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NDT Advance Access originally published online on April 23, 2007
Nephrology Dialysis Transplantation 2007 22(8):2328-2333; doi:10.1093/ndt/gfm110
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Reduced coronary flow reserve in young adults with renal transplant

Sara Maria Viganò1,2,3, Maurizio Turiel4,5, Valentina Martina1,2,3, Elisa Meregalli2, Livio Tomasoni4,5, Giuseppe De Blasio4, Luigi Delfino4, Alberto Edefonti2, Paolo Grillo6, Mirella Procaccio1,3, Daniele Cusi1,3 and Luciana Ghio2

1Chair and Graduate School of Nephrology, Department of Sciences and Biomedical Technologies University of Milano, 20090 Segrate (MI), 2Pediatric Nephrology Unit, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, 20122, 3Hypertension and Preventive Nephrology Unit, IRCCS Multimedica, 20099, Sesto San Giovanni (MI) 4Cardiology Unit, IRCCS Istituto Ortopedico Galeazzi, 20161, 5Department of Clinical Sciences L. Sacco, University of Milano, 20157 and 6Epidemology Unit, Department of Occupational and Environmental Health, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, 20122, Milano, Italy

Correspondence and offprint requests to: S. M. Viganò, Chair and Graduate School of Nephrology, Department of Sciences and Biomedical Technologies, University of Milano, Via Fratelli Cervi 93, 20090 Segrate (MI), Italy. Email: saramaria.vigano{at}studenti.unimi.it



   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
Background. Some degree of cardiovascular disease should be suspected in young adults who have been paediatric renal transplant recipients also if no systematic data collection is routinely performed in clinical setting. The aim of our work was to evaluate the degree of cardiovascular damage in these young patients, using a minimally invasive technique. We then evaluated coronary flow reserve (CFR) and carotid intima-media thickness (IMT) in 25 patients (13 males, median age 23.7 years).

Methods. Coronary flow velocity on the left anterior descending coronary artery was assessed by transthoracic echocardiography, before and after dipyridamole, after standard echocardiography. CFR was compared with that of a small control group (n = 16; median age 25 yrs).

Results. In this relatively young sample, mean CFR was 2.8 ± 0.6 (median 2.75), and half of the patients had reduced coronary reserve (P = 0.01). Mean IMT (0.48 ± 0.08 mm) was only slightly, though significantly larger compared with the reference standard (P < 0.05) but was significantly thinner in normotensive than in hypertensive patients (0.42 ± 0.06 vs 0.49 ± 0.05 mm, P < 0.05). The time on dialysis prior to transplantation, hypertension and age at the time of CFR evaluation affect CFR. IMT did not correlate with CFR.

Conclusions: CFR and IMT abnormalities are common in young transplant recipients, in spite of the fact that our paediatric population has much less of the atherosclerotic ‘legacy’ common to adult patients.

Keywords: paediatrics; kidney transplantation; cardiovascular risk; stress echography



   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 
Cardiovascular diseases (CVD) are the most common cause of morbidity and mortality in patients that underwent renal transplant during adulthood [1]. The incidence of CVD in kidney transplant recipients appears to be 3- to 4-fold that observed in age-matched healthy subjects [2].

Independent risk factors for CVD in kidney transplant recipients include age, obesity, diabetes, male gender, acute rejection episodes, pretransplant peripheral vascular, cerebrovascular or ischaemic heart disease [3]. Risk factors, peculiar to transplant recipients, include disturbances in haemostasis, immuno-suppressive therapy and time on dialysis prior to immunosuppression transplantation [4].

Over the past 20 years, transplantation has become routine treatment for children with end-stage renal disease (ESRD). The improvement in the treatment of these patients has determined the creation of a population of young adults, with a long life-expectancy, but with a potentially severe burden of risk factors for the development of CVD, compared with healthy subjects of the same age. In spite of the fact that CVD accounts for 35 to over 50% of all deaths in children with ESRD [5–7], and asymptomatic CVD due to atherosclerosis and coronary artery disease (CAD) (eventually leading also to sudden death) appears highly prevalent in both transplanted and dialysis paediatric and post-paediatric patients [7,8], little is routinely done for quantifying the cardiovascular risk in transplanted children.

