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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2016  |  Volume : 27  |  Issue : 3  |  Page : 467-472
Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis


1 Department of Biotechnology, Periyar Maniammai University, Thanjavur, India; Department of Biochemistry, Institute of Biomedical Sciences, College of Health Sciences, Mekelle University (Ayder Campus), Mekelle, Ethiopia
2 Kidney Care, C 50, 10thB Cross, East Thillai Nagar,Tiruchirappalli, Tamil Nadu, India

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Date of Web Publication13-May-2016
 

   Abstract 

Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

How to cite this article:
Ramanathan K, Padmanabhan G, Vijayaraghavan B. Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis. Saudi J Kidney Dis Transpl 2016;27:467-72

How to cite this URL:
Ramanathan K, Padmanabhan G, Vijayaraghavan B. Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Jan 16];27:467-72. Available from: https://www.sjkdt.org/text.asp?2016/27/3/467/182378

   Introduction Top


Peritonitis is the main complication of conti- nuous ambulatory peritoneal dialysis (CAPD),[1],[2],[3],[4]and the frequent occurrence of peritonitis may limit the treatment by reducing the permea- bility of the peritoneal lining. The diagnosis and effective treatment of peritonitis depend on proper clinical evaluation of the patient and correlation with laboratory estimation of various parameters. Unfortunately, these procedures are generally followed after the development of peritonitis leading to many life-threatening complications. To avoid such consequences, early diagnosis and suitable treatment of intra- peritoneal sepsis are therefore very important. Several studies have reported that elevated serum C-reactive protein (CRP) is a potent predictor of mortality in dialysis patients as well as general population, and numerous published articles have shown that cardio- vascular diseases are the most common cause of mortality among the dialysis patients.[5],[6],[7],[8],[9],[10],[11],[12]

Early diagnosis of peritonitis could be made by the estimation of CRP, the acute phase pro- tein, which increases depending on the seve- rity of the microbial infections. The elevation of serum CRP (S. CRP) could also be found in other situations, and most of the estimations are made from blood samples only. To avoid such unreliable estimations, use of blood as sample should be avoided and a different and suitable marker are needed. To the best of our knowledge, there are no studies available on the estimation of CRP in dialysate fluid. An elevated S. CRP being associated with sepsis is well documented. However, its predictive value in peritoneal dialysis (PD) fluid has not been assessed. Hence, the objective of the pre- sent study is to evaluate the predictive value and clinical correlation of CRP in PD fluid in patients on CAPD with peritonitis. This study is the first such attempt in the global arena.


   Materials and Methods Top


Patients

This study was carried out on one hundred and twenty patients (76 male, 44 female) who underwent CAPD at a private nephrology clinic from May 2012 to April 2014. Their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD and again at the time of presentation to the outpatient department, usually within 24 h of onset of abdominal pain or cloudy effluent. All patients who developed peritonitis were evaluated for serum and Fl. CRP and were followed-up regarding their disease status. The patients were categorized into four groups, namely; normal patients (control group), patients with peritonitis, pa- tients with peritonitis leading to catheter remo- val, and death due to peritonitis.

Written informed consent was obtained from the patients prior to the study. This study was approved by the Local Ethics Committee.

Clinical and biochemistry details

All patients underwent routine estimation of biochemical parameters along with the esti- mation of CRP in fluid, as well as serum, using A15 auto analyzer (Biosystems,USA).

Bacteriological methods

The dialysate was taken for testing as follows: the injection ports were initially disinfected with methanol and allowed to dry for 2 min. About 50 mL of the dialysate was then aspi- rated into a sterile container and centrifuged at 2000 g at room temperature. The sediment was used for making a smear for Gram-stain and inoculated to the following media: blood agar, MacConkey agar, chocolate agar, thioglycolate broth, and blood culture medium. All cultures were incubated and examined daily for seven days. Identification of isolates was determined by standard methods.


   Statistical Analyses Top


Numerical data are expressed as a mean ± standard deviation. The statistical analyses were carried out using MedCalc version 12.7.0.0 (Belgium) statistical software. The degree of association between two variables was ana- lyzed by using correlation coefficient. Multiple regression was used to analyze the relationship between a dependent variable and independent variables. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic performance of two or more labo- ratory or diagnostic tests. The differences were considered significant when the probability was P <0.05.


