1. Saudi J Kidney Dis Transpl 2015;26(6):1130-1134
© 2015 Saudi Center for Organ Transplantation
Original Article
Predictive Factors for Increased Aortic Pulse Wave Velocity in Renal
Transplant Recipients and Its Relation to Graft Outcome
Muazam Ayub, Kifayat Ullah, Imtiaz Masroor, Ghias Uddin Butt
Department of Nephrology, Pakistan Institute of Medical Sciences, Islamabad, Pakistan
ABSTRACT. To evaluate aortic stiffness in renal transplant patients and to determine the
correlation of renal insufficiency and estimated glomerular filtration rate (eGFR) with aortic pulse
wave velocity (APWV), we studied 96 renal transplant patients followed-up at our center. We
measured the APWV using transcutaneous Doppler flow recordings and the foot-to-foot method,
and calculated the eGFR using the Modification of Diet in Renal Disease equation. The study
included 81 (84.4%) males and 15 (15.6%) females. The mean age of the patients was 37.84  10.10
years. The mean duration of transplant was 47.90  34.40 months. The eGFR of the patients ranged
from 1 to 120 mL/min, with a mean GFR of 72.6  23.2 mL/min. Sixty-seven (69.8%) patients had
eGFR > 60 mL/min and hence had stages 1 and 2 chronic kidney disease (CKD), 27 (28.1%)
patients had eGFR 30–60 mL/min and hence had stage 3 CKD and two (2.1%) patients had eGFR
<30 mL/min and hence had stages 4 and 5 CKD. The APWV of the patients ranged from 4 to 14.2
m/s, with a mean of 7.49  2.47 m/s. A significant inverse correlation was found between the
APWV and eGFR (Pearson correlation coefficient, -0.427, P = 0.00). The mean APWV was
significantly higher among patients with higher CKD stage, P = 0.004. We conclude that the
APWV is related to the renal graft dysfunction as measured by eGFR. The poorer the renal
function, the higher was the APWV. Determination of the APWV may be helpful in predicting the
outcome in renal transplant recipients.
Introduction
Successful renal transplantation confers signi-
ficant survival advantage compared with dialy-
sis.1,2
Nevertheless, mortality from cardiovas-
Correspondence to:
Dr. Kifayat Ullah
Department of Nephrology, Pakistan Institute
of Medical Sciences, Islamabad, Pakistan
E-mail: getursain@hotmail.com
cular disease (CVD) still remains at least three-
to five-times higher in renal transplant reci-
pients than in the general population.3
Tradi-
tional risk factors do not fully explain the
excess CVD risk in renal transplant patients,
and accurate identification of the CVD risk in
this population is warranted because of the
longer potential life-time exposure owing to the
improved graft survival. Large-artery damage is
one of the most important factors responsible
for the high prevalence of CVD in renal pa-
Saudi Journal
of Kidney Diseases
and Transplantation
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2. tients. Evaluation of central arterial stiffening
can be helpful for more accurate risk strati-
fication at a stage when intervention may still
modify this risk.4
When the aorta stiffens,5
the forward pulse
wave travels faster and the arterial waves
reflected from the periphery reach the heart
early during systole, which leads to higher
systolic and lower diastolic blood pressure with
an increased cardiac workload and a decreased
coronary perfusion pressure.6
Accordingly, the
aortic pulse wave velocity (APWV) is a pre-
dictor of cardiovascular outcome in patients
with hypertension,7-9
diabetes,10
end-stage renal
disease and elderly hospitalized subjects.11
The predictive value of the APWV is beco-
ming increasingly recognized and is one of the
classical indices of arterial stiffness, and can be
directly measured by non-invasive techniques
such as computerized oscillometry, tonometry
and ultrasonography. The high diagnostic accu-
racy of the APWV ranks it as the gold standard
method for assessing the central arterial stiff-
ness.12-14
In milder forms of renal insufficiency, APWV
is inversely related.15
However, the impact of
renal transplantation on recipient aortic stiffness
remains poorly defined. Some studies in trans-
plant patients have shown associations bet-
ween the APWV and the outcome of transplan-
tation.15-19
The aim of our study was to determine the
factors related to increased APWV in transplant
recipients and to evaluate the correlation of
values of aortic PWV with the renal insuffi-
ciency (GFR estimates) in renal transplant
patients.
