- Email: [email protected]
Graft Function and Arterial Stiffness: Can Bioimpedance Analysis Be Useful in Renal Transplant Recipients?
Graft Function and Arterial Stiffness: Can Bioimpedance Analysis Be Useful in Renal Transplant Recipients? S. Sezera, B. Gurlek Demircia,*, O. Guliyeva, C.B. Sayina, T. Colaka, F.N. Ozdemir Acarb, and M. Haberalc a Department of Nephrology, Baskent University Faculty of Medicine, Ankara, Turkey; bDepartment of Nephrology, Baskent University Faculty of Medicine, Istanbul, Turkey; and cDepartment of General Surgery, Baskent University Faculty of Medicine, Ankara, Turkey
ABSTRACT Objective. We aimed to determine the total body water (TBW) by means of bioimpedance analysis (BIA) and to analyze the association of TBW, graft function, and arterial stiffness by means of pulse-wave velocity (PWV) and echocardiographic measurements in renal transplant (RT) recipients. Methods. Eighty-two RT recipients (mean age, 38.7 11.5 y; 58 male) who were using 1 antihypertensive treatment were enrolled in the study. Biochemical parameters, 24-hour urinary protein loss, estimated glomerular filtration rate (eGFR), transthoracic echocardiography, bioimpedance analysis according to systolic blood pressure, TBW, lean tissue index (LTI), extracellular water (ECW), intracellular water (ICW), lean tissue mass (LTM), phase angle (Phi50) levels, and renal resistive index (RRI) were evaluated. Results. TBW and ECW were significantly correlated with systolic blood pressure. Urinary protein loss, pulmonary artery pressure, frequency of overhydration, systolic blood pressure, TBW, LTI, ECW, ICW, LTM, and Phi50 values were significantly higher in patients with estimated glomerular filtration rate (eGFR) 15e49 mL/min but similar in patients with eGFR 50e70 mL/min. Conclusions. Hypertensive RT recipients have increased TBW, LTI, ICW, FTI, LTM, and Phi50 values. Graft function is positively correlated with systolic blood pressure and BIA parameters. Therefore, hypertensive RT recipients should be closely followed with the use of BIA for an early diagnosis of loss of graft function.
R
ENAL TRANSPLANTATION (RT) is the best treatment of choice for patients with end-stage renal disease. Despite improving of renal dysfunction, patients are at risk for existing or new onset of conditions as hypertension after transplantation. In RT recipients, hypertension is usually defined as blood pressure (BP) >140/90 mm Hg or if a patient is on treatment with antihypertensive drugs [1]. Hypertension in RT recipients is a major traditional risk factor for atherosclerotic cardiovascular (CV) disease, which is the leading cause of premature death and a major factor in death-censored graft failure. There are several causes of hypertension in RT patients, such as pre-transplantation factors (preexisting hypertension, obesity, primary kidney disease), donor-related factors (elderly or hypertensive donor), transplant-related factors (prolonged ischemia time, delayed graft function), immunosuppressive therapy (calcineurin inhibitors, corticosteroids), renal transplant artery stenosis,
chronic allograft nephropathy, and extracellular fluid volume expansion [2]. Although biochemical markers, such as A-type natriuretic peptide or cyclic guanidine monophosphate, represent sensible methods for assessing overload, there are specific limitations, such as congestive heart failure and valve disease. In addition, they require expensive technology available to few centers, making their determination unsuitable for routine clinical use. Bioimpedance spectroscopy analysis (BIA) is a noninvasive tool, useful both for measuring body fluid and for evaluating fat mass (FM) and lean mass, which is really the expression of muscle mass [3]. This tool has *Address correspondence to Bahar Gurlek Demirci, Department of Nephrology, Baskent University Faculty of Medicine, 5th street, Nb:48, postal code: 06490, Ankara, Turkey. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.10.067
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1182
Transplantation Proceedings, 47, 1182e1185 (2015)
GRAFT FUNCTION AND ARTERIAL STIFFNESS IN RENAL TX
revealed that overhydration (OH) is a strong predictor of left ventricular hypertrophy and mortality [3], whereas blood pressure is a poor predictor of OH during heart failure [4]. Another CV risk factor in RT recipients is increased arterial stiffness despite partial restoration of kidney function. Patient and donor characteristics that have been related to measures of arterial stiffness or wave reflection include donor age [5], graft function [6], microinflammation [7], and use of cyclosporine [8]. Furthermore, hypervolemia, anemia, and increased cardiac output, which is increased by arteriovenous access, are factors contributing to the elevation of pulmonary blood flow rate, which may lead to increased pulmonary artery pressure [9]. In the present study, we aimed to determine the total body water (TBW) by means of BIA and to analyze the association of TBW, graft function, arterial stiffness by means of pulse-wave velocity (PWV) and echocardiographic measurements in RT recipients. MATERIALS AND METHODS Patients and Clinical Evaluation Eighty-two RT recipients (mean age, 38.7 11.5 y; 58 male) being followed in our center who were using 1 antihypertensive treatment were enrolled into the study. Brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with the use of a mercury sphygmomanometer with the appropriate cuff size for arm circumference after 15 minutes of rest. All data, such as lipid profile (total, high-density lipoprotein, and low-density lipoprotein cholesterol, triglyceride), parathyroid hormone, 24-hour urinary protein loss, and complete blood count, were collected during the routine clinical follow-up of the transplant recipients. Each patient provided written informed consent to use their clinical data for study purposes. The estimated glomerular filtration rate (eGFR) was calculated with the use of the Cockroft-Gault formula, adjusted for sex (30.85 for females) and expressed in mL/min/1.73 m2.
