].

The assessment of RV function by tissue Doppler imaging (TDI) has been established as a common approach to detect preclinical abnormalities of cardiac function and has also been proposed as a reliable predictor of prognosis [6].

Previous works regarding the relationship between PHT and dialysis have mostly investigated the effect of volume overload on TDI indices of left ventricular function, showing an increased prevalence of diastolic dysfunction in these patients [7]; however, data on the prevalence of RVD in patients undergoing chronic dialysis and the response to improvement of dialysis adequacy are still lacking.

Our study aimed to assess the prevalence of RVD in patients undergoing chronic HD and the effect of improvement of dialysis adequacy on the RV functions, evaluated by TDI-derived myocardial performance index (MPI).


  Patients and methods Top


This is a cohort study including 60 adult patients with CKD on maintenance HD for at least 3 months (4 h/session, three sessions/week, and bicarbonate-buffered dialysate) admitted in Mansoura University Hospital, Nephrology Unit, from November 2016 to May 2017.

The research project is approved by the Human Research Ethics Committee of Faculty of Medicine, Mansoura University. All participants provided written informed consents.

Patients with advanced malignancy, advanced cerebrovascular disorders, dementia, advanced chronic liver disease, and clinical conditions that might predispose to PHT such as chronic obstructive pulmonary disease, interstitial lung diseases, connective tissue diseases, and congenital left-to-right shunts were excluded from the study. The cutoff point of the study was 6 months between the first and the second patient evaluation; during this period, initiation of protocols needed for improvement of dialysis adequacy was done.

All studied individuals were subjected to thorough history taking and complete medical examination, and blood samples were collected from each patient at the beginning of the study and 6 months after for laboratory investigations in the form of complete blood count, blood glucose level (fasting and 2 h postprandial), urea, creatinine, calcium, phosphate, hemoglobin, and parathormone (PTH) level assessment.

Assessment of Kt/V and URR was done at the beginning and 6 months after. Calculation of Kt/V was done by using Daugirdas equation [8]:



In is the natural logarithm, R is the ratio of postdialysis to predialysis serum urea nitrogen, t is the length of HD session (in h), UF is the volume of fluid removed during dialysis session (in l), and W is the postdialysis weight.

Echocardiographic evaluation was done at the beginning of the study and 6 months after initiation of protocols of therapy needed for improvement of dialysis adequacy, anemia, and hypertension. The entire study population underwent transthoracic echocardiography, including both conventional and TDI of the left ventricle and the RV. Echocardiography was performed 1 h after the completion of HD at an optimal dry weight to avoid overestimation of any echocardiographic value owing to volume overload. Images were obtained using a high-resolution scanner (SONOACE X6; Samsung Medison Hongcheon Factory, Gyeonggi-do, Republic of Korea) equipped with 3.5-MHz sector transducer equipped with the TDI mode. Special stress was applied to the RV obtaining TDI-derived MPI as the main index for RVD. The procedure was performed with patients in left lateral decubitus position in accordance with the recommendation of American Society of Echocardiography [9].

Dialysis adequacy was assessed and the cause of inadequate dialysis was determined, then efforts were done to improve the dialysis adequacy using the following steps: confirming dialysis inadequacy by assessing procedural issues, assessment of vascular access function, increasing HD time, dialysis frequency, needle diameter, blood flow rate, using specific dialyzer, managing intradialytic hypotension, confirming adequate anticoagulant, appropriate needle placement, appropriate dialyzer total cell volume, strict regimen for blood pressure-lowering agents, and management of anemia.

Statistical analysis

Data were collected, tabulated, and statistically analyzed using a personal computer with Statistical Package of Social Science (IBM Corp., Armonk, NY, USA), version 20 and EPI Info 2000 programs, where the following statistics were applied. The results were summarized as the mean±SD. Differences in the distributions of demographic characteristics and selected variables between the examined groups were analyzed by the Student t test for nonpaired data if distribution of variables was normal or the Mann–Whitney U test for other than normal distributions between responders and nonresponders. P value less than 0.05 was taken as statistically significant.


