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Parenchymal consequences of fibromuscular dysplasia renal artery stenosis
Parenchymal Consequences of Fibromuscular Dysplasia Renal Artery Stenosis Claire Mounier-Vehier, MD, PhD, Christophe Lions, MD, Olivier Jaboureck, MD, Patrick Devos, Stephan Haulon, MD, PhD, Maud Wibaux, MD, Alain Carre´, MD, and Jean-Paul Beregi, MD, PhD ● Purpose: The aim of this study is to assess parenchymal consequences of fibromuscular dysplasia (FMD) renal artery stenosis (RAS) in hypertensive patients by spiral computed tomographic angiography (CTA). Methods: Spiral CTA was performed in 20 essential hypertensive (EH) patients (40 EH kidneys and 20 hypertensive patients with unilateral FMD stenosis (20 poststenotic [S] kidneys, 20 opposite [OPP] kidneys). Renal length (RL; in millimeters), mean cortical thickness (MCT; in millimeters), cortical area (CA; in square millimeters), and medullary length (ML; in millimeters) were evaluated. Results: Blood pressure, creatinine clearance, and long-standing hypertension were similar in both groups of patients. Compared with EH kidneys, S and OPP kidneys showed significant cortical thinning (MCTEH ⴝ 9.2 ⴞ 0.8 mm versus MCTOPP ⴝ 7.8 ⴞ 1.0 mm versus MCTS ⴝ 7.3 ⴞ 1.0 mm; P < 0.0001). RL and ML were reduced only in the S kidney group, with RLEH ⴝ 103 ⴞ 11 mm versus RLOPP ⴝ 105 ⴞ10 mm versus RLS ⴝ 96 ⴞ 11 mm; P ⴝ 0.05; and MLEH ⴝ 84 ⴞ 11 mm versus MLOPP ⴝ 89 ⴞ 9 mm versus MLS ⴝ 81 ⴞ 10 mm; P ⴝ 0.05, respectively. CA and MCT correlated significantly with creatinine clearance in the entire population (r ⴝ 0.43; P ⴝ 0.005; r ⴝ 0.35; P ⴝ 0.02, respectively). Conclusion: Unilateral RAS was associated with bilateral cortical thinning in FMD disease. Cortical atrophy appears to be an accurate marker of unilateral RAS. Its use as a potential screening method for RAS should be investigated further. Am J Kidney Dis 40:1138-1145. © 2002 by the National Kidney Foundation, Inc. INDEX WORDS: Hypertension; cortical thickness; fibromuscular dysplasia (FMD); vascular nephropathy; renal artery stenosis (RAS).
I
DENTIFICATION of patients with renovascular hypertension is an important clinical problem, especially in fibromuscular dysplasia (FMD) disease, because revascularization of renal artery stenosis (RAS) improves the control of hypertension and contributes to preserve renal function.1 FMD is a nonatherosclerotic and noninflammatory vascular disease, occurring in less than 2% of the hypertensive population.2-4 There is increasing concern about renovascular disease as a growing cause of chronic renal failure. Renal ischemia–caused stenosis or obstruction of the main renal arteries and/or intraparenchymal preglomerular arteries induces a proFrom the Service de Me´decine Interne et HTA and Service de Chirurgie Vasculaire, Hoˆpital Cardiologique; Service de Radiologie Vasculaire Diagnostique et Interventionnelle, CHRU; and CERIM, De´partement de Biostatistiques, Faculte´ de Me´decine, Lille, France. Received January 24, 2002; accepted in revised form July 9, 2002. Supported in part by grants from MNERT EA 2691 and MNERT EA 2693, University of Lille-2, France. Address reprint requests to Claire Mounier-Vehier, MD, PhD, Service de Me´decine Interne et HTA, Hoˆpital Cardiologique, CHRU, 59037 Lille Cedex, France. E-mail: [email protected] © 2002 by the National Kidney Foundation, Inc. 0272-6386/02/4006-0003$35.00/0 doi:10.1053/ajkd.2002.36855 1138
gressive loss of renal mass.5-7 Additionally, the focus on parenchymal injury is timely and appropriate because recent studies indicate that renal parenchymal status is a major factor in determining prognosis and response to revascularization. Although this concept is new, vascular nephropathy probably is underestimated in clinical practice because of the lack of accurate markers of distal disease.8-29 In addition, there are few studies, with small patient numbers, that examined renal consequences of dysplastic stenoses.2,3,8,10,13-15,26 It is difficult to investigate distal lesions using conventional investigation methods. Functional markers are more pertinent for the diagnosis of vascular nephropathy compared with morphological markers; they include the reduction in glomerular filtration rate on scintigraphic studies,13,18-20 intrarenal resistive index measurements with echo Doppler,1,17,21 and intra-arterial Doppler flow wire evaluation of renal blood flow reserve.22 Although reduced renal length (RL) is a classic morphological marker of vascular nephropathy, it is not sensitive enough for an early diagnosis.1,6-8,10,14,17,21,23-26 However, it recently was reported that cortical thickness measurements, especially mean cortical thickness (MCT) and cortical area (CA), could be more pertinent for the diagnosis of
American Journal of Kidney Diseases, Vol 40, No 6 (December), 2002: pp 1138-1145
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES
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intraparenchymal disease compared with RL.23,27-29 Additionally, we identified threshold values of 800 mm2 for CA and 8 mm for MCT that allowed us to distinguish essential hypertensive (EH) kidneys from poststenotic (S) kidneys. Sensitivity and specificity of these markers were 85% and 89% (CA) and 73% and 93% (MCT), respectively.29 The purpose of this work is to assess more accurately the parenchymal consequences of FMD RAS on S and contralateral (OPP) kidneys in hypertensive patients by using spiral computed tomographic angiography (CTA). METHODS
Population Between 1995 and 2000, a total of 577 hypertensive patients showing several clinical and biological criteria suggestive of RAS were investigated in our department.1,2,11 All subsequent causes of endocrinopathy and other causes of cortical atrophy, such as reflux nephropathy, previous stone passage with intermittent hydronephrosis, previous pyelonephritis, hypoplasic kidney, and associated polycystic kidney disease, were excluded from the initial selection. To further homogenize our patient cohort, we excluded atherosclerotic RAS (520 cases), FMD disease with coexisting atherosclerotic RAS (9 cases), and bilateral FMD stenoses (8 cases). As a result, 49 patients were included in the study. The protocol was approved by the university ethical committee. The purpose of the study was explained to the patients at an outpatient visit, and written informed consent was obtained. Systolic (SBP) and diastolic blood pressure (DBP) were measured in supine position on the day of spiral CTA, according to World Health Organization (WHO) recommendations. Pulse blood pressure was defined as the difference between SBP and DBP. Hypertension was defined as SBP greater than 140 mm Hg and/or DBP greater than 90 mm Hg in accordance with the WHO recommendations. Heart rate was measured on resting electrocardiogram. Demographic parameters also included smoking habit; body mass index (BMI; weight [kg]/height [m]2); age; sex; longstanding hypertension (ⱖ2 years); cigarette smoking; family history of cardiovascular disease; diabetes mellitus, defined as fasting glycemia in excess of 1.40 g/L that was treated by diet, oral hypoglycemics, or insulin treatment; and dyslipidemia, with a total cholesterol level in excess of 2.50 g/L or current hypolipemic. Serum potassium and serum creatinine levels also were measured. Creatinine clearance was calculated using the Cockcroft-Gault formula. In preparation for angiography and spiral CTA, hydration was ensured by not restricting fluid intake and by administering 500 mL of intravenous saline the day of the examination.5
Spiral CTA Spiral CTA (Somatom plus 4A; Siemens, Erlanger, Germany) was conducted in all patients to assess FMD stenosis and its parenchymal consequences. Beregi et al30 showed
Fig 1. Box plots of (A) RL and (B) MCT in the three groups of kidneys; comparison between EH, OPP, and S kidneys. (A) EH versus OPP, not significant; S versus OPP, significant at the 0.05 level (risk ␣); EH versus S, not significant; (B) EH versus OPP, significant at the 0.05 level (risk ␣); S versus OPP, not significant; EH versus S, significant at the 0.05 level (risk ␣).
