Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Epidemiology and Outcomes
You have accessRestricted Access

Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?

Angela Yee-Moon Wang, Jean Woo, Christopher Wai-Kei Lam, Mei Wang, Mandy Man-Mei Sea, Siu-Fai Lui, Philip Kam-Tao Li and John Sanderson
JASN July 2003, 14 (7) 1871-1879; DOI: https://doi.org/10.1097/01.ASN.0000070071.57901.B3
Angela Yee-Moon Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jean Woo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christopher Wai-Kei Lam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mei Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mandy Man-Mei Sea
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Siu-Fai Lui
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip Kam-Tao Li
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Sanderson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

Abstract

ABSTRACT. C-reactive protein is the prototype marker of inflammation and has been shown to predict mortality in hemodialysis patients. However, it remains uncertain as to whether a single C-reactive protein level has similar prognostic significance in peritoneal dialysis patients. A single high-sensitivity C-reactive protein (hs-CRP) level was measured in 246 continuous ambulatory peritoneal dialysis patients without active infections at study baseline together with indices of dialysis adequacy, echocardiographic parameters (left ventricular mass index, left ventricular dimensions, and ejection fraction), nutrition markers (serum albumin, dietary intake, and subjective global assessment) and biochemical parameters (hemoglobin, lipids, calcium, and phosphate). The cohort was then followed-up prospectively for a median of 24 mo (range, 2 to 34 mo), and outcomes were studied in relation to these parameters. Fifty-nine patients died (36 from cardiovascular causes) during the follow-up period. The median hs-CRP level was 2.84 mg/L (range, 0.20 to 94.24 mg/L). Patients were stratified into tertiles according to baseline hs-CRP, namely those with hs-CRP ≤ 1.26 mg/L, 1.27 to 5.54 mg/L, and ≥ 5.55 mg/L. Those with higher hs-CRP were significantly older (P < 0.001), had greater body mass index (P < 0.001), higher prevalence of coronary artery disease (P = 0.003), and greater left ventricular mass index (P < 0.001). One-year overall mortality was 3.9% (lower) versus 8.8% (middle) versus 21.3% (upper tertile) (P < 0.0001). Cardiovascular death rate was 2.7% (lower) versus 5.2% (middle) versus 16.2% (upper tertile) (P < 0.0001). Multivariable Cox regression analysis showed that every 1 mg/L increase in hs-CRP was independently predictive of higher all-cause mortality (hazard ratio [HR], 1.02; 95% CI, 1.01 to 1.04; P = 0.002) and cardiovascular mortality (HR, 1.03; 95% CI, 1.01 to 1.05; P = 0.001) in peritoneal dialysis patients. Other significant predictors for all-cause mortality included age (HR, 1.07; 95% CI, 1.04 to 1.10), gender (HR, 0.49; 95% CI, 0.27 to 0.90), atherosclerotic vascular disease (HR, 2.65; 95% CI, 1.46 to 4.80), left ventricular mass index (HR, 1.01; 95% CI, 1.00 to 1.01) and residual GFR (HR, 0.53; 95% CI, 0.38 to 0.75). Age (HR, 1.06; 95% CI, 1.02 to 1.10), history of heart failure (HR, 3.31; 95% CI, 1.36 to 8.08), atherosclerotic vascular disease (HR, 3.20; 95% CI, 1.43 to 7.13), and residual GFR (HR, 0.57; 95% CI, 0.38 to 0.86) were also independently predictive of cardiovascular mortality. In conclusion, a single, random hs-CRP level has significant and independent prognostic value in PD patients. E-mail: awang@cuhk.edu.hk

Received November 29, 2002. Accepted March 14, 2003.

Elevated plasma C-reactive protein (CRP) level, the prototypic marker of inflammation, has been shown to be strongly predictive of an increased risk of future myocardial infarction and predicts mortality in apparently healthy people (1–3⇓⇓) as well as in patients with established coronary artery disease (4–6⇓⇓). On the other hand, increased CRP is also frequently observed in chronic renal failure patients (7–11⇓⇓⇓⇓) and is associated with atherosclerosis (11). Whether CRP is simply a marker of atherosclerosis or is causally related to the development of atherosclerosis remains an open question. However, prospective cohort studies showed that CRP is one of the important predictors for mortality in hemodialysis patients (7–8,12⇓⇓). What is more intriguing is that a single determination of CRP is predictive of all-cause mortality and cardiovascular death even after a follow-up period of 4 yr in patients on hemodialysis treatment (12), although there is also a study showing that the predictive value of CRP is not independent of nutritional and cardiovascular risk factors (13).

On the other hand, very few studies examined the role of CRP in predicting outcome of peritoneal dialysis (PD) patients, and the results were inconclusive. One study showed that CRP is associated with increased mortality independent of cardiovascular disease (14). Another study showed that CRP is predictive of nonfatal myocardial infarction but not all-cause mortality (15). Although the negative finding may be partly explained by the small sample size, there is recent data to suggest that CRP is increased in a significant proportion of PD patients without any obvious cause and in approximately one third of these patients with raised CRP without an apparent cause, the repeat levels become normal in 40% over the next few months (16). Moreover, CRP level was noted to fall with time on PD and was significantly lower in PD compared with hemodialysis patients (17). Hence the question as to whether a single CRP level has prognostic significance in PD patients remains unanswered.