Measurement of Bioimpedance After measurement of body weight and height, BIA was measured with the use of the Body Composition Monitor (BCM) from Fresenius Medical Care (Germany). Four electrodes were placed on the right hand and foot on the side contralateral to the arteriovenous fistula (if present) of the supine patient. Two electrodes were dorsally placed on the hand: in the metacarpophalangeal articulations and in the corpus, 5 cm apart. The pair on the foot were located in the metatarsophalangeal and in the articulation, 6 cm apart. The following were determined: extracellular water (ECW), intracellular water (ICW), and total body water (TBW) in L, total lean tissue mass (LTM) in kg, lean tissue index (LTI) in g/m2, phase angle (Phi50), and OH in liters.
1183 performed consecutively at 2 superficial artery sites (carotid-femoral segment). Integral software was used to process each set of pulse-wave and electrocardiographic data to calculate the mean time difference between R-wave and pulse-wave on a beat-to-beat basis, with an average of 10 consecutive cardiac cycles. The PWV was calculated with the use of the distance and mean time difference between the 2 recorded points.
Doppler Echocardiography Complete 2-dimensional and Doppler echocardiography was recorded with the use of various models of commercially available echocardiographic equipment. Patients were placed in the left lateral decubitus position, and standard parasternal and 4-chamber apical views were obtained. Pulmonary arterial pressure (PAP) was calculated, and values >25 mm Hg were accepted as pulmonary hypertension [10].
Statistical Analyses Statistical analyses were performed with the use of SPSS software (v11.0; IBM, Armonk, New York). All numeric data are expressed as mean SD. Data normality was analyzed by means of KolmogorovSmirnov test. All numeric variables with normal distribution are expressed as mean SD, whereas variables with skew distribution are expressed as median and interquartile range. Categoric variables are given as percentages and were compared with the use of the chi-square test. Normally distributed numeric variables were compared by means of independent-samples Student t test.
RESULTS
Demographic characteristics and BIA data for the study group are summarized in Table 1. Mean TBW (31.0 11.1 L) and mean ECW (25.5 12.7 L) were significantly correlated with mean SBP (117.4 27.3 mm Hg; P ¼ .001). Patients with eGFR <70 mL/min (n ¼ 40) were divided into 2 groups according to eGFR as group 1 (eGFR 15e49 mL/min; n ¼ 29) and group 2 (eGFR: 50e69 mL/min; n ¼ 11). Urinary protein loss (1,713.2 50.0 vs 170.2 15.4 mg/d; P ¼ .001), PAP (45.6 0.61 vs 18.7 0.56 mm Hg; P ¼ .001), OH (0.9 0.2 vs 0.68 0.2; P ¼ .004), SBP (144.0 3.0 vs 102.8 2.7 mm Hg; P ¼ .04), TBW (45.1 1.0 vs 23.3 0.3 L; P ¼ .001), ECW (21.0 1.0 vs 17.1 0.7 L; P ¼ .032), and Phi50 (552.4 19.6 vs 218.6 0.8; P < .05) were significantly higher in group 1. LTI (8.7 0.2 vs 11.7 0.3 kg/m2; P < .005) and LTM (15.8 0.4 vs 38.1 2.5 kg; P ¼ .002) were significantly lower in group 1. Mean PWV was 7.4 0.6 vs 6.1 0.4 cm/s in groups 1 and 2, respectively (P ¼ .001). However, body mass indexes were similar in the 2 groups (22.0 0.7 vs 17.1 0.7 kg/m2; P ¼ .624). In regression analysis, TBW and ECW were detected as the predictors of PWV (r ¼ .216; P < .05).
