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Rheumatology 2001; 40: 406-409
© 2001 British Society for Rheumatology
Renal vascular damage in Japanese patients with systemic sclerosis
Department of Dermatology and
1 Department of Urology, Kanazawa University School of Medicine, Kanazawa 920-8641, Japan
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Abstract |
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Objective. To evaluate renal vascular damage in Japanese patients with systemic sclerosis (SSc) by colour-flow Doppler ultrasonography.
Methods. The pulsatility index (PI) was measured in renal interlobar and segmental arteries by colour-flow Doppler ultrasonography.
Results. PI values of interlobar arteries were increased in SSc patients (n=53) with normal renal function compared with healthy persons (n=16), systemic lupus erythematosus patients (n=12) and dermatomyositis patients (n=3). SSc patients with elevated PI levels had digital pitting scar, short sublingual frenulum, contracture of phalanges, pulmonary fibrosis, decreased per cent vital capacity, heart involvement, positivity for anti-topoisomerase I antibody, and elevated C-reactive protein more frequently than those with normal PI levels.
Conclusion. Although renal crisis is rare in Japanese SSc patients, our study suggests that latent and subclinical renal damage exists in these patients.
KEY WORDS: Systemic sclerosis, Colour-flow Doppler ultrasonography, Pulsatility index, Vascular damage, Kidney.
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Introduction |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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Vascular lesions are prominent in systemic sclerosis (SSc), which is characterized by fibrosis in the skin and internal organs. Scleroderma renal crisis (SRC) has been considered one of the most severe complications of SSc. Although the pathogenesis of SRC remains unknown, the primary process is considered to be endothelial cell injury, leading to narrowing and obliteration of the lumen of the vessel. The thickening in the arteries of SSc patients without SRC is similar to that in SSc patients with SRC, but to a lesser degree [1]. This suggests the presence of renal vascular damage even in SSc patients without SRC.
The frequency of SRC in Japanese SSc patients (<5%) is much lower than that in Caucasian SSc patients (
20%) [2, 3]. Although SRC is rare in Japanese patients with SSc, the prevalence of subclinical renal vascular damage is unknown in Japanese SSc patients without SRC. Recently, Rivolta et al. [4] reported that subclinical renal vascular damage in patients with SSc was detected by colour-flow Doppler ultrasonography. They showed that renal vascular resistance was significantly increased in main, interlobar and cortical vessels of SSc patients with apparently normal renal function when compared with normal controls. Scorza et al. [5] also reported that renal vascular resistance determined by colour-flow Doppler ultrasonography was reduced after SSc patients with elevated renal vascular resistance were treated with Iloprost. These studies suggest that colour-flow Doppler ultrasonography is a sensitive and non-invasive technique for evaluating vascular damage of the kidneys in SSc patients without SRC. In this study, we assessed renal vascular damage in Japanese SSc patients with normal renal function by this technique.
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Patients and methods |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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Subjects
We studied 53 SSc patients (49 women and four men) who fulfilled the American College of Rheumatology (ACR) criteria for SSc [6]. These patients were grouped according to LeRoy et al. [7]: 31 patients had limited cutaneous SSc (lSSc) and 22 had diffuse cutaneous SSc (dSSc). None of the patients had hypertension or diabetes. Twelve patients with systemic lupus erythematosus (SLE), three with dermatomyositis (DM) and five with mixed connective tissue disease (MCTD) were also studied. SLE, DM and MCTD were diagnosed according to the criteria proposed by the ACR [8], by the Bohan and Peter criteria [9, 10], and by Kasukawa et al. [11] respectively. Sixteen age- and sex-matched healthy Japanese persons were used as normal controls.
Clinical assessment
Patients underwent detailed clinical assessment and the involvement of various organ systems was investigated in each patient. Organ system involvement was defined as described by Steen et al. [12]. Pulmonary function, including vital capacity (VC) and the diffusion capacity for carbon monoxide (DLCO) were also tested. All patients examined in this study were free of clinical symptoms of renal damage. In addition, urinalysis, 24-h protein excretion, plasma creatinine levels and endogenous creatinine clearance corrected for 1.73 m2 body surface area were within normal limits (data not shown).
Measurement of renal vascular resistance
Colour-flow Doppler scanning of the right and left kidneys was performed with an Aloka SSD-2000 scanner (Aloka, Tokyo, Japan), using a 3.5 MHz broadband convex probe. The pulsatility index (PI) was determined on segmental and interlobar arteries. These vascular sites were chosen because small and medium sized arteries are damaged in SSc [1]. The PI was calculated as A-B/mean, where A is the peak systolic frequency, B is the end diastolic frequency, and the mean is the time-averaged frequency. PI was calculated as an average value obtained with four waveforms each on the interlobar and segmental arteries in each kidney. The same urologist performed all the Doppler examinations blind with respect to clinical information about each patient. Five of the 53 patients were excluded, as kidney blood flow was not clearly detected due to thick subcutaneous fat tissue.
Statistical analysis
The Mann–Whitney U-test, Fisher's exact probability test and Bonferroni's test were used for comparison between pairs of groups, analysis of frequency and multiple comparisons respectively. Spearman's rank correlation coefficient was used to study the relationship between two continuous variables. A P value of less than 0.05 was considered significant. All data are shown as mean±S.D.