that spiral CTA, especially the combination of transverse sections and maximum intensity projection reconstructions, reliably shows FMD RAS. The protocol for spiral CTA has been described elsewhere30,31; it was independent from age and weight. Briefly, a total of 120 to 150 mL of iodinated contrast material (Telebrix 30; meglumine ioxithalamate; Guerbet, Villepinte, France) was injected during the procedure. Volume acquisition was obtained by rotating the X-ray tube (X-ray source collimated to 3 mm) and simultaneous translation of the patient with the table moving at 3 mm/s. The two poles were investigated in fewer than 20 seconds with the spiral acquisition. Total examination time ranged from 15 to 25 minutes. Markers of parenchymal disease were derived from renal geometry: RL, medullary length (ML), cortical thickness, and CA. Morphological characteristics of kidneys were studied from the transverse axial sections (Figs 1 and 2). RL was referred to as the difference between the first section that showed the superior pole of the kidney and the first section that showed the inferior pole of the kidney. We studied the superior and inferior poles separately, based on the measurement of three cortical thicknesses: anterior, posterior, and lateral.
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MOUNIER-VEHIER ET AL
pressure gradient across the stenosis greater than 20 mm Hg was considered significant.5,15,32
Evaluation Criteria and Statistical Analysis
Fig 2. Spiral CTA of a left kidney in an EH patient (transverse axial section). The superior pole of the left kidney presents MCTs greater than the 8-mm threshold if we refer to the measurement scale, in which each increment corresponds to 10 mm.
Superior cortical thickness was studied 2 cm below the superior pole of the kidney, and inferior cortical thickness, 2 cm above the inferior pole of the kidney. We considered the width of the dense peripheral band on spiral CTA to be equivalent to cortical width. We measured this band in six areas: anterosuperior (AST), laterosuperior (LST), posterosuperior (PST), anteroinferior (AIT), lateroinferior (LIT), and posteroinferior (PIT). MCT, CA, and ML also were calculated as follows: MCT 共mm兲 ⫽ 共AST ⫹ LST ⫹ PST ⫹ AIT ⫹ LIT ⫹ PIT兲/6
The entire population was divided into two groups depending on the presence or absence of FMD stenosis. Patients with normal Doppler and spiral CTA results were considered to have essential hypertension (group 1, with 20 EH patients), ie, a group of 40 EH kidneys (EH group). Patients with unilateral RAS formed a second group (group 2, with 20 patients), ie, 20 kidneys with RAS (S group) and 20 contralateral or OPP kidneys (OPP group). The morphological study took into account: (1) status of the kidney (EH, S, or OPP), and (2) location of the kidney (right or left side) in group 1. Statistical analysis yielded a descriptive analysis of the population (mean ⫾ SD for numerical parameters, frequencies for qualitative ones). The two groups of patients were compared using Wilcoxon’s test for numerical parameters and chi-square test for frequencies. Right- and left-sided EH kidneys were pooled together in a single group (EH group) because the location of the kidney had no effect on morphological parameters. Morphological differences between EH, OPP, and S kidneys were assessed by a nonparametric analysis of variance and a post hoc test using a Bonferroni correction. A study of Spearman’s coefficient also was performed to evaluate the relationship between morphological, clinical, and biochemical indices; specifically, the relationship between serum creatinine clearance and the sum of cortical indices from the two kidneys in a given patient. The threshold significance level (risk ␣) was set at 5%. Data analysis was performed using SAS software (version 8.1; SAS Institute Inc, Cary, NC).
CA 共mm 2 兲 ⫽ 共RL ⫻ MCT兲 ML 共mm兲 ⫽ RL–关共AST ⫹ LST ⫹ PST兲/3 ⫹ 共AIT ⫹ LIT ⫹ PIT兲/3兴 Radiologists were blinded to the patient group when they analyzed spiral CTA. Reproducibility and agreement of these measurements were assessed during a preliminary phase.28 The term atrophy was used to refer to an RL less than 80 mm and/or an MCT less than 8mm and/or a CA less than 800 mm2.
Digital Substraction Renal Angiography Digital substraction angiography (Integris V 3000; Philips, Best, Holland) only was performed in 20 of 40 patients who were suspected to have FMD stenosis on spiral CTA and/or on Doppler ultrasonography (128 XP; Acuson, Mountain View, CA). A total of 50 to 120 mL of iodinated contrast material (Hexabrix; Guerbet) was injected. Stenoses were classified on the basis of angiographic appearance, as proposed by Mc Cormack et al4 and Harrison and McCormack.31 In all cases, pressure measurements were drawn to assess the physiological significance of the lesion; a mean systolic
RESULTS
Clinical and biological indices of the two groups of patients are listed in Table 1. Except for sex ratio and BMI, clinical and biological characteristics were similar in both groups of patients, especially age and history of hypertension. Dyslipidemia, diabetes mellitus, and smoking were more frequent in group 1 compared with group 2, but differences were not significant. Fifty-two renal arteries (40 main and 12 accessory arteries) and 20 stenoses were assessed by spiral CTA and angiography in group 2. RAS diagnosed by spiral CTA always was confirmed by angiography. Right-sided renal arteries were involved in 19 of 20 cases (18 main and 1 accessory arteries). Three types of FMD were identified: intimal fibroplasias, which consisted of unifocal stenosis (5 cases); medial fibroplasias, which consisted of multifocal stenoses with the classic “string of beads” appearance (13
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES Table 1.