Carotid-Femoral Pulse-Wave Velocity Measurements
DISCUSSION
Measurements of PWV were performed with the use of a pressure tonometer to transcutaneously record the pressure-pulse waveform in the underlying artery (Sphygmocor system; Atcor Medical, Australia), as previously described. Pulse-wave recordings (Sphygmocor system; Atcor Medical, Australia) from carotid-femoral segment were
Although the survival advantage offered by successful renal transplantation can be attributed in large part to a longterm reduction of CV disease progression and mortality, the annual risk of CV death remains 50-fold higher than in the general population [11,12]. The present study revealed
1184
SEZER, GURLEK DEMIRCI, GULIYEV ET AL Table 1. Demographic Characteristics and Bioimpedance Analysis Data for the Study Group Patient Characteristic
eGFR 15e49 mL/min
eGFR 50e69 mL/min
eGFR 70 mL/min
P Value
No of patients Age (y) Sex male (n) Age of transplantation (mo) Hemoglobin (g/dL) Body mass index (kg/m2) Glomerular filtration rate (mL/min) Total body water (L) Extracellular body water (L) Intracellular body water (L) Lean tissue index (kg/m2) Lean tissue mass (kg) Fat tissue index (kg/m2) Ejection fraction (%) Pulmonary arterial pressure (mm Hg)
29 (35%) 39.5 2.1 21 62.2 9.6 11.6 0.3 22.0 3.7 32.6 3.7 45.1 1.0 21.0 1.0 17.1 0.8 17.7 0.3 38.1 1.0 18.3 0.4 60.2 0.3 45.6 0.6
11 (13%) 39.8 4.1 11 55.7 11.0 12.1 0.7 17.1 0.6 56.7 2.6 23.3 0.3 17.1 0.7 12.5 1.4 10.5 0.2 16.0 1.0 9.7 0.4 60.5 0.7 18.7 0.56
42 (52%) 38.0 1.7 26 73.0 8.5 12.4 0.4 18.6 0.1 86.4 4.2 26.5 0.3 16.1 0.6 10.4 1.2 8.3 0.2 15.7 0.4 7.2 0.3 60.4 0.3 17.3 0.3
.524 .684 .320 .614 .210 .624 .001 .001 .032 .216 <.005 .002 .06 .210 .001
that hypertensive RT recipients have increased TBW, LTI, ECW, FTI, LTM, and Phi50 values, allograft function is positively correlated with systolic blood pressure, renal resistive index, and BIA parameters, and aortic PWV is positively correlated with OH. It is well known that the causality of hypertension in the general population may be different from that in patients with chronic renal disease, which probably includes fluid overload [13]. A large number of studies have examined the relationship between fluid overload and hypertension in patients with chronic renal disease however have not been studied in renal transplant recipients [14,15]. In the present study, patients with lower eGFR, particularly 15e50 mL/min, have higher SBP, urinary protein loss, TBW, ECW, ICW, and Phi50 values compared with patients with eGFR >50 mL/min. In the literature, the relationship of increased ECW and blood pressure in patients with poor renal function were also demonstrated [16,17]. Opelz et al demonstrated a striking association between systolic and diastolic BP levels and kidney graft survival. In their follow-up study of >29,000 cadaveric renal transplant recipients, they found that increasing levels of systolic and diastolic BP after transplantation were associated with a graded increase of subsequent graft failure [18]. In the present study, TBW and its distribution among compartments plays a critical role in predicting renal outcome, as similarly found in Saxena et al’s study, who showed that SBP was associated with TBW (P ¼ .016), ECW (L; r ¼ 0.99), and ECW% (r ¼ 0.78) [19]. In the present study, although body mass indexes were similar, LTI and LTM were significantly lower in patients with eGFR <50 mL/min. Similarly in a recent study, Chan et al showed a positive correlation between graft function and LTI in 106 stable RT recipients [20]. To our knowledge, BIA should be applied regularly to RT recipients, and patients with high FM and low LTM should be offered for reduction in dietary fat and regular exercise to improve graft function and survival. In patients with chronic renal disease, hypervolemia, anemia, and increased cardiac output, which is increased by
arteriovenous access, are factors contributing to the elevation of pulmonary blood flow rate, which may lead to pulmonary hypertension. In the present study, increased ECW and TBW were significantly positively correlated with PAP. These findings demonstrate that hypervolemia is an important determining factor for the development of pulmonary hypertension in RTRs. All findings that are related to changes in intravascular volume, such as ejection fraction and volume expansion, may lead to increased atrial pressure and thus to pulmonary hypertension. Finally, we found that aortic PWV is positively correlated with OH. Reduced aortic compliance leads to increased aortic systolic pressures that results in increased PWV [21,22]. In addition, in patients with renal dysfunction, the compliance of the artery may be decreased as a result of altered intrinsic elastic properties [23], associated with fibroelastic intimal thickening and calcifications [24]. The relationship among arterial stiffness, graft function, and blood pressure can be explained by side effects of immunosuppressive drugs in addition to donor age, microinflammation, and vascular damage that occurred during the pre-transplantation period. Our single-center study has several limitations. Although it was adequately powered to detect a significant association among the volume status, blood pressure, and graft outcome, the number of patients was relatively small. Furthermore, demographic characteristics of donors and data about pre-transplantation recipient PWV were not available. Furthermore, demographic characteristics of donors and data about pre-transplantation recipient PWV were not reported. CONCLUSION
Our study confirms the association between hypertension, OH, and graft function. For patients with declining eGFR, close follow-up of TBW by means of BIA may be an early indicator and prevent CV complications in RT recipients. Further studies with larger populations and including
GRAFT FUNCTION AND ARTERIAL STIFFNESS IN RENAL TX
donor-related factors are needed to demonstrate the effects of volume status on graft function and arterial stiffness. ACKNOWLEDGMENTS The authors are very grateful to the team of physicians, residents, and nurses from the Baskent University Hospital Faculty of Medicine for providing technical support in the development of this research and for the outstanding assistance provided to the patients.