In this study, we hypothesized that a C-reactive protein level at a single time point predicts all-cause mortality and cardiovascular mortality in a prevalent cohort of PD patients. Our study differs from previous studies in PD patients in that not only do we take into account of inflammatory parameters but also clinical, cardiovascular, echocardiographic, dialysis, nutritional, and biochemical factors — other well-known predictors for mortality in PD patients.

Materials and Methods

Study Population

The prospective study was carried out at the dialysis unit in the Prince of Wales Hospital in Hong Kong in September 1999. Altogether 246 continuous ambulatory peritoneal dialysis (CAPD) patients who had been on dialysis treatment for at least 3 mo were recruited into the study over a period of 20 mo. Our study cohort represented 91% of the total number of patients on PD treatment at our unit. All patients are of Chinese origin. The remaining 9% of patients were excluded from the study because of underlying malignancy, chronic liver disease, systemic lupus erythematosus, chronic rheumatic heart disease, congenital heart disease, or because they received PD treatment for less than 3 mo or were on automated PD. The study protocol was approved by the Human Research Ethics Committee of the Chinese University of Hong Kong. Informed consent was obtained from all study participants.

At study baseline, demographic and clinical parameters, cardiovascular and echocardiographic parameters, nutritional indices, biochemical and inflammatory parameters as well as indices of dialysis adequacy were assessed.

Clinical and Demographic Parameters

Clinical and demographic data, including the duration on CAPD at study entry, underlying cause of renal failure, smoking history, presence of diabetes, ischemic heart disease, history of heart failure, cerebrovascular disease and peripheral vascular disease, history of exit site infection and peritonitis within 1 yr before study entry were recorded at study baseline. Clinical atherosclerotic vascular disease was defined as the presence of ischemic heart disease and history of angina, previous myocardial infarction, coronary artery bypass surgery or stenting, cerebrovascular event, transient ischemic attack, or peripheral vascular disease with or without amputation. Use of erythropoietin as well as the number and type of antihypertensive medication at study baseline were recorded. These include the use of calcium channel blocker, angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), and beta-blocker. Use of HMG-CoA-reductase inhibitor and aspirin were also recorded.

Biochemical and Inflammatory Parameters

Twenty milliliters of fasting venous blood was collected at the time of nutrition assessment, which was also the time of study entry for measurement of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, parathyroid hormone (PTH), total, HDL- and LDL-cholesterol, triglyceride, urea, creatinine, calcium, phosphate, and hemoglobin. hs-CRP was measured using the Tina-quant CRP (Latex) ultrasensitive assay (Roche Diagnostics GmbH, Mannheim, Germany). The coefficient of variation of the hs-CRP assay was 4.7% and 1.6% at concentrations of 4.3 mg/L and 2.0 mg/L, respectively. Fibrinogen was measured by a prothrombin time-derived and turbidimetric clot detection method using the ACL Futura (Instrumentation Laboratory). Serum albumin was measured by the bromcresol purple method. PTH was measured by the chemiluminescence immunoassay on the Immunlite analyzer (Diagnostic Products Corp, Los Angeles, CA). Total cholesterol and triglyceride were measured by the Hitachi 911 analyzer (Roche Diagnostics GmbH, Mannheim, Germany). HDL-cholesterol was measured by the precipitation of Apo B containing lipoproteins with phosphotungstate, whereas LDL-cholesterol was calculated using the Friedwald formula. Serum urea, creatinine, calcium, and phosphate were measured by dye-binding methods on the Dimension AR automatic analyzer (Du Pont Co, Wilmington, DE). Hemoglobin was measured in the standard hematology laboratory.

Echocardiographic Parameters

Two-dimensional echocardiography was performed with a GE-VingMed System 5 echocardiographic machine (GE-VingMed Sound AB, Horten, Norway) with a 3.3-mHz multiphase array probe in subjects lying in the left decubitus position by a single experienced cardiologist blinded to all clinical details of patients. All echocardiographic data were recorded according to the guidelines of the American Society of Echocardiography (18–19⇓). Left ventricular mass (LVM) was corrected by the body surface area and expressed as LVM index, an index reflecting the severity of LVH. LVH was defined as LVM index ≥ 131 g/m2 in men and ≥ 100 g/m2 in women in accordance with Framingham criteria (20). Systolic and diastolic BP was measured at the time of echocardiography after resting for 15 min.

Nutrition Indices

Subjective global assessment (SGA) was used to evaluate the overall protein-energy nutritional status (21–22⇓). The SGA includes six subjective assessments; three are based on the patient’s history of weight loss, presence of anorexia, and vomiting, and three are based on the physician’s grading of muscle wasting, presence of edema, and loss of subcutaneous fat. Although edema is not a useful index of malnutrition (22), its presence or absence has to be taken into account when assessing changes in body weight. On the basis of these assessments, each patient was graded a score that reflected the nutrition status: 1, normal nutrition; 2, mild malnutrition; 3, moderate malnutrition; and 4, severe malnutrition (22). A 7-d dietary survey questionnaire that has previously been validated in the Chinese population was administered in all study patients to estimate the average daily dietary protein and energy intake. Details and validation of the questionnaire was described elsewhere (23). Dietary protein and energy intake was normalized for dry weight (measured by a weighing scale with abdomen drained dry of peritoneal dialysis fluid). Body mass index was calculated by dividing dry weight (in kilograms) by the square of the height (in meters). Both the SGA and dietary survey questionnaire were performed by experienced research staff blinded to all clinical, biochemical, dialysis, and echocardiographic data of patients.