As coronary angiography remains the gold standard for diagnosing the presence and extent of CAD, its cost, invasiveness and potential harm limit its use as a screening tool. Large efforts are then devoted to the search and validation of alternative methods. Recently Ishitani used the electron-beam computed tomography (EBCT) to determine the quantity of coronary artery calcification as early index of coronary disease [9] and demonstrated that ~50% of his patients had significant coronary calcification. However, EBCT is expansive and not available routinely.

The aim of the present study was then the search for another, reliable, cost-effective and minimally invasive method for the detection of significant coronary stenosis, myocardial ischemia and/or generalized arterial damage in asymptomatic patients. We then evaluated coronary flow reserve (CFR) [10] with transthoracic Doppler echocardiography after dipyridamole-induced stress (as it correlates well with intra-coronary Doppler wire [11] and PET [12]) and intima-media thickness (IMT) of the carotid artery [13,14] with B-mode echography in asymptomatic young adults who had ESRD during childhood and then underwent kidney transplantation.



   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Discussion
 Acknowledgements
 References
 
Overall, kidney transplant recipients attending our Pediatric Nephrology Unit are 133 (mean age 20.4 ± 8.7 years). For ethical reasons, we decided to propose the study only to those older than 18 with a graft well functioning for at least 1 year and without mental retardation, psychiatric problems or any other clinical complication (ranging from the less severe, as brachial arterial aneurysm with a large arterio-venous shunt, to the most severe as post-transplant lymphoproliferative disorder). The mean age of such sample was 25.8 ± 5.6 years. Of the 32 eligible, 25 accepted. The study was approved by the Institutional Ethical Committee. All those who accepted signed an informed consent.

Echocardiography and coronary flow reserve measurements
The patients were instructed to avoid caffeine, chocolate and smoking for 24 h before echocardiography, which was carried out with a Philips 5500 SONOS echocardiograph. All measurements were performed by the same investigator (Dr De Blasio). Left ventricular internal diameters, septal thickness (ST) and posterior wall thickness (PWT) were measured at end diastole and end systole, according to the guidelines of the American Society of Echocardiography (ASE) [15], using standard parasternal and apical views. No patient showed dyssynergic areas that would invalidate the theoretical assumptions behind the cardiac mass calculations. Left ventricular mass was calculated at end diastole by applying Devereux correction to the ASE-cube LVM formula [16]. Wall thickness and chamber volumes were measured by mono- and bi-dimensional echocardiograms with a 3.5 MHz transducer. The intra-observer coefficient of variation for measurements of left ventricular end-diastolic diameter, septal and posterior left ventricular wall thickness were 0.4, 2.8 and 3.2%.

For CFR measurement, a cannula was inserted in an antecubital vein for the infusion of dipyridamole (0.56 mg/kg in 4 min and 0.28 mg/kg in the next 2 min). The coronary flow velocity on the left anterior descending coronary artery was studied before and after dipyridamole infusion according to standard techniques [17] with an 8 MHz transducer, assessing systolic and diastolic components of the Doppler signal. The coronary flow reserve was calculated as the ratio of diastolic velocity during hyperaemia to diastolic velocity at baseline (Figure 1). All the exams were digitally recorded for later analysis. During the session, the electrocardiogram was monitored continuosly, and blood pressure (BP) was recorded at 2-min interval with a digital BP monitoring. One of the most difficult points in this kind of study intervals is that of an appropriate control sample. In fact, ethical and practical reasons make dipyridamole infusion data difficult to collect in large samples of normal people, especially in the young age range. We then compared CFR values of our cases with percentiles for age and gender we derived from an Italian sample [17] and with a relatively small sample (n = 16) of volunteers recruited within hospital staff with similar median age (25 years) and gender distribution (eight males and eight females).


Figure 1
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  		Fig. 1. Normal (A: CFR = 3.19) and pathological (B: CFR = 1.38) coronary flow Doppler signal.

 
Obviously, the occurrence of changes in heart wall motion during stress were looked for both in cases and controls, but none was observed.

