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NDT Advance Access originally published online on November 27, 2007
Nephrology Dialysis Transplantation 2008 23(3):1005-1010; doi:10.1093/ndt/gfm726
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Peritoneal thickening is not inevitable in long-term peritoneal dialysis and is associated with peritoneal transport characteristics: a two-centre sonographic study

Tsung-Chun Lee1,4, Ju-Yeh Yang2,4, Hsiu-Po Wang1, Tun-Jun Tsai1 and Yu Yang3

1 Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan Univeristy, Taipei, Taiwan 3 Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Dr Yu Yang, No. 135, Nanhsiao Street, Changhua City, 500, Taiwan. Tel: +886-4-7238595; Fax: +886-4-7232942; E-mail: 2219{at}cch.org.tw



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The peritoneum is subject to alterations in the life-long course of peritoneal dialysis (PD). Studies of the parietal peritoneum by non-invasive ultrasonography in PD patients are limited. We hypothesize that a prolonged PD duration is associated with a thicker peritoneum on ultrasonography and alterations in Doppler indexes of mesenteric vessels.

Methods. We recruited two groups of patients, 18 who had >7 years of PD and 18 who had <12 months of PD. We excluded patients with active peritonitis, history of major abdominal surgery, cirrhosis or malignancy. We measured the sonographic thickness of the parietal peritoneum and Doppler indexes of mesenteric vessels by trans-abdominal ultrasonography at two PD units in Taiwan.

Results. We found no significant difference between two groups of PD patients in peritoneal thickness and in Doppler indexes. However, our univariate and multivariate analysis indicated that peritoneal thickness is associated with peritoneal transport characteristics (dialysate/plasma creatinine) but not with age, duration of dialysis, body height, body weight or Doppler index. The peritoneum is significantly thicker in rapid transporters than in slow transporters (RUQ: 0.59 ± 0.40 mm versus 0.27 ± 0.29 mm, P = 0.01; LUQ: 0.60 ± 0.40 mm versus 0.27 ± 0.32 mm, P = 0.016; LQ: 1.07 ± 0.85 mm versus 0.48 ± 0.53 mm, P = 0.026). In addition, rapid transporters have a marginally lower Doppler resistive index of the superior mesenteric artery (0.87 ± 0.08 versus 0.90 ± 0.10, P = 0.028).

Conclusions. Our data showed that peritoneal thickening is not inevitable in long-term PD patients. Sonographic thickness in the parietal peritoneum is associated with transport characteristics. Rapid transporters have a significantly thicker peritoneum. The Doppler index of mesenteric vessels had no association with PD duration or transport characteristics. Trans-abdominal ultrasonography is non-invasive and useful in evaluating peritoneal characteristics of PD patients.

Keywords: doppler; encapsulating peritoneal sclerosis; peritoneum; peritoneal dialysis; peritoneal transport characteristic; ultrasonography



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
The peritoneum is subject to alterations in the life-long course of peritoneal dialysis (PD) [1]. The extreme alteration of the peritoneum and resultant membrane failure lead to encapsulating peritoneal sclerosis (EPS). EPS is characterized by marked sclerotic thickening of the peritoneal membrane, microvasculopathy and partial or diffuse bowel obstruction [2,3]. EPS is a serious complication of peritoneal dialysis (PD) and early detection of EPS may prevent devastating peritoneal sclerosis [4].

The current literature indicates that prolonged duration of PD is the most significant risk factor for EPS [2]. For example, Rigby et al. reported the incidence of EPS as 1.9%, 6.4%, 10.8% and 19.4% in patients on PD for <2, 5, 6 and 8 years, respectively [5]. Similarly, Kawanishi et al. reported the incidence of EPS as 0%, 0.7%, 2.1%, 5.9%, 5.8% and 17.2% in patients on PD for 3, 5, 8, 10, 15 and >15 years, respectively [6]. These figures suggested a differential risk of EPS between long-term and short-term PD patients. EPS patients have thickened and failed peritoneal membranes; however, PD patients we care for in daily practice mostly have functionally preserved membranes, even in long-term PD patients. The question whether long-term PD patients without membrane failure in our daily PD clinics have different peritoneal membranes from those of short-term PD patients has not been answered clinically.