  Results Top


[Table 1] shows the basal characteristics and medical history of our studied patients including 60 HD patients, with mean age of 46.6 years old and mean BMI of 27.1. Overall, 83.3% of patients were hypertensive, 17% were diabetics, 35% had PHT, 68% with RVD, 85% were anemic, whereas 60% of patients were inadequately dialyzed (Kt/V<1.2). When comparing the patients’ results at the start of the study with the results at the end of the study (6 months later), there was a significant increase in URR, Kt/V, ultrafiltration values, and hemoglobin level of studied HD patients at the end of the study, with P values of 0.01, 0.02, 0.001, and 0.001, respectively, and a significant decrease in systolic and diastolic blood pressures and PTH level of patients on HD at the end of the study, with P values of 0.003, 0.05, and 0.01, respectively. Regarding the comparison of the RV echocardiographic data of studied patients at the start and at the end of the study, there was a significant improvement of mean tissue Doppler-derived MPI in the current studied patients at the end of the study as compared with the initial values at the start of the study, from 0.54±0.03 to 0.48±0.02, with significant P value of 0.001. Tissue Doppler indices revealed also significantly higher E1, E1/A1, isovolumetric relaxation time (IVRT), isovolumic contraction time, and ejection time (ET) when compared with the initial measurements. Conventional Doppler revealed significantly lower right ventricular end-diastolic diameter, right ventricular end systolic diameter, right ventricular end systolic volume, and right ventricular end-diastolic volume at the end of the study with significant higher E, E/A, and right ventricular ejection fraction (RVEF), as shown in [Table 2]. At the start of the study, there were 50 hypertensive patients; when comparing the data of these patients at the start and 6 months after, there was a significant improvement of MPI and RVEF in hypertensive at the end of the study when comparing their initial values at the start of the study, with P values of 0.001 and 0.001, respectively, after improvement of their blood pressure, as shown in [Table 3]. [Table 3] also shows the significant improvement of mean hemoglobin (HB) level of the anemic patients (n=51) at the end of the study compared with its level at the start of the study, with P value less than 0.001. Moreover, there was a significant change of MPI, ET, right ventricular end systolic diameter, right ventricular end-diastolic diameter, RVEF, right ventricular end systolic volume, and right ventricular cardiac output between anemic patients in our study at the start and at the end of the study. [Table 4] shows the comparison of echocardiographic parameters between the adequately dialyzed patients (Kt/V >1.2) with inadequately dialyzed patients (Kt/V <1.2). There was a statistically significant difference between patients who reached minimally desired Kt/V (45 patients) and patients below minimally desired Kt/V (15 patients) regarding MPI improvement (0.49±0.02 and 51±0.03, respectively, with P value of 0.005). In addition, there was a statistically significant change in RVEF (P=0.01) and right ventricular cardiac output (P=0.03).
Table 1 Anthropometric measurements, medical history, and some basic parameters of the studied patients (N=60)

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Table 2 Comparison of dialysis adequacy, blood pressure, hemoglobin level, parathormone level, and dry weight and right ventricular echocardiographic data of the studied patients at the start and at the end of the study(N=60)

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Table 3 Comparison of Kt/V, clinical and some echo parameters of studied hypertensive patients (N=50) and anemic patient (N=51) at start and at the end of the study

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Table 4 Comparison of echo parameters in hemodialysis patients according to dialysis adequacy (minimally desired Kt/V at the end of the study)

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  Discussion Top


More than 50% of the individuals starting HD program present with some type of pre-existed cardiovascular disease [10]. HD, which is usually carried out via a surgically created native AVF, has been associated with an increased risk of PHT, a condition reported as a predictor of mortality in these patients [11].