Ultrasound evaluation of carotid intima-media thickness (IMT)
Ultrasonic examinations were performed with the same Philips 5500 Sonos echocardiograph as before, after CFR measurement with an 11 MHz linear array transducer (Philips). Using antero-oblique insonation, the imaging of IMT and lumen diameter of the distal segment of the common carotid artery on both sides was performed, according to a standardized procedure [18]. IMT image, obtained in the far wall of the artery, consisted of two parallel echogenic lumen-intima and media-adventitia interfaces (double-line pattern) visible on at least 1 cm of longitudinal length. Lumen diameter was imaged between the near- and far-wall intima-media interfaces along the same vessel length as for IMT. Once the optimal quality images were obtained, the images of at least three consecutive heartbeats were frozen and stored on magnetic disk. As for echocardiography, measurements of IMT and lumen diameter were performed by the same operator (Dr Tomasoni). IMT values were evaluated using as reference the percentiles for age and gender [19].

Clinical data
The body max index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Data on immuno-suppressive treatment were recoded as drug class, whereas the other treatments (antihypertensive and/or hypocholesterolemic) were recorded and summarized as dichotomous variable (treatment present, absent or by class for antihypertensives). Time on dialysis and time with a functioning graft were measured in months. Serum biochemistry and urinary protein excretion (expressed as urinary protein/urinary creatinine ratio) were measured by autoanalyzer. Glomerular filtration rate (GFR) was estimated by the Cockcroft–Gault formula [20]. BP values recorded at clinic follow-up visits during the last year before cardiovascular assessment were averaged and considered in the analysis. Mean BP (MBP) was computed from systolic BP (SBP) and diastolic BP (DBP) according to the standard formula (Formula )

Statistical analysis
Data are presented as means ± SEM and, due to the small sample size, also as range and median. For the same reason, non-parametric Kruskal–Wallis (K–W) test was applied for comparison between groups, when needed. Association between continuous variables was tested with simple regression, using SPSS 11.0.4 statistical software.



   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Discussion
 Acknowledgements
 References
 
Descriptive statistics of our population as well as haemodynamic data are summarized in Tables 1 and 2 (in which the population was divided in two groups according to CFR values).


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  		Table 1. Descriptive statistics for patients who underwent cardiovascular evaluation

 

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  		Table 2. Descriptive statistics for patients who underwent cardiovascular evaluation divided according to CFR value in 2 groups (CFR = 2.7, it was the minimum CFR value in control group)

 
ESRD in the sample studied was in large part due to malformations of the kidney and/or urinary tract (40%, a proportion similar to that of all kidney transplant recipients attending our Pediatric Nephrology Unit and to that of the Italian population [21]). Mean age as well as the cause of ESDR of the patients who accepted to participate in the study were not different from those of the seven who did not accept.

Before transplantation, 16 patients were treated with haemodialysis and nine with peritoneal dialysis. The mean age at time of transplantation was 18.5 ± 5 years (vs 10.9 ± 8.7 years of the whole population of the 133 transplant recipient) and was 18.9 ± 3.9 in the seven who did not accept. The patients underwent CFR evaluation 100.6 ± 75 months after transplantation (range 13–216). One patient received a live-related donor transplant and another one a combined liver-kidney transplant. One patient required a second transplant (for chronic transplant rejection). Two patients were smokers. Nine subjects were hypercholesterolemic, requiring HMG-CoA reductase inhibitors. One patient had glucose intolerance. Twenty-one were hypertensive, requiring treatment. One was frankly obese (BMI = 31 kg/m2). Immuno-suppressive treatment was as follows: one patient took azathioprine plus corticosteroids (CS), 19 a calcineurin inhibitor (tacrolimus or ciclosporin) plus mycophenolate mofetil and CS and five took a calcineurin inhibitor plus mycophenolate mofetil alone (without CS). All the electrocardiograms taken at rest were normal.

As expected, a large number of our patients were hypertensive in spite of their young age, most likely due to the immuno-suppressive treatment. Although overall hypertension control was acceptable (Table 1), such control was obtained using several (and different among the different patients) classes of antihypertensive drugs. To take this into account, all the BP values recorded during the last year before cardiovascular investigation were averaged and correlated to the number of classes of antihypertensive treatment. The data, reported in Figure 2 for mean BP, show that BP tended to be higher in patients taking the largest number of antihypertensive drug classes (R2 = 0.30; P = 0.005). Similar results were obtained also for systolic and diastolic BP (data not shown).


