evaluation of kidney graft function by arterial flow using colour doppler flowmetry

~ EUROPEAN JOURNAL OF

( ~ ' [ ~ ( ~ E L S E V I E R European Journal of Ultrasound 3 (1996) 223 229

Clinical paper

Evaluation of kidney graft function by arterial flow using colour Doppler flowmetry

Roberto Rivolta a'*, Daniela Castagnone ~', Attilio Elli b, Filippo Quarto Di P a l o b

~'Di~'isione di Radiologia 2", Ospedale Maggiore di Milano, Via F. SJbrza, 35, 20122 Milan, Italy blstituto di Medicina Interna Universitgt di Milano, Pad Granelli, Ospedale Maggiore di Milano, Via F. SJbrza, 35, 20122

Milan, Italy

Received 6 April 1995; revised 15 September 1995; accepted 20 September 1995

Abstract

Objective: Two-hundred thirty-two stable renal transplant outpatients were studied to identify the most useful colour flow Doppler ultrasound indices defining graft function in the long-term follow-up. Method: Renal artery mean velocity (Vm), renal blood flow (RBF), and resistance index (RI) on the renal and interlobar arteries were measured by the same operator. Results: V m and RBF averaged respectively 42.1 _+ 18.4 cm/s and 32l + 95 ml/min in 85 patients with normal creatinine levels ( < 105/~mol/1). RBF significantly decreased in patients with plasma creatinine > 105 /tmol/1 (P < 0.0001). An inverse correlation with the degree of renal impairment, measured by plasma creatinine levels, was shown by RBF (r = 0.73) and Vm (r = 0.69). RI increased along with the reduction of renal function (interlobar artery: r = 0.63 and renal artery: r = 0.57). Conclusions: Vm, RBF and interlobar RI appear to be sensitive parameters to describe the hemodynamical status of the graft. The hemodynamical status appears to be influenced by the graft function. RBF appears the most useful index to evaluate the blood supply in the transplanted kidney.

Keywords: Ultrasonography; Color flow Doppler; Renal transplantation; Renal blood flow; Resistance index

I . Introduction

U l t r a sound eva lua t ion o f the graf t has become

* Corresponding author. Tel.: + 39-2-55033535; fax: + 39- a p o p u l a r d iagnos t ic technique in renal t r ansp lan t 2-5516626. fol low up. Grey scale and, more recently, co lour

0929-8266/96/$15.00 © 1996 Elsevier Science Ireland Ltd. All rights reserved PH S0929-8266(95)001 53-X

224 R. Rivolta et al. / European Journal of Ultrasound 3 (1996) 223 229

Table 1 Composition of the two study groups

Normal renal function (plasma creatinine < 105 /~mol/1)

Impaired renal function (plasma creatinine > 105 /~mol/1)

P-value*

Number of patients 85 147 Gender (M/F) 51./34 92/55 Plasma creatinine (/~mol/1) 89 _+ 14 271 _+ 96 Age (years) 43 _+ 10 44 _+ 11 Transplant age (months) 77 _+ 60 66 +_ 65 Mean blood pressure (mmHg) 97.5 +_ 9.4 104.1 + 14.3 Weight (kg) 61 _+ 11 63 _+ 12 Height (m) 1.63 _+ 0.09 1.62 _+ 0.11 Body surface area (m -~) 1.62 _+ 0.20 1.65 _+ 0.19 Treatment (cyclosporin + steroids/ 60/25 101/46

azathioprine + steroids)

N.S,

N.S. N.S. 0.001 N.S. N.S. N.S. N.S.

Plus-minus values are means _+ 1 S.D. *Chi-square analysis for gender and treatment; t-test for independent groups for other variables.

flow Doppler u l t rasonography have been used, not always with concordan t results (Perchik et al., 1991; Renowden et al., 1992), to diagnose acute tubular necrosis (Allen et al., 1988; George et al., 1991), and transplant rejection or acute cyclosporine toxicity (Rigsby et al., 1987; W a n et al., 1989). Doppler methods can also be em- ployed to screen for arterial stenosis o f the graft (Taylor et al., 1987; Grenier et al., 1991) or noninvasive measurement o f renal b lood flow (Greene et al., 1981; Avasthi et al., 1987; Greene and Avasthi, 1989).