REFERENCES [1] Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis 2011;57:331e41. [2] First MR, Neylan JF, Rocher LL, Tejani A. Hypertension after renal transplantation. J Am Soc Nephrol 1994;4:30e6. [3] Wizemann V, Wabel P, Chamney P, Zaluska W, Moiss L, Rodes CH, et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant 2009;24:1574e9. [4] Wabel P, Moissl U, Chamney P, et al. Toward improved cardiovascular management: the necessity of combining blood pressure and fluid overload. Nephrol Dial Transplant 2008;23: 2965e71. [5] Delahousse M, Chaignon M, Mesnard L, Boutouyrie P, Safar ME, Lebret T, et al. Aortic stiffness of kidney transplant recipients correlates with donor age. J Am Soc Nephrol 2008;19: 798e805. [6] Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236e41. [7] Verbeke F, van Biesen W, Peeters P, van Bortel LM, Vanholder RC. Arterial stiffness and wave reflections in renal transplant recipients. Nephrol Dial Transplant 2007;22:3021e7. [8] Ferro CJ, Savage T, Pinder SJ, Tomson CR. Central aortic pressure augmentation in stable renal transplant recipients. Kidney Int 2002;62:166e71. [9] Unal A, Sipahioglu M, Oguz F, Kaya M, Kucuk H, Tokgoz B, et al. Pulmonary hypertension in peritoneal dialysis patients: prevalence and risk factors. Perit Dial Int 2009;29:191e8. [10] Proceedings of the 4th World Symposium on Pulmonary Hypertension. J Am Coll Cardiol 2009;54:s1e117.
1185 [11] Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant 2004;4:1662e8. [12] Aakhus S, Dahl K, Wideroe TE. Cardiovascular disease in stable renal transplant patients in Norway: morbidity and mortality during a 5-yr follow-up. Clin Transplant 2004;18:596e604. [13] Horl MP, Horl WH. Hemodialysis-associated hypertension: pathophysiology and therapy. Am J Kidney Dis 2002;39:227e44. [14] Rahman M, Fu P, Sehgal AR, Smith MC. Interdialytic weight gain, compliance with dialysis regimen, and age are independent predictors of blood pressure in hemodialysis patients. Am J Kidney Dis 2000;35:257e65. [15] Chen YC, Chen HH, Yeh JC, Chen SY. Adjusting dry weight by extracellular volume and body composition in hemodialysis patients. Nephron 2002;92:91e6. [16] Koomans HA, Roos JC, Boer P, Geyskes GG, Mees EJ. Salt sensitivity of blood pressure in chronic renal failure. Evidence for renal control of body fluid distribution in man. Hypertension 1982;4:190e7. [17] Fagugli RM, Pasini P, Quintaliani Q, et al. Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients. Nephrol Dial Transplant 2003;18:2332e8. [18] Opelz G, Dohler B. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant 2005;5:2725e31. [19] Saxena A, Sharma RK. Hypertension in post-renal transplant patients: pilot study. Saudi J Kidney Dis Transpl 2014;25: 22e8. [20] Chan W, Bosch JA, Jones D, Kaur O, Inston N, Moore S, et al. Predictors and consequences of fatigue in prevalent kidney transplant recipients. Transplantation 2013;96(11):987e94. doi: 10.1097/TP.0b013e3182a2e88b. PMID: 23982341. [21] London G, Guerin A, Pannier B, Marchais S, Benetos A, Safar M. Increased systolic pressure in chronic uremia. Role of arterial wave reflections. Hypertension 1992;20:10e9. [22] London GM, Marchais SJ, Guerin AP, Metivier F, Pannier B. Cardiac hypertrophy and arterial alterations in end-stage renal disease: hemodynamic factors. Kidney Int 1993;43:42e9. [23] Mourad J-J, Girerd X, Boutouyrie P, Laurent S, Safar M, London G. Increased stiffness of radial artery wall material in endstage renal disease. Hypertension 1997;30:1425e30. [24] Ibels LS, Alfrey AC, Hufer WE, Craswell PW, Anderson JT, Weil R. Arterial calcification and pathology in uremic patients undergoing dialysis. Am J Med 1979;66:790e6.
