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 Table of Contents  
ORIGINAL RESEARCH
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 127-133

Study of the Prevalence of Echocardiographic Abnormalities and Their Relation to Disease Progression in Chronic Kidney Disease


1 Department of Cardiology, Santokba Durlabhji Memorial Hospital and Research Centre, Jaipur, Rajasthan, India
2 Department of Nephrology, Santokba Durlabhji Memorial Hospital and Research Centre, Jaipur, Rajasthan, India

Date of Submission16-Aug-2020
Date of Decision02-Oct-2020
Date of Web Publication24-Mar-2021

Correspondence Address:
Dr. Nitin Kansal
Department of Cardiology, Santokba Durlabhji Memorial Hospital and Research Centre, Bhawani Singh Marg, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiae.jiae_44_20

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  Abstract 

Context: Study of the prevalence of echocardiographic abnormalities and there relation to disease progression in chronic kidney disease (CKD). Aims: Study correlation of echocardiographic changes and CKD progression. Settings and Design: A prospective, cross-sectional, observational, analytical study, where we performed complete echocardiographic evaluation of patients with CKD stage II–V. We compared various echocardiographic parameters to predict the progression of CKD. Subjects and Methods: Ninety CKD patients stage II–V presenting to our hospital from November 2016 to December 2017 were included in the study. A complete echocardiographic evaluation was done. Left ventricular hypertrophy (LVH), systolic and diastolic dysfunction using Doppler indices at mitral inflow, left atrial volume, speckle tracking, and global longitudinal strain (GLS) were studied. Results: Patients were age and sex matched in all the groups with a male preponderance. Forty-one patients (45.56%) were diabetic and 74 (82.22%) were hypertensive. The prevalence of hypertension increased from 66.67% to 89.29% as CKD stage progressed from stage II to stage V. There were significant echocardiographic abnormalities seen in CKD patients. The severity increased with worsening of the stages of CKD. LVH and early diastolic mitral inflow to annular velocity ratio progression was statistically significant when stage V was compared to stage II. Left atrial volume, mitral early diastolic to late diastolic velocity ratio, maximum tricuspid regurgitation (TRmax) velocity, and diastolic dysfunction prevalence were significantly raised in stage IV and stage V compared to stage II. Only GLS showed statistical significance between stage II to stage III, stage IV and stage V and thus predicting progression of CKD. Conclusions: LVH, dilated left atrium, abnormal GLS, TRmax, diastolic dysfunction, and related tissue Doppler imaging parameters correlate with worsening renal function. GLS was the only parameter showing significant difference between stage II and stage III. This can be used as a novel modality for detection of subclinical cardiac dysfunction in CKD.

Keywords: Chronic kidney disease, diastolic dysfunction, echocardiography, global logitudinal strain


How to cite this article:
Garg P, Mathur P, Kansal N, Sharma P, Shrivastava M. Study of the Prevalence of Echocardiographic Abnormalities and Their Relation to Disease Progression in Chronic Kidney Disease. J Indian Acad Echocardiogr Cardiovasc Imaging 2021;5:127-33

How to cite this URL:
Garg P, Mathur P, Kansal N, Sharma P, Shrivastava M. Study of the Prevalence of Echocardiographic Abnormalities and Their Relation to Disease Progression in Chronic Kidney Disease. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2021 [cited 2021 Oct 24];5:127-33. Available from: https://www.jiaecho.org/text.asp?2021/5/2/127/311856


  Introduction Top


The kidneys play a central role in fluid, electrolyte, and acid–base homeostasis in humans. Chronic kidney disease (CKD) is the presence of kidney damage, manifested by abnormal albumin excretion or decreased kidney function that lasts longer than 3 months as quantified by measured or estimated glomerular filtration rate (eGFR).[1] Cardiovascular complications are the main cause of death in patients with CKD on renal replacement therapy.[2] Patients with CKD also have a high prevalence of cardiomyopathy.[2] The presence of any cardiovascular disease, be it congestive cardiac failure, ischemic heart disease or left ventricular hypertrophy (LVH), predicts a faster decline in kidney function when adjusted for baseline glomerular filtration rate (GFR).[3] Echocardiography offers an easy noninvasive way to assess and follow-up cardiac dysfunction[4] and structural changes. Doppler evaluation helps in evaluating diastolic function better. Novel techniques such as speckle-tracking echocardiography (STE) and longitudinal strain[5] are well studied to detect subtle deterioration in left ventricular (LV) global and regional systolic functions. LV global peak systolic longitudinal strain (GLS) obtained from two-dimensional (2D)-STE with strain analysis is the ratio of the maximal change in myocardial longitudinal length in systole to the original length. The more negative the GLS value, the better the LV function. GLS is a powerful prognostic predictor in stable CKD patients with preserved left ventricular ejection fraction (LVEF) and on renal replacement therapy.[6],[7]