Dialysis Adequacy

Patients were asked to bring back 24-h urine and dialysate on the morning of nutrition assessment for measurement of urea and creatinine concentration. Adequacy of dialysis was determined by measuring total weekly urea clearance (Kt/V) and creatinine clearance (CrCl) using standard methods (24). Weekly CrCl was normalized to 1.73 m2 of body surface area. Contribution of urea clearance by peritoneal dialysis was estimated separately. Residual GFR was calculated as an average of the 24-h urine urea and creatinine clearance (25). Dialysate creatinine concentration was corrected for interference by glucose according to the reference formula determined in our laboratory (26). Total body water (V) was derived from Watson formula (27). The dialysate/plasma creatinine ratio (D/PCr) was calculated from the concentrations of creatinine in the 24 h dialysate and the plasma (28).

Study Outcome

All patients were then followed up prospectively after all the baseline assessments. No patient was lost to follow-up. Patients who underwent kidney transplant or transferred to hemodialysis were censored at the time of transfer to alternative renal replacement therapy. If a patient died within 3 mo of transfer to hemodialysis, then he or she was not censored as the early mortality was considered to reflect the health status during the period of failing CAPD treatment. During the period of follow-up, all deaths were accurately recorded with the exact cause of death provided by the attending physician who had no knowledge of the echocardiography results. In the case of death out of hospital, family members were interviewed by telephone to ascertain the circumstances surrounding death. The clinical outcomes evaluated were all-cause mortality and cardiovascular mortality. Cardiovascular mortality included death associated with a definite myocardial ischemic event, heart failure, cerebrovascular accident, arrhythmia, or peripheral vascular accident, all of which defined according to standard clinical criteria and sudden death, which was defined as unexpected natural death within 1 h from the symptom onset and without any prior condition that would appear fatal (29,30⇓).

Statistical Analyses

Statistical analyses were performed using SPSS software, version 10.0 (SPSS, Inc., Chicago, IL). Continuous data are expressed as mean ± SD or median (interquartile range [IQR]), and categorical data are expressed as percentages. Patients were stratified into tertiles according to the single hs-CRP level at study baseline. Comparisons of characteristics of patients across the different tertiles were performed using the one-way ANOVA for mean data, Kruskal-Wallis test for median data, and χ2 test for categorical data. Factors predictive of all-cause mortality and cardiovascular mortality were further determined with multivariable Cox regression analysis. Any variables with difference between tertiles of hs-CRP found at P < 0.20 were considered as potential confounders and were adjusted for in the Cox regression analysis (31). A backward elimination procedure was performed with P > 0.05 to remove to identify independent predictors for all-cause mortality and cardiovascular mortality in PD patients. Survival curves were generated according to the Kaplan-Meier method. Differences in the survival curves among the three tertiles were compared by the log-rank test. A P-value of less than 0.05 was considered statistically significant.

Results

Patient Characteristics

The baseline characteristics of the study cohort are shown in Tables 1 and 2⇓. There were altogether 128 men and 118 women. The mean age was 55 ± 12 yr. The study cohort was dialyzed for a mean duration of 38 mo (range, 4 to 151 mo) at the time of study entry. Ninety-five patients (39%) had no residual renal function. Forty percent of our patients were prescribed erythropoietin. Antihypertensive medications including beta-blockers, ACE inhibitors/ARB, and calcium channel blockers were used in 52%, 25%, and 62% of patients, respectively. Fourteen percent of patients were treated with HMG Co-A reductase inhibitors, and 6% took aspirin. The distribution of hs-CRP of our study cohort taken at the time of study entry was shown in Figure 1. The median (IQR) hs-CRP level was 2.84 mg/L (0.92 to 9.10 mg/L). hs-CRP level was below 5 mg/L in 64% of patients, between 5 and 10 mg/L in 12%, between 10 and 15 mg/L in 7%, and over 15 mg/L in 17% of patients.

View this table:
  • View inline
  • View popup

Table 1. Comparison of baseline demographic, clinical, and cardiovascular characteristics of study patients stratified according to tertiles of high-sensitivity C-reactive proteina

View this table:
  • View inline
  • View popup

Table 2. Comparison of baseline biochemical, dialysis, and nutritional indices of study patients stratified according to tertiles of high-sensitivity C-reactive proteina

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 1. Frequency distribution of high sensitivity C-reactive protein (hs-CRP) in Chinese continuous ambulatory peritoneal dialysis (PD) patients.

Comparisons among Patients of the Different Tertiles of hs-CRP

Comparisons among patients of the different tertiles of hs-CRP level, namely those with hs-CRP ≤ 1.26 mg/L (lower tertile), between 1.26 and 5.56 mg/L (middle tertile), and ≥ 5.56 mg/L (upper tertile) are shown in Tables 1 and 2⇑. A significant increase in age (P < 0.001), body weight (P = 0.041), and body mass index (P < 0.001) was observed across the three tertiles of increasing hs-CRP. More patients in the upper tertile had ischemic heart disease (P = 0.003). Thirty-seven percent of patients in the lower versus 45% in the middle and 50% in the upper tertile had exit site infections (P = 0.215), and 29% of patients in the lower versus 39% in the middle and 31% in the upper tertile were complicated with peritonitis within 1 yr before study entry (P = 0.350). A significant decrease in diastolic BP was observed across the three tertiles (P = 0.018). The left ventricular mass index (P < 0.001), left ventricular end-diastolic diameter (P = 0.001), ejection fraction (P = 0.002), and fractional shortening (P = 0.001) showed significant increase across the three tertiles of increasing hs-CRP. Patients in the upper tertile had the lowest residual GFR (P = 0.018) but received the highest average daily PD exchanges (P = 0.028).