Materials and Methods
This descriptive one-point study was conduc-
ted at the Department of Nephrology, Pakistan
Institute of Medical Sciences (PIMS),
Islamabad over six months (June–December
2013). We studied 96 stable renal transplant pa-
tients visiting our transplant clinic. The study
was performed in accordance with the prin-
ciples laid down in the declaration of Helsinki.
For each patient, the APWV was determined
using transcutaneous Doppler flow recordings
and the foot-to-foot method. The pressure
wave-form was recorded non-invasively with a
high-fidelity strain gauge transducer (SPT-301,
Millar Instruments, Houston, Texas, USA). The
aortic flow velocity and pressure were simul-
taneously recorded with a muti-sensor catheter
that has an electromagnetic velocity probe and a
pressure sensor mounted at the same location.
Another pressure sensor at the catheter tip
provided left ventricular pressure or a second
aortic pressure to determine the APVW. The
Flick cardiac output was used to scale the velo-
city signal to instantaneous volumetric flow.
Using pulse wave velocity, the effective re-
flection site distance was determined from both
pressure and impedance data, implying that the
region of the terminal abdominal aorta acts as
the major reflection site in the normal adult
man.
The augmented pressure was determined as
the height of the late systolic peak above the
inflection and the ratio of augmented pressure
to the augmentation index. Left ventricular
ejection time was determined from the foot of
the pressure wave to the diastolic incisura. Aug-
mented index ranged from 10 to 12 successive
waves. Two simultaneous Doppler flow tracings
were taken at the aortic arch and femoral artery
in the groin using a non-directional Doppler
unit with a hand-held probe, and were recorded
at a speed of 100–200 mm/s. For aortic flow,
the transducer was placed in the supra-sternal
notch. The time delay (t) was measured bet-
ween the feet of the flow waves recorded at
these different points and averaged over ten
beats. The distance (D) travelled by the pulse
wave was measured over the body surface as
the distance between the two recording sites.
The APWV was calculated as pulse wave velo-
city = D/t and was expressed in m/s. The same
specialist doctor performed all the measure-
ments. All the data were collected on a performa.
Statistical analysis
Data were analyzed using SPSS version 15. The
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3. descriptive analysis was carried out and repor-
ted as means, with standard deviations and
medians for continuous variables such as age of
patients. For categorical variables such as gen-
der, acute rejection, smoking, causes of renal
diseases for transplantation and aortic stiffness,
frequencies and percentages were reported. To
determine the correlation of renal insufficiency
(estimated GFR) with the APWV, the Pearson
correlation coefficient was calculated. P-values
<0.05 were considered significant.
Results
The study included 81 (84.4%) males and 15
(15.6%) females. The age of the patients ranged
from 18 to 60 years, with a mean of 37.8  10.1
years. The post-renal transplant duration ranged
from eight to 132 months, with a mean of 47.9
 34.4 months.
The weight of the patients ranged from 48 to
70 kg, with a mean of 57.5  5.3 kg. The height
of the patients ranged from 150 to 167.50 cm,
with a mean of 158 3.36 cm. The body mass
index of the patients ranged from 17.6 to 33.8,
with a mean of 23.3  2.83 (Table 1).
The reasons for renal transplant were as fol-
lows: Diabetes (35%), chronic glomeruloneph-
ritis (20%), polycystic kidney disease (3%),
nephrosclerosis (hypertensive) (12%), systemic
lupus erythematosis (SLE) (2.3%), stone di-
sease (5%) and idiopathic (22.7%).
The eGFR of the patients ranged from 16 to
120 mL/min, with a mean GFR of 72.6  23.2
mL/min (Table 1).
Depending on the eGFR using the MDRD
equation, the patients were categorized into
stages 1–5 chronic kidney disease (CKD). Sixty-
seven (69.8%) patients had eGFR >60 mL/min
and hence were in stages 1 and 2 CKD.