In this prospective, cross-sectional, observational, analytical study, we performed complete echocardiographic evaluation of patients with CKD stage II–V. We compared various echocardiographic parameters to predict the progression of CKD.


  Subjects and Methods Top


CKD patients stage II–V at our hospital, referred for cardiac evaluation during the study period November 2016 till December 2017, were included in the study. Study was done after clearance from the Institutional Ethics Committee. A total of 90 patients were included after satisfying all inclusion and exclusion criteria. All patients with CKD stage II–V on or off renal replacement therapy, irrespective of etiology were included. A person was considered having CKD if his illness was of more than 3 months duration and had abnormal ultrasound (USG) findings and reduced creatinine clearance pointing to CKD. Patients with documented ischemic/coronary artery disease, congenital heart disease, valvular heart disease, age <18 years, chronic alcoholism, acute kidney injury, hypothyroidism or hyperthyroidism, and patients who were not willing to give consent for participation in the study were excluded.

In all eligible patients, after a detailed informed consent, a detailed history and clinical examination were performed. All routine investigations to ascertain cause and stage of CKD were done, including urine routine examination, complete blood count, fasting blood sugar, blood urea nitrogen, serum creatinine, electrolytes, and USG abdomen.GFR estimation was done using Modification of Diet in Renal Disease (MDRD) equation. CKD classification was done according to GFR based on MDRD equation as shown in [Table 1].
Table 1: Chronic kidney disease classification was done according to glomerular filtration rate based on the Modification of Diet in Renal Disease equation

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All patients underwent 12-lead electrocardiogram, transthoracic echocardiography using Philips iE33 echocardiography machine and matrix X5-1 probe. The cardiologist was blinded to the CKD stage of the patient. Examination was done using all standard echocardiographic views. Measurements were made in the M-mode and 2D presentation. Flow parameters were evaluated using Doppler (continuous-wave method, pulsed-wave method, and tissue Doppler imaging [TDI]).

LV measurements such as end-diastolic and systolic dimension of inter ventricular septum (IVS), posterior wall (PW), and LV were done. LVEF (Simpson's Biplane method) was calculated. Depressed systolic dysfunction was defined as LVEF of <50%.[8] LVH was labeled when IVS thickness or LV PW thickness in diastole was equal or more than 12 mm.[9]

Diastolic dysfunction was calculated by the mitral inflow pattern. Diastolic function was assessed by determining the velocities of early (E) and late (A) diastolic transmitral flow, the ratio of E-to-A (E/A),[10] early diastolic septal and lateral mitral annular velocities (E'), E/average E',[11] left atrial (LA) volume,[12] and the maximum tricuspid regurgitation (TRmax) velocity. Different algorithms were used in calculating diastolic dysfunction in patients with normal LVEF and in patients with depressed EF as per the American Society of Echocardiography (ASE) guidelines.[13]

LA volume index (Biplane method) as in [Figure 1], more than 34 mL/m2 was considered LA enlargement.[14] LV internal diameter diastolic in M-mode at the tips of the mitral leaflets above 5.3 cm in females and above 5.9 cm in males was considered as dilated LV.[13] TRmax above 2.8 m/s was considered abnormal. Valvular calcification either in aortic or mitral valve or in both valves was considered abnormal. Pericardial effusion present to any degree was considered abnormal.
Figure 1: Left atrial volume measurement by biplane method

