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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 RenalTransplant 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 thecorrelation of renal insufficiency and estimated glomerular filtration rate (eGFR) with aortic pulsewave velocity (APWV), we studied 96 renal transplant patients followed-up at our center. Wemeasured 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 studyincluded 81 (84.4%) males and 15 (15.6%) females. The mean age of the patients was 37.84 10.10years. The mean duration of transplant was 47.90 34.40 months. The eGFR of the patients rangedfrom 1 to 120 mL/min, with a mean GFR of 72.6 23.2 mL/min. Sixty-seven (69.8%) patients hadeGFR > 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 14.2m/s, with a mean of 7.49 2.47 m/s. A significant inverse correlation was found between theAPWV and eGFR (Pearson correlation coefficient, -0.427, P = 0.00). The mean APWV wassignificantly higher among patients with higher CKD stage, P = 0.004. We conclude that theAPWV is related to the renal graft dysfunction as measured by eGFR. The poorer the renalfunction, the higher was the APWV. Determination of the APWV may be helpful in predicting theoutcome 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 UllahDepartment of Nephrology, Pakistan Instituteof Medical Sciences, Islamabad, PakistanE-mail: [email protected]

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 theexcess CVD risk in renal transplant patients,and accurate identification of the CVD risk inthis population is warranted because of thelonger potential life-time exposure owing to theimproved graft survival. Large-artery damage isone of the most important factors responsiblefor the high prevalence of CVD in renal pa-

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tients. Evaluation of central arterial stiffeningcan be helpful for more accurate risk strati-fication at a stage when intervention may stillmodify this risk.4

When the aorta stiffens,5 the forward pulsewave travels faster and the arterial wavesreflected from the periphery reach the heartearly during systole, which leads to highersystolic and lower diastolic blood pressure withan increased cardiac workload and a decreasedcoronary perfusion pressure.6 Accordingly, theaortic pulse wave velocity (APWV) is a pre-dictor of cardiovascular outcome in patientswith hypertension,7-9 diabetes,10 end-stage renaldisease and elderly hospitalized subjects.11

The predictive value of the APWV is beco-ming increasingly recognized and is one of theclassical indices of arterial stiffness, and can bedirectly measured by non-invasive techniquessuch as computerized oscillometry, tonometryand ultrasonography. The high diagnostic accu-racy of the APWV ranks it as the gold standardmethod for assessing the central arterial stiff-ness.12-14

In milder forms of renal insufficiency, APWVis inversely related.15 However, the impact ofrenal transplantation on recipient aortic stiffnessremains 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 thefactors related to increased APWV in transplantrecipients and to evaluate the correlation ofvalues of aortic PWV with the renal insuffi-ciency (GFR estimates) in renal transplantpatients.

Materials and Methods

This descriptive one-point study was conduc-ted at the Department of Nephrology, PakistanInstitute of Medical Sciences (PIMS),Islamabad over six months (June–December2013). We studied 96 stable renal transplant pa-tients visiting our transplant clinic. The studywas performed in accordance with the prin-ciples laid down in the declaration of Helsinki.

For each patient, the APWV was determinedusing transcutaneous Doppler flow recordingsand the foot-to-foot method. The pressurewave-form was recorded non-invasively with ahigh-fidelity strain gauge transducer (SPT-301,Millar Instruments, Houston, Texas, USA). Theaortic flow velocity and pressure were simul-taneously recorded with a muti-sensor catheterthat has an electromagnetic velocity probe and apressure sensor mounted at the same location.Another pressure sensor at the catheter tipprovided left ventricular pressure or a secondaortic pressure to determine the APVW. TheFlick 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 bothpressure and impedance data, implying that theregion of the terminal abdominal aorta acts asthe major reflection site in the normal adultman.

The augmented pressure was determined asthe height of the late systolic peak above theinflection and the ratio of augmented pressureto the augmentation index. Left ventricularejection time was determined from the foot ofthe pressure wave to the diastolic incisura. Aug-mented index ranged from 10 to 12 successivewaves. Two simultaneous Doppler flow tracingswere taken at the aortic arch and femoral arteryin the groin using a non-directional Dopplerunit with a hand-held probe, and were recordedat a speed of 100–200 mm/s. For aortic flow,the transducer was placed in the supra-sternalnotch. The time delay (t) was measured bet-ween the feet of the flow waves recorded atthese different points and averaged over tenbeats. The distance (D) travelled by the pulsewave was measured over the body surface asthe distance between the two recording sites.The APWV was calculated as pulse wave velo-city = D/t and was expressed in m/s. The samespecialist doctor performed all the measure-ments. All the data were collected on a performa.