Twenty-seven (28.1%) patients had eGFR 30–
60 mL/min and hence were in stage 3 CKD.
Two (2.1%) patients had eGFR <30 mL/min
and hence were in stages 4 and 5 CKD.
The APWV of the patients ranged from 4 to
14.2 m/s, with a mean of 7.49  2.47 m/s, and
the mean increased with the more advanced
stage of CKD (Figure 1). The APWV and the
estimated GFR were inversely correlated
(Pearson correlation coefficient was -0.427),
and this correlation was statistically significant
(P = 0.00) (Figure 2).
The duration of transplant and the APWV was
directly correlated (Pearson correlation coeffi-
cient was -0.103), but the correlation was not
statistically significant (P = 0.361).
The mean blood pressure and the APWV were
directly correlated (Pearson correlation coeffi-
cient was 0.176), and the relation was statis-
tically significant (P = 0.05).
Table 1. Descriptive data of the study patients.
Minimum Maximum Mean Std. deviation
Age (years) 18 60 37.8 10.10
Duration (months) 8 132 47.9 34.4
Weight (kg) 48 70 57.5 5.37
Height (cm) 150 167 158.7 3.35
Body mass index (kg/m2
) 17 33.75 23.2 2.83
Systolic blood pressure (mm Hg) 100 160 135.1 13.6
Diastolic blood pressure (mm Hg) 70 100 81.87 9.65
Pulse pressure (mm Hg) 20 90 52.76 16.2
Mean blood pressure (mm Hg) 70 136 103.2 13.8
eGFR 16 120 72.6 23.2
Neutrophils 4800 12,600 8612.5 2615
Hemoglobin (gm%) 8.2 16.5 12.2 2.266
Platelets 105 405 239.2 78.50
BSR (mg/dL) 85 232 119.0 39.22
Total cholesterol (mg/dL) 125 314 176.5 38.02
1132 Ayub M, Ullah K, Masroor M, et al
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4. Discussion
Damage to the large arteries is a major factor
in the high cardiovascular morbidity and morta-
lity of patients with end-stage renal disease
(ESRD).15
Bahous et al16
demonstrated that in patients with
ESRD, there was an increased prevalence of
aortic stiffness determined by the measurement
of APWV, which was a strong independent
predictor of all-cause and cardiovascular
mortality.
Verbeke et al attributed the increased arterial
stiffness and wave reflections in renal trans-
plant recipients to incomplete restoration of
GFR and the presence of subclinical inflam-
mation.4
Zoungas et al and Kneifel et al found
that impairment of the renal allograft function is
associated with an increased arterial stiffness in
renal transplant recipients.17,18
Mitchell et al
demonstrated that the impact of kidney trans-
plantation on recipient aortic stiffness is depen-
dent on donor age and suggest that ongoing
damage to large arteries might contribute to the
mechanism underlying the association of old-
donor kidneys and increased cardiovascular
mortality.19
In our study, we found that APWV
was significantly higher among patients with
higher CKD stages and that the APWV and
eGFR inversely correlated. Accordingly, the
APWV correlated inversely with worsening of
renal graft dysfunction.
Stiffness markers are increasingly used in
population studies to evaluate cardiovascular
morbidity and mortality. Our data suggest that
in renal transplant subjects, stiffness markers
may also be used as tools for the prediction of
all-cause mortality. However, more studies on a
larger scale are required to document the clin-
ical utility of APWV in predicting the outcome
in renal transplant recipients.
We conclude from our study that the APWV
correlated with the renal graft dysfunction as
measured by eGFR. The poorer the renal func-
tion, the faster was the APWV. Hence, the
determination of the APWV can be helpful in
predicting the outcome in renal transplant
recipients.
Conflict of interest: None declared.
References
1. Schnuelle P, Lorenz D, Trede M, Van Der Woude
FJ. Impact of renal cadaveric transplantation on
survival in end-stage renal failure: Evidence for
Figure 1. The means of the aortic pulse wave
velocity (APWV) among different chronic kidney
disease (CKD) stages.
