EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Cardiovascular diseases are an important cause of mortality and morbidity in children with chronic renal failure. Cardiac evaluation and follow-up are crucial for these patients before and after renal transplant. Echocardiography is a noninvasive imaging modality that allows for the assessment of cardiac structure and function.

Materials and Methods: We retrospectively investigated pretransplant and posttransplant echocardiography findings for 55 pediatric patients who had underwent kidney transplant. We recorded patient characteristics before and after transplant, including age, sex, follow-up period, etiology of renal failure, left ventricular systolic and diastolic diameters and the associated z scores, left ventricular mass indexes and z scores, ejection fraction and fractional shortening, aortic valve and atrioventricular valve insufficiencies, presence of pulmonary hypertension, and pericardial effusion (if any) in echocardiography. All participants underwent echocardiography at baseline and after 6 months following the transplant procedure.

Results: Posttransplant echocardiography evaluations showed that the z scores of left ventricular systolic and diastolic diameters decreased significantly, mitral regurgitation decreased, and left ventricular systolic functions and left ventricular mass index increased.

Conclusions: Our study revealed that kidney transplant has a beneficial effect on the cardiovascular status of patients with end-stage renal disease, as shown by improvements in both structural and functional echocardiographic features. Cardiac functions must be monitored regularly before and after transplant. Transplantation is the optimal treatment option for preservation and improvement of cardiovascular functions.

Key words : Echocardiography, Left ventricular hypertrophy, Mitral regurgitation, Systolic dysfunction

Cardiovascular diseases are an important cause of mortality and morbidity in children with chronic renal failure. The etiology of increased incidence of cardiovascular events for patients on dialysis includes decreased coronary perfusion due to hypotension during dialysis; left ventricular hypertrophy due to volume load, pressure load, and anemia; electrolyte imbalance; and increased levels of inflammatory cytokines due to uremia and stress.¹ Renal transplant offers higher likelihood of patient survival and improved quality of life compared with chronic dialysis; however, pediatric kidney recipients remain at higher risk of cardiovascular events throughout their lives. Although the risk of death from cardiovascular diseases is significantly reduced after renal transplant, this risk remains 3 times higher than for the general pediatric population.² It has been suggested that this risk is caused by accelerated cardiomyopathy and coronary artery disease.³

For these reasons, cardiac evaluation and follow-up are important for these patients before and after renal transplant. Echocardiography plays an important role in the evaluation of these patients by providing valuable information about their cardiac function to help to guide treatment strategies. The aim of this study was to investigate the effect of kidney transplant on cardiac structure and function in pediatric patients with end-stage renal disease.

Materials and Methods

We retrospectively investigated 55 pediatric patients who underwent kidney transplant during the period 2013-2023 and were being followed up at Ba?kent University Ankara Hospital in terms of pretransplant and posttransplant echocardiography findings. We recorded patient characteristics before and after transplant, including age, sex, follow-up period, etiology of renal failure, left ventricular systolic and diastolic diameters and the associated z scores, left ventricular mass indexes (LVMI) and z scores, ejection fraction (EF) and fractional shortening (FS), aortic valve and atrioventricular valve insufficiencies, presence of pulmonary hypertension, and pericardial effusion (if any) in echocardiography.

Echocardiography assessments were performed by experienced physicians from the Pediatric Cardiology Department at Ba?kent University, Ankara Hospital. Before transplant surgery, all patients underwent an assessment of cardiac structure and function using echocardiography, which was repeated 6 months after transplant. Patients’ weight and height at the time of echocardiography evaluation were recorded, and body mass indexes were calculated. Left ventricular systolic and diastolic diameters and EF and FS were measured using parasternal long-axis view and M-mode echocardiography. Ejection fraction less than 55% was defined as systolic dysfunction. Fractional shortening below 25% was considered low. We calculated the z scores for the end-systolic and end-diastolic left ventricular diameter data according to the study of Kampmann and colleagues,⁴ and a z score ?2.5 was defined as left ventricular dilatation. We calculated the LVMI according to the study of Foster and colleagues,^{5 rf} for which a z score ?2.5 was defined as left ventricular hypertrophy. Valve insufficiencies were evaluated using color Doppler echocardiography. The pulmonary arterial pressure was estimated from tricuspid regurgitation velocity with the modified Bernoulli equation, and mean pulmonary arterial pressure greater than 25 mm Hg was defined as pulmonary hypertension.⁶