Statistical analysis

Data were analyzed using SPSS version 15. The

Aortic pulse wave velocity in renal transplant recipients 1131


descriptive analysis was carried out and repor-ted as means, with standard deviations andmedians for continuous variables such as age ofpatients. For categorical variables such as gen-der, acute rejection, smoking, causes of renaldiseases for transplantation and aortic stiffness,frequencies and percentages were reported. Todetermine the correlation of renal insufficiency(estimated GFR) with the APWV, the Pearsoncorrelation 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 rangedfrom 18 to 60 years, with a mean of 37.8 10.1years. The post-renal transplant duration rangedfrom eight to 132 months, with a mean of 47.9 34.4 months.

The weight of the patients ranged from 48 to70 kg, with a mean of 57.5 5.3 kg. The heightof the patients ranged from 150 to 167.50 cm,with a mean of 158 3.36 cm. The body massindex 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 to120 mL/min, with a mean GFR of 72.6 23.2mL/min (Table 1).

Depending on the eGFR using the MDRDequation, the patients were categorized intostages 1–5 chronic kidney disease (CKD). Sixty-seven (69.8%) patients had eGFR >60 mL/minand 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/minand hence were in stages 4 and 5 CKD.

The APWV of the patients ranged from 4 to14.2 m/s, with a mean of 7.49 2.47 m/s, andthe mean increased with the more advancedstage of CKD (Figure 1). The APWV and theestimated 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 wasdirectly correlated (Pearson correlation coeffi-cient was -0.103), but the correlation was notstatistically significant (P = 0.361).

The mean blood pressure and the APWV weredirectly 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 10.10Duration (months) 8 132 47.9 34.4Weight (kg) 48 70 57.5 5.37Height (cm) 150 167 158.7 3.35Body mass index (kg/m2) 17 33.75 23.2 2.83Systolic blood pressure (mm Hg) 100 160 135.1 13.6Diastolic blood pressure (mm Hg) 70 100 81.87 9.65Pulse pressure (mm Hg) 20 90 52.76 16.2Mean blood pressure (mm Hg) 70 136 103.2 13.8eGFR 16 120 72.6 23.2Neutrophils 4800 12,600 8612.5 2615Hemoglobin (gm%) 8.2 16.5 12.2 2.266Platelets 105 405 239.2 78.50BSR (mg/dL) 85 232 119.0 39.22Total cholesterol (mg/dL) 125 314 176.5 38.02

1132 Ayub M, Ullah K, Masroor M, et al


Discussion

Damage to the large arteries is a major factorin 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 ofaortic stiffness determined by the measurementof APWV, which was a strong independentpredictor of all-cause and cardiovascularmortality.

Verbeke et al attributed the increased arterialstiffness and wave reflections in renal trans-plant recipients to incomplete restoration ofGFR and the presence of subclinical inflam-mation.4 Zoungas et al and Kneifel et al foundthat impairment of the renal allograft function isassociated with an increased arterial stiffness inrenal transplant recipients.17,18 Mitchell et aldemonstrated that the impact of kidney trans-plantation on recipient aortic stiffness is depen-dent on donor age and suggest that ongoingdamage to large arteries might contribute to themechanism underlying the association of old-donor kidneys and increased cardiovascularmortality.19 In our study, we found that APWVwas significantly higher among patients withhigher CKD stages and that the APWV andeGFR inversely correlated. Accordingly, theAPWV correlated inversely with worsening ofrenal graft dysfunction.

Stiffness markers are increasingly used inpopulation studies to evaluate cardiovascularmorbidity and mortality. Our data suggest thatin renal transplant subjects, stiffness markersmay also be used as tools for the prediction ofall-cause mortality. However, more studies on alarger scale are required to document the clin-ical utility of APWV in predicting the outcomein renal transplant recipients.

We conclude from our study that the APWVcorrelated with the renal graft dysfunction asmeasured by eGFR. The poorer the renal func-tion, the faster was the APWV. Hence, thedetermination of the APWV can be helpful inpredicting the outcome in renal transplantrecipients.

Conflict of interest: None declared.

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Figure 1. The means of the aortic pulse wavevelocity (APWV) among different chronic kidneydisease (CKD) stages.

Figure 2. The estimated glomerular filtration rate(eGFR) and the inverse correlation with the aorticpulse wave velocity (APWV).

Aortic pulse wave velocity in renal transplant recipients 1133


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