Williams et al. conducted a large series of pathological examinations on biopsy specimens of parietal peritoneal membranes. Among patients with membrane failures, they found that peritoneal membrane thickness was associated with PD duration [7]. However, this study was performed by invasive biopsy on the peritoneal membrane. Moreover, the association was only seen in membrane failure PD patients but not in non-failure PD patients.

Non-invasive studies of the parietal peritoneum by ultrasonographic examination in PD patients are limited. Faller et al. used trans-abdominal ultrasonography to evaluate peritoneal thickness in paediatric subjects and showed that this method was a simple, non-invasive and precise method to measure peritoneal changes [8].

In addition to the parietal peritoneum, the visceral peritoneum also contributes to the dialysis process of PD, sharing an even larger percentage of surface area, and also vulnerable to alterations during the life-long course of PD. The previous study showed that the prevalence of vasculopathy in the peritoneum was found to increase with PD duration. The visceral peritoneum is perfused by mesenteric vessels. Thus, we also tried to investigate the Doppler indexes of mesenteric vessels in reflection of the histological vasculopathy during the course of PD.

In this study, we investigated the peritoneal thickness and mesenteric Doppler indexes by non-invasive trans-abdominal ultrasonography in adult PD patients at two PD centres in Taiwan. We compared the sonographic layer of parietal peritoneum and Doppler indexes of mesenteric vessels in short-term and long-term PD patients to investigate the association between the duration of PD and the peritoneal characteristics.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Subjects
We recruited eligible PD patients from the National Taiwan University Hospital (NTUH), a university affiliated hospital in northern Taiwan, and Changhua Christian Hospital (CCH), a tertiary referred hospital in central Taiwan. Eighteen adult end-stage renal disease (ESRD) patients undergoing PD for >7 years (long-term) and 18 adult ESRD patients undergoing PD for >3 months but <12 months (short-term) signed informed consent forms to participate in this cross-sectional study. None of the participating patients had peritonitis in the preceding 3 months and none had a history of major abdominal surgery, cirrhosis or malignancy. The institutional review boards of the two hospitals reviewed and approved the study protocol.

Methods
We examined the parietal peritoneum of fasting patients in the supine position by trans-abdominal ultrasonography. We indwelled at least 1000 mL of dialysate inside the peritoneal cavity and measured peritoneal thickness at three different ventral windows, as modified from the study by Faller et al. [8]. We made horizontal sections at the middle clavicular line of right-upper, left-upper and lower quadrants of abdomen without the port of Tenckhoff catheter and made recordings and measurements at the maximal enlargement of the still photographs. The accessible target of trans-abdominal ultrasonographic examination was focused on the submesothelial compact collagen zone, which appeared as distinct and measurable hyperechoic layer (Figure 1). The values are expressed as the average of three measurements ± standard deviation in a unit of mm.


Figure 1
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  		Fig. 1 Representative trans-abdominal ultrasonograph of the parietal peritoneum.

 
We made all measurements with a high-resolution two-dimensional real-time scanner with a linear 10.5 MHz probe (At National Taiwan University Hospital: Toshiba SSA-550A, Toshiba Corp., Tokyo, Japan; At Changhua Christian Hospital: Shimadzu SDU-1100, Shimadzu Corp. Tokyo, Japan). With the real-time scanner, we obtained resolution distances of 0.01 mm.

We obtained the Doppler indexes of two mesenteric vessels, the celiac trunk (CT) and the superior mesenteric artery (SMA) with another convex probe. Patients remained in supine position and maintained casual breathing during the Doppler ultrasonographic examination. We adjusted the scale of the velocity range to avoid over-scaling and aimed the sampling gate of Doppler ultrasonography at the centre of the target vessels. We performed angular adjustment in parallel to the direction of the target vessels (if necessary) and then performed simultaneous real-time observation to ensure an accurate Doppler measurement. When the pulse Doppler waveform appeared constant and uniform, we recorded the maximal velocity, minimal velocity, pulsatility index (PI) and the resistive index (RI) of the CT and SMA. Tracing of the waveform was limited to single or double complete cardiac cycles. The in-built ultrasonography processor unit automatically executed tracing and calculation of the indexes. An experienced doctor (T.C. Lee), who was blind to the PD status of the patients, performed the ultrasonographic measurements.