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Demographic Characteristics in the Two Groups of Hypertensive Patients
Age (y) Men/Women Longstanding hypertension ⬎2 y Cigarette smoking Diabete mellitus Dyslipidemia Family history of cardiovascular disease SBP (mm Hg) DBP (mm Hg) Pulsed blood pressure (mm Hg) BMI (kg/m2) Creatinine clearance (mL/min) Serum potassium (mmol/L)
Group 1 (n ⫽ 20)
Group 2 (n ⫽ 20)
P
49 ⫾ 11 10/10 11 (55) 4 (20) 5 (25) 14 (70) 6 (30) 167 ⫾ 16 102 ⫾ 14 65 ⫾ 16 29 ⫾ 6 90 ⫾ 20 3.9 ⫾ 0.4
48 ⫾ 15 2/18 9 (45) 2 (10) 1 (5) 9 (45) 14 (70) 163 ⫾ 26 96 ⫾ 18 67 ⫾ 17 25 ⫾ 5 80 ⫾ 23 4.1 ⫾ 0.3
NS 0.005 NS NS NS NS 0.01 NS NS NS 0.005 NS NS
NOTE. Results shows as mean ⫾ SD for numerical parameters and frequency (percentage) for categorical parameters. Group 1 includes EH patients, and group 2, hypertensive patients with significant unilateral FMD stenosis. Abbreviation: NS, not significant.
cases), and subadventitial fibroplasias, which appeared as “tubular” stenoses (2 cases). Results of morphological indices are listed in Table 2. OPP and EH kidneys were of similar length (Fig 1). S kidneys were significantly smaller compared with OPP kidneys, with an averTable 2.
age difference of 9 mm (Fig 1). ML was reduced only in S kidneys. OPP and S kidneys showed significant cortical thinning, with MCTs of 1.4 and 1.9 mm lower compared with EH kidneys, respectively (Figs 2 and 3). The post hoc test showed that only MCT
Morphological Differences Between EH, OPP, and S Kidneys
EH Kidneys* (n ⫽ 40)
OPP Kidneys (n ⫽ 20)
S Kidneys (n ⫽ 20)
Overall† P
103 ⫾ 11
105 ⫾ 10
96 ⫾ 11
0.05
9.4 ⫾ 1.1
7.6 ⫾ 1.2
6.9 ⫾ 1.1
⬍0.0001
LST
8.9 ⫾ 1.3
7.9 ⫾ 1.5
7.0 ⫾ 1.3
⬍0.0001
PST
8.9 ⫾ 1.3
7.7 ⫾ 1.2
7.0 ⫾ 1.4
⬍0.0001
AIT
8.8 ⫾ 1.1
7.7 ⫾ 0.9
7.2 ⫾ 1.1
⬍0.0001
LIT
9.7 ⫾ 0.9
8.1 ⫾ 1.0
7.5 ⫾ 1.0
⬍0.0001
PIT
9.3 ⫾ 1.0
8.1 ⫾ 1.1
8.0 ⫾ 1.0
⬍0.0001
MCT (mm)
9.2 ⫾ 0.8
7.8 ⫾ 1.0
7.3 ⫾ 1.0
⬍0.0001
CA (mm2) ML (mm)
945 ⫾ 141 84 ⫾ 11
824 ⫾ 149 89 ⫾ 9
703 ⫾ 156 81 ⫾ 10
⬍0.0001 0.05
RL (mm) Cortical thickness (mm) AST
Significant Post-Hoc Tests‡ P ⬍ 0.05
OPP v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S
NOTE. Results shown as mean ⫾ SD. *Right- and left-sided EH kidneys were pooled because they were of similar morphological characteristics. †Results of nonparametric analysis of variance for repeated measurements. ‡Results of post-hoc test using Bonferroni correction (2 ⫻ 2 comparison of means between the three kidney groups).
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MOUNIER-VEHIER ET AL
Fig 3. Spiral CTA in a hypertensive woman with a right FMD stenosis (transverse axial sections). (A) The superior cortical thicknesses of the S kidney show diffuse damage, with values of 7.5 mm on average if we refer to the same measurement scale. (B) The superior cortical thicknesses of the OPP kidney are 8 mm on average.
was significantly different between EH, OPP, and S kidneys (Table 2). In the group of S kidneys, 15 kidneys (75%) had an MCT and/or CA less than their threshold values of 8 mm and 800 mm2, respectively. In the group of OPP kidneys, 10 kidneys (50%) had significant cortical atrophy. Cortical atrophy significantly correlated with serum creatinine clearance (CA, r ⫽ 0.43; P ⫽ 0.005; MCT, r ⫽ 0.35; P ⫽ 0.02) in the entire population (n ⫽ 40). CA correlated with serum creatinine clearance in group 1 (r ⫽ 0.46; P ⫽ 0.04). We did not find a significant correlation between renal function and morphological indices in group 2. DISCUSSION
This study shows the presence of significant cortical thinning in S and OPP kidneys in hyper-
tensive patients with unilateral FMD stenosis compared with EH patients. RL in all kidney groups was within normal range.33 However, kidney length was less in the S kidney group compared with the EH and OPP groups. In many respects, the group of patients with unilateral RAS (group 2) was similar to other series.10,13-15,20 The predominance of young women (19 of 20 patients) and the greater incidence of right-sided lesions (21 of 22 lesions) suggested hormonal influences and arterial stretching as possible etiologic factors.2-4,14 It already was reported that renal morphological characteristics were influenced by body size and age.33 In our study, 10 of the 20 EH patients were men, and mean BMI in the EH group was 29 kg/m2. Only 2 subjects with FMD were men, and mean BMI in this group was 25 kg/m2. Consequently, a difference in average body size and/or sex could account for differences in renal morphological characteristics between groups 1 and 2. Although our results should be interpreted with caution given the small size of the population, we did not find a significant correlation between age, BMI, sex, and morphological indices in the two groups of patients. Mean creatinine clearance was within normal range in both groups of patients. We reported a significant relationship between creatinine clearance and the sum of cortical indices (MCT, CA) from the two kidneys in the entire population. However, creatinine clearance is a rough indicator of individual renal function because the OPP kidney may compensate for the loss of S kidney glomerular filtration.13,18-20 In consequence, creatinine clearance did not appear to be an accurate marker of FMD nephropathy. Spiral CTA is a recent technique that is still debated in the clinical management of patients suspected to have RAS1,34 because it involves the use of both X-ray radiation and iodinated contrast material. However, since this present work, we use a multidetector CT Scan (Somatom Plus 4 Volume Zoom; Siemens) that allows data acquisition in a shorter time with 90 mL of iodinated contrast material. Additionally, a recent metaanalysis showed that spiral CTA and magnetic resonance angiography (MRA) were significantly superior for the diagnosis of RAS compared with ultrasonography, captopril renal scintigraphy, and the captopril test.34 We also showed
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES
that spiral CTA precisely evaluated cortical parameters and RL with satisfactory reproducibility and concordance. Axial transverse sections are automated, and there is no bias in image acquisition.28,29 Last, because Beregi et al35 and Elkohen et al36 showed very satisfactory levels of specificity (96%) and sensitivity (100%) arising from combining Doppler ultrasonography and spiral CTA in RAS diagnosis, for ethical consideration, we did not perform renal angiography in 20 patients presenting with normal spiral CTA and Doppler results. FMD stenosis may lead to some loss of renal parenchyma, resulting in lower kidney size.5,8,10,14,15,26 Reduced kidney length usually is uncommon in FMD disease.2,3,16,18,19 In the current study, although S kidneys were smaller compared with EH and OPP kidneys, their RL was still within normal range. Consequently, we assessed that the measurement of the only kidney length could lead to the false conclusion of the absence of distal lesions. Conversely, cortical thickness measurements assessed significant lesions in S kidneys, as well as OPP kidneys. These data show that cortical thickness parameters, especially MCT and CA, were more accurate for the diagnosis of intraparenchymal FMD disease compared with classic kidney length. Thus, we assumed, although we did not undertake prospective follow-up, that cortical lesions appear before the reduction in kidney length. In the current study, the term atrophy was used to refer to an RL less than 80 mm and/or an MCT less than 8 mm and/or a CA less than 800 mm2. To our knowledge, there is no consensus definition of cortical atrophy because it is a new morphological marker. We therefore have proposed our own definition of cortical atrophy from threshold values of MCT (8 mm) and CA (800 mm2).29 However, these threshold values should be confirmed by a larger prospective study. Studying intrarenal vascular resistance with echo Doppler also should be of benefit in screening for distal vascular lesions in FMD disease. A renal resistance index of at least 80 before revascularization was a strong predictor of worsening arteriolar vascularization and lack of improvement in blood pressure despite revascularization.21 The study by Caps et al24 using ultrasonog-
1143
raphy only examined changes in renal size over time as a function of the severity of RAS. However, ultrasonography is time consuming and operator dependent. The echogenicity of patients is a limiting factor. A separate evaluation of the renal cortex and medulla also is more difficult than with spiral CTA27 or MRA.23 Few studies have examined the renal cortex, and they did not undertake comparative evaluations using Doppler ultrasonography. Most studies have examined renal size in dysplasic and atherosclerotic models. Cortical thickness and cortical volumes have been studied only in EH patients and patients with atherosclerotic renal disease. Scintigraphic studies have assessed changes in glomerular filtration rate after angioplasty in dysplasic and atherosclerotic disease.13,18-20 The study of the prognostic value of arteriolar resistance has been performed only in atherosclerotic disease.21 Finally, the accuracy of these markers in FMD and atherosclerosis has not yet been studied to our knowledge. Cortical atrophy in S and OPP kidneys could be a direct consequence of renal hypoperfusion.7,8,13,18-20,23-26,37 RAS activation resulting from hypoperfusion has several deleterious effects, such as inducing tubulointerstitial atrophy5-7,16,26,38 and systemic hypertension.1,7,9,14,17,26,38 In addition, several scintigraphic works have shown a reduction in glomerular filtration in S kidneys and a nephrotoxic compensatory glomerular hyperfiltration in OPP kidneys.13,18-20 These hyperfiltration processes could produce focal sclerosing glomerulonephritis and inflammatory tubulointerstitial lesions that could have an aggravating role in the course of cortical thinning.34 Associated structural alterations in distal arteries induced by long-standing hypertension (⬎2 years) could not be excluded in OPP and S kidneys.7,8,27 Finally, we cannot exclude undetected distal dysplasic lesions. Assessment of the hemodynamic significance of FMD stenosis is often difficult, particularly in medial lesions. Showing cortical atrophy in an S kidney therefore is an interesting result because it shows the hemodynamic renal impact of the lesion and may be considered an indirect marker of the significance of the stenosis. There is no consensus about which patients should undergo revascularization or the type of revascularization that should be used. The deci-
1144
sion to revascularize the kidney to preserve renal function is based on the assumption that angioplasty will stabilize or improve renal function. Diagnosis of cortical atrophy has not made revascularization irrelevant because it was an unknown morphological parameter. However, we must remain cautious about the therapeutic applications of cortical atrophy because the prognostic value of these parameters is still unknown. Kidneys less than 8 cm and a Doppler resistance index greater than 0.8 only are considered of poor prognosis and do not imply revascularization. Results of this cross-sectional study are limited by the size of our populations. Group 1 contained only EH patients because, for ethical reasons, spiral CTA could not be performed on healthy volunteers. Consequently, values of cortical parameters in group 1 cannot be extrapolated to healthy volunteers if we refer to the recent work of Kojima et al,27 which showed significant cortical thinning in EH patients. However, the purpose of the current work is not to establish reference values, but to identify possible morphological differences between kidneys with FMD stenosis and EH kidneys. Cortical atrophy is not specific of renovascular disease. Other common causes of renal atrophy could cause the same morphological aspect. However, in a context of RAS, cortical thinning could be considered a more accurate marker of vascular nephropathy compared with RL. We cannot draw conclusions about the prognostic value of MCT and CA because this was a cross-sectional study. We did not perform a comparison between cortical thickness and resistance indices; therefore, we are not able to prejudge whether cortical atrophy was adverse in nature. It may be possible that functional lesions appear before morphological lesions, but to our knowledge, this has not been shown. It therefore would be interesting to conduct a further prospective study that would examine functional lesions using ultrasound and/or scintigraphy and morphological characteristics using spiral CTA or MRA. In conclusion, spiral CTA provides useful data about distal consequences of FMD stenosis. We show that S and OPP FMD kidneys had significant cortical atrophy despite preserved overall size compared with EH kidneys.
