THE INFLUENCE OF RENAL ALOGRAFT FUNCTION ON CARDIOVSCULAR STATUS AND LEFT VENTRICULAR REMODELLING

Th e synergy and shared co-morbidity, certainly interplay between kidney and cardiovascular disease, where advanced renal failure infl uences on progression of cardiac disease in bi-direction relationship. Cardiovascular diseases are cause of death in almost  of uremic patients. Correction of uremia after successful renal transplantation leads to improved cardiovascular status in the majority of kidney transplanted patients. Th e aim of this study was an evaluation of the infl uence of renal allograft function on left ventricular remodelling in the fi rst year after transplantation comparing echocardiographic fi ndings before and twelve months after transplantation had been done. In retrospective-prospective study we followed up  patients with renal allograft in the fi rst post transplant year. During the study values of serum creatinine and creatinine clearance were monthly monitored. Echocardiographic examination was done before transplantation and one year after the kidney transplantation. Results of our study showed that before transplantation  of patients had echocardiographic signs of left ventricular (LV) hypertrophy, while  of patients had normal echocardiographic fi ndings. After fi rst post transplant year,  of patients showed normal view of LV, and  remained with LV hypertrophy. Diastolic dysfunction of LV till the end of study had been reduced from  to  of patients. Th e positive echocardiographic remodelling of LV signifi cantly correlated with the rise in creatinine clearance and with the reduction of the serum creatinine. Th ese results confi rm positive correlation between renal allograft functional status and remodelling of left ventricular hypertrophy after successful renal


Introduction
Cardiovascular diseases are leading cause of morbidity and mortality in the uremic patients (, ).Left ventricular hypertrophy (LVH) is a well-established marker of cardiovascular risk.The prevalence of LVH increases with progression of renal insufficiency.Left ventricular hypertrophy is frequently present among transplant patients ().Many traditional and non-traditional factors appear to be the stimuli for left ventricular growth in renal failure patients.In renal transplant recipients, relatively little is known about the prognostic factors which infl uence on causes and consequences of LVH.Th e high prevalence of cardiovascular disease in renal transplant recipients could be attributing to both pretransplant and posttransplant risk factors.Cardiovascular mortality in the transplant population has been linked to reduced renal function.Some recently published studies emphasize cardiovascular consequences of improved kidney function in renal transplant patients ().We hypothesized that renal allograft function could influence on course and outcome of left ventricular hypertrophy in the fi rst posttransplant year.Th e objectives of this analysis were to describe the prevalence of LVH and prognostic impact of serum creatinine and creatinine clearance levels on LVH at first year after renal transplantation.Investigation was made by the comparison of echocardiographic findings made before and twelve months after transplantation.

Materials and Methods
The retrospective-prospective clinical study of relationship between renal function and left ventricular remodelling in the renal transplant patients in the fi rst year after transplantation was done at Clinic of Nephrology, University of Sarajevo Clinics Centre.Thirty patients with kidney transplant were studied / male with the average of age , ±, years and  female with the average of age ,± years/ in the first transplant year.All evaluated patients underwent renal transplantation between  and  (two cadavers and  living related kidney transplantation).Patients with severe vascular disease and heart failure, with acute renal rejection, chronic allograft nephropathy with progressively decreased renal function in the fi rst three posttransplant months, and patients older than  years were not included in the study.All patients data were collected at clinic visits and by direct patient communication.Haematological and biochemical param-eters were recorded just before renal transplantation and in one month interval after kidney transplantation in the first posttransplant year, and included control of serum creatinine and creatinine clearance values.Echocardiographic examination was done prior to kidney transplantation and one year after the kidney transplantation at Clinic of Cardiology, University of Sarajevo Clinics Centre.Echocardiographic analysis was performed on M mod, two-dimension and pulse Doppler apparatus.During evaluated period all patients were without signs of fluid overload, with good control of blood pressure.Immunosuppressive drugs /cyclosporine, mycophenolate mofetil, pronisone/ were prescribed by accepted protocol during follow-up.Th e criterion accepted for left ventricular hypertrophy was: left ventricular mass index (LVMI) for male > g/m, for female LVMI >  g/m ().Systolic left ventricular function was estimated by ejection function (EF), where systolic dysfunction was defined as EF<.Left ventricular diastolic function was observed through relationship between early and late atrial phase of rapid left ventricular filling (E/A).Left ventricular diastolic dysfunction was defined as E/A value <,.

Statistical analysis
Th e data were analyzed using the descriptive statistics for each parameter that was followed.Students' t-test was used to compare arithmetic means of numeric variables of each parameters, with the acceptance of statistical signifi cance at the level p<,.Logistic regression was used to establish the independent relationship between left ventricular mass index on echocardiographic fi ndings, and renal function measured by creatinine clearance.