A significant decrease in dietary energy (P < 0.001) and protein intake (P = 0.003), as well as serum albumin (P = 0.005), was observed across the three tertiles of increasing hs-CRP. According to SGA, a trend toward greater prevalence of moderate and severe malnutrition was observed in the upper tertile though not reaching statistical significance. Biochemical parameters including fibrinogen and triglyceride increased significantly while HDL- and LDL-cholesterol decreased significantly across the three tertiles of increasing hs-CRP (Table 2). Calcium, phosphate, and PTH did not differ significantly among the three tertiles.

Thirty-eight percent of patients (lower tertile) versus 38% (middle tertile) versus 45% (upper) were prescribed erythropoietin (P = 0.544). Beta-blocker was used in 56% versus 44% versus 57% of patients in the lower versus middle versus upper tertiles, respectively (P = 0.164). Slightly more frequent use of ACE inhibitor or ARB was observed in the upper (33%) than lower (20%) and middle tertiles (22%) (P = 0.106). Use of calcium channel blocker (66% versus 61% versus 59%; P = 0.617), HMG Co-A reductase inhibitor (11% versus 15% versus 16%; P = 0.642) and aspirin (5% versus 4% versus 9%; P = 0.374) did not differ significantly across the three tertiles. Twenty-one percent of patients with versus 12% of patients without atherosclerotic complications were treated with statin (P = 0.061). Among patients with atherosclerotic complications, hs-CRP was not significantly different for those treated (5.9 mg/L [1.2 to 13.3 mg/L]) and not treated with statin (5.4 mg/L [1.4 to 22.3 mg/L]; P = 0.83).

Patient Survival and Causes of Death in Relation to hs-CRP

Our study cohort was followed-up for a median duration of 24 mo (range, 2 to 34 mo) after all the baseline assessments including hs-CRP. During this period of follow-up, there were 59 deaths (24%). Twenty-three patients (9.3%) were transferred to long-term hemodialysis, and 19 patients (7.7%) received a kidney transplant. More men (30%) than women (18%) died during the period of follow-up. On the other hand, more women (12%) than men (7%) were transferred to long-term hemodialysis. The causes of death of our study cohort were shown in Table 3. The main cause of death was cardiovascular disease in 36 patients (61%), followed by infections in 15 patients (25%); 19 of the 36 patients (53%) had sudden cardiac death. Patients in the upper tertile had the shortest follow-up duration, yet they had the highest mortality (41.5%) compared with patients in the lower and middle tertiles (11% and 19.5%, respectively; P < 0.001). Death from cardiovascular causes was 7.3%, 9.8%, and 26.8% for patients in the lower, middle, and upper tertiles, respectively. Noncardiovascular deaths were 3.7%, 9.8% and, 14.6% for patients in the lower, middle, and upper tertiles, respectively (P < 0.001). The overall 1-yr survival was 79% for patients in the upper tertile compared with 91% for patients in the middle tertile (P = 0.0006) and 96% for patients in the lower tertile (P < 0.0001; Figure 2A). The survival rate was not significantly different for patients in the lower and middle tertiles. Cardiovascular death rate at 1 yr was 16% for patients in the upper tertile compared with 5% for patients in the middle tertile (P = 0.0003) and 3% for patients in the lower tertile (P = 0.0001; Figure 2B). Patients in the upper tertile had a 4.7-fold increased risk (95% CI, 2.23 to 9.73; P < 0.001) for all-cause mortality and a 4.9-fold higher risk (95% CI, 2.00 to 12.01; P = 0.001) for cardiovascular mortality than those in the lower tertile. Patients in the middle tertile showed no significant increase in the risk for all-cause (P = 0.232) and cardiovascular mortality (P = 0.785) than those in the lower tertile.

View this table:
  • View inline
  • View popup

Table 3. Clinical outcome of patients according to the hs-CRP level at study baselinea

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Figure 2. Kaplan-Meier analysis of (A) overall survival and (B) cardiovascular event-free survival in relation to tertiles of high sensitivity C-reactive protein (hs-CRP).

Multivariable Cox regression analysis was used to determine the independent effects of a single random hs-CRP in predicting all-cause and cardiovascular mortality and included terms for age, gender, duration of dialysis, body mass index, positive smoking history, diabetic nephropathy, atherosclerotic vascular disease, history of heart failure, left ventricular mass index, left ventricular end-diastolic diameter, ejection fraction, fractional shortening, diastolic BP, weekly total and peritoneal dialysis Kt/V, residual GFR, hemoglobin, fibrinogen, cholesterol, triglyceride, and serum albumin. Every 1 mg/L increase in hs-CRP was independently predictive of a 2% increase in all-cause mortality (95% CI, 1.01 to 1.04; P = 0.002) and a 3% increase in cardiovascular mortality (95% CI, 1.01 to 1.05; P = 0.001) in PD patients. Other significant and independent predictors for mortality included age, male gender, presence of atherosclerotic vascular disease, history of heart failure, left ventricular mass index, and residual GFR (Table 4). Correlation analysis showed a small but significant correlation between hs-CRP with residual GFR (r = −0.16; P = 0.011) and duration of dialysis (r = 0.147; P = 0.018), suggesting residual GFR and duration of dialysis may have confounding influence on the association between CRP and mortality, although statistical analysis showed no significant colinear relationships between hs-CRP and GFR as well as between hs-CRP and duration of dialysis.