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The endocardial borders were traced in the end-systolic frame of the 2D images from the three apical views. Speckles were tracked frame-by-frame throughout the LV wall during the cardiac cycle and basal, mid, and apical regions of interest were created. GLS was calculated as the mean strain of all 18 segments, as shown in [Figure 2]. Impaired GLS was defined as >−17% (a less negative value suggested more impairment).
Figure 2: Global longitudinal strain measurement

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Statistical analysis

Continuous variables were summarized as mean and standard deviations. P < 0.05 was considered as statistically significant. One-way analysis of variance test were used for calculating P value of age, body mass index (BMI), body surface area (BSA), hemodynamic parameter, GFR, hemoglobin, serum creatinine and mitral E and A values. Fisher's exact test was used for the distribution of sex ratio, diabetes mellitus (DM), hypertension, diastolic dysfunction, pericardial effusion, and calcification among our patients. The Chi-square test was used to calculate P value among patients with LVH, dilated LV, LV systolic dysfunction, LA enlargement, and abnormal mitral E', TRmax, and GLS. The echocardiographic parameters which were found to be significant (P < 0.05) were compared with stage II CKD patient as a reference value with stage III, IV, and V patients separately by using the Chi-square test. Medcal 16.8.4 version software was used for statistical calculations.


  Results Top


In our study, we performed echocardiography in CKD patients stage II to V and studied the prevalence of various echocardiographic abnormalities. We also studied their relation to the progression of CKD stages.

A total of 90 patients in four groups - CKD stage II, stage III, stage IV, and stage V- were studied, and a full echocardiographic examination was performed on them. There were 15, 26, 21, and 28 patients in stage II, III, IV, and V, respectively. Out of 28 patients in stage V, 12 on maintenance dialysis.

The mean age of our study group was 59.36 ± 16.07 years. Mean BMI of patients was 23.77 ± 4.60 kg/m2, and mean BSA was 1.74 ± 0.18 m2. Baseline parameters of the patients are given in [Table 2].
Table 2: Baseline parameters of the patients

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Echocardiography parameters of our patients are given in [Table 3]. LVH was present in 46.67% patients in CKD stage II, 69.23% in stage III, 76.19% in stage IV, and 92.86% in stage V. Mean IVS thickness was 1.19, 1.30, 1.30, and 1.42 cm in stage II, III, IV, and V CKD patients, respectively. LA enlargement (LA volume more than 34 ml/m2) was seen maximum (82.14%) in patients of stage V. Maximum mean E/A ratio of 1.22 was seen in stage V patients. Stage V patients were having maximum number of patients (89.28%) with reduced septal E'. Lateral E' showed similar results. Maximum number of patients with E/E' ratio of more than > 14 were in stage V (57.14%), and only 1 patient had E/E' >14 in stage II CKD. Maximum mean TRmax velocity was 2.89 m/s in stage V CKD disease. Diastolic dysfunction was seen in no patient in stage II, 5 patients (19.23%) in stage III, 10 (47.62%) in stage IV, and 20 (71.42%) in stage V. A maximum mean GLS was seen in stage V CKD patients, which was −12.86% and minimum mean GLS was seen in stage II CKD patients which was −18.8%.
Table 3: Echo parameters of chronic kidney disease patients in various stages

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P value was calculated for all the echo parameters in the various stages of CKD when compared to stage II. This is depicted in [Table 4]. LVH and E/E' were significantly increased only when stage V was compared to stage II. LA volume, mitral E/A, TRmax velocity, and diastolic dysfunction prevalence were significantly raised when compared between stage IV and stage II and also stage V to stage II. Only GLS showed statistical significance between stage II to stage III, stage IV, and stage V and thus predicting the progression of CKD.
Table 4: P value of echo features in chronic kidney disease compared to Stage 2

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  Discussion Top


Cardiovascular disease is a significant cause of morbidity and mortality among patients with CKD. Cardiac structural as well as functional abnormalities are common in patients with end-stage renal disease (ESRD) and CKD. Echocardiography is an easily performed, noninvasive, cost-effective, safe, reproducible, and accurate modality for the early detection of cardiac dysfunction in CKD. It detects even asymptomatic cardiovascular abnormalities such as LVH, minimal pericardial effusion, diastolic dysfunction, and can permit timely intervention and help delay further progression of the diseases.