Figure 2. The estimated glomerular filtration rate
(eGFR) and the inverse correlation with the aortic
pulse wave velocity (APWV).
Aortic pulse wave velocity in renal transplant recipients 1133
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5. reduced mortality risk compared with hemo-
dialysis during long-term follow-up. J Am Soc
Nephrol 1998;9:2135-41.
2. Sarnak MJ, Levey AS, Schoolwerth AC, et al.
Kidney disease as a risk factor for development
of cardiovascular disease: A statement from the
American Heart Association Councils on
Kidney in Cardiovascular Disease, High Blood
Pressure Research, Clinical Cardiology, and
Epidemiology and Prevention. Circulation
2003;108:2154-69.
3. Ojo AO. Cardiovascular complications after
renal transplantation and their prevention.
Transplantation 2006;82:603-11.
4. 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;22:3021-7.
5. Willum-Hansen T, Staessen JA, Torp-Pedersen
C, et al. Prognostic value of aortic pulse wave
velocity as index of arterial stiffness in the
general population. Circulation 2006;113:664-
70.
6. O'Rourke MF, Staessen JA, Vlachopoulos C,
Duprez D, Plante GE. Clinical applications of
arterial stiffness; definitions and reference
values. Am J Hypertens 2002;15:426-44.
7. Laurent S, Boutouyrie P, Asmar R, et al. Aortic
stiffness is an independent predictor of all-cause
and cardiovascular mortality in hypertensive
patients. Hypertension 2001;37:1236-41.
8. Laurent S, Katsahian S, Fassot C, et al. Aortic
stiffness is an independent predictor of fatal
stroke in essential hypertension. Stroke 2003;
34:1203-6.
9. Boutouyrie P, Tropeano AI, Asmar R, et al.
Aortic stiffness is an independent predictor of
primary coronary events in hypertensive pa-
tients: A longitudinal study. Hypertension 2002;
39:10-5.
10. Cruickshank K, Riste L, Anderson SG, Wright JS,
Dunn G, Gosling RG. Aortic pulse-wave velocity
and its relationship to mortality in diabetes and
glucose intolerance: An integrated index of
vascular function? Circulation 2002; 106:2085-
90.
11. Meaume S, Rudnichi A, Lynch A, et al. Aortic
pulse wave velocity as a marker of cardio-
vascular disease in subjects over 70 years old. J
Hypertens 2001;19:871-7.
12. Oliver JJ, Webb DJ. Noninvasive assessment of
arterial stiffness and risk of atherosclerotic
events. Arterioscler Thromb Vasc Biol 2003;23:
554-66.
13. Naidu MU, Reddy BM, Yashmaina S, Patnaik
AN, Rani PU. Validity and reproducibility of
arterial pulse wave velocity measurement using
new device with oscillometric technique: A
pilot study. Biomed Eng Online 2005;4:49.
14. Laurent S, Cockcroft J, Van Bortel L, et al.
Expert consensus document on arterial stiffness:
Methodological issues and clinical applications.
Eur Heart J 2006;27:2588-605.
15. Covic A, Goldsmith DJ, Gusbeth-Tatomir P,
Buhaescu I, Covic M. Successful renal trans-
plantation decreases aortic stiffness and increa-
ses vascular reactivity in dialysis patients.
Transplantation 2003;76:1573-7.
16. Bahous SA, Stephan A, Barakat W, Blacher J,
Asmar R, Safar ME. Aortic pulse wave velocity
in renal transplant patients. Kidney Int 2004;66:
1486-92.
17. Zoungas S, Kerr PG, Chadban S, et al. Arterial
function after successful renal transplantation.
Kidney Int 2004;65:1882-9.
18. Kneifel M, Scholze A, Burkert A, et al.
Impaired renal allograft function is associated
with increased arterial stiffness in renal
transplant recipients. Am J Transplant 2006;6:
1624-30.
19. Mitchell A, Opazo Saez A, Kos M, Witzke O,
Kribben A, Nürnberger J. Pulse wave velocity
predicts mortality in renal transplant patients.
Eur J Med Res 2010;15:452-5.
1134 Ayub M, Ullah K, Masroor M, et al
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