MOUNIER-VEHIER ET AL
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21. Radermacher J, Chavan A, Bleck J, et al: Use of Doppler ultrasonography to predict the outcome of therapy for renal-artery stenosis. N Engl J Med 344:410-417, 2001 22. Beregi JP, Mounier-Vehier C, Devos P, et al: Doppler flow wire evaluation of renal blood flow reserve in hypertensive patients with normal renal arteries. Cardiovasc Intervent Radiol 23:340-346, 2000 23. Prince MR, Schoenberg SO, Ward JS: Hemodynamically significant atherosclerotic renal artery stenosis: MR angiographic features. Radiology 205:128-136, 1997 24. Caps MT, Zierler RE, Polissar NL, et al: Risk of atrophy in kidneys with atherosclerotic renal artery stenosis. Kidney Int 53:735-742, 1998 25. Guzman RP: Renal atrophy and arterial stenosis. A prospective study with duplex ultrasound. Hypertension 23:346-350, 1994 26. Schreiber MJ, Pohl MA, Novick AC: The natural history of atherosclerotic and fibrous artery disease. Urol Clin North Am 11:383-392, 1984 27. Kojima S, Shida M, Tanaka KE, Takano H, Yokoyama H, Kuramochi M: Renal macrostructure and cortical circulation in hypertension assessed by dynamic computed tomography. Am J Hypertens 14:516-523, 2001 28. Mounier-Vehier C, Jaboureck O, Devos P, et al: Method of studying renal morphology in hypertensive patients with and without renal artery stenosis. Arch Mal Coeur Vaiss 94:919-924, 2001 29. Mounier-Vehier C, Lions C, Devos P, et al: An early morphological marker of atherosclerotic renal disease. Kidney Int 61:591-598, 2002 30. Beregi JP, Louvegny S, Gautier C, et al: Fibromuscular dysplasia of the renal arteries. AJR Am J Roentgenol 172:27-34, 1999 31. Harrison EG, McCormack LJ: Natural classification
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of renal arterial disease in renovascular hypertension. Mayo Clin Proc 46:161-167, 1971 32. Gross CM, Kramer J, Weingartner O, et al: Determination of renal arterial stenosis severity: Comparison of pressure gradient and vessel. Radiology 220:751-756, 2001 33. Emamian SA, Nielson MB, Pederson JF, Ytte L: Kidney dimensions at sonography: Correlation with age, sex and habitus in 665 adult volunteers. AJR Am J Roentgenol 163:83-86, 1993 34. Vasbinder C, Nelemans PJ, Kessels AG, Kroon AA, de Leeuw PW, Van Engelshoven JM: Diagnosis tests for renal artery stenosis in patients suspected of renovascular hypertension: A meta-analysis. Ann Intern Med 135:401411, 2001 35. Beregi JP, Elkohen M, Deklunder G, Artaud D, Coullet JM, Wattine L: Helical CT angiography compared with arteriography in the detection of renal artery stenosis. AJR Am J Roentgenol 167:495-501, 1996 36. Elkohen M, Beregi JP, Deklunder G, et al: Evaluation of spiral computed tomography of the renal arteries alone or combined with Doppler ultrasonography in the detection of renal artery stenosis. Prospective study of 114 renal arteries. Arch Mal Coeur Vaiss 88:1159-1164, 1995 37. Goldblatt H, Lynch J, Hanzal RF, Summerville WW: Studies on experimental hypertension: The production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59:345-379, 1934 38. Brenner BM, Meyer TW, Hostetter TH: Dietary protein intake and the progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 307:652-659, 1982
I
DENTIFICATION of patients with renovascular hypertension is an important clinical problem, especially in fibromuscular dysplasia (FMD) disease, because revascularization of renal artery stenosis (RAS) improves the control of hypertension and contributes to preserve renal function.1 FMD is a nonatherosclerotic and noninflammatory vascular disease, occurring in less than 2% of the hypertensive population.2-4 There is increasing concern about renovascular disease as a growing cause of chronic renal failure. Renal ischemia–caused stenosis or obstruction of the main renal arteries and/or intraparenchymal preglomerular arteries induces a proFrom the Service de Me´decine Interne et HTA and Service de Chirurgie Vasculaire, Hoˆpital Cardiologique; Service de Radiologie Vasculaire Diagnostique et Interventionnelle, CHRU; and CERIM, De´partement de Biostatistiques, Faculte´ de Me´decine, Lille, France. Received January 24, 2002; accepted in revised form July 9, 2002. Supported in part by grants from MNERT EA 2691 and MNERT EA 2693, University of Lille-2, France. Address reprint requests to Claire Mounier-Vehier, MD, PhD, Service de Me´decine Interne et HTA, Hoˆpital Cardiologique, CHRU, 59037 Lille Cedex, France. E-mail: [email protected] © 2002 by the National Kidney Foundation, Inc. 0272-6386/02/4006-0003$35.00/0 doi:10.1053/ajkd.2002.36855 1138
gressive loss of renal mass.5-7 Additionally, the focus on parenchymal injury is timely and appropriate because recent studies indicate that renal parenchymal status is a major factor in determining prognosis and response to revascularization. Although this concept is new, vascular nephropathy probably is underestimated in clinical practice because of the lack of accurate markers of distal disease.8-29 In addition, there are few studies, with small patient numbers, that examined renal consequences of dysplastic stenoses.2,3,8,10,13-15,26 It is difficult to investigate distal lesions using conventional investigation methods. Functional markers are more pertinent for the diagnosis of vascular nephropathy compared with morphological markers; they include the reduction in glomerular filtration rate on scintigraphic studies,13,18-20 intrarenal resistive index measurements with echo Doppler,1,17,21 and intra-arterial Doppler flow wire evaluation of renal blood flow reserve.22 Although reduced renal length (RL) is a classic morphological marker of vascular nephropathy, it is not sensitive enough for an early diagnosis.1,6-8,10,14,17,21,23-26 However, it recently was reported that cortical thickness measurements, especially mean cortical thickness (MCT) and cortical area (CA), could be more pertinent for the diagnosis of
American Journal of Kidney Diseases, Vol 40, No 6 (December), 2002: pp 1138-1145
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES
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intraparenchymal disease compared with RL.23,27-29 Additionally, we identified threshold values of 800 mm2 for CA and 8 mm for MCT that allowed us to distinguish essential hypertensive (EH) kidneys from poststenotic (S) kidneys. Sensitivity and specificity of these markers were 85% and 89% (CA) and 73% and 93% (MCT), respectively.29 The purpose of this work is to assess more accurately the parenchymal consequences of FMD RAS on S and contralateral (OPP) kidneys in hypertensive patients by using spiral computed tomographic angiography (CTA). METHODS
Population Between 1995 and 2000, a total of 577 hypertensive patients showing several clinical and biological criteria suggestive of RAS were investigated in our department.1,2,11 All subsequent causes of endocrinopathy and other causes of cortical atrophy, such as reflux nephropathy, previous stone passage with intermittent hydronephrosis, previous pyelonephritis, hypoplasic kidney, and associated polycystic kidney disease, were excluded from the initial selection. To further homogenize our patient cohort, we excluded atherosclerotic RAS (520 cases), FMD disease with coexisting atherosclerotic RAS (9 cases), and bilateral FMD stenoses (8 cases). As a result, 49 patients were included in the study. The protocol was approved by the university ethical committee. The purpose of the study was explained to the patients at an outpatient visit, and written informed consent was obtained. Systolic (SBP) and diastolic blood pressure (DBP) were measured in supine position on the day of spiral CTA, according to World Health Organization (WHO) recommendations. Pulse blood pressure was defined as the difference between SBP and DBP. Hypertension was defined as SBP greater than 140 mm Hg and/or DBP greater than 90 mm Hg in accordance with the WHO recommendations. Heart rate was measured on resting electrocardiogram. Demographic parameters also included smoking habit; body mass index (BMI; weight [kg]/height [m]2); age; sex; longstanding hypertension (ⱖ2 years); cigarette smoking; family history of cardiovascular disease; diabetes mellitus, defined as fasting glycemia in excess of 1.40 g/L that was treated by diet, oral hypoglycemics, or insulin treatment; and dyslipidemia, with a total cholesterol level in excess of 2.50 g/L or current hypolipemic. Serum potassium and serum creatinine levels also were measured. Creatinine clearance was calculated using the Cockcroft-Gault formula. In preparation for angiography and spiral CTA, hydration was ensured by not restricting fluid intake and by administering 500 mL of intravenous saline the day of the examination.5
Spiral CTA Spiral CTA (Somatom plus 4A; Siemens, Erlanger, Germany) was conducted in all patients to assess FMD stenosis and its parenchymal consequences. Beregi et al30 showed
Fig 1. Box plots of (A) RL and (B) MCT in the three groups of kidneys; comparison between EH, OPP, and S kidneys. (A) EH versus OPP, not significant; S versus OPP, significant at the 0.05 level (risk ␣); EH versus S, not significant; (B) EH versus OPP, significant at the 0.05 level (risk ␣); S versus OPP, not significant; EH versus S, significant at the 0.05 level (risk ␣).
that spiral CTA, especially the combination of transverse sections and maximum intensity projection reconstructions, reliably shows FMD RAS. The protocol for spiral CTA has been described elsewhere30,31; it was independent from age and weight. Briefly, a total of 120 to 150 mL of iodinated contrast material (Telebrix 30; meglumine ioxithalamate; Guerbet, Villepinte, France) was injected during the procedure. Volume acquisition was obtained by rotating the X-ray tube (X-ray source collimated to 3 mm) and simultaneous translation of the patient with the table moving at 3 mm/s. The two poles were investigated in fewer than 20 seconds with the spiral acquisition. Total examination time ranged from 15 to 25 minutes. Markers of parenchymal disease were derived from renal geometry: RL, medullary length (ML), cortical thickness, and CA. Morphological characteristics of kidneys were studied from the transverse axial sections (Figs 1 and 2). RL was referred to as the difference between the first section that showed the superior pole of the kidney and the first section that showed the inferior pole of the kidney. We studied the superior and inferior poles separately, based on the measurement of three cortical thicknesses: anterior, posterior, and lateral.
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MOUNIER-VEHIER ET AL
pressure gradient across the stenosis greater than 20 mm Hg was considered significant.5,15,32
Evaluation Criteria and Statistical Analysis
Fig 2. Spiral CTA of a left kidney in an EH patient (transverse axial section). The superior pole of the left kidney presents MCTs greater than the 8-mm threshold if we refer to the measurement scale, in which each increment corresponds to 10 mm.
Superior cortical thickness was studied 2 cm below the superior pole of the kidney, and inferior cortical thickness, 2 cm above the inferior pole of the kidney. We considered the width of the dense peripheral band on spiral CTA to be equivalent to cortical width. We measured this band in six areas: anterosuperior (AST), laterosuperior (LST), posterosuperior (PST), anteroinferior (AIT), lateroinferior (LIT), and posteroinferior (PIT). MCT, CA, and ML also were calculated as follows: MCT 共mm兲 ⫽ 共AST ⫹ LST ⫹ PST ⫹ AIT ⫹ LIT ⫹ PIT兲/6
The entire population was divided into two groups depending on the presence or absence of FMD stenosis. Patients with normal Doppler and spiral CTA results were considered to have essential hypertension (group 1, with 20 EH patients), ie, a group of 40 EH kidneys (EH group). Patients with unilateral RAS formed a second group (group 2, with 20 patients), ie, 20 kidneys with RAS (S group) and 20 contralateral or OPP kidneys (OPP group). The morphological study took into account: (1) status of the kidney (EH, S, or OPP), and (2) location of the kidney (right or left side) in group 1. Statistical analysis yielded a descriptive analysis of the population (mean ⫾ SD for numerical parameters, frequencies for qualitative ones). The two groups of patients were compared using Wilcoxon’s test for numerical parameters and chi-square test for frequencies. Right- and left-sided EH kidneys were pooled together in a single group (EH group) because the location of the kidney had no effect on morphological parameters. Morphological differences between EH, OPP, and S kidneys were assessed by a nonparametric analysis of variance and a post hoc test using a Bonferroni correction. A study of Spearman’s coefficient also was performed to evaluate the relationship between morphological, clinical, and biochemical indices; specifically, the relationship between serum creatinine clearance and the sum of cortical indices from the two kidneys in a given patient. The threshold significance level (risk ␣) was set at 5%. Data analysis was performed using SAS software (version 8.1; SAS Institute Inc, Cary, NC).
CA 共mm 2 兲 ⫽ 共RL ⫻ MCT兲 ML 共mm兲 ⫽ RL–关共AST ⫹ LST ⫹ PST兲/3 ⫹ 共AIT ⫹ LIT ⫹ PIT兲/3兴 Radiologists were blinded to the patient group when they analyzed spiral CTA. Reproducibility and agreement of these measurements were assessed during a preliminary phase.28 The term atrophy was used to refer to an RL less than 80 mm and/or an MCT less than 8mm and/or a CA less than 800 mm2.
Digital Substraction Renal Angiography Digital substraction angiography (Integris V 3000; Philips, Best, Holland) only was performed in 20 of 40 patients who were suspected to have FMD stenosis on spiral CTA and/or on Doppler ultrasonography (128 XP; Acuson, Mountain View, CA). A total of 50 to 120 mL of iodinated contrast material (Hexabrix; Guerbet) was injected. Stenoses were classified on the basis of angiographic appearance, as proposed by Mc Cormack et al4 and Harrison and McCormack.31 In all cases, pressure measurements were drawn to assess the physiological significance of the lesion; a mean systolic
RESULTS
Clinical and biological indices of the two groups of patients are listed in Table 1. Except for sex ratio and BMI, clinical and biological characteristics were similar in both groups of patients, especially age and history of hypertension. Dyslipidemia, diabetes mellitus, and smoking were more frequent in group 1 compared with group 2, but differences were not significant. Fifty-two renal arteries (40 main and 12 accessory arteries) and 20 stenoses were assessed by spiral CTA and angiography in group 2. RAS diagnosed by spiral CTA always was confirmed by angiography. Right-sided renal arteries were involved in 19 of 20 cases (18 main and 1 accessory arteries). Three types of FMD were identified: intimal fibroplasias, which consisted of unifocal stenosis (5 cases); medial fibroplasias, which consisted of multifocal stenoses with the classic “string of beads” appearance (13
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES Table 1.