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Results |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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PI values in renal arteries of SSc patients
PI values in the interlobar arteries of patients with SSc (1.218±0.170) were significantly higher than those in healthy controls (1.080±0.179, P<0.05), SLE patients (1.066±0.151, P<0.05) and DM patients (0.968±0.070, P<0.05) (Fig. 1A
). PI values in patients with dSSc (1.240±0.194) or lSSc (1.199±0.148) were significantly higher than those in healthy controls (P<0.05), SLE patients (P<0.05) and DM patients (P<0.05). PI levels in dSSc patients tended to be higher than those in lSSc patients. Similar results were obtained for PI values of segmental arteries, although the difference was smaller in segmental arteries than in interlobar arteries (Fig. 1B). This increase in the PI values of both interlobar and segmental arteries was identical and was similar in the two kidneys of SSc patients (data not shown). Thus, PI values in the renal arteries of SSc patients with normal renal function were elevated, and this was specific to SSc patients.
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Clinical correlation of PI values
PI values in the interlobar arteries higher than 1.387 (mean for healthy controls plus two standard deviations) were considered to be elevated in this study. Elevated PI levels in the interlobar arteries were observed in 15% (7/48) of SSc patients, 4% (1/26) of lSSc patients and 27% (6/22) of dSSc patients. SSc patients with elevated PI levels of the interlobar arteries had digital pitting scar (P<0.05), a short sublingual frenulum (P<0.05) and contracture of the phalanges (P<0.05) more frequently than those with normal PI levels (Table 1). The frequencies of pulmonary fibrosis (P<0.05) and decreased per cent VC (P<0.01) were also significantly higher in patients with elevated PI levels than in those with normal PI levels. Heart involvement was seen exclusively in patients with elevated PI levels (P<0.0001). Frequency of anti-topoisomerase I antibody positivity (P<0.01) and elevated C-reactive protein (CRP) (P<0.01) was significantly higher in patients with elevated PI levels than in those with normal PI levels.
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The PI value of 1.321 (mean for healthy controls plus two standard deviations) was used as a cut-off value for the segmental arteries. Elevated PI levels in the segmental arteries were observed in 25% (12/48) of SSc patients, 19% (5/31) of lSSc patients and 32% (7/22) of dSSc patients. Elevated concentrations of immunoglobulins (Ig) G and M were more frequent in patients with elevated PI levels than in those with normal PI levels (IgG, 67 vs 26%, P<0.05; IgM, 58 vs 11%, P<0.05).
The PI levels in the interlobar arteries correlated positively with serum IgG levels (r=0.31, P<0.01) and inversely with per cent DLCO (r=-0.37, P<0.05). Similarly, the PI levels in the segmental arteries correlated positively with serum IgG levels (r=0.41, P<0.01) and inversely with per cent DLCO (r=-0.36, P<0.05). However, blood pressure, serum creatinine, urine protein, static 99mtechnetium diethylenetriamine pentaacetic acid (99mTc-DTPA) scans, creatinine clearance value and plasma renin levels did not correlate with PI levels in patients with SSc.
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Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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Our study showed that Japanese SSc patients with normal renal function had a significant increase in PI in both the segmental and the interlobar arteries compared with normal controls. Of the various Doppler parameters, PI was selected because it is the ultrasonographic index that has the least error in representing vascular impedance. In most of our patients the PI value was calculated repeatedly, with reproducible results (data not shown). Japanese SSc patients have a very low incidence of SRC compared with Caucasian SSc patients [2, 3]; we have experienced only one SRC patient in 147 patients at our clinic. Nonetheless, significant renal vascular changes were detected in our study. This suggests that latent and subclinical renal damage exists in Japanese SSc patients. Moreover, our finding that PI values in SSc patients were significantly higher than those in patients with SLE or DM suggests that the renal PI elevation is specific for SSc patients.
Consistent with our results, subclinical renal changes have been found in SSc patients histologically. Histological changes similar to those in the kidneys of SSc patients with SRC have been detected in SSc patients who do not have SRC and those who do not subsequently develop SRC, but to a lesser degree [1]. Therefore, the elevation in PI may be associated with these histological changes [4]. Since this subclinical histological change has never been assessed directly or correctly by any of the usual non-invasive techniques, including xenon-133 washout and [131I]hippurate and static 99mTc-DTPA scans, previous studies and our results suggest that colour-flow Doppler ultrasonography is useful for evaluating latent vascular damage in patients with SSc [4].
SSc patients with elevated PI levels of the interlobar arteries more frequently had digital pitting scar, a short sublingual frenulum, contracture of the phalanges, pulmonary fibrosis, decreased per cent VC, heart involvement, positivity for anti-topoisomerase I antibody and elevated CRP compared with those who had normal PI values. In addition, the PI levels correlated significantly with serum IgG levels and per cent DLCO. Thus, these clinical features might be helpful in identifying patients with subclinical renal damage among patients with SSc. It was reported that the subset of patients with dSSc who show rapid progression of their skin thickening early in the illness, with the development of anaemia, pericardial effusion or congestive heart failure, have a high risk of SRC [2]. Although these clinical features are not identical with those seen in our study, cardiac involvement was common in both studies.
In the present study, patients with SRC were not examined by colour-flow Doppler ultrasonography. Therefore, it is unknown whether patients with SRC have elevated PI levels. In addition, it is not clear whether patients with increased PI levels will develop SRC in the future. To clarify these points, prospective studies will be needed.
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Notes |
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Correspondence to: S. Sato, Department of Dermatology, Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan
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References |
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