In our study, the patients were age matched in all the stages of CKD. No statistically significant difference was found between age and worsening renal function. This matches with the study by Laddha et al.[15] and Park et al.[16]

There was a male preponderance in all the stages of CKD, possibly due to selection bias as male population visits health-care facility more frequently than female population in our country. No statistically significant difference between gender and CKD was found in our study. Park et al.[16] had 45% of patients as females which is more compared to 36.67% females in our study population.

Type II DM and hypertension are the most common causes of CKD as well as cardiovascular disease. In our study, there was a high prevalence of both the diseases in each stage of CKD. Out of 90 patients, 41 (45.56%) were diabetic and 74 (82.22%) were hypertensive. The prevalence of hypertension increased from 66.67% to 89.29% as we progressed from stage II to stage V. In a study done by Park et al.,[16] the prevalence of DM was 30%, 45%, 53%, and 59% in GFR >60, 45–59, 30–44, and <30, respectively. The prevalence of hypertension in the same study increased from 77% in GFR > 60% to 96% in GFR <30.

Hemoglobin fall from stage II to V was statistically significant as P < 0.001. It signifies that as renal function deteriorates patients are more likely to have anemia. Agarwal et al.[17] found mean hemoglobin of 9.3 ± 1.5 g% in mild to moderate CKD and 7.3 ± 1.7 g% in advanced CKD which was lower than our study population.

LVH is one of the most common abnormalities on echocardiography in CKD patients. It is associated with the greater rate of declining renal function, greater morbidity, and mortality. Sixty-seven patients (74.44%) had LVH in our study. There was significant association between LVH and CKD stages as P = 0.008. Mean septal thickness increased from 1.19 ± 0.10 cm in stage II to 1.42 ± 0.19 cm in stage V. When we compared the patients of stage II with rest of CKD patients, we found significant difference in the prevalence of LVH only in stage II versus V as P = 0.001. Park et al.[16] measured LV mass for LVH and found linear correlation and significant association between LV mass and worsening kidney functions. These results correlated with our study.

There was no statistically significant correlation between CKD stages and incidence of dilated left ventricle as P = 0.11. Hensen et al.[18] found mean LV end diastolic diameter of 5.3 ± 0.9 cm which was quite similar to our study.

An LVEF (Simpson's method) <50% was seen in 22 (24.44%) of our patients. Although mean LVEF decreased as we progressed from stage II to stage V CKD, it was statistically nonsignificant. Study by Barde et al.[19] on 100 patients on maintenance dialysis found systolic dysfunction in 28 (28%) patients, but they used the criteria of LVEF <55% as systolic dysfunction. We found similar prevalence of systolic dysfunction in our CKD stage V (28.57%). Park et al.[16] found systolic dysfunction (defined as LVEF <45%) in only 8% of cohort. There was no association between kidney function and systolic dysfunction in demographic, multivariate, or fully adjusted models. The results were similar in our study.

LA volume was considered increased when the LA volume was more than 34 ml/m2. The LA enlargement indicates diastolic dysfunction among CKD patients.[20] In our study, 45 (50%) patients had LA enlargement. We found significant association between various CKD stages and prevalence of LA enlargement as P < 0.001. LA enlargement progressively increased from 6.67% in stage II, 26.92% in stage III, 66.67% in stage III, to 82.14% in stage V. There was a statistically significant difference only between stage II versus IV and stage II versus V as P < 0.001. A study by Franczyk-Skóra et al.[21] found increasing LA size as CKD stages progressed from stage I to V. They found linear correlation and strong association between LA size and worsening CKD stage which matches our study. Hensen et al.[18] found mean LA volume index 29 ± 15 ml/m2 in CKD stage IIIb to V which was lower than our study. Progressive LA enlargement predisposes CKD patient to various arrhythmias, diastolic heart failure, and is strongly associated with diastolic dysfunction in these patients.

Mitral E and A velocities and their ratio were calculated using the Doppler study. There was no significant association between various CKD stages and mitral inflow velocities. Laddha et al.[15] in their study found mean mitral E 73.47 ± 16.21 cm/s, mean mitral A 83.8 ± 24.5 cm/s, mean E/A value of 0.95 ± 0.35 which was quite similar to our CKD groups from stage II to V. They found significant association between CKD and abnormal E/A ratio which differs from our study.