RVD has been defined as a state where stroke volume still increases in the presence of increased RV end-diastolic volume [12]. RVD in HD patients may be owing to pathophysiological mechanisms like anemia, erythropoietin deficiency, dysregulation of calcium-phosphorus balance, systemic hypertension, activation of renin-angiotensin-aldosterone system, sympathetic activation, and oxidative stress and are usually associated with inadequate HD [13].

Echocardiographic measurement of MPI is one of the accurate indices of ventricular performance, as it is a combined index of systolic and diastolic functions independent of age, ventricular geometry, or heart rate. Obtaining MPI by tissue Doppler rather than the pulsed Doppler method allows measuring of all time intervals from a single cardiac cycle using one imaging view [14].

Most available studies on the RV focused on the acute effect of HD sessions on the RV dysfunction by assessing predialysis and postdialysis values; for example, in 2010, Paneni et al. [15] investigated the effect of different dialysis treatments on RV function showing that HD increases the risk of RVD, particularly in the presence of brachial AVF.

To the best of our knowledge, this is the first study concerning the effect of improving dialysis adequacy (Kt/V), together with other factors like anemia and blood pressure management on RV function using TDI-derived MPI as the main index for assessment of the RV function.

Regarding dialysis adequacy, our study revealed that ∼60% (36 patients out of 60) of HD patients in our study had Kt/V less than 1.2, indicating that patients were receiving an inadequate dose of dialysis .These results were in agreement with other studies carried out in other developing countries such as Brazil, Nigeria, Nepal, Pakistan, and Iran, which found that ∼55–65% of patients had a Kt/V less than 1.2 [16]. On the contrary, the results of the present study were in disagreement with those reported from developed countries such as the USA according to the 2007 annual report, where more than 90% of the patients had a Kt/V more than 1.2 [17].

Patients in our study showed a significant improvement of Kt/V (P=0.02) and URR (P=0.01) after 6 months of improving their HD prescription. Despite great efforts done to achieve target recommended dose, which is 1.4 according to Gotch and Sargent [18], 1985, yet we achieved a Kt/V of 1.2, which is in accordance with the minimally desired goal submitted by them.

Our study revealed high prevalence of RVD as estimated by TDI-derived MPI among HD patients (68%) and this is in concordance with that of Said et al. [19]. Moreover, this also agrees with Paneni et al. [15] who found that RVD assessed by TDI-derived MPI was higher in HD patients compared with PD patients (71.3 vs. 34.6%). Possible causes of the high prevalence of RV dysfunction in our study may be attributed to the substantially high prevalence of systemic hypertension (83% of our patients), and many of them have uncontrolled blood pressure. Systemic hypertension and related LV hypertrophy were reported to be associated with RV dysfunction [20].

The duration of our study was 6 months, during which intensive measures were taken to improve dialysis adequacy, anemia, and hypertension management. At the end of 6 months, TDI indices revealed significant improvement of mean MPI, significantly lower E/E1 ratio and isovolumetric contraction time (IVCT), and significantly higher E1, E1/A1, IVRT, and ET when compared with initial measurements. These results may demonstrate that adequate HD treatment may play a role (even partially) in improving RVD, and this is in accordance with what was reported by Huang and Zhao [21].

Our study revealed that hypertension prevalence in our patients is 83% (50 out of 60 patients), and this is in accordance with Said et al. [19] and Buckalew et al. [22], who revealed similar prevalence. In contrast, Ridao et al. [23] revealed 60.5% prevalence. The increased prevalence in our study may be owing to the fact that blood pressure is influenced by multifactorial pathogenesis such as age, weight, type of renal affliction, depth of renal dysfunction, presence of diabetes, hypertriglyceridemia, severity of proteinuria, socioeconomic, and racial considerations.

Regarding MPI improvement, there was significant improvement of MPI in the hypertensive HD patients (50 patients) after improvement of their blood pressure, with P value of 0.001, and this is in concordance with Karaye et al. [24].