Until now, the use of ul t rasound was almost always reserved for solving problems determined by an acute graft disfunction. But, if the precision and repeatability o f these data are adequate, as many data o f the literature suggest (Tessler et al., 1990; Rasmussen and Pedersen, 1990; Veille et al., 1992), these measures could also be used in long-term transplant monitoring.

In this study, the results obtained in a group of renal transplants with different levels o f graft function and durat ion were collected to evaluate the use o f the colour flow Doppler u l t rasound technique in these patients.

2. Materials and methods

2.1. Pat ient selection

A cross-sectional study was performed in a group o f 232 stable, non-diabetic, renal transplant outpatients. Patients, 149 males and 83 females, were aged between 16 and 62 years. Median transplant age was 78 months (range, 6-210) . Plasma creatinine levels ranged between 60 and 870/~mol/l.

Patients were divided in two groups: G r o u p A, composed o f 85 cases in which plasma creatinine was within normal limits ( < 105 /~mol/l), and G r o u p B composed of 147 cases with elevated levels ( > 105 /~mol/1) (Table 1). Patients were matched for age, t ransplant age, gender and body surface area.

2.2. Assessment o f renal f i tnct ion

At 09:00 h, after 1 h o f rest in supine position, brachial arterial pressure was measured on fasting patients free from medicat ion for 12 h. Mean arterial pressure (MAP) was calculated by the formula {[systolic pressure + (2 x diastolic pressure)]: 3}. The colour flow Doppler scan of

R. Rivolta et al. / European Journal of Ultrasound 3 (1996) 223-229 225

the graft was subsequently performed by the same opera tor (R.R.).

The measurements were taken f rom the main renal- or interlobar artery using an A T L Ultra- mark 9DP scanner (Bothell, WA) and a 3 .5-MHz convex probe. The Doppler wall filter setting was standardized to 50 Hz.

Parameters were determined in the order Resis- tance index (RI) then renal b lood flow (RBF). Resistance index (RI), derived f rom the characteristics o f the spectral waveform, was calculated for the main renal and interlobar artery. R I was determined as follows: the peak systolic frequency shift minus the lowest diastolic frequency shift divided by the peak systolic frequency shift. RI was calculated as an average value obtained from five repeated waveform measurements on the main renal artery and on the interlobar artery.

Renal b lood flow (RBF) was measured f rom the Doppler spectrum time-averaged mean velocity (V m = velocity time integral/time of spectral trace in seconds) and vessel diameter (Greene et al., 1981; Avasthi et al., 1987; Greene and Avasthi, 1989; Quar to di Palo et al., 1993) (RBF = V m × 60 × 3.14r2; R B F = ml/min; Vm = cm/s; 3.14 r 2 = vessel area in cm2). To obtain these data, a rectilinear segment of the graft 's renal artery was visualized. The sample volume was centered in the vessel, and completely insonated the vessel. The angle o f insonat ion was kept < 60 degrees. The angle correct ion cursor was parallel to the direction o f flow. Two calipers were posit ioned on the borders o f the internal diameter to obtain a vessel diameter assessment f rom the grey scale image (Fig. 1).

At the end of the test, a b lood sample was taken for plasma creatinine analysis. The body weight and surface area o f the fasting patient, were also recorded.

2.3. S ta t i s t ica l analysis

Results were analyzed to assess for a normal distribution o f the variables. Lilliefors test, a mod- ification o f the K o l m o g o r o v - S m i r n o v test, was used with the aid o f SPSS software (SPSS Inc., Chicago, 1990). The outcome variables considered were: renal artery diameter, Doppler wave mean velocity, renal b lood flow and resistance index.

Fig. 1. Colour flow Doppler ultrasound measurement of renal blood flow. (A) A rectilinear segment of the grafted renal artery is visualized; the sample volume is centered in and completely insonates the vessel; the angle correction cursor is parallel to the direction of flow. (B) The two calipers are positioned on the borders of internal arterial wall to obtain the vessel diameter from the grey scale. (C) The sectional area is then calculated and time-averaged mean velocity obtained. Blood flow is calculated from these elements (see box on lower right).

226 R. Rivolta et al. / European Journal o f Ultrasound 3 (1996) 223 229

Table 2 Coefficient of variation (CV%) of five different colour flow Doppler measurements

Intraexamination Interexamination CV %~ CV %b

No. of patients 232 40 Renal artery 3.2 + 3.1 6.8 + 4.2

diameter

Renal artery 4.4 _ 2.7 6.8 + 6.6 mean velocity

Renal blood flow 4.3 + 3.6 6.0 + 4.1 Resistive index 4.1 + 2.5 5.2 + 3.8

(renal artery) Resistive index 4.0 + 2.2 4.9 + 3.7

(interlobar artery)

aData are means + 1 S.D. of five independent measurements. bMeasurements were repeated after 24 h.

Stepwise multiple linear regression, using the SPSS software, was used to evaluate the significance o f patients ' confounding factors on outcome variables: age, gender, MAP, weight, body surface area and immunosuppressive regimens.

The results obtained in the groups with different creatinine plasma levels were compared with chi-square and t-test for independent data. P-values less than 0.05 were considered to indicate statistical significance. Values were expressed as mean + s tandard deviation, unless otherwise in- dicated.

To assess the intraexaminat ion precision o f flow Doppler measurements, the coefficient o f variation (CV%) was obtained f rom repeating data five times. In 40 patients, the scan was repeated after 1 day to calculate interexamination precision.

3 . R e s u l t s

The characteristics o f the two study groups are given in Table 1. In patients with impaired renal function, M A P was statistically increased (P < 0.001). Intra- and interexamination precision o f all the measurements are shown in Table 2. All the outcome variables studied had a frequency distribution not significantly different f rom a normal curve. The confounding factors considered

(i.e. age, gender, MAP, weight, body surface area and immunosuppressive regimens) did not significantly influence the variables studied.

The RI o f the renal artery was not significantly different in the two groups (0.68 _+ 0.06 in group A vs. 0.71 _+ 0.07 in group B; P = 0.15). Regression analysis revealed a positive correlation with plasma creatinine; the best fit was obtained with a linear model (r = 0.57, P = 0.01). R I o f the interlobar artery had a mean value o f 0.63 _+ 0.05 in group A and 0.67 _+ 0.09 in group B (P = 0.03). Also in this case, regression analysis showed that the best fit was obtained with a linear model (r = 0.63, P < 0.001) (Fig. 2).

As shown in Table 3, the mean renal artery diameter in the group with normal renal function was 0.40 _+ 0.06 cm. These values were unrelated to the other variables studied.

Vm, in group A averaged 42.1 _+ 18.4 cm/s, and 27.3 + 15.5 cm/s in group B (P < 0.01). Regression analysis demonst ra ted an inverse rela- t ionship between Vm and plasma creatinine. The best fit was an exponential model (r = 0.69; P = 0.0001).

Mean RBF in patients o f group A was 321 + 95 ml/min and in group B, 187 _+ 88 ml/min, a very significant difference (P < 0.0001). Regres- sion analysis demonst ra ted a highly positive correlation with Vm (r = 0.86, P < 0.00001) (Fig. 3)

1.0" o o • •

, ~

.e_ 0.11"

~ • •

~ o.~-

~ 0.'/"

" " :

,~

• 0.5 ~ . 0 0 1 c

0.4, 0 200 400 600 800 1000

plasme creatlnlne (~mol/L)

Fig. 2. Relation between interlobar artery Resistance index and plasma creatinine in 232 renal transplant patients with different levels of graft function.


Table 3 Colour flow Doppler ultrasound measurements

Normal renal function (plasma creatinine < 105/~mol/I)

Impaired renal function (plasma creatinine > 105 /~mol/1)

P-value*

Mean ± 1 S.D. (95% C.I. of the Mean ± I S.D. mean)

(95%C.1. of the mean)

Renal artery internal 0.40 + 0.06 diameter (cm)

Renal artery mean 42.1 + 18.4 velocity (cm/s)

Renal blood flow (ml/ 32I +_ 95 min)

Resistive index (renal 0.68 ± 0.06 artery)

Resistive index 0.63 + 0.05 (interlobar artery)

(0.38 0.42) 0.37 _+ 0.06

(34.8-56.7) 27.3 _+ 15.5

(302 359) 187 ± 88

(0.67-0.69) 0.71 _+ 0.07

(0.62-0.64) 0.67 ± 0.09

(0.36 0.38) N.S.