Results
In the total group of patients, on baseline echocardiography before kidney transplantation,  of subjects () showed normal mass of left ventricle,  had left ventricular hypertrophy, out of which fourteen () had concentric and six () had eccentric hypertrophy (Figure ).
Normal function of LV in the beginning of the study had  of patients, while  had dysfunction of left ventricle, out of which  had diastolic and  had systolic-diastolic dysfunction (Figure ).
Ehocardiographic findings in patients first year after transplantation showed normal LV mass index in nineteen patients (), among them  were male (Figure ).LV hypertrophy had  of patients, with dominant concentric type ().Among patients with LV hypertrophy, females were numerous.
All patients with normal LV mass index in the beginning of this study remained with normal LV mass index till the end of this study.From the group of patients with LV hypertrophy ( patients), nine patients had reached normal LV mass index till the end of this study.Patients with LV hypertrophy ( patients) had shown significantly lower LV mass index compared with the start values (p=,), which is presented in Table .In the same time, normal function of LV had been observed in  of patients, while  of patients were with diastolic dysfunction, and  of patients were with systolic-diastolic LV dysfunction.
In the end of first year after the transplantation, the group with normal morphology of LV had higher values of creatinine clearance compared with LV hypertrophy group.The difference in mean values of creatinine clearance between the tested groups was statistically signifi cant (p=,), as it is shown in Table .
In respect of LV functional status, group of patients with normal LV function had signifi cantly higher creatinine clearance (p=,) compared to the group of patients with diastolic dysfunction of LV (, ml/min ± , vs. , ml/min ± ,), as it is presented in Table .
The logistic regression showed independent association between normalization of LV mass on the second echocardiography with each decrease in serum creatinine for  μmol/L (p=,), and with each increase of creatinine clearance for  ml/min (p=,), as it is shown in Table .

Discussion
Cardiovascular disease is the main cause of death in patients with end-stage renal disease.Th e prevalence of cardiovascular diseases, fi rst of all left ventricular hypertrophy, coronary disease, congestive heart failure, among patients with end stage of renal disease (ESRD) on dialysis and transplant renal patients has been higher than in general population.Mortality rate is almost , and it is  to  times higher than in general population ().In the fi rst  years after renal transplantation, half of all deaths are cardiac, often in the presence of a functional  ().
Presence of left ventricular hypertrophy among dialysis patients, determined by echocardiography, reliable, non-invasive and reproducible method of examination, is from   to , and it is the most important factor for survival of this category of patients ().By analyzed echocardiographic findings among our patients before renal transplantation, left ventricular hypertrophy is the most common alteration ().Compared with left ventricular functional status, only  of patients had normal function, diastolic dysfunction was predominated and had been found in  of cases.Th e left ventricular normal view till the end of fi rst year after transplantation had been observed in  of patients compared with  on the start, while  of patients remained with left ventricular hypertrophy ( of patients on the start), with LV mass index signifi cantly lower compared with the start values (, vs. ,, p=,).In the end of this study, the reduction of diastolic dysfunction was signifi cant (p=,).Hernandez et al. () reported that regression of left ventricular hypertrophy partially starts at fi rst year after transplantation, is raised up to maximum value between first two years, persists between third and forth year, while long evolutions of this fi ndings are still unknown.Rigatto et al. () followed up  kidney transplant patients in fi rst year after transplantation, and showed left ventricular hypertrophy as the independent risk factor for mortality and congestive cardiac insuffi ciency.
Epidemiological studies show that about  of renal transplant patients have glomerular fi ltration rate lower then  ml/min, and about  of patients < ml/min ().Correlation between kidney failure and cardiovascular risk factors has important implications for the management of renal transplant recipients.Cardiac remodelling after successful renal transplantation could be based on uremia elimination, and modification of structural and functional characteristics of heart and blood vessels, especially in left ventricular hypertrophy.Good renal allograft function in the fi rst posttransplant year by removed different traditional and non-traditional risk factors for cardiovascular disease confirms the existence of cardio-renal axis and interrelated functions of these two organic systems.

Conclusion
In our study we found that left ventricular hypertrophy is the most frequent cardiac abnormality, present immediately prior to renal transplantation in   patients.Signifi cant association between regression of LV mass on the second echocardiography with improvement of renal allograft function showed that creatinine clearance in the fi rst posttransplant year is an independent predictor of cardiovascular status and outcomes.Mild renal insuffi ciency in renal transplant patients is the risk factor for diastolic dysfunction of LV.

TABLE 1 .
Left ventricular mass index in group with LVH in the beginning and in the end of the study

TABLE 4 .
Interplay between LV mass index on second echocardiography and renal allograft function

TABLE 2 .
Inter-group relationship between mean values of creatinine clearance compared to morphology status of LV in the end of follow up

TABLE 3 .
Inter-group relationship between mean values of creatinine clearance compared to functional status of LV