   Results Top


A total of one hundred and twenty patients were included in the study. The mean age was 58.2 ± 9.78 years, and male:female ratio was 76:44. Routine laboratory tests were per formed on all and the results are shown in [Table 1]. Sixty-five patients (male: 31, female: 34) developed peritonitis during the study period (54%). Of them, catheter removal was required in eight patients (12.3 %) (male: 3, female: 5). Five patients (8%) (all males) died due to peritonitis-related complications. The S. CRP was 6.26 ± 3.0 and Fl. CRP was 0.51 ± 0.46 in the control group. These were com- pared with the other three subgroups. In pa- tients with peritonitis, the S. CRP was 6.48 ± 3.46 which was not statistically significant and Fl. CRP was 2.59 ± 0.98 (P <0.0001), which was statistically significant when compared to the control group. The most commonly en- countered microorganisms were Escherichia coli (50%), coagulase-negative Staphylococcus (35%), Candida Sp. (10%), and Staphylococcus aureus (5%). In patients who required catheter removal, S. CRP was 7.8 ± 4.5 (P <0.0001) and Fl. CRP value was 5.8 ± 0.19 (P <0.0001) [Table 2]. In patients, who died due to peri- tonitis, the S. CRP was 6.3 ± 1.35 and Fl. CRP was 10.35 ± 1.06 (P <0.0001). The ROC curve analysis shows the sensitivity, specificity, area under curve, and 95% confidence interval of Fl. CRP and S. CRP [Table 3]. The sensitivity and specificity of Fl. CRP showed higher sig- nificance (sensitivity: 95.2% and specificity: 100%) [Figure 1]a than the S. CRP in the infection group (sensitivity: 75% and specifi- city: 100%) [Figure 1]b. In the group requiring catheter removal, the Fl. CRP showed lower sensitivity but higher specificity (sensitivity: 83.3% and specificity: 100%) [Figure 2]a than S. CRP (sensitivity: 100% and specificity: 66.7%) [Figure 2]b. In patients who died, the Fl. CRP was sensitive and highly specific (sen- sitivity: 80% and specificity: 100%) [Figure 3]a than S. CRP (sensitivity: 100% and speci- ficity: 66.7%) [Figure 3]b. In these patient groups, the Fl. CRP showed significant diffe- rence than the S. CRP when compared with control subjects [Figure 4]. All deaths related to peritonitis were due to persistent hypotension, not responding to therapy resulting in cardiac arrest. The S. CRP did not show significant variation among the patient groups and it showed high levels even in patients without infection. However, the Fl. CRP significantly increased depending on the severity of the infection. These results indicate that the Fl. CRP is directly proportional to the severity of the infection.
Figure 1:

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Figure 2:

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Figure 3:

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Figure 4. Comparison of serum and fluid C-reactive protein levels in the study groups

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Table 1. Routine laboratory parameters of the study patients

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Table 2. Comparison of serum and fluid C-reactive protein levels among the three groups

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Table 3. Receiver operating characteristic curve analysis of the parameters in the three study groups

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   Discussion Top


To the best of our knowledge, the estimation of CRP in CAPD fluid is the first of its kind in the globe. Detailed literature survey revealed that many studies have prominently noted that CAPD-associated peritonitis can be effectively cured in up to 80-85% of cases.[13]The inci- dence of peritonitis in the present study was 54%. Similar results were obtained by Sten- vinkel et al. One of the most interesting findings in the present study is the association of elevated levels of Fl. CRP with the ability to predict the severity of peritonitis in terms of catheter removal and mortality in PD patients due to peritonitis. Catheter removal was re- quired in 12.3% of the cases in the present study and this is similar to the 10-15% repor- ted in previous studies.[14],[15],[16],[17]The present study showed that the mortality rate is 8%, similar to a previous study which showed 6%. [14],[18]In about 1-6% of patients, death was associated with the peritonitis episode.[14],[15]Thus, perito- nitis plays an important role in the mortality rate associated with CAPD. It causes severe local inflammation leading to rise in Fl. CRP more than S. CRP. Previous studies had shown coagulase-negative Staphylococcus as the pre- dominant causative organism in peritonitis. However, the causative microorganism in the present study was E. coli affecting more than 50% of the cases of peritonitis.

The acute phase protein, CRP has been shown to be significantly elevated in the initial 48 h of peritonitis and may remain elevated for weeks after the peritonitis episode.[19]This pro- tein marker, linked to the diagnosis of cardio- vascular mortality, may possibly provide an association between peritonitis and the asso- ciated mortality. In recent years, because of the technical advances in CAPD technology, the peritonitis rates have decreased signifi- cantly.

Presently, estimation of inflammatory mar- kers like CRP has become mandatory for pre- dicting the inflammatory status. Several studies have revealed that S. CRP is not a specific marker for predicting peritonitis, but remains an independent marker for predicting inflam- mation. With this in mind, we estimated the CRP in both serum as well as PD fluid to identify which of the two is a suitable pre- dictor for peritonitis. From the present study, we conclude that estimation of Fl. CRP is di- rectly proportional to the severity of infection.