View this table:
  • View inline
  • View popup

Table 4. Cox regression analysis showing important predictors for mortality in CAPD patients after a median follow-up of 24 moa

To determine whether there is nonlinear association between CRP and mortality, a quadratic term, namely “square of CRP,” is fitted to the final model in Table 4. However, the quadratic term is not significant in the model predicting all-cause mortality (P = 0.369) as well as in the model predicting cardiovascular mortality (P = 0.604). This suggests that imposing a nonlinear term does not provide additional predictive power to the models in Table 4.

Discussion

This study shows that a considerable proportion (36%) of the Chinese PD patients exhibited evidence of an activated acute phase response as denoted by a hs-CRP level ≥ 5 mg/L. The prevalence of inflammation was considered much lower when compared with the white dialysis cohorts, in whom the prevalence was estimated to be at least 50 to 60% (32). Another study in the Asian population reported that only 12% of the PD patients had CRP > 8 mg/L (14). This may reflect difference in inflammatory response or genetic susceptibility to develop inflammation between Asian and white populations and will require further investigation.

Our results demonstrate the usefulness of a single random CRP in predicting all-cause and cardiovascular mortality, independent of other cardiovascular, echocardiographic, dialysis, biochemical, and nutritional parameters in PD patients. This is in keeping with studies in both the general and hemodialysis populations as well as very recent study in patients initiating PD showing that a single time point measurement of CRP is predictive of overall mortality and cardiovascular death even after prolonged period of follow-up (12,33–34⇓⇓). Our results however differed from those reported by Owen and Lowrie (13) in hemodialysis patients and by Herzig et al. (15) in PD patients that failed to show a significant relationship between CRP and risk of death on multivariate analysis. Both these studies showed that the depletion of body proteins and not inflammation is a more important contributor to mortality risk in dialysis patients. The study by Owen and Lowrie was however limited in that it only had 6 mo of follow-up and that by Herzig included only 50 patients. The difference in sample size, follow-up duration, and the extent of adjustment for confounding covariates may well explain the disparity between our findings and these studies.

The finding that a single, cross-sectional measurement of a plasma protein with such a short half-life (19 h) carries significant long-term prognostic information is intriguing, as some studies demonstrated marked variations of CRP levels in individual patients (16,35⇓). On the other hand, others reported relative stability of CRP as shown by the high concordance for CRP levels measured at baseline and 6 mo later (15,17,36⇓⇓). Recent study showed that a persistently elevated CRP for more than 6 mo is largely related to the presence of ischemic heart disease or other atherosclerotic complications (37). This is in keeping with our current finding of higher prevalence of ischemic heart disease and atherosclerotic complications as well as increased cardiovascular mortality among patients of the upper tertile.

The clinical outcomes of patients in the middle tertile were not significantly different from the lower tertile. This is in contrast to study in cardiac patients (4–6⇓⇓) and general population (3,33⇓) showing that even high normal CRP levels are associated with adverse prognosis. The exact reason for this difference is not clear, but it may be partly related to the study power. Our study only had 83 patients in each tertile and may not be adequately powered to detect difference in outcome between high normal and low normal CRP. The other explanation may relate to the numerous cardiovascular risk factors uniquely operating in renal failure patients namely, calcium phosphate parameters, anemia, hypoalbuminemia, dialysis adequacy, and volume status other than inflammation and traditional Framingham risk factors. These different factors are well known to affect clinical outcomes of renal failure patients and may influence the association of CRP with survival.

A novel finding was that patients in the upper tertile had the greatest left ventricular mass index and left ventricular end-diastolic diameter as well as the lowest ejection fraction and fractional shortening. They were also dialyzed for the longest duration, had the lowest residual GFR, and were the most malnourished according to nutrition assessments. It is therefore intriguing to find that these patients, on the contrary, had the highest body weight and BMI. We hypothesized that these patients were also volume overloaded. This may explain why they had the highest BMI despite being more malnourished and had the worst cardiac status. Indeed, previous study demonstrated immune activation in patients with fluid overload (38). Increased extracellular fluid volume was shown to cause hypoalbuminemia (39) and was linked to hypertension, progressive LV hypertrophy, and dilatation in PD patients (40–41⇓). Increased extracellular fluid removal reduced dry weight, improved BP control, and increased serum albumin in PD patients (42). Whether CRP is elevated in volume overload state and is in turn associated with more LV hypertrophy and dilatation or CRP is simply a marker of the degree of LV hypertrophy and dilatation in PD patients requires further investigation. The small association between body height and CRP may be due to more female patients in the upper tertile and is unlikely to be of real clinical significance.