All data were analyzed using the Jamovi statistical program (version 2.3.21.0). The Shapiro-Wilk test was used to evaluate whether the data were normally distributed. We used mean values (with SD) for normally distributed continuous variables and median values (with quartiles, Q1-Q3 [ie, min-max]) for nonnormally distributed ordinal data. Categorical variables were presented as number (n) and percentage (%) of cases. Continuous variables were compared with a paired t test and the Wilcoxon test, as appropriate for dependent group data. Categorical variables were compared with the McNemar test. P < .05 was considered statistically significant. This study was approved by Ba?kent University Institutional Review Board. (Project no: KA 24/149).

The median age of the study group (45.5% female, 54.5% male) at transplant was 12 years (2-17 years), with a median follow-up period of 84.5 months (9.5-125.5 months) (Table 1). Kidney transplant was performed in 43.6% of the patients due to glomerular diseases, 29.1% due to congenital renal and urinary tract anomalies, 18.2% due to cystic renal diseases, and 9.1% due to tubular diseases (Figure 1).

We found no significant differences in measurements of left ventricular systolic diameter, left ventricular diastolic diameter, pulmonary arterial pressure, and EF before and after transplant. However, there was a significant decrease in the posttransplant left ventricular systolic diameter z score by 0.88 (P = .020) and left ventricular diastolic diameter z score by 0.81 (P = .013). There was a significant increase in LVMI in the posttransplant period (pretransplant 126.6 g vs posttransplant 141.9 g). Fractional shortening was significantly greater after transplant versus before transplant (P = .024). No significant differences were observed in the presence of pericardial effusion, aortic regurgitation, and tricuspid regurgitation before and after transplant. Mitral regurgitation was present in 65.5% of patients before transplant and in 47.3% of patients after transplant (P = .021), indicating a significant improvement in mitral regurgitation. Echocardiography data before and after transplant are shown in Table 2.

We investigated the effects of transplant on cardiac structure and function by evaluation of echocardiographic variables before transplant and 6 months after transplant in patients who underwent kidney transplant to treat chronic renal failure.

Patients with chronic kidney failure are at higher risk for cardiovascular disease as a result of increased left ventricular mass, hypertrophy, and functional changes (diastolic and systolic dysfunction). A number of risk factors, such as hypertension, anemia, fluid overload, and hyperparathyroidism, may cause left ventricular pathology in these patients. Typically, increased left ventricular mass is the most common myocardial change.¹ Similarly, in our study, the most important changes were observed in the left ventricular geometry. We detected left ventricular dilatation in 29.1% and left ventricular hypertrophy in 38.2% of patients before transplant.

Kidney transplant has become a safe and effective treatment for patients with end-stage renal disease.⁷ Studies have shown significant improvements in heart structure and function after kidney transplant. Beneficial cardiac effects after transplant are attributed to correction of uremia, restoration of electrolyte balance, and reduction of chronic inflammation.⁸ In our study, we observed an improvement in left ventricular diameter and function after transplant. However, the risk of cardiovascular disease persists after transplant due to various factors, such as hypertension, increased arterial stiffness, components of metabolic syndrome, consequences of immunosuppressive therapy, and chronic graft dysfunction.^9-12 We observed that left ventricular dilatation returned to normal in almost all patients after transplant.