ABSTRACT Objective. We aimed to determine the total body water (TBW) by means of bioimpedance analysis (BIA) and to analyze the association of TBW, graft function, and arterial stiffness by means of pulse-wave velocity (PWV) and echocardiographic measurements in renal transplant (RT) recipients. Methods. Eighty-two RT recipients (mean age, 38.7 11.5 y; 58 male) who were using 1 antihypertensive treatment were enrolled in the study. Biochemical parameters, 24-hour urinary protein loss, estimated glomerular filtration rate (eGFR), transthoracic echocardiography, bioimpedance analysis according to systolic blood pressure, TBW, lean tissue index (LTI), extracellular water (ECW), intracellular water (ICW), lean tissue mass (LTM), phase angle (Phi50) levels, and renal resistive index (RRI) were evaluated. Results. TBW and ECW were significantly correlated with systolic blood pressure. Urinary protein loss, pulmonary artery pressure, frequency of overhydration, systolic blood pressure, TBW, LTI, ECW, ICW, LTM, and Phi50 values were significantly higher in patients with estimated glomerular filtration rate (eGFR) 15e49 mL/min but similar in patients with eGFR 50e70 mL/min. Conclusions. Hypertensive RT recipients have increased TBW, LTI, ICW, FTI, LTM, and Phi50 values. Graft function is positively correlated with systolic blood pressure and BIA parameters. Therefore, hypertensive RT recipients should be closely followed with the use of BIA for an early diagnosis of loss of graft function.
R
ENAL TRANSPLANTATION (RT) is the best treatment of choice for patients with end-stage renal disease. Despite improving of renal dysfunction, patients are at risk for existing or new onset of conditions as hypertension after transplantation. In RT recipients, hypertension is usually defined as blood pressure (BP) >140/90 mm Hg or if a patient is on treatment with antihypertensive drugs [1]. Hypertension in RT recipients is a major traditional risk factor for atherosclerotic cardiovascular (CV) disease, which is the leading cause of premature death and a major factor in death-censored graft failure. There are several causes of hypertension in RT patients, such as pre-transplantation factors (preexisting hypertension, obesity, primary kidney disease), donor-related factors (elderly or hypertensive donor), transplant-related factors (prolonged ischemia time, delayed graft function), immunosuppressive therapy (calcineurin inhibitors, corticosteroids), renal transplant artery stenosis,
chronic allograft nephropathy, and extracellular fluid volume expansion [2]. Although biochemical markers, such as A-type natriuretic peptide or cyclic guanidine monophosphate, represent sensible methods for assessing overload, there are specific limitations, such as congestive heart failure and valve disease. In addition, they require expensive technology available to few centers, making their determination unsuitable for routine clinical use. Bioimpedance spectroscopy analysis (BIA) is a noninvasive tool, useful both for measuring body fluid and for evaluating fat mass (FM) and lean mass, which is really the expression of muscle mass [3]. This tool has *Address correspondence to Bahar Gurlek Demirci, Department of Nephrology, Baskent University Faculty of Medicine, 5th street, Nb:48, postal code: 06490, Ankara, Turkey. E-mail: [email protected]
0041-1345/15 http://dx.doi.org/10.1016/j.transproceed.2014.10.067
ª 2015 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
1182
Transplantation Proceedings, 47, 1182e1185 (2015)
GRAFT FUNCTION AND ARTERIAL STIFFNESS IN RENAL TX
revealed that overhydration (OH) is a strong predictor of left ventricular hypertrophy and mortality [3], whereas blood pressure is a poor predictor of OH during heart failure [4]. Another CV risk factor in RT recipients is increased arterial stiffness despite partial restoration of kidney function. Patient and donor characteristics that have been related to measures of arterial stiffness or wave reflection include donor age [5], graft function [6], microinflammation [7], and use of cyclosporine [8]. Furthermore, hypervolemia, anemia, and increased cardiac output, which is increased by arteriovenous access, are factors contributing to the elevation of pulmonary blood flow rate, which may lead to increased pulmonary artery pressure [9]. In the present study, we aimed to determine the total body water (TBW) by means of BIA and to analyze the association of TBW, graft function, arterial stiffness by means of pulse-wave velocity (PWV) and echocardiographic measurements in RT recipients. MATERIALS AND METHODS Patients and Clinical Evaluation Eighty-two RT recipients (mean age, 38.7 11.5 y; 58 male) being followed in our center who were using 1 antihypertensive treatment were enrolled into the study. Brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured with the use of a mercury sphygmomanometer with the appropriate cuff size for arm circumference after 15 minutes of rest. All data, such as lipid profile (total, high-density lipoprotein, and low-density lipoprotein cholesterol, triglyceride), parathyroid hormone, 24-hour urinary protein loss, and complete blood count, were collected during the routine clinical follow-up of the transplant recipients. Each patient provided written informed consent to use their clinical data for study purposes. The estimated glomerular filtration rate (eGFR) was calculated with the use of the Cockroft-Gault formula, adjusted for sex (30.85 for females) and expressed in mL/min/1.73 m2.