Hypoalbuminemia (43), hyperfibrinogenemia, hypercholesterolemia, and hypertriglyceridemia (44–46⇓⇓) were important cardiovascular risk factors and predictors of mortality in dialysis patients. In this study, serum albumin, fibrinogen, HDL and LDL-cholesterol, and triglyceride were significantly associated with CRP but lost their significance in predicting mortality and cardiovascular death on multivariate analysis. This is consistent with the study by Zimmerman et al. (7) and suggests that, other than being cardiovascular risk factors, serum albumin, fibrinogen, cholesterol, and triglyceride behave like markers of acute phase response though not as powerful as CRP in predicting outcome of PD patients. The cause of lower LDL in patients with higher CRP is not clear but may be related to more frequent use of statins.

Patients with higher hs-CRP were older and may be explained by higher prevalence of vascular complications with increasing age. The association between CRP and residual renal function was well described in previous study (47). CRP was positively associated with the time on dialysis. Although being adjusted for in the multivariate analysis, the time on dialysis may well have a confounding effect on the association between CRP and mortality as with time on dialysis, there is decline of residual GFR, increasing LV hypertrophy, higher prevalence of atherosclerotic complications, more malnutrition, and inflammation in PD patients.

In summary, this study clearly confirms the significance of a single random hs-CRP in predicting all-cause mortality and cardiovascular mortality in PD patients. Our results indicate that determination of CRP by a high-sensitive assay should be considered in all PD patients without active infections in order for risk stratification. Whether lowering CRP level will improve outcome of these patients requires further determination.

Acknowledgments

This study was supported by the Hong Kong Health Services Research Fund and the Bristol Myers Squibb Unrestricted Nutrition Grant Program. We express sincere gratitude to Mr. Lam Peggo Kwok Wai from the Center of Clinical Trials and Epidemiological Research for providing statistical support for the study, Mr. Chan Joseph Fat Yiu for performing the hs-CRP assay, and Miss Law Man Ching and Miss Wong Esther for collecting data for this study.