(25.1-31.5) <0.01

(177-207) <0.0001

(0.69-0.71) N.S.

(0.66-0.68) <0.03

*t-test for independent groups.

and an inverse correlation between RBF and plasma creatinine levels (exponential model, r = 0.73, P < 0.00001) (Fig. 4).

4. Discussion

This study considered a group of stable patients with a wide range of graft functional status to evaluate the relative usefulness of some colour flow Doppler parameters in the follow-up of renal transplant recipients.

Each method of measurement is subject to er- rors and it is important that these are appreciated if the best possible precision is to be achieved. With care, reasonably accurate measurement of blood flow can be made (Evans et al., 1991). Moreover the superficial allocation of the allografts allows relatively easy examination of the renal vessels with high technical adequacy (Avasthi et al., 1992).

r: 0.73 90" e~• * p < 0.00001

A 500 • •

• " ~ ~e" ~ ~ • e o o •

° , 60" • • 300 •

• . . . . , - : ' " " . 1 • • "~ • • O "

_

~ ' ~ ~ ~ 0 . i ~ ._ i e l . . l ~ e

I ~ e ~ l ~ 0 0 r :0.86 ] " " " ~

1 5 " ~ 0 0 ~ 2 0 0 400 600 800 1000

0" Plasma creatlnlne (~mol/L) 0 100 200 300 400 500 600

Renal Blood Flow (mllm) Fig. 4. Relation between renal blood flow and plasma creatinine in 232 renal transplant patients with different levels of graft function. The best fit was obtained with a negative exponential model.

E

O

.~ 0 0

~- m q)

Fig. 3. Correlation between V m and renal blood flow in 232 renal transplant patients with different levels of graft function.

228 R. Rivolta et al. / European Journal of Ultrasound 3 (1996) 223-229

We studied the statistical significance of our findings and tested their reproducibility. In our study, the technique showed a good intraindivid- ual precision, as already reported by several au- thors who found variation coefficients ranging between 6 and 15% (Tessler et al., 1990; Ras- mussen and Pedersen, 1990; Veille et al., 1992).

Of the various indices examined, renal artery diameter was not statistically related to changes in renal function.

RI was the most precise index but showed low sensitivity in discriminating normal from pathological values. When taken on the interlobar artery, RI increased in sensitivity.

The measure of Doppler wave mean velocity was closely related to renal blood flow and to plasma creatinine levels. RBF, due to its greater sensitivity in distinguishing between normal and pathological conditions (Quarto di Pato et al., 1993), was the most useful variable for evaluating blood supply to the graft.

As with other ultrasound techniques, flow measurements by Doppler ultrasound have the great virtue of not interfering with the parameters being measured: flow can therefore be evaluated and repeated at will so as to monitor the progress of a disease process or the effect of a therapy. This benefit may far outweigh the cost of any inaccura- cies when compared with other methods of functional investigation (Evans et al., 1991).

In our experience, the measure of renal blood flow, of Vm and RI proved to be useful in renal transplantation follow-up. A daily repeatable functional assessment was useful in the manage- ment of acute rejection (Quarto Di Palo et al., 1994). When the frequency of laboratory controls is reduced, as in the long-term period, the limita- tions of the standard diagnostic tests utilized become more evident. Plasma creatinine lacks sensitivity in the normal range of values, creatinine clearance overestimates graft function (Mobb et al., 1990; Levey et al., 1991; Ham and Piepsz, 1992) and suffers because of frequent in- adequate urine collection. Renal biopsy and iso- topic clearances cannot be used too frequently. For these reasons, colour flow Doppler imaging techniques which are sensitive, safe and non-invasive, may represent a significant aid for improved

monitoring of long-term graft function, especially if regularly scheduled. Above all, a repeated con- trol of the same patient is important because RBF measurements suffer a certain amount of inaccu- racy and also because, in the normal range, there is a large distribution of RBF values.

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evaluation of kidney graft function by arterial flow using colour doppler flowmetry

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