Measurement of Bioimpedance After measurement of body weight and height, BIA was measured with the use of the Body Composition Monitor (BCM) from Fresenius Medical Care (Germany). Four electrodes were placed on the right hand and foot on the side contralateral to the arteriovenous fistula (if present) of the supine patient. Two electrodes were dorsally placed on the hand: in the metacarpophalangeal articulations and in the corpus, 5 cm apart. The pair on the foot were located in the metatarsophalangeal and in the articulation, 6 cm apart. The following were determined: extracellular water (ECW), intracellular water (ICW), and total body water (TBW) in L, total lean tissue mass (LTM) in kg, lean tissue index (LTI) in g/m2, phase angle (Phi50), and OH in liters.
1183 performed consecutively at 2 superficial artery sites (carotid-femoral segment). Integral software was used to process each set of pulse-wave and electrocardiographic data to calculate the mean time difference between R-wave and pulse-wave on a beat-to-beat basis, with an average of 10 consecutive cardiac cycles. The PWV was calculated with the use of the distance and mean time difference between the 2 recorded points.
Doppler Echocardiography Complete 2-dimensional and Doppler echocardiography was recorded with the use of various models of commercially available echocardiographic equipment. Patients were placed in the left lateral decubitus position, and standard parasternal and 4-chamber apical views were obtained. Pulmonary arterial pressure (PAP) was calculated, and values >25 mm Hg were accepted as pulmonary hypertension [10].
Statistical Analyses Statistical analyses were performed with the use of SPSS software (v11.0; IBM, Armonk, New York). All numeric data are expressed as mean SD. Data normality was analyzed by means of KolmogorovSmirnov test. All numeric variables with normal distribution are expressed as mean SD, whereas variables with skew distribution are expressed as median and interquartile range. Categoric variables are given as percentages and were compared with the use of the chi-square test. Normally distributed numeric variables were compared by means of independent-samples Student t test.
RESULTS
Demographic characteristics and BIA data for the study group are summarized in Table 1. Mean TBW (31.0 11.1 L) and mean ECW (25.5 12.7 L) were significantly correlated with mean SBP (117.4 27.3 mm Hg; P ¼ .001). Patients with eGFR <70 mL/min (n ¼ 40) were divided into 2 groups according to eGFR as group 1 (eGFR 15e49 mL/min; n ¼ 29) and group 2 (eGFR: 50e69 mL/min; n ¼ 11). Urinary protein loss (1,713.2 50.0 vs 170.2 15.4 mg/d; P ¼ .001), PAP (45.6 0.61 vs 18.7 0.56 mm Hg; P ¼ .001), OH (0.9 0.2 vs 0.68 0.2; P ¼ .004), SBP (144.0 3.0 vs 102.8 2.7 mm Hg; P ¼ .04), TBW (45.1 1.0 vs 23.3 0.3 L; P ¼ .001), ECW (21.0 1.0 vs 17.1 0.7 L; P ¼ .032), and Phi50 (552.4 19.6 vs 218.6 0.8; P < .05) were significantly higher in group 1. LTI (8.7 0.2 vs 11.7 0.3 kg/m2; P < .005) and LTM (15.8 0.4 vs 38.1 2.5 kg; P ¼ .002) were significantly lower in group 1. Mean PWV was 7.4 0.6 vs 6.1 0.4 cm/s in groups 1 and 2, respectively (P ¼ .001). However, body mass indexes were similar in the 2 groups (22.0 0.7 vs 17.1 0.7 kg/m2; P ¼ .624). In regression analysis, TBW and ECW were detected as the predictors of PWV (r ¼ .216; P < .05).
Carotid-Femoral Pulse-Wave Velocity Measurements
DISCUSSION
Measurements of PWV were performed with the use of a pressure tonometer to transcutaneously record the pressure-pulse waveform in the underlying artery (Sphygmocor system; Atcor Medical, Australia), as previously described. Pulse-wave recordings (Sphygmocor system; Atcor Medical, Australia) from carotid-femoral segment were
Although the survival advantage offered by successful renal transplantation can be attributed in large part to a longterm reduction of CV disease progression and mortality, the annual risk of CV death remains 50-fold higher than in the general population [11,12]. The present study revealed
1184
SEZER, GURLEK DEMIRCI, GULIYEV ET AL Table 1. Demographic Characteristics and Bioimpedance Analysis Data for the Study Group Patient Characteristic
eGFR 15e49 mL/min
eGFR 50e69 mL/min
eGFR 70 mL/min
P Value
No of patients Age (y) Sex male (n) Age of transplantation (mo) Hemoglobin (g/dL) Body mass index (kg/m2) Glomerular filtration rate (mL/min) Total body water (L) Extracellular body water (L) Intracellular body water (L) Lean tissue index (kg/m2) Lean tissue mass (kg) Fat tissue index (kg/m2) Ejection fraction (%) Pulmonary arterial pressure (mm Hg)
29 (35%) 39.5 2.1 21 62.2 9.6 11.6 0.3 22.0 3.7 32.6 3.7 45.1 1.0 21.0 1.0 17.1 0.8 17.7 0.3 38.1 1.0 18.3 0.4 60.2 0.3 45.6 0.6
11 (13%) 39.8 4.1 11 55.7 11.0 12.1 0.7 17.1 0.6 56.7 2.6 23.3 0.3 17.1 0.7 12.5 1.4 10.5 0.2 16.0 1.0 9.7 0.4 60.5 0.7 18.7 0.56
42 (52%) 38.0 1.7 26 73.0 8.5 12.4 0.4 18.6 0.1 86.4 4.2 26.5 0.3 16.1 0.6 10.4 1.2 8.3 0.2 15.7 0.4 7.2 0.3 60.4 0.3 17.3 0.3
.524 .684 .320 .614 .210 .624 .001 .001 .032 .216 <.005 .002 .06 .210 .001
that hypertensive RT recipients have increased TBW, LTI, ECW, FTI, LTM, and Phi50 values, allograft function is positively correlated with systolic blood pressure, renal resistive index, and BIA parameters, and aortic PWV is positively correlated with OH. It is well known that the causality of hypertension in the general population may be different from that in patients with chronic renal disease, which probably includes fluid overload [13]. A large number of studies have examined the relationship between fluid overload and hypertension in patients with chronic renal disease however have not been studied in renal transplant recipients [14,15]. In the present study, patients with lower eGFR, particularly 15e50 mL/min, have higher SBP, urinary protein loss, TBW, ECW, ICW, and Phi50 values compared with patients with eGFR >50 mL/min. In the literature, the relationship of increased ECW and blood pressure in patients with poor renal function were also demonstrated [16,17]. Opelz et al demonstrated a striking association between systolic and diastolic BP levels and kidney graft survival. In their follow-up study of >29,000 cadaveric renal transplant recipients, they found that increasing levels of systolic and diastolic BP after transplantation were associated with a graded increase of subsequent graft failure [18]. In the present study, TBW and its distribution among compartments plays a critical role in predicting renal outcome, as similarly found in Saxena et al’s study, who showed that SBP was associated with TBW (P ¼ .016), ECW (L; r ¼ 0.99), and ECW% (r ¼ 0.78) [19]. In the present study, although body mass indexes were similar, LTI and LTM were significantly lower in patients with eGFR <50 mL/min. Similarly in a recent study, Chan et al showed a positive correlation between graft function and LTI in 106 stable RT recipients [20]. To our knowledge, BIA should be applied regularly to RT recipients, and patients with high FM and low LTM should be offered for reduction in dietary fat and regular exercise to improve graft function and survival. In patients with chronic renal disease, hypervolemia, anemia, and increased cardiac output, which is increased by
arteriovenous access, are factors contributing to the elevation of pulmonary blood flow rate, which may lead to pulmonary hypertension. In the present study, increased ECW and TBW were significantly positively correlated with PAP. These findings demonstrate that hypervolemia is an important determining factor for the development of pulmonary hypertension in RTRs. All findings that are related to changes in intravascular volume, such as ejection fraction and volume expansion, may lead to increased atrial pressure and thus to pulmonary hypertension. Finally, we found that aortic PWV is positively correlated with OH. Reduced aortic compliance leads to increased aortic systolic pressures that results in increased PWV [21,22]. In addition, in patients with renal dysfunction, the compliance of the artery may be decreased as a result of altered intrinsic elastic properties [23], associated with fibroelastic intimal thickening and calcifications [24]. The relationship among arterial stiffness, graft function, and blood pressure can be explained by side effects of immunosuppressive drugs in addition to donor age, microinflammation, and vascular damage that occurred during the pre-transplantation period. Our single-center study has several limitations. Although it was adequately powered to detect a significant association among the volume status, blood pressure, and graft outcome, the number of patients was relatively small. Furthermore, demographic characteristics of donors and data about pre-transplantation recipient PWV were not available. Furthermore, demographic characteristics of donors and data about pre-transplantation recipient PWV were not reported. CONCLUSION
Our study confirms the association between hypertension, OH, and graft function. For patients with declining eGFR, close follow-up of TBW by means of BIA may be an early indicator and prevent CV complications in RT recipients. Further studies with larger populations and including
GRAFT FUNCTION AND ARTERIAL STIFFNESS IN RENAL TX
donor-related factors are needed to demonstrate the effects of volume status on graft function and arterial stiffness. ACKNOWLEDGMENTS The authors are very grateful to the team of physicians, residents, and nurses from the Baskent University Hospital Faculty of Medicine for providing technical support in the development of this research and for the outstanding assistance provided to the patients.