  • © 2003 American Society of Nephrology

References

  1. ↵
    Ridker PM, Glynn RJ, Hennekens CH: C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97: 2007–2011, 1998
    OpenUrlAbstract/FREE Full Text
  2. ↵
    Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH: Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation 97: 425–428, 1998
    OpenUrlAbstract/FREE Full Text
  3. ↵
    Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH: Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98: 731–733, 1998
    OpenUrlAbstract/FREE Full Text
  4. ↵
    Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A: The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 331: 417–424, 1994
    OpenUrlCrossRefPubMed
  5. ↵
    Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB: Production of C-reactive protein and risk of coronary events in stable and unstable angina. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Lancet 349: 462–466, 1997
    OpenUrlCrossRefPubMed
  6. ↵
    Morrow DA, Rifai N, Antman EM, Weiner DL, McCabe CH, Cannon CP, Braunwald E: C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes. A TIMI 11A substudy. Thrombolysis in Myocardial Infarction. J Am Coll Cardiol 31: 1460–1465, 1998
    OpenUrlCrossRefPubMed
  7. ↵
    Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C: Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 55: 1956–1960, 1999
    OpenUrl
  8. ↵
    Yeun JY, Levine RA, Mantadilok V, Kaysen GA: C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 35: 469–476, 2000
    OpenUrlPubMed
  9. ↵
    Docci D, Bilancioni R, Buscaroli A, Baldrati L, Capponcini C, Mengozzi S, Turci F, Feletti C: Elevated serum levels of C-reactive protein in hemodialysis patients. Nephron 56: 364–367, 1990
    OpenUrlPubMed
  10. ↵
    Ortega O, Rodriguez I, Gallar P, Carreno A, Ortiz M, Espejo B, Jimenez J, Gutierrez M, Oliet A, Vigil A: Significance of high C-reactive protein levels in pre-dialysis patients. Nephrol Dial Transplant 17: 1105–1109, 2002
    OpenUrlCrossRefPubMed
  11. ↵
    Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T: Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 55: 1899–1911, 1999
    OpenUrlCrossRefPubMed
  12. ↵
    Wanner C, Zimmermann, Susanne Schwedler, Metzger T: Inflammation and cardiovascular risk in dialysis patients. Kidney Int 61: S99–S102, 2002
    OpenUrlPubMed
  13. ↵
    Owen WF, Lowrie EG: C-reactive protein as an outcome predictor for maintenance hemodialysis patients. Kidney Int 54: 627–636, 1998
    OpenUrlCrossRefPubMed
  14. ↵
    Noh H, Lee SW, Kang SW: Serum C-reactive protein: A predictor of mortality in continuous ambulatory peritoneal dialysis patients. Perit Dial Int 18: 387–394, 1998
    OpenUrlAbstract/FREE Full Text
  15. ↵
    Herzig KA, Purdie DM, Chang W, Brown AM, Hawley CM, Campbell SB, Sturtevant JM, Isbel NM, Nicol DL, Johnson DW: Is C-reactive protein a useful predictor of outcome in peritoneal dialysis patients? J Am Soc Nephrol 12: 814–821, 2001
    OpenUrlAbstract/FREE Full Text
  16. ↵
    Fine A: Relevance of C-reactive protein levels in peritoneal dialysis patients. Kidney Int 61: 615–620, 2002
    OpenUrlCrossRefPubMed
  17. ↵
    Haubitz M, Brunkhorst R, Wrenger E, Froese P, Schulze M, Koch KM: Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal dialysis therapy. Perit Dial Int 16: 158–162, 1996
    OpenUrlAbstract/FREE Full Text
  18. ↵
    Sahn DJ, De Maria A, Kisslo J, Weyman A: Committee on M-mode standardization of the American Society of Echocardiography. Recommendations regarding quantification in M-mode echocardiography: Results of a survey of echocardiographic measurements. Circulation 58: 1072–1083, 1978
    OpenUrlAbstract/FREE Full Text
  19. ↵
    Schiller NB, Shah PM, Crawford M, et al: Recommendations for quantification of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 2: 358–367, 1989
    OpenUrlCrossRefPubMed
  20. ↵
    Krumholz HM, Larson M, Levy D: Prognosis of left ventricular geometric patterns in the Framingham heart study. J Am Coll Cardiol 25: 879–884, 1995
    OpenUrlCrossRefPubMed
  21. ↵
    Young GA, Kopple JD, Lindholm B, et al: Nutritional assessment of continuous ambulatory peritoneal dialysis patients: An international study. Am J Kidney Dis 17: 462–471, 1991
    OpenUrlPubMed
  22. ↵
    Enia G, Sicuso C, Alati G, Zoccali C: Subjective global assessment of nutrition in dialysis patients. Nephrol Dial Transplant 8: 1094–1098, 1993
    OpenUrlPubMed
  23. ↵
    Woo J, Leung SSF, Ho SC, Lam TH, Janus ED: A food frequency questionnaire for use in the Chinese population in Hong Kong: Description and examination of validity. Nutr Res 17: 1633–1641, 1997
    OpenUrlCrossRef
  24. ↵
    Nolph KD, Moore HL, Twardowski ZJ, Khanna R, Prowant B, Meyer M, Ponferrada L: Cross-sectional assessment of weekly urea and creatinine clearances in patients on continuous ambulatory peritoneal dialysis. ASAIO J 38: M139–M142, 1992
    OpenUrlCrossRefPubMed
  25. ↵
    Van Olden RW, Krediet RT, Struijk DG, Arisz L: Measurement of residual renal function in patients treated with continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 7: 745–748, 1996
    OpenUrlAbstract
  26. ↵
    Mak TW, Cheung CK, Cheung CM, Leung CB, Lam CW, Lai KN: Interference of creatinine measurement in CAPD fluid was dependent on glucose and creatinine concentrations. Nephrol Dial Transplant 12: 184–186, 1997
    OpenUrlCrossRefPubMed
  27. ↵
    Watson PE, Watson ID, Batt RD: Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr 33: 27–39, 1980
    OpenUrlAbstract/FREE Full Text
  28. ↵
    Twardowski ZJ, Noplh KD, Khanna R: Peritoneal equilibration test. Perit Dial Bull 7: 138–147, 1987
    OpenUrl
  29. ↵
    Engelstein ED, Zipes DP: Sudden cardiac death. In: The Heart, Arteries and Veins,edited by Alexander RW, Schlant RC, Fuster V, New York, McGraw-Hill, 1998, pp 1081–111
  30. ↵
    Myerburg RJ, Castellanos A: Cardiac arrest and sudden death. In: Heart Disease: A Textbook of Cardiovascular Medicine,edited by Braunwald E, Philadelphia, WB Saunders, 742–779, 1997
  31. ↵
    Parmar MKB, Machin D: Survival Analysis: A Practical Approach, New York, John Wiley & Sons, 1995
  32. ↵
    Stenvinkel P, Wanner C, Metzger T, Heimburger O, Mallamaci F, Tripepi G, Malatino L, Zoccali C: Inflammation and outcome in end-stage renal failure: Does female gender constitute a survival advantage? Kidney Int 62: 1791–1798, 2002
    OpenUrlCrossRefPubMed
  33. ↵
    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 336: 973–979, 1997
    OpenUrlCrossRefPubMed
  34. ↵
    Ducloux D, Bresson-Vautrin C, Kribs M, Abdelfatah A, Chalopin JM: C-reactive protein and cardiovascular disease in peritoneal dialysis patients. Kidney Int 62: 1417–1422, 2002
    OpenUrlCrossRefPubMed
  35. ↵
    Kaysen GA, Dubin JA, Muller HG, Rosales LM, Levin NW: The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO study group. Kidney Int 58: 346–352, 2000
    OpenUrlCrossRefPubMed
  36. ↵
    Macy EM, Hayes TE, Tracy RP: Variability in the measurement of C-reactive protein in healthy subjects: Implications for reference intervals and epidemiological applications. Clin Chem 43: 52–58, 1997
    OpenUrlAbstract/FREE Full Text
  37. ↵
    Kim SB, Min WK, Lee SK, Park JS, Hong CD, Yang WS: Persistent elevation of C-reactive protein and ischemic heart disease in patients with continuous ambulatory peritoneal dialysis. Am J Kidney Dis 39: 342–346, 2002
    OpenUrlPubMed
  38. ↵
    Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, Poole-Wilson PA, Coats AJ, Anker SD: Endotoxin and immune activation in chronic heart failure: A prospective cohort study. Lancet 353: 1838–1842, 1999
    OpenUrlCrossRefPubMed
  39. ↵
    Jones CH, Smye SW, Newstead CG, Will EJ, Davison AM: Extracellular fluid volume determined by bio-electric impedance and serum albumin in CAPD patients. Nephrol Dial Transplant 13: 393–397, 1998
  40. ↵
    Amann K, Mandelbaum A, Schwarz U, Ritz E: Hypertension and left ventricular hypertrophy in the CAPD patient. Kidney Int 50: S37–S40, 1996
    OpenUrl
  41. ↵
    Huting J, Alpert MA: Progression of left ventricular hypertrophy in end-stage renal disease treated by continuous ambulatory peritoneal dialysis depends on hypertension and hypercirculation. Clin Cardiol 15: 190–196, 1992
    OpenUrlPubMed
  42. ↵
    Jones CH, Wells L, Stoves J, Farquhar F, Woodrow G: Can a reduction of extracellular fluid volume result in increased serum albumin in peritoneal dialysis patients? Am J Kidney Dis 39: 872–875, 2002
    OpenUrlCrossRefPubMed
  43. ↵
    Owen WF Jr, Lew NL, Liu Y, Lowrie EG, Lazarus JM: The urea reduction ratio and serum albumin concentration as predictors of mortality in patients undergoing hemodialysis. N Engl J Med 329: 1001–1006, 1993
    OpenUrlCrossRefPubMed
  44. ↵
    Koch M, Kutkuhn B, Grabensee B, Ritz E: Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialyzed diabetic patients: A prospective study in 412 subjects. Nephrol Dial Transplant 12: 2603–2611, 1997
    OpenUrlCrossRefPubMed
  45. ↵
    Koch M, Kutkuhn B, Trenkwalder E, Bach D, Grabensee B, Dieplinger H, Kronenberg F: Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein (a) phenotypes predict coronary artery disease in hemodialysis patients. J Am Soc Nephrol 8: 1889–1898, 1997
    OpenUrlAbstract
  46. ↵
    Tomura S, Nakamura Y, Doi M, Ando R, Ida T, Chida Y, Ootsuka S, Shinoda T, Yanagi H, Tsuchiya S, Marumo F: Fibrinogen, coagulation factor VII, tissue plasminogen activator, plasminogen activator inhibitor-1, and lipid as cardiovascular risk factors in chronic hemodialysis and continuous ambulatory peritoneal dialysis patients. Am J Kidney Dis 27: 848–854, 1996
    OpenUrlPubMed
  47. ↵
    Chung SH, Heimburger O, Stenvinkel P, Bergstrom J, Lindholm B: Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis. Nephrol Dial Transplant 16: 2240–2245, 2001
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 14 (7)
Journal of the American Society of Nephrology
Vol. 14, Issue 7
1 Jul 2003
  • Table of Contents
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?
Angela Yee-Moon Wang, Jean Woo, Christopher Wai-Kei Lam, Mei Wang, Mandy Man-Mei Sea, Siu-Fai Lui, Philip Kam-Tao Li, John Sanderson
JASN Jul 2003, 14 (7) 1871-1879; DOI: 10.1097/01.ASN.0000070071.57901.B3

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Is a Single Time Point C-Reactive Protein Predictive of Outcome in Peritoneal Dialysis Patients?
Angela Yee-Moon Wang, Jean Woo, Christopher Wai-Kei Lam, Mei Wang, Mandy Man-Mei Sea, Siu-Fai Lui, Philip Kam-Tao Li, John Sanderson
JASN Jul 2003, 14 (7) 1871-1879; DOI: 10.1097/01.ASN.0000070071.57901.B3
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Survival among Patients with Kidney Failure in Jalisco, Mexico
  • A Population-Based, Prospective Study of Blood Pressure and Risk for End-Stage Renal Disease in China
  • Hepatitis C Virus and Death Risk in Hemodialysis Patients
Show more Epidemiology and Outcomes

Cited By...

  • The 24-Month Changes in Body Fat Mass and Adipokines in Patients Starting Peritoneal Dialysis
  • ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I - Assessment and Management of Various Cardiovascular Risk Factors
  • Heart Failure in Long-Term Peritoneal Dialysis Patients: A 4-Year Prospective Analysis
  • Peritoneal Albumin and Protein Losses Do Not Predict Outcome in Peritoneal Dialysis Patients
  • CHANGES IN BODY FAT MASS IN PATIENTS AFTER STARTING PERITONEAL DIALYSIS
  • Residual Renal Function in Peritoneal Dialysis After Renal Transplant Failure
  • Is Valvular Calcification a Part of the Missing Link between Residual Kidney Function and Cardiac Hypertrophy in Peritoneal Dialysis Patients?
  • CARDIOVASCULAR RISK FACTORS IN PERITONEAL DIALYSIS PATIENTS REVISITED
  • CONTROLLING INFLAMMATION IN PERITONEAL DIALYSIS: THE ROLE OF PD-RELATED FACTORS AS POTENTIAL INTERVENTION TARGETS
  • THE "HEART" OF PERITONEAL DIALYSIS
  • Prognostic Value of Cardiac Troponin T Is Independent of Inflammation, Residual Renal Function, and Cardiac Hypertrophy and Dysfunction in Peritoneal Dialysis Patients
  • Inflammatory Syndrome in Patients on Hemodialysis
  • Evaluation of handgrip strength as a nutritional marker and prognostic indicator in peritoneal dialysis patients
  • Resting Energy Expenditure and Subsequent Mortality Risk in Peritoneal Dialysis Patients
  • Inflammation, Residual Kidney Function, and Cardiac Hypertrophy Are Interrelated and Combine Adversely to Enhance Mortality and Cardiovascular Death Risk of Peritoneal Dialysis Patients
  • Google Scholar

Similar Articles

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals
  • Wolters Kluwer Partnership

© 2022 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire