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(Radiology. 2001;219:712-715.)
© RSNA, 2001

Ultrasonography

Renovascular Impedance and Esophageal Varices in Patients with Child-Pugh Class A Cirrhosis1

Agostino Colli, MD, Mirella Fraquelli, MD, PhD, Roberta Pometta, MD, Massimo Cocciolo, MD, Stefania Visentin, MD and Dario Conte, MD

1 From the Division of Medicine, Ospedale di Lecco, Italy (A.C., M.C.), and the Cattedra di Gastroenterologia, IRCCS Ospedale Maggiore, Via F Sforza 35, 20122 Milan, Italy (M.F., R.P., S.V., D.C.). Received May 22, 2000; revision requested July 2; final revision received October 2; accepted November 1. Supported by a research grant (1998–1999) from the CARIPLO Foundation and the Associazione Amici Gastroenterologia del Granelli, Milan, Italy. Address correspondence to D.C. (e-mail: dario.conte@unimi.it).


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
PURPOSE: To evaluate the frequency of increased renovascular impedance and its relationship with the presence of esophageal varices in patients with Child-Pugh class A cirrhosis without ascites.

MATERIALS AND METHODS: The intraparenchymal renal resistive index (RI) (reference value, <0.7) and portal congestive index (ie, the ratio between the portal cross-sectional area and mean flow velocity; reference value, <0.07) were measured by using duplex Doppler ultrasonography in 50 consecutive patients. The frequency of varices was assessed endoscopically. The data were analyzed with the Fisher exact test.

RESULTS: The renal RI was consistent with increased impedance (ie, >0.7) in 18 (36%) patients and was normal in 32 (64%). The proportion of patients with varices was significantly higher in the former group: 14 (78%) versus 10 (31%) (P = .002). In detection of the presence of varices, the renal RI was uniformly better than the portal congestive index in terms of sensitivity (58% vs 48%), specificity (84% vs 54%), and positive (3.60 vs 1.04) and negative (0.50 vs 0.96) likelihood ratios. RI determination improved the ability to exclude the presence of varices from a basal pretest probability of 52% (26 of 50 patients) to a final one of 69% (22 of 32 patients) and that of predicting the presence of varices from 48% (24 of 50 patients) to 78% (14 of 18 patients).

CONCLUSION: A substantial proportion of patients with Child-Pugh class A cirrhosis without ascites have increased renovascular impedance; this significantly correlates with the presence of varices.

Index terms: Endoscopy, 70.129, 70.75 • Esophagus, varices, 71.75 • Hypertension, portal, 76.794 • Kidney, perfusion, 81.72 • Liver, cirrhosis, 76.794 • Ultrasound (US), Doppler studies, 81.12984


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The duplex Doppler waveform analysis of intrarenal arteriolar vessels provides a noninvasive estimate of renovascular impedance; in particular, the renal resistive index (RI) is a reliable indicator of renal blood flow in control subjects and patients with different pathologic conditions (1–3).

Renal arteriolar vasoconstriction, which is characterized by an increased RI, has been reported (4,5) in patients with cirrhosis with functional renal failure (ie, hepatorenal syndrome) and in those with ascites, even in the absence of any apparent renal dysfunction (6).

It has been reported (7,8) that intrahepatic sinusoidal hypertension with portal vein sequestration of blood and increased hepatoportal-lymphatic dead space precedes renal sodium and water retention in patients with cirrhosis without ascitic decompensation, as a result of a neurohumoral response.

In addition, recent studies based on the evaluation of inulin and p-aminohippuric acid clearance showed that patients with Child-Pugh class A cirrhosis without ascites (ie, those patients without ascites and/or hepatic encephalopathy and with serum albumin level, bilirubin value, and prothrombin time elongation greater than 3.5 g/dL [35 g/L], less than 2.0 mg/dL [34.2 µmol/L], and less than 3 seconds, respectively, as compared with those in the control subjects) (9) have an impaired glomerular filtration rate in the presence of portal hypertension (10). Furthermore, conflicting data have been reported (6,11–13) concerning renovascular impedance in patients with Child-Pugh class A cirrhosis without ascites, and the possible association between an increase in renal RI and the presence of portal hypertension in these patients, to our knowledge, has never been investigated.

The purpose of our study was to evaluate renovascular impedance in patients with well-compensated Child-Pugh class A cirrhosis and its possible relationship with the presence of esophageal varices (EV).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Fifty-three consecutive patients (40 men, 13 women; mean age, 49.3 years ± 9 [SD]; age range, 39–64 years) with histologically proved liver cirrhosis were enrolled in the study. All of the patients gave their written informed consent for the study, which was approved by the relevant ethics committees. The cirrhosis was related to past chronic alcohol abuse (arbitrarily defined as daily alcohol consumption greater than 80 g or 0.75 L of red wine with 11 g of ethanol per deciliter for more than 10 years) in 19 patients, hepatitis C virus infection in 24 patients (with concomitant past alcohol abuse in six patients), genetic hemochromatosis in six patients, and miscellaneous causes in the remaining four patients.

All of the patients had Child-Pugh class A cirrhosis and no history of the major complications of cirrhosis (eg, hepatic encephalopathy and/or gastrointestinal bleeding). None of the patients had a history of past or current ascitic decompensation or was receiving diuretics, vasoactive drugs (eg, ß-blockers), or drugs that negatively influence renal function (eg, nonsteroidal antiinflammatory drugs); in all patients, blood urea nitrogen level was less than 0.20 mg/dL (0.07 mmol/L), and serum creatinine level was less than 0.80 mg/dL (70.72 µmol/L).

After an overnight fast, all of the patients underwent abdominal ultrasonography (US) as a part of routine clinical evaluation. The procedure was performed by two trained operators (A.C., M.F.), blinded to both the aim of the study and the results of duplex Doppler evaluation, by using commercially available US equipment with Doppler capability (a 3.5- or 5-MHz transducer). Since three patients were excluded from the study because of umbilical vein patency (one patient) or abnormal gaseous distention that interfered with an adequate evaluation of portal flow (two patients), a total of 50 patients (38 men, 12 women; mean age, 49.8 years ± 8; age range, 43–64 years) completed the study.

The intraparenchymal renal arterial RI was determined according to Platt et al (1–3,11) and was as follows: RI equals (peak systolic frequency shift minus minimum diastolic frequency shift) divided by peak systolic frequency shift. The Doppler signal was recorded from both kidneys, from arcuate arteries at the level of the corticomedullary junction, or from interlobar arteries along the margin of the medullary pyramids. To minimize sampling error, the Doppler spectrum was increased by using the lowest frequency-shift range possible without aliasing and a low-frequency (100-MHz) wall filter (Fig 1). The RI of three renal vessels, obtained in three renal areas, was measured in each patient by using at least three Doppler spectra, and the mean value was calculated. A renal RI of 0.70 or more was considered abnormal and consistent with the presence of high renal vascular resistance and renal vasoconstriction (11).



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  		Figure 1. Intrarenal duplex Doppler tracing indicates the waveform on the basis of which renal RI was calculated. Calipers indicate the peak systolic frequency shift and the minimum diastolic frequency shift. Renal RI equals (peak systolic frequency shift minus minimum diastolic frequency shift) divided by peak systolic frequency shift. Tracing refers to a patient with well-compensated cirrhosis with a normal renal RI, and it details the methods used in this study. In the top right corner of the figure are detailed the Doppler angle (Ang VC), 60°; depth (Prof.), 3.3 cm; size of the sample volume (Dim.), 2.0 mm; frequency (Freq), 2.5 MHz; wall filter cutoff frequency (FP Basso [low]); and pulse repetition frequency (FRI), 2,500 Hz. Col = color, Dop = Doppler, DS = standard deviation, IR = resistive index, Opz. flusso: Ris = flow options: resolution.

 
To evaluate the portal congestive index, the portal vein was longitudinally scanned and measured as closely as possible to the crossing of the hepatic artery. It was calculated as follows: portal congestive index equals ({pi}PVD2 divided by 4) divided by PBFVel, where PVD represents the portal vein diameter (in centimeters); and PBFVel, portal blood flow velocity (in centimeters per second). Duplex Doppler measurements were obtained in the same position at an angle less than 55°. In accordance with Merkel et al (14), the portal congestive index was considered normal, moderately increased, or severely increased if it was less than 0.07, between 0.07 and 0.11, or 0.12 or greater, respectively.

For both renal RI and portal congestive index, the estimate of the intra- and interobserver variability was based on the findings obtained twice in each patient by each operator.

Within 1 week of the US examination, the patients also underwent upper gastrointestinal endoscopy to identify the possible presence and degree of EV, which were classified according to accepted criteria (15). The well-trained endoscopists of both centers were unaware of both the aim of the study and the results of the duplex Doppler evaluation.

Differences between the proportion of patients with a normal or increased renal RI and a portal congestive index, according to the presence or absence of EV, were analyzed by using the Fisher exact test. To assess the diagnostic accuracy of renal RI and portal congestive index in the detection of EV, the following parameters were determined: sensitivity (number of true-positive test results divided by the number of all patients with the disease), specificity (number of true-negative test results divided by the number of all patients without the disease), positive predictive value (number of true-positive test results divided by the number of all patients with positive test results), negative predictive value (number of true-negative test results divided by the number of all patients with negative test results), positive likelihood ratio (sensitivity divided by [1 minus specificity]), and negative likelihood ratio ([1 minus sensitivity] divided by specificity).

The coefficient of variation was calculated as follows: SD divided by the mean value; the 95% CI was estimated in absolute terms as 1.96 x SD (16).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
As detailed in Table 1, the renal RI, whose intra- and interobserver variability ranged from 2% (mean, 0.65 ± 0.01; 95% CI: 0.63, 0.67) to 4% (mean, 0.64 ± 0.02; 95% CI: 0.60, 0.68), was 0.7 or greater in 18 (36%) patients and normal in 32 (64%). The portal congestive index, which showed an intra- and interobserver variability ranging from 4% (mean, 0.13 ± 0.005; 95% CI: 0.12, 0.14) to 7% (mean, 0.13 ± 0.009; 95% CI: 0.12, 0.14), was 0.07 or greater in 39 (78%) patients, 20 of whom had index values of 0.12 or greater.


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  		TABLE 1. Renal Resistive and Portal Congestive Indexes in 50 Patients with Child-Pugh Class A Cirrhosis without Ascites, according to Presence or Absence of EV

 
Endoscopy revealed that 24 (48%) patients had EV; the proportion of patients with EV was significantly higher among those with a renal RI of 0.7 or greater (14 of 18 vs 10 of 32; P = .002). Of the 20 patients with a portal congestive index of 0.12 or greater, 12 had concomitant portal hypertension (with a renal RI of 0.7 or greater in eight). The frequency of EV was not significantly related to the congestive index. Table 2 also indicates the sensitivity, specificity (with 95% CIs), and positive and negative likelihood ratios of both renal RI and portal congestive index.


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  		TABLE 2. Sensitivity, Specificity, and Likelihood Ratios in 50 Patients with Child-Pugh Class A Cirrhosis without Ascites

 
As detailed in Figure 2, of the 18 patients with an increased RI (range, 0.71–0.77), 14 (78%) had concomitant EV; in addition, an increased RI, without concomitant EV, was observed in four patients in whom the RI value was 0.70 (two patients) and 0.71 (two patients). In patients with Child-Pugh class A cirrhosis, the positive and negative predictive values of RI, according to the presence of EV, were 78% and 68%, respectively.



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  		Figure 2. Plot shows distribution of RI according to the presence or absence of EV in 50 patients with Child-Pugh class A cirrhosis without ascites. Individual data are given.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Duplex Doppler examination is a safe and reproducible technique for evaluating arterial blood flow, and it has been extensively validated as an indicator of renal vasoconstriction in various pathologic conditions, including obstructive or interstitial nephropathy, acute tubular necrosis, latent or full-blown hepatorenal syndrome (1–5), and cirrhosis with ascites (6,12–13). Furthermore, in two studies (5,11) of patients with cirrhosis, investigators have found a statistically significant correlation between increased renal RI values and the development of impaired renal function, and even survival (5). In one of these studies (5), investigators also found a direct correlation between renal RI values and plasma renin activity, which proved to be an independent predictor of survival (together with plasma antidiuretic hormone and serum sodium concentrations).

However, it is difficult to extrapolate the real proportion of patients with Child-Pugh class A cirrhosis without ascites from the populations considered in the different studies. Furthermore, in these patients, the renal RI value was found to be increased in a proportion ranging from 0% to 25%, and no details concerning the actual prevalence of EV were given (5,6,11–13).

Abnormal renal RI values were detected in 18 (36%) patients in our series of carefully selected and consecutively enrolled treatment-free patients with stable Child-Pugh class A cirrhosis who did not have fluid retention. EV were present in 24 (48%) of the patients, which is probably slightly higher than that observed in a random sample of patients with well-compensated cirrhosis but comparable to that reported in other series (17–19). The renal RI values significantly correlated with the presence of EV that complicated portal hypertension, with a positive predictive value of 78%. It will be of particular interest to follow up those patients with increased RI, in the absence of EV (four patients; Figure 2, left column), to evaluate if they are at increased risk of developing EV, as compared with those with a normal RI.

These data in patients with clinically compensated Child-Pugh class A cirrhosis support the hypothesis that portal hypertension may be associated with an impairment in renal blood flow, even in the absence of ascites and fluid retention, and that an increase in renovascular impedance reflects a hemodynamic derangement even before any clinical manifestation. Thus, duplex Doppler evaluation of renal perfusion could represent a simple and inexpensive method to identify a subset of symptomless patients with Child-Pugh class A cirrhosis who deserve special follow-up due to the presence of portal hypertension. The information arising from the present findings could be even more interesting if one were to consider the presence or absence of EV as equivalent to the presence or absence of portal hypertension.

Our own arbitrarily chosen cutoff value of 0.70 has been shown in different series (4–6,11) to be an accurate index in identifying renal vasoconstriction in patients with cirrhosis. In the present series, 26 of 50 patients were free of EV (pretest probability). Determination of renal RI, taking into consideration a cutoff of 0.70 or greater, improved the ability to exclude varices with a posttest probability of 69% (22 of 32 patients). On the other hand, the ability to predict varices improved from a pretest probability of 24 (48%) of 50 to 14 (78%) of 18 (Table 1). Our data also show that the correlation between the renal RI and the presence of EV is better than that offered with the portal congestive index (Table 1), as is indicated by the fact that an increased portal congestive index was observed in 20 of 26 patients, without any endoscopic evidence of portal hypertension. An increase in the renal RI alone (two patients) or together with an increase in the portal congestive index (12 patients) reflected the presence of EV. These data are in line with those relating to other series (13,14,17), indicating that portal congestive index values do not accurately reflect portal hypertension and/or its major complications (ie, the presence of EV).

The presence of increased renovascular impedance in about one-third of patients with cirrhosis without fluid retention and/or hepatic decompensation and the association between renal vasoconstriction and the presence of EV represent the main findings in our series. Further studies could help in the assessment of the role of duplex Doppler evaluation of renal arteries with other parameters, for example, platelet count and spleen size, as recently suggested (20,21), to screen which patients with cirrhosis should undergo endoscopy for detection of EV.

Our ongoing follow-up evaluation of this subgroup of patients with cirrhosis may make it possible to elucidate the clinical meaning of the alterations just described.


   ACKNOWLEDGMENTS
 
The authors thank Mario Angelico, MD, for the useful criticisms.


   FOOTNOTES
 
Abbreviations: EV = esophageal varices, RI = resistive index

Author contributions: Guarantor of integrity of entire study, D.C.; study concepts, M.F., A.C., M.C.; study design, A.C., D.C.; literature research, M.C., S.V.; clinical studies, M.F., D.C., A.C.; data acquisition, A.C., M.F., R.P.; data analysis/interpretation, M.C., D.C.; statistical analysis, R.P., M.F., D.C.; manuscript definition of intellectual content, S.V., D.C.; manuscript editing, S.V., M.F.; manuscript preparation, revision/review, and final version approval, A.C., D.C.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Platt JF, Rubin JM, Ellis JH, DiPietro MA. Duplex Doppler US of the kidney: differentiation of obstructive from non-obstructive dilatation. Radiology 1989; 171:515-517.[Abstract/Free Full Text]
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