We obtained the clinical and dialysis-related parameters prospectively and recorded data in two PD units. We tested the transport characteristics of the peritoneum in PD patients in a standard peritoneal equilibration test by calculating the dialysate to plasma ratio of creatinine after a 4-h dwell [9,10].

Statistical analysis
We analysed data with SPSS (version 12.0 for Windows, SPSS, Inc., Chicago, IL, USA) and expressed data as mean ± standard deviation. We analysed differences in proportions with Yates’ chi-square test or Fisher's exact test. We compared baseline characteristics and studied results with a Student's t-test and considered a P value < 0.05 as statistically significant.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Table 1 showed the characteristics of our two groups of patients. There was no difference in the age, gender, body mass index, dialysate concentration or the peritoneal transport characteristics between the two groups. The group with long-term PD had more previous experience with peritonitis (2/18 versus 11/18, P = 0.002) that had been tolerable to allow for subsequent PD therapy without having shifted to haemodialysis or death.


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  		Table 1 Patient characteristics

 
The sonographic thickness of the peritoneum at three anatomic locations was similar in short-term and long-term patients (Table 2). The Doppler indexes of mesenteric vessels, including the maximal velocity, minimal velocity, PI and RI, showed no statistical difference (Table 2).


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  		Table 2 Comparison of sonographic peritoneal thickness and Doppler indexes between short-term and long-term PD patients

 
We evaluated the association between clinical parameters, dialysis measurements and sonographic parameters with the sonographic peritoneal thickness in all 36 patients. Sonographic peritoneal thicknesses at different anatomical locations (RUQ, LUQ or LQ) were significantly correlated (Pearson correlation coefficient between measured RUQ, LUQ, LQ: 0.813–0.897, P < 0.01), which suggested consistent results of sonographic measurements. In the univariate analysis of the association between clinical parameters and sonographic parameters, only the peritoneal transport characteristics (D/P creatinine) and the clearance of PD (CCr_PD) showed significant association with peritoneal thickness (data not shown).

In multivariate analysis (Table 3), the D/P creatinine remained a significant independent predictor of sonographic thickness after controlling for age, gender, PD duration, peritonitis history and BMI. Therefore, we re-categorized all 36 patients into rapid transporters (D/P creatinine ratio >0.72) and slow transporters (D/P creatinine ratio <0.72) [9]. We compared the sonographic peritoneal thickness and Doppler indexes between these two groups (Table 4). The sonographic peritoneal thickness was significantly higher in the rapid transporters at three quadrants (RUQ: 0.59 ± 0.40 mm versus 0.27 ± 0.29 mm, P = 0.01; LUQ: 0.60 ± 0.40 mm versus 0.27 ± 0.32 mm, P = 0.016; LQ: 1.07 ± 0.85 mm versus 0.48 ± 0.53 mm, P = 0.026) (Table 4). All Doppler indexes, however, showed no significant difference, except for a marginally smaller RI of SMA in rapid transporters than in slow transporters (0.87 ± 0.08 versus 0.90 ± 0.10, P = 0.028).


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  		Table 3 Stepwise multivariate linear regression analysis of sonographic peritoneal thickness and patient characteristics

 

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  		Table 4 Comparison of sonographic peritoneal thickness and Doppler indexes between patients with rapid and slow peritoneal transport

 


   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
There have been many experimental studies of the functional and morphological alterations of the peritoneum during the life-long course of PD. However, there have been few non-invasive ultrasonographic studies in this field. Faller et al. utilized trans-abdominal ultrasonography to measure peritoneal thickness in paediatric subjects [8]. To our knowledge, the present study is the first full report in the English literature that examines sonographic peritoneal thickness and Doppler indexes of mesenteric vessels in adult PD patients.

With a high-frequency ultrasonography transducer, we identified a hyperechoic band between the anechoic dialysate and the hypoechoic abdominal wall muscles (Figure 1) that was proposed to represent the submesothelial compact collagen zone in the parietal peritoneum.