Conclusion

Fl. CRP is a very good marker for diagnosing peritonitis in CAPD patients. Based on this estimation, we can diagnose peritonitis early and this may help to avoid life-threatening consequences. Moreover, E. coli was the most commonly encountered microorganism in the present study. More studies are needed to validate our results.

Conflict of interest: None.



 
   References Top

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Gould IM, Casewell MW. The laboratory diagnosis of peritonitis during continuous ambulatory peritoneal dialysis. J Hosp Infect 1986;7:155-60.  Back to cited text no. 1
[PUBMED]    
2.
Korzets Z, Korzets A, Golan E, Zevin D, Bernheim J. CAPD peritonitis - initial presen- tation as an acute abdomen with a clear peri- toneal effluent. Clin Nephrol 1992;37:155-7.  Back to cited text no. 2
    
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Morduchowicz G, van Dyk DJ, Wittenberg C, Winkler J, Boner G. Bacteremia complicating peritonitis in peritoneal dialysis patients. Am J Nephrol 1993;13:278-80.  Back to cited text no. 3
    
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Males BM, Walshe JJ, Amsterdam D. Labo- ratory indices of clinical peritonitis: total leukocyte count, microscopy, and micro- biologic culture of peritoneal dialysis effluent. J Clin Microbiol 1987;25:2367-71.  Back to cited text no. 4
    
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Bergstriim J, Heimblirger O, Lindholm B, Qureshi AR. Elevated serum C-reactive pro- tein is a strong predictor of increased mortality and low serum albumin in hemodialysis (HD) patients [Abstract]. J Am Soc Nephrol 1995; 6:573.  Back to cited text no. 5
    
6.
Noh H, Lee SW, Kang SW, et al. Serum C- reactive protein: a predictor of mortality in continuous ambulatory peritoneal dialysis patients. Perit Dial Int 1998;18:387-94.  Back to cited text no. 6
    
7.
Iseki K, Tozawa M, Yoshi S, Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999;14:1956-60.  Back to cited text no. 7
    
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Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardio- vascular risk and mortality in hemodialysis patients. Kidney Int 1999;55:648-58.  Back to cited text no. 8
    
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Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis pa- tients. Am J Kidney Dis 2000;35:469-76.  Back to cited text no. 9
    
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Haubitz M, Brunkhorst R. C-reactive protein and chronic Chlamydia pneumoniae infection - long-term predictors for cardiovascular disease and survival in patients on peritoneal diaysis. Nephrol Dial Transplant 2001;16: 809-15.  Back to cited text no. 10
    
11.
Wang AY, Woo J, Lam CW, et al. Is a single time point C-reactive protein predictive of outcome in peritoneal dialysis patients? J Am Soc Nephrol 2003;14:1871-9.  Back to cited text no. 11
    
12.
Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 1994;331:417-24.  Back to cited text no. 12
    
13.
Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997;336:973-9.  Back to cited text no. 13
    
14.
Troidle L, Finkelstein F. Treatment and out- come of CPD-associated peritonitis. Ann Clin Microbiol Antimicrob 2006;5:6.  Back to cited text no. 14
    
15.
Pérez Fontan M, Rodríguez-Carmona A, García-Naveiro R, Rosales M, Villaverde P, Valdés F. Peritonitis-related mortality in pa- tients undergoing chronic peritoneal dialysis. Perit Dial Int 2005;25:274-84.  Back to cited text no. 15
    
16.
Troidle L, Gorban-Brennan N, Kliger A, Finkelstein F. Differing outcomes of gram- positive and gram-negative peritonitis. Am J Kidney Dis 1998;32:623-8.  Back to cited text no. 16
    
17.
Bunke CM, Brier ME, Golper TA. Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study. Kidney Int 1997;52:524-9.  Back to cited text no. 17
    
18.
van Esch S, Krediet RT, Struijk DG. 32 years' experience of peritoneal dialysis-related peri- tonitis in a University Hospital. Perit Dial Int 2014;34:162-70.  Back to cited text no. 18
    
19.
Troidle L, Kliger A, Gorban-Brennan N, Finkelstein F. Course of C-reactive protein during continuous peritoneal dialysis-asso- ciated peritonitis. Nephrology (Carlton) 2005; 10:442-5  Back to cited text no. 19
    

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Correspondence Address:
Kumaresan Ramanathan
Department of Biochemistry, College of Health Sciences, Mekelle University, Mekelle

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DOI: 10.4103/1319-2442.182378

PMID: 27215236

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