Kwok-Yi Chung

Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients.

BACKGROUND AND OBJECTIVES Systemic inflammatory state is a hallmark of peritoneal dialysis (PD) patients, but its etiology remains obscure. Because circulating microbial products are an important cause of systemic immune activation in other conditions such as HIV infection, it was hypothesized that endotoxemia is a cause of systemic inflammatory state and atherosclerosis in PD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Plasma lipopolysaccharide (LPS) levels in 30 consecutive new PD patients were measured. The result was compared with serum C-reactive protein (CRP) level, peritoneal transport status, history of pre-existing cardiovascular diseases, and carotid intima media thickness (IMT) by Doppler ultrasound. RESULTS Among the 30 PD patients, there were 17 men. The average age was 53.7 +/- 15.1 yr. The average endotoxin concentration of PD patients was 0.44 +/- 0.18 EU/ml, which was significantly higher than that of patients with chronic kidney disease secondary to Ig-A nephropathy (IgAN) (0.035 +/- 0.009 EU/ml, P < 0.0001) and the controls (0.013 +/- 0.007 EU/ml, P < 0.0001). In PD patients, plasma LPS concentration had a significant correlation with serum CRP (r = 0.415, P = 0.025) and serum albumin level (r = -0.394, P = 0.034). In contrast, plasma LPS level did not correlate with Charlsons Comorbidity Index, peritoneal transport characteristics, or nutritional indices. Patients with pre-existing cardiovascular disease (CVD) had higher plasma LPS level than those without CVD (0.53 +/- 0.19 versus 0.36 +/- 0.16 EU/ml, P = 0.016). Plasma LPS level correlated with carotid IMT (r = 0.438, P = 0.016). CONCLUSIONS It was found that endotoxemia was probably common in PD patients, and the degree of circulating endotoxemia might be related to the severity of systemic inflammation and features of atherosclerosis. This result suggests that endotoxemia may have a contributory role to the systemic inflammatory state and accelerated atherosclerosis in PD patients.

Oral Calcitriol for the Treatment of Persistent Proteinuria in Immunoglobulin A Nephropathy: An Uncontrolled Trial

BACKGROUND Laboratory research and previous retrospective study suggest that vitamin D and its analogues have profound effects on immune system function and glomerular mesangial cell proliferation. We conducted an open-label study to evaluate the antiproteinuric effect of calcitriol on proteinuria in patients with immunoglobulin A (IgA) nephropathy. STUDY DESIGN Open-label prospective uncontrolled trial. SETTING & PARTICIPANTS 10 patients (3 men) with biopsy-proven IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy in a tertiary referral center. INTERVENTION Calcitriol, 0.5 microg, twice weekly for 12 weeks. OUTCOME MEASURES Changes in proteinuria, renal function, serum transforming growth factor beta (TGF-beta) and angiotensin II levels. RESULTS After calcitriol treatment, there was a significant overall decrease in proteinuria with time by using a general linear model with repeated measures (P = 0.03). There was a progressive decrease in urine protein-creatinine ratio from 1.98 +/- 0.74 to 1.48 +/- 0.81 g/g (P = 0.007) during the first 6 weeks that persisted throughout the study period. No significant change in blood pressure or renal function was noted. There was a simultaneous decrease in serum TGF-beta level, and percentage of decrease in serum TGF-beta level significantly correlated with percentage of change in proteinuria (Spearman r = 0.643; P = 0.02). Serum angiotensin II level did not change throughout the study. One patient experienced transient hypercalcemia that normalized after a dosage decrease. No other major adverse effect was reported. LIMITATIONS This small study is uncontrolled and does not examine the long-term effect of calcitriol therapy. CONCLUSION Twice-weekly oral calcitriol has a modest antiproteinuric effect in patients with IgA nephropathy and persistent proteinuria despite angiotensin-converting enzyme-inhibitor or angiotensin receptor blocker therapy. Additional studies are needed to confirm the renal protecting effect of calcitriol in patients with chronic proteinuric kidney diseases.

Staphylococcus aureus Peritonitis Complicates Peritoneal Dialysis: Review of 245 Consecutive Cases

Peritonitis that is caused by Staphylococcus aureus is a serious complication in peritoneal dialysis (PD), but the clinical course of PD-related S. aureus peritonitis remains unclear. All of the S. aureus peritonitis in a dialysis unit from 1994 to 2005 were reviewed. During this period, 2065 episodes of peritonitis were recorded; 245 (11.9%) episodes in 152 patients were caused by S. aureus and 45 (18.4%) episodes were caused by methicillin-resistant S. aureus (MRSA). Patients with a history of recent hospitalization had a higher risk for isolation of MRSA than the others (30.6 versus 14.2%; P = 0.004). The overall primary response rate was 87.8%; the complete cure rate was 74.3%. However, 21 (8.6%) episodes developed relapse and 59 (24.1%) developed repeat S. aureus peritonitis. Episodes that were caused by MRSA had a lower primary response rate (64.4 versus 93.0%; P < 0.001) and complete cure rate (60.0 versus 77.5%; P = 0.023) than the others. Episodes that were treated initially with vancomycin had better primary response rate than those that were treated with cefazolin (98.0 versus 85.2%; P = 0.001), but the complete cure rate was similar. Adjuvant rifampicin treatment was associated with a significantly lower risk for relapse or repeat S. aureus peritonitis than was treatment without rifampicin (21.4 versus 42.8%; P = 0.004). In contrast, initial antibiotic regimen (cefazolin versus vancomycin) and concomitant exit-site infection did not have any effect on the risk for relapse or repeat peritonitis. S. aureus peritonitis is a serious complication of PD. Recent hospitalization is a major risk factor of methicillin resistance in the bacterial isolate. Rifampicin is a valuable adjunct in preventing relapse and repeat S. aureus peritonitis after the index episode.

Coagulase Negative Staphylococcal Peritonitis in