1141
Demographic Characteristics in the Two Groups of Hypertensive Patients
Age (y) Men/Women Longstanding hypertension ⬎2 y Cigarette smoking Diabete mellitus Dyslipidemia Family history of cardiovascular disease SBP (mm Hg) DBP (mm Hg) Pulsed blood pressure (mm Hg) BMI (kg/m2) Creatinine clearance (mL/min) Serum potassium (mmol/L)
Group 1 (n ⫽ 20)
Group 2 (n ⫽ 20)
P
49 ⫾ 11 10/10 11 (55) 4 (20) 5 (25) 14 (70) 6 (30) 167 ⫾ 16 102 ⫾ 14 65 ⫾ 16 29 ⫾ 6 90 ⫾ 20 3.9 ⫾ 0.4
48 ⫾ 15 2/18 9 (45) 2 (10) 1 (5) 9 (45) 14 (70) 163 ⫾ 26 96 ⫾ 18 67 ⫾ 17 25 ⫾ 5 80 ⫾ 23 4.1 ⫾ 0.3
NS 0.005 NS NS NS NS 0.01 NS NS NS 0.005 NS NS
NOTE. Results shows as mean ⫾ SD for numerical parameters and frequency (percentage) for categorical parameters. Group 1 includes EH patients, and group 2, hypertensive patients with significant unilateral FMD stenosis. Abbreviation: NS, not significant.
cases), and subadventitial fibroplasias, which appeared as “tubular” stenoses (2 cases). Results of morphological indices are listed in Table 2. OPP and EH kidneys were of similar length (Fig 1). S kidneys were significantly smaller compared with OPP kidneys, with an averTable 2.
age difference of 9 mm (Fig 1). ML was reduced only in S kidneys. OPP and S kidneys showed significant cortical thinning, with MCTs of 1.4 and 1.9 mm lower compared with EH kidneys, respectively (Figs 2 and 3). The post hoc test showed that only MCT
Morphological Differences Between EH, OPP, and S Kidneys
EH Kidneys* (n ⫽ 40)
OPP Kidneys (n ⫽ 20)
S Kidneys (n ⫽ 20)
Overall† P
103 ⫾ 11
105 ⫾ 10
96 ⫾ 11
0.05
9.4 ⫾ 1.1
7.6 ⫾ 1.2
6.9 ⫾ 1.1
⬍0.0001
LST
8.9 ⫾ 1.3
7.9 ⫾ 1.5
7.0 ⫾ 1.3
⬍0.0001
PST
8.9 ⫾ 1.3
7.7 ⫾ 1.2
7.0 ⫾ 1.4
⬍0.0001
AIT
8.8 ⫾ 1.1
7.7 ⫾ 0.9
7.2 ⫾ 1.1
⬍0.0001
LIT
9.7 ⫾ 0.9
8.1 ⫾ 1.0
7.5 ⫾ 1.0
⬍0.0001
PIT
9.3 ⫾ 1.0
8.1 ⫾ 1.1
8.0 ⫾ 1.0
⬍0.0001
MCT (mm)
9.2 ⫾ 0.8
7.8 ⫾ 1.0
7.3 ⫾ 1.0
⬍0.0001
CA (mm2) ML (mm)
945 ⫾ 141 84 ⫾ 11
824 ⫾ 149 89 ⫾ 9
703 ⫾ 156 81 ⫾ 10
⬍0.0001 0.05
RL (mm) Cortical thickness (mm) AST
Significant Post-Hoc Tests‡ P ⬍ 0.05
OPP v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S EH v OPP EH v S
NOTE. Results shown as mean ⫾ SD. *Right- and left-sided EH kidneys were pooled because they were of similar morphological characteristics. †Results of nonparametric analysis of variance for repeated measurements. ‡Results of post-hoc test using Bonferroni correction (2 ⫻ 2 comparison of means between the three kidney groups).
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MOUNIER-VEHIER ET AL
Fig 3. Spiral CTA in a hypertensive woman with a right FMD stenosis (transverse axial sections). (A) The superior cortical thicknesses of the S kidney show diffuse damage, with values of 7.5 mm on average if we refer to the same measurement scale. (B) The superior cortical thicknesses of the OPP kidney are 8 mm on average.
was significantly different between EH, OPP, and S kidneys (Table 2). In the group of S kidneys, 15 kidneys (75%) had an MCT and/or CA less than their threshold values of 8 mm and 800 mm2, respectively. In the group of OPP kidneys, 10 kidneys (50%) had significant cortical atrophy. Cortical atrophy significantly correlated with serum creatinine clearance (CA, r ⫽ 0.43; P ⫽ 0.005; MCT, r ⫽ 0.35; P ⫽ 0.02) in the entire population (n ⫽ 40). CA correlated with serum creatinine clearance in group 1 (r ⫽ 0.46; P ⫽ 0.04). We did not find a significant correlation between renal function and morphological indices in group 2. DISCUSSION
This study shows the presence of significant cortical thinning in S and OPP kidneys in hyper-
tensive patients with unilateral FMD stenosis compared with EH patients. RL in all kidney groups was within normal range.33 However, kidney length was less in the S kidney group compared with the EH and OPP groups. In many respects, the group of patients with unilateral RAS (group 2) was similar to other series.10,13-15,20 The predominance of young women (19 of 20 patients) and the greater incidence of right-sided lesions (21 of 22 lesions) suggested hormonal influences and arterial stretching as possible etiologic factors.2-4,14 It already was reported that renal morphological characteristics were influenced by body size and age.33 In our study, 10 of the 20 EH patients were men, and mean BMI in the EH group was 29 kg/m2. Only 2 subjects with FMD were men, and mean BMI in this group was 25 kg/m2. Consequently, a difference in average body size and/or sex could account for differences in renal morphological characteristics between groups 1 and 2. Although our results should be interpreted with caution given the small size of the population, we did not find a significant correlation between age, BMI, sex, and morphological indices in the two groups of patients. Mean creatinine clearance was within normal range in both groups of patients. We reported a significant relationship between creatinine clearance and the sum of cortical indices (MCT, CA) from the two kidneys in the entire population. However, creatinine clearance is a rough indicator of individual renal function because the OPP kidney may compensate for the loss of S kidney glomerular filtration.13,18-20 In consequence, creatinine clearance did not appear to be an accurate marker of FMD nephropathy. Spiral CTA is a recent technique that is still debated in the clinical management of patients suspected to have RAS1,34 because it involves the use of both X-ray radiation and iodinated contrast material. However, since this present work, we use a multidetector CT Scan (Somatom Plus 4 Volume Zoom; Siemens) that allows data acquisition in a shorter time with 90 mL of iodinated contrast material. Additionally, a recent metaanalysis showed that spiral CTA and magnetic resonance angiography (MRA) were significantly superior for the diagnosis of RAS compared with ultrasonography, captopril renal scintigraphy, and the captopril test.34 We also showed
FIBRODYSPLASIA STENOSIS RENAL CONSEQUENCES
that spiral CTA precisely evaluated cortical parameters and RL with satisfactory reproducibility and concordance. Axial transverse sections are automated, and there is no bias in image acquisition.28,29 Last, because Beregi et al35 and Elkohen et al36 showed very satisfactory levels of specificity (96%) and sensitivity (100%) arising from combining Doppler ultrasonography and spiral CTA in RAS diagnosis, for ethical consideration, we did not perform renal angiography in 20 patients presenting with normal spiral CTA and Doppler results. FMD stenosis may lead to some loss of renal parenchyma, resulting in lower kidney size.5,8,10,14,15,26 Reduced kidney length usually is uncommon in FMD disease.2,3,16,18,19 In the current study, although S kidneys were smaller compared with EH and OPP kidneys, their RL was still within normal range. Consequently, we assessed that the measurement of the only kidney length could lead to the false conclusion of the absence of distal lesions. Conversely, cortical thickness measurements assessed significant lesions in S kidneys, as well as OPP kidneys. These data show that cortical thickness parameters, especially MCT and CA, were more accurate for the diagnosis of intraparenchymal FMD disease compared with classic kidney length. Thus, we assumed, although we did not undertake prospective follow-up, that cortical lesions appear before the reduction in kidney length. In the current study, the term atrophy was used to refer to an RL less than 80 mm and/or an MCT less than 8 mm and/or a CA less than 800 mm2. To our knowledge, there is no consensus definition of cortical atrophy because it is a new morphological marker. We therefore have proposed our own definition of cortical atrophy from threshold values of MCT (8 mm) and CA (800 mm2).29 However, these threshold values should be confirmed by a larger prospective study. Studying intrarenal vascular resistance with echo Doppler also should be of benefit in screening for distal vascular lesions in FMD disease. A renal resistance index of at least 80 before revascularization was a strong predictor of worsening arteriolar vascularization and lack of improvement in blood pressure despite revascularization.21 The study by Caps et al24 using ultrasonog-
1143
raphy only examined changes in renal size over time as a function of the severity of RAS. However, ultrasonography is time consuming and operator dependent. The echogenicity of patients is a limiting factor. A separate evaluation of the renal cortex and medulla also is more difficult than with spiral CTA27 or MRA.23 Few studies have examined the renal cortex, and they did not undertake comparative evaluations using Doppler ultrasonography. Most studies have examined renal size in dysplasic and atherosclerotic models. Cortical thickness and cortical volumes have been studied only in EH patients and patients with atherosclerotic renal disease. Scintigraphic studies have assessed changes in glomerular filtration rate after angioplasty in dysplasic and atherosclerotic disease.13,18-20 The study of the prognostic value of arteriolar resistance has been performed only in atherosclerotic disease.21 Finally, the accuracy of these markers in FMD and atherosclerosis has not yet been studied to our knowledge. Cortical atrophy in S and OPP kidneys could be a direct consequence of renal hypoperfusion.7,8,13,18-20,23-26,37 RAS activation resulting from hypoperfusion has several deleterious effects, such as inducing tubulointerstitial atrophy5-7,16,26,38 and systemic hypertension.1,7,9,14,17,26,38 In addition, several scintigraphic works have shown a reduction in glomerular filtration in S kidneys and a nephrotoxic compensatory glomerular hyperfiltration in OPP kidneys.13,18-20 These hyperfiltration processes could produce focal sclerosing glomerulonephritis and inflammatory tubulointerstitial lesions that could have an aggravating role in the course of cortical thinning.34 Associated structural alterations in distal arteries induced by long-standing hypertension (⬎2 years) could not be excluded in OPP and S kidneys.7,8,27 Finally, we cannot exclude undetected distal dysplasic lesions. Assessment of the hemodynamic significance of FMD stenosis is often difficult, particularly in medial lesions. Showing cortical atrophy in an S kidney therefore is an interesting result because it shows the hemodynamic renal impact of the lesion and may be considered an indirect marker of the significance of the stenosis. There is no consensus about which patients should undergo revascularization or the type of revascularization that should be used. The deci-
1144
sion to revascularize the kidney to preserve renal function is based on the assumption that angioplasty will stabilize or improve renal function. Diagnosis of cortical atrophy has not made revascularization irrelevant because it was an unknown morphological parameter. However, we must remain cautious about the therapeutic applications of cortical atrophy because the prognostic value of these parameters is still unknown. Kidneys less than 8 cm and a Doppler resistance index greater than 0.8 only are considered of poor prognosis and do not imply revascularization. Results of this cross-sectional study are limited by the size of our populations. Group 1 contained only EH patients because, for ethical reasons, spiral CTA could not be performed on healthy volunteers. Consequently, values of cortical parameters in group 1 cannot be extrapolated to healthy volunteers if we refer to the recent work of Kojima et al,27 which showed significant cortical thinning in EH patients. However, the purpose of the current work is not to establish reference values, but to identify possible morphological differences between kidneys with FMD stenosis and EH kidneys. Cortical atrophy is not specific of renovascular disease. Other common causes of renal atrophy could cause the same morphological aspect. However, in a context of RAS, cortical thinning could be considered a more accurate marker of vascular nephropathy compared with RL. We cannot draw conclusions about the prognostic value of MCT and CA because this was a cross-sectional study. We did not perform a comparison between cortical thickness and resistance indices; therefore, we are not able to prejudge whether cortical atrophy was adverse in nature. It may be possible that functional lesions appear before morphological lesions, but to our knowledge, this has not been shown. It therefore would be interesting to conduct a further prospective study that would examine functional lesions using ultrasound and/or scintigraphy and morphological characteristics using spiral CTA or MRA. In conclusion, spiral CTA provides useful data about distal consequences of FMD stenosis. We show that S and OPP FMD kidneys had significant cortical atrophy despite preserved overall size compared with EH kidneys.
MOUNIER-VEHIER ET AL
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