TDI of mitral septal and lateral annulus helped us classify diastolic dysfunction accurately. Sixty-three patients (70%) had decreased septal E' (<6 cm/s). We found statistically significant association between CKD stages and prevalence of decreased E' as P = 0.001. This means mitral E' decreases with worsening renal function. There was a statistically significant difference between stage II versus IV and stage II versus V as P = 0.002 and < 0.001, respectively. Similar results were obtained with lateral E'. There was a strong correlation between CKD stages and E/average E' value as P < 0.001. There was statistical difference between stage II versus IV and stage II versus V as P = 0.01 and 0.001. Franczyk-Skóra et al.[21] found similar result in the E/E' ratio with P < 0.001. Hensen et al.[18] showed similar results.

TRmax on continuous wave Doppler more than 2.8 m/s was considered abnormal. We found statistically significant association between CKD stages and TRmax as P < 0.001. It means deteriorating renal function is associated with increasing TRmax velocity, hence associated with pulmonary artery hypertension. We further compared stage II with rest of CKD patients and found significant association between stage II versus IV (P = 0.004) and stage II versus V (P < 0.001).

Diastolic dysfunction was graded as per the new recommendation by the ASE.[13] Some studies did not take consideration of mitral annular velocities and reported pseudonormal mitral inflow pattern as normal and some classified grade I diastolic dysfunction with normal LA pressure as diastolic dysfunction.[22] We took only definite grade II or grade III diastolic dysfunction. Only 35 patients (38.89%) had the diastolic dysfunction in our study. We found strong correlation between CKD patients and diastolic dysfunction as P < 0.001. There was statistically significant difference only between stage II versus stage IV and stage V as P value was 0.001 and < 0.001, respectively. Park et al.[16] found diastolic dysfunction in 71% of their patients while Saxena et al.[23] found in 50% of the patients.

We calculated GLS in our patients to detect subclinical abnormalities in myocardium. GLS more than − 17% (a less negative value) was considered abnormal. In our study, we found statistically significant association between GLS and CKD patients as our P < 0.001. As we progress from stage II to stage V, GLS progressively increased (became less negative). There was significant difference between stage II versus III, II versus IV and II versus V, as P < 0.001 in all three comparison groups. It means GLS detects subclinical changes in myocardium even when the patient progress from stage II to stage III. Hensen et al.[18] in 304 patients in stage IIIb to V found mean GLS of −14% ± 5%, and they found GLS was associated significantly with all-cause mortality in renal transplant patients with P = 0.019. Krishnasamy et al.[24] on CKD patients found mean GLS of −16.6% ± 4.2%. eGFR correlated negatively with GLS (r = −0.14, P = 0.004) similar to our study.

We found no statistically significant association between CKD patients and valvular calcification as P value in our study was 0.24. Barde et al.[19] found valvular calcification only in 5% of the patients of CKD. Laddha et al.[15] found valvular calcification in 5 patients (7.1%) out of 70 ESRD patients.

We found that there was no significant association between pericardial effusion and CKD patients as P = 0.24. Barde et al.[19] in their study on 100 ESRD patients found pericardial effusion in 13% of the patients. Laddha et al.[15] found pericardial effusion in 5 patients (7.1%) out of 70 ESRD patients.

Limitations

It was a small study from a single center. There were some confounding factors which could have influenced the results of our study. Patients were not followed up for morbidity and mortality so association between echocardiographic abnormalities and clinical deterioration could not be established in our study.


  Conclusions Top


Thus, we conclude from our study that a significant number of CKD patients have echocardiographic abnormalities. We found significant correlation between LVH, dilated LA, abnormal GLS, TRmax, diastolic dysfunction prevalence, and related TDI parameters with worsening renal function. Severities of these abnormalities are progressively increased as kidney function worsens. When compared with stage II CKD, GLS was the only parameter among other abnormalities which showed significant difference between stage II and stage III. This can be used as a novel modality for subclinical detection of cardiac dysfunction as patient progresses from stage II to stage III CKD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

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