Left ventricular hypertrophy is one of the strongest independent risk factors for adult cardiac death in patients on chronic dialysis and in kidney transplant recipients.³ Increased left ventricular mass is the most commonly reported condition and may persist after kidney transplant.¹³ Hernandez and colleagues have reported that successful kidney transplant does not normalize posttransplant LVMI values.¹⁴ Mitsnefes and colleagues pointed out that left ventricular hypertrophy persists even after kidney transplant in children.¹⁵ In another study, LVMI was found to be higher in transplant recipients versus in patients with chronic kidney disease, similar to our study.¹³ A follow-up study reported that left ventricular hypertrophy persisted in the first posttransplant echocardiography evaluation but regressed in the second session of echocardiography.¹⁶ This study showed that long-term follow-up results may be improved with regard to left ventricular hypertrophy. Although the definitive criteria are different, the incidence of left ventricular hypertrophy in pediatric kidney transplant recipients has been reported to be between 48% and 82%.^17-19 In a study that compared LVMI of patients on dialysis versus after transplant, no significant difference was found in terms of left ventricular hypertrophy. Left ventricular hypertrophy was seen in 52% of patients on dialysis, but this incidence rate was 56% after transplant.¹⁵ In our study, left ventricular hypertrophy was detected in 38.2% of patients on dialysis, whereas it was 34.5% in recipients after transplant. The LVMI was calculated to be 126.6 g before transplant, but it increased after transplant to 141.9 g. Left ventricular hypertrophy persisted after transplant, consistent with the literature. Long-term studies may be needed to demonstrate regression of left ventricular hypertrophy.

In an echocardiography evaluation study conducted with a small number of patients, left ventricular end-diastolic and end-systolic diameters of children after renal transplant decreased significantly.²⁰ In our study, we showed a significant decrease in the z scores of left ventricular end-systolic and end-diastolic diameters, indicating that left ventricular dilatation regresses even in the early period after transplant.

Global left ventricle function (EF and FS) is mostly normal in pediatric chronic kidney failure.²¹ In our study, EF was normal in 80% of the patients before transplant and in 92.7% of the patients after transplant. Left ventricular systolic dysfunction was observed in a small number of our patients, and most of these cases of dysfunction returned to normal early after transplant. In adults, FS has been reported to be a more accurate predictor of cardiovascular mortality than EF.²² In our study, there was no significant change in EF after transplant, but the FS increased significantly.

Because cardiovascular diseases are often asymptomatic, it is difficult to prevent cardiovascular events. Regular echocardiography evaluation allows identification of modifiable cardiovascular risk factors, detection of end-organ damage, assessment of graft function, and monitoring of transplant-related complications such as transplant vasculopathy and calcineurin inhibitor-induced cardiotoxicity.¹ Despite the high rate of echocardiographic abnormalities in pediatric patients on dialysis and in pediatric transplant recipients, pediatric guidelines for echocardiography screening are limited. Previous studies have shown that mortality is associated with increased LVMI, systolic and diastolic dysfunction, strain, and cardiovascular events in adults. However, long-term consequences of echocardiographic variables have not been investigated in children.¹ More studies are needed in the pediatric field on this subject. In our clinic, patients on a dialysis regimen are always evaluated with echocardiography during the pretransplant period and at posttransplant follow-up.

This study had some limitations. Because of the retrospective nature of the study, the echocardiography records of some patients were not accessible. The effects of medications such as antihypertensive agents, renin-angiotensin inhibitors, and immunosuppressive drugs before and after kidney transplant were not taken into account in the study. High-risk patients with low EF and who require daily dialysis should be evaluated separately. Our sample was relatively small. In addition, 6 months is insufficient to predict long-term results. Further studies with longer terms and with larger sample sizes are needed.

Chronic renal failure and dialysis significantly increase cardiovascular risks. Cardiac functions must be regularly monitored before and after transplant. Regular echocardiography evaluation allows clinicians to intervene promptly in case of deterioration and to adjust treatment strategies accordingly. Cardiovascular problems must be optimally managed before transplant with effective dialysis and inotropic treatment if required. Transplantation is the optimal treatment option for preservation and improvement of cardiovascular structure and function. A multidisciplinary approach with a cardiologist, a nephrologist, and a surgeon is the key to success.

Volume: 22 Issue: 10 October 2024 - Supplement - 5

FULL TEXT