REFERENCES [1] Mangray M, Vella JP. Hypertension after kidney transplant. Am J Kidney Dis 2011;57:331e41. [2] First MR, Neylan JF, Rocher LL, Tejani A. Hypertension after renal transplantation. J Am Soc Nephrol 1994;4:30e6. [3] Wizemann V, Wabel P, Chamney P, Zaluska W, Moiss L, Rodes CH, et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant 2009;24:1574e9. [4] Wabel P, Moissl U, Chamney P, et al. Toward improved cardiovascular management: the necessity of combining blood pressure and fluid overload. Nephrol Dial Transplant 2008;23: 2965e71. [5] Delahousse M, Chaignon M, Mesnard L, Boutouyrie P, Safar ME, Lebret T, et al. Aortic stiffness of kidney transplant recipients correlates with donor age. J Am Soc Nephrol 2008;19: 798e805. [6] Laurent S, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001;37:1236e41. [7] Verbeke F, van Biesen W, Peeters P, van Bortel LM, Vanholder RC. Arterial stiffness and wave reflections in renal transplant recipients. Nephrol Dial Transplant 2007;22:3021e7. [8] Ferro CJ, Savage T, Pinder SJ, Tomson CR. Central aortic pressure augmentation in stable renal transplant recipients. Kidney Int 2002;62:166e71. [9] Unal A, Sipahioglu M, Oguz F, Kaya M, Kucuk H, Tokgoz B, et al. Pulmonary hypertension in peritoneal dialysis patients: prevalence and risk factors. Perit Dial Int 2009;29:191e8. [10] Proceedings of the 4th World Symposium on Pulmonary Hypertension. J Am Coll Cardiol 2009;54:s1e117.
1185 [11] Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant 2004;4:1662e8. [12] Aakhus S, Dahl K, Wideroe TE. Cardiovascular disease in stable renal transplant patients in Norway: morbidity and mortality during a 5-yr follow-up. Clin Transplant 2004;18:596e604. [13] Horl MP, Horl WH. Hemodialysis-associated hypertension: pathophysiology and therapy. Am J Kidney Dis 2002;39:227e44. [14] Rahman M, Fu P, Sehgal AR, Smith MC. Interdialytic weight gain, compliance with dialysis regimen, and age are independent predictors of blood pressure in hemodialysis patients. Am J Kidney Dis 2000;35:257e65. [15] Chen YC, Chen HH, Yeh JC, Chen SY. Adjusting dry weight by extracellular volume and body composition in hemodialysis patients. Nephron 2002;92:91e6. [16] Koomans HA, Roos JC, Boer P, Geyskes GG, Mees EJ. Salt sensitivity of blood pressure in chronic renal failure. Evidence for renal control of body fluid distribution in man. Hypertension 1982;4:190e7. [17] Fagugli RM, Pasini P, Quintaliani Q, et al. Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients. Nephrol Dial Transplant 2003;18:2332e8. [18] Opelz G, Dohler B. Improved long-term outcomes after renal transplantation associated with blood pressure control. Am J Transplant 2005;5:2725e31. [19] Saxena A, Sharma RK. Hypertension in post-renal transplant patients: pilot study. Saudi J Kidney Dis Transpl 2014;25: 22e8. [20] Chan W, Bosch JA, Jones D, Kaur O, Inston N, Moore S, et al. Predictors and consequences of fatigue in prevalent kidney transplant recipients. Transplantation 2013;96(11):987e94. doi: 10.1097/TP.0b013e3182a2e88b. PMID: 23982341. [21] London G, Guerin A, Pannier B, Marchais S, Benetos A, Safar M. Increased systolic pressure in chronic uremia. Role of arterial wave reflections. Hypertension 1992;20:10e9. [22] London GM, Marchais SJ, Guerin AP, Metivier F, Pannier B. Cardiac hypertrophy and arterial alterations in end-stage renal disease: hemodynamic factors. Kidney Int 1993;43:42e9. [23] Mourad J-J, Girerd X, Boutouyrie P, Laurent S, Safar M, London G. Increased stiffness of radial artery wall material in endstage renal disease. Hypertension 1997;30:1425e30. [24] Ibels LS, Alfrey AC, Hufer WE, Craswell PW, Anderson JT, Weil R. Arterial calcification and pathology in uremic patients undergoing dialysis. Am J Med 1979;66:790e6.