National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF K/DOQI) defines anemia in dialysis patients as a hematocrit value less than 33% or a hemoglobin level less than 11 g/dl. Accordingly, the prevalence of anemia in HD patients of our study was 85%. This prevalence is in relative agreement with Bibek et al. [25], who documented 80% prevalence of anemia with the same cutoff level. However, there was disagreement with Valderrabano et al. [26] who documented 68% prevalence of anemia in their cohort of HD patients.

The mean HB level was 9.2 g/dl in our patients at the start of the study, which was lower compared with other developed countries: mean HB levels were 12 g/dl in Sweden [27]. The factors responsible for the low initial HB levels in our patients compared with the K/DOQI guidelines and other countries may include blood loss, lack of consistent supplies of erythropoietin, and insufficient dialysis dose. There is good evidence that dialysis adequacy has resulted in better control of anemia and other parameters correlating with dialysis adequacy such as hypertension and patients’ nutritional status [28].

The mean HB level at the end of the study was 10.7 g/dl, and also this value is still lower than the recommended K/DOQI guideline, but there was a significant improvement compared with the initial values at the beginning of the study, with P value of 0.001.

There was a significant improvement of MPI in our patients with anemia at the end of the study. This improvement occurred after improvement of their HB level, with P value less than 0.001 for each. These findings are in accordance with Silverberg et al. [29], which demonstrated that correction of anemia would play a major role in the reduction of the severity of the congestive heart failure (CHF) in HD patients.

On the contrary, our result does not agree with Guglin et al. [30], which demonstrated that anemia level is weakly but consistently inversely related to RV systolic dysfunction. They hypothesized that hemodilution, or lower hematocrit level, results in decreased blood viscosity and so cardiac work becomes easier, leading to an increase in systolic function.

In the current study, the prevalence of PHT was 35%, and this is in agreement with available data from several studies that reported the prevalence of PHT from 16 to 59% [31].

There was no significant improvement of the mean pulmonary artery pressure at the end of the study in spite of significant increase in the ultrafiltrated volume; this may be owing to the impeding effect of AVF in these patients [32].

Although the main cause of RVD is PHT, which resulted mainly from AVF insertion, and although there was no significant improvement in PHT, MPI showed significant improvement. These results may be owing to the multifactorial pathogenesis involved in RVD development [13], so improvement of other variants may have a role in RVD improvement. Moreover, Guglin et al. [30] demonstrated that RVD is present in patients with CKD even before initiation of HD and even before creation of the AVF required for dialysis.Regarding PTH level, in our study, despite significant reduction of PTH level as compared with initial values, no correlation was found between MPI and PTH improvement, and this is in agreement with that of Saleh et al. [33], who founding that serum PTH was not associated with electrocardiographic measures, fractional shortening, and E/A ratio, and concluding that PTH is involved in hypertrophic cell growth and myocardial stretch than to cardiac output and diastolic function.

Interestingly, although RVD in HD patients is difficult to be treated owing to the direct effect of AVF leading to PHT and thus ventricular dysfunction, the partial but statistically significant improvement of MPI in our study may be owing to synergism between improving dialysis adequacy, improvement of anemia level, and lowering of systemic blood pressure, and this explanation agrees with that of Milani-Nejad et al. [34].

Limitations of the study

The limited number of our study population, which may be due to strict exclusions, was insufficient for general conclusions; moreover, the follow-up duration was relatively short. A better long-term study may be needed in the future. Moreover, the target dry weights of each patient were determined based on physicians’ judgments; therefore, we could not completely exclude the possibility of hypervolemia and hypovolemia at the time of echocardiography.


  Conclusion Top


Patients with ESRD on maintenance HD have a high prevalence of RVD. Insufficient dialysis may contribute to some degree toward the development of RVD, hence improving dialysis adequacy together with other factors like hypertension and anemia management plays an essential role in the management of RVD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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