Williams et al. performed a comprehensive morphological study of the parietal peritoneum using peritoneal biopsy specimens in 130 patients undergoing PD [7]. Although in all patients, the submesothelial compact collagenous zone increased significantly with the duration of PD [0–24 months PD, median thickness 0.18 mm (n = 58); 73–96 months PD, median thickness 0.75 mm (n = 16); >97 months PD, 0.7 mm (n = 19)], this finding could not be observed in the subgroup of patients without PD-related problems or membrane failure [7]. The authors suggested that the thickening of the membrane is not inevitable for all patients undergoing PD. Our findings exactly support their biopsy-specimen-based findings by means of non-invasive ultrasonographic examinations. Long-term patients of our cohort experienced few or mild episodes of peritonitis and none of them had membrane failure; hence, they survived for a lengthy period of 7 years on PD.

From the opposite point of view, these long-term patients might have been naturally ‘selected’ during the natural course of PD; thus the average membrane thicknesses are not thicker than those for short-term patients. Another possible explanation for our results might be the smaller number of patients in our study. The prevalence of EPS among PD patients of >8 years’ duration was only 2.1% in Kawanishi's report [6]. For a cross-sectional study, a larger number of patients might be needed to increase the power to test the effect of PD duration on peritoneal thickness.

Previous studies have shown that increased blood vessel density beneath the submesothelial zone was found to be a characteristic in patients with peritoneal sclerosis and membrane failure [7,11], which suggested an interplay between morphologic alterations and functional characteristics of the peritoneal membrane. In a biopsy-specimen-based study, Plum et al. showed that rapid transporters had a significantly increased submesothelial fibrous layer compared with the slow transporters (559 ± 246 µm versus 360 ± 257 µm, P < 0.05) [12]. Our multivariate analysis indicated D/P creatinine as an independent predictor of peritoneal thickness. When we re-categorized our data according to peritoneal transport characteristics (Table 4), we confirmed that rapid transporters had a thicker peritoneum by means of non-invasive ultrasonographic examination, which was shown in the biopsy-specimen-based study. The interplay between the three components can be explained as follows: the more vessels beneath the compact collagen zone of the peritoneum, the higher the D/P creatinine. Meanwhile, the more vessels beneath the compact collagen zone of the peritoneum, the thicker the compact collagen zone. The intervening role of vascular density could probably explain our seemingly counter-intuitive finding that the higher the D/P creatinine (rapid transporters), the thicker the peritoneum [13].

In addition to the parietal peritoneum, the visceral peritoneum also contributes to the dialysis process of PD, sharing an even larger percentage of surface area, and is also vulnerable to alterations during the life-long course of PD. The previous study showed that the prevalence of vasculopathy in the peritoneum was found to increase with the PD duration [7]. The visceral peritoneum is perfused by mesenteric vessels. Thus, we tried to investigate the Doppler indexes of mesenteric vessels in relation to the histological vasculopathy during the course of PD. However, the Doppler indexes of mesenteric vessels failed to show any difference either among PD patients of different PD duration or among PD patients of different membrane transport characteristics (except for a marginal difference in the RI of SMA, Table 4). Previous experimental studies showed that RI decreases with an increase of the distal arterial bed [14,15]. The marginally lower RI of SMA in rapid transporters might reflect the increased neovascularization in morphologically altered peritoneal membranes of these patients.

The single sonographer, who was blind to the PD status of patients, performed all ultrasonographic examinations to reduce the examiner-related error. We found that the sonographic measurements at three locations correlated significantly with one another, indicating the consistency of our ultrasonographic measurements (Pearson correlation coefficient between measured RUQ, LUQ, LQ: 0.813–0.897, P < 0.01).

In a recent study, researchers measured sonographic peritoneal thickness in PD patients of 14 to 84 months’ duration and examined correlations with body height, body weight, D/P creatinine and PD duration [16]. They found that the peritoneum was thicker in patients who had >6 years of PD compared with those who had <24 months of PD (median 0.66 mm versus 0.37 mm). There are two fundamental differences between the designs of their study and our own. First, they examined all PD patients in a single centre, while we recruited PD patients from two PD centres. Second, our patients had longer periods of PD (18 patients with >7 years of PD in our study, compared to zero patient of >7 years in their study). Despite the differences in design and results, both studies confirm the clinical usefulness of ultrasonography in the evaluation of the parietal peritoneum in PD patients.