Figure 2
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  		Fig. 2. Degree of blood pressure control according to the number of antihypertensive classes of drugs.

 
Coronary reserve
The mean CFR was 2.8 ± 0.6 (median 2.75). CFR was within 2 and 2.5 in six and <2 in two other patients. CFR correlated negatively with age, number of months on dialysis prior to transplant and marginally with urinary protein excretion (Table 3). The effect of hypertension on CFR was tested with K–W test and showed that normotensive patients had a significantly better CFR then the others (3.45 ± 0.58 vs 2.68 ± 0.56, P = 0.03). The distribution of CFR values of cases and of the small sample of volunteers is reported in Figure 3 and shows that half of the cases have CFR value less that the smallest value of controls (P = 0.01, K–W test). Cardiac hypertrophy, left posterior and septal wall thickness, kind of dialysis (peritoneal or haemodialysis) or number of months between transplantation and CFR assessment did not correlate with CFR.


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  		Table 3. Results of the bivariate regression analysis with CFR as the dependent variable and the most potentially relevant predictors: time on dialysis, age, urinary protein over creatinine excretion (U Prot/Creatinine), left ventricular mass index (LVMI) and intima-media thickness (IMT)

 

Figure 3
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  		Fig. 3. CFR in controls and transplant recipients.

 
Carotid artery intima-media thickness
The mean IMT was 0.48 ± 0.08 mm (median 0.48 mm), a value slightly larger compared to the reference standard of our laboratory (0.44 ± 0.04 P < 0.05), although none of our patients showed a severe impairment as was the case for CFR. In particular, only one had plaque on the left common carotid artery. IMT was significantly thinner in normotensive patients (0.42 ± 0.06 vs 0.49 ± 0.05 mm, P < 0.05) and did not correlate with any other clinical parameter tested (data not shown), nor with CFR (Table 3), left ventricular mass, wall thickness, BP or kind of dialysis.

Clinical events during cardiovascular evaluation
One patient had chest pain during dipyridamole infusion, with no ECG, nor wall motion changes. He was later studied with myocardioscintigraphy and coronarography, which were negative for coronary stenosis, and the angina was interpreted as microvascular spasm. None of the patients had changes in wall motion during dipyridamole infusion as well.



   Discussion
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
Acknowledgements
 References
 
The main finding of our report is that about half of our sample has CFR values below the minimum value observed in the control sample, and that IMT is slightly increased, in spite of a relatively long duration of a well functioning transplant. Though very small for ethical reasons, our control group behaves similarly to another Italian reference standard where normality of CFR is >3 [22]. Furthermore, the development of hypertension after transplantation and the number of months of dialysis prior transplantation affect the coronary reserve, indicating that a successful renal transplantation may not be sufficient, per se, to improve the CV prognosis [23]. Differently from CFR, IMT was affected only by the development of hypertension. The lack of correlation between IMT and CFR suggests that the two measurements reflect different pathogenetic mechanisms of cardiovascular damage in the present peculiar class of patients.

CFR is a useful marker of functional coronary artery changes in clinical and subclinical stages of CVD [24–26]. Two distinct pathophysiological scenarios may reduce CFR in the presence of normal wall motion response during stress: (i) mild-to-moderate epicardial coronary artery stenosis and (ii) microvascular disease with patent epicardial coronary arteries: i.e. lesions which happen before or after the point of CFR measurement [27]. Whatever the case, both impair cardiovascular survival, so that the observation that half of our patients had CFR values below the lower normal limit, suggests that they are at higher risk.

Besides being only marginally significant, the correlation between CFR and urinary protein excretion may be a simple indicator of initial graft dysfunction, as urinary protein excretion correlated negatively with GFR (R2 = 0.20, P < 0.03). We may speculate that graft dysfunction may aggravate a pro-inflammatory status able per se to induce endothelial dysfunction.

The present report suffers from the intrinsic limitations of the retrospective nature of its design, the small number of patients, the non-homogeneous pharmacological treatment (immuno-suppressive and antihypertensive), as well as the different duration of pre- and post-transplant observation among the patients. Another limitation is that of the representativeness of a sample of only 25 patients of the 133 available. The small sample size was mainly due to ethical considerations. As CFR implies a minimum risk due to dypiridamole infusion, we studied only those patients who could give a ‘really informed consent’, i.e. older than 18 and without cognitive problems. We excluded as well one patient with a large arterio-venous fistula and one with linphoproliferative disorder, since their clinical status could affect the results. Another important weakness is that we cannot correlate reduced CFR with long-term outcome in this particular set of patients, as no follow up data are available. In this regard, our cohort will be easily followed up as all patients are regularly seen at our out-patient clinic. Besides that of correlating CFR with outcome, a secondary important aim will be to analyse CFR changes over times

The results presented pertain then only to individuals older than 18 and draw our attention to two major clinical issues: (i) duration of dialysis and (ii) development of post-transplant hypertension affect myocardial perfusion. Also, if we cannot prove that the observed association has a causal meaning indeed, such observation supports the common clinical behavior of keeping as short as possible the time spent in dialysis by paediatric patients for a long life expectancy. One third of our patients (8 over 25) had CFR <2.5, compatible with reduced coronary perfusion and two of them had CFR <2, consistent with a potentially dangerous impairment of myocardial perfusion. Also, if a clear understanding of the meaning of reduced CFF in our patients is to be reached, patients will need adequate follow-up. Whatever the case, we never observed abnormalities in wall motion, or reduction in ejection fraction. This underscores the fact that conventional echocardiography may be of little value in detecting already impaired coronary perfusion in such set of patients. Translated into clinical practice, CFR may be seen as a promising technique for a more appropriate management of these patients. Our IMT data agree with a previous report [28] and provide only slight support for accelerated atherosclerosis.

To conclude, though retrospective in nature and limited in the applicability to the small size of the sample and lack of follow up data, our result may be relevant since paediatric population has much less of an atherosclerotic ‘legacy’ common to adult patients. If confirmed, our data may point to a primary defect in microcirculation causing diffuse endothelial dysfunction, with impaired vasodilatory reserve, rather than to global arteriosclerosis. Such hypothesis may find support in the only minimal IMT increase observed.



   Acknowledgements
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
References
 
Study supported in part by FIRB grant RBLA038RMA_010 of the Italian Ministry of University and Scientific Research to CD and by IngeniousHyperCare a UE funded Network of Excellence to CD.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Chuang P, Gibney EM, Chan L, Ho PM, Parikh CR. Predictors of cardiovascular events and asociated mortality within two years of kidney transplantation. Transplant Proc (2004) 36:1387–1391.[CrossRef][Web of Science][Medline]
  2. Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. Cardiovascular disease after renal transplantation. J Am Soc Nephrol (1996) 7:158–165.[Abstract]
  3. Kasiske BL, Chakkera HA, Roel J. Explained and unexplained ischemic heart disease in renal transplant recipients. J Am Soc Nephrol (2000) 11:1735–1743.[Abstract/Free Full Text]
  4. Gill JS, Pereira BJ. Death in the first year after kidney transplantation: implications for patients on the transplant waiting list. Transplantation (2003) 75:113–117.[CrossRef][Web of Science][Medline]
  5. McDonald SP, Craig JC. Long-term survival of children with end-stage renal disease. N Engl J Med (2004) 350:2654–2662.[Abstract/Free Full Text]
  6. van der Heijden BJ, van Dijk PC, Verrier-Jones K, Jager KJ, Briggs JD. Renal replacement therapy in children: data from 12 registries in Europe. Pediatr Nephrol (2004) 19:213–221.[CrossRef][Web of Science][Medline]
  7. Oh J, Wunsch R, Turzer M, et al. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation (2002) 106:100–105.[Abstract/Free Full Text]
  8. Gruppen MP, Groothoff JW, Prins M, et al. Cardiac disease in young adult patients with end-stage renal disease since childhood: a Dutch cohort study. Kidney Int (2003) 63:1058–1065.[CrossRef][Web of Science][Medline]
  9. Ishitani MB, Milliner DS, Kim DY, et al. Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients. Am J Transplant (2005) 5:1689–1693.[CrossRef][Web of Science][Medline]
  10. Caiati C, Montaldo C, Zedda N, Bina A, Iliceto S. New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo. Circulation (1999) 99:771–778.[Abstract/Free Full Text]
  11. Hozumi T, Yoshida K, Akasaka T, et al. Noninvasive assessment of coronary flow velocity and coronary flow reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. J Am Coll Cardiol (1998) 32:1251–1259.[Abstract/Free Full Text]
  12. Crowley JJ, Shapiro LM. Noninvasive analysis of coronary artery poststenotic flow characteristics by using transthoracic echocardiography. J Am Soc Echocardiogr (1998) 11:1–9.[CrossRef][Web of Science][Medline]
  13. Grobbee DE, Bots ML. Carotid artery intima-media thickness as an indicator of generalized atherosclerosis. J Intern Med (1994) 236:567–573.[Web of Science][Medline]
  14. Chambless LE, Heiss G, Folsom AR, et al. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol (1997) 146:483–494.[Abstract/Free Full Text]
  15. Sahn DJ, De Maria A, Kisslo J, et al. The Committee on M-Mode Standardization of the American Society of Echocardiography. Recommendations regarding quantitation in M-mode echocardiography: result of a survey of echocardiographic measurements. Circulation (1978) 58:1072–1083.[Abstract/Free Full Text]
  16. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Circulation (1977) 55:613–618.[Abstract/Free Full Text]
  17. Rigo F. Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool. Cardiovasc Ultrasound (2005) 3:8–18.[CrossRef][Medline]
  18. O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid artery intima-media thickness as a risk factor for myocarial infarction and stroke in older adults. N Eng J Med (1999) 340:14–22.[Abstract/Free Full Text]
  19. Denarie N, Gariepy J, Chironi G, et al. Distribution of ultrasonographically-assessed dimensions of common carotid arteries in healty adults of both sexes. Atherosclerosis (2000) 148:297–302.[CrossRef][Web of Science][Medline]
  20. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron (1976) 16:31–41.[Web of Science][Medline]
  21. Ardissino G, Daccò V, Testa S, et al. Epidemiology of Chronic Renal Failure in Children: Data From the ItalKid. Pediatrics (2003) 111:382–387.[CrossRef]
  22. Dimitrow PP, Galderisi M, Rigo F. The non-invasive documentation of coronary microcirculation impairment: role of transthoracic echocardiography. Cardiovasc Ultrasound (2005) 3:18–26.[CrossRef][Medline]
  23. Parekh RS, Carroll CE, Wolfe RA, Port FK. Cardiovascular mortality in children and young adults with end-stage kidney disease. J Pediatr (2002) 141:191–197.[CrossRef][Web of Science][Medline]
  24. Pitkänen OP, Raitakari OT, Rönnemaa T, et al. Influence of cardiovascular risk status on coronary flow reserve in healthy young men. Am J Cardiol (1997) 79:1690–1692.[CrossRef][Web of Science][Medline]
  25. Raitakari OT, Niinikoski H, Pitkänen OP, et al. Early impairment of coronary flow reserve in young men with borderline hypertension. J Am Coll Cardiol (1998) 32:147–153.[Abstract/Free Full Text]
  26. Pitkänen OP, Nuutila P, Raitakari OT, et al. Coronary flow reserve is reduced in young men with IDDM. Diabetes (1998) 47:248–254.[Abstract]
  27. Rigo F, Cortigiani L, Pasanisi E, et al. The additional prognostic value of coronary flow reserve on left anterior descending artery in patients with negative stress echo by wall motion criteria. A Transthoracic Vasodilator Stress Echocardiography Study. Am Heart J (2006) 151:124–130.[CrossRef][Web of Science][Medline]
  28. Mitsnefes MM, Kimball TR, Witt SA, Glascock BJ, Khoury PR, Daniels SR. Abnormal Carotid Artery Structure and Function in Children and Adolescents With Successful Renal Transplantation. Circulation (2004) 110:97–101.[Abstract/Free Full Text]
Received for publication: 9.11.06
Accepted in revised form: 8. 2.07


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