Our study has certain limitations. Firstly, the large variation of sonographic thickness (Table 2) within our two groups decreases the likelihood of establishing a statistically significant difference between the groups. However, this large variation might simply indicate that peritoneal thickness was not uniform in the same patient or among different patients. Because of this, we performed multiple measurements at three anatomical quadrants of the abdomen, to reduce the sampling error. Second, our study was a cross-sectional design. A longitudinal prospective follow-up study would reduce the ‘selection bias effect’ we encountered in the patients who experienced long-term PD. An in vitro ultrasound–pathology correlation study would be useful to support our proposal that our measurements reflect the submesothelial compact collagen zone of the parietal peritoneum.

In conclusion, our study confirmed previous biopsy-specimen-based studies by means of non-invasive ultrasonographic examinations. Our data showed that peritoneal thickening is not inevitable in long-term PD patients. Sonographic thickness in the parietal peritoneum is associated with transport characteristics. Rapid transporters had a thicker peritoneum. The Doppler index of mesenteric vessels hardly had any significant association with PD duration or transport characteristics. Trans-abdominal ultrasonography is non-invasive, easy and useful in evaluating peritoneal characteristics of PD patients.



   Acknowledgments
 
The authors would like to express gratitude to Ms Hui-Jen Roan, to the staff of the ultrasonography unit of the Emergency Department in NTUH and to the staff of the PD units both in NTUH and CCH. The authors also express gratitude to Dr Chen-Chung Liu for his assistance in statistics.

Conflict of interest statement. None declared.



   Notes
 
4 Dr T.-C. Lee and Dr J.-Y. Yang contributed equally to the work. Back



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Margetts PJ, Brimble KS. Peritoneal dialysis, membranes and beyond. Curr Opin Nephrol Hypertens (2006) 15:571–576.[Web of Science][Medline]
  2. Kawaguchi Y, Saito A, Kawanishi H, et al. Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures. Perit Dial Int (2005) 25:S83–S95.[Abstract/Free Full Text]
  3. Honda K, Oda H. Pathology of encapsulating peritoneal sclerosis. Perit Dial Int (2005) 25:S19–S29.[Abstract/Free Full Text]
  4. Kawanishi H. Encapsulating peritoneal sclerosis. Nephrology (Carlton) (2005) 10:249–255.[CrossRef][Medline]
  5. Rigby RJ, Hawley CM. Sclerosing peritonitis: the experience in Australia. Nephrol Dial Transplant (1998) 13:154–159.[Abstract/Free Full Text]
  6. Kawanishi H, Moriishi M. Epidemiology of encapsulating peritoneal sclerosis in Japan. Perit Dial Int (2005) 25:S14–S18.[Abstract/Free Full Text]
  7. Williams JD, Craig KJ, Topley N, et al. Morphologic changes in the peritoneal membrane of patients with renal disease. J Am Soc Nephrol (2002) 13:470–479.[Abstract/Free Full Text]
  8. Faller U, Stegen P, Klaus G, et al. Sonographic determination of the thickness of the peritoneum in healthy children and paediatric patients on CAPD. Nephrol Dial Transplant (1998) 13:3172–3177.[Abstract/Free Full Text]
  9. Smit W. Estimates of peritoneal membrane function—new insights. Nephrol Dial Transplant (2006) 21(Suppl 2):ii16–ii19.
  10. Twardowski Z, Nolph K, Khanna R. Peritoneal equilibration test. Perit Dial Bull (1987) 7:138–147.
  11. Mateijsen MA, van der Wal AC, Hendriks PM, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis. Perit Dial Int (1999) 19:517–525.[Abstract/Free Full Text]
  12. Plum J, Hermann S, Fussholler A, et al. Peritoneal sclerosis in peritoneal dialysis patients related to dialysis settings and peritoneal transport properties. Kidney Int Suppl (2001) 78:S42–S47.[Medline]
  13. Van Biesen W, Mortier S, Lameire N, et al. Effects of peritoneal dialysis on the vascular bed of peritoneal membrane. Contrib Nephrol (2006) 150:84–89.[Web of Science][Medline]
  14. Bude RO, Rubin JM. Relationship between the resistive index and vascular compliance and resistance. Radiology (1999) 211:411–417.[Abstract/Free Full Text]
  15. Tublin ME, Bude RO, Platt JF. Review. The resistive index in renal Doppler sonography: where do we stand? AJR Am J Roentgenol (2003) 180:885–892.[Free Full Text]
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Received for publication: 19. 2.07
Accepted in revised form: 18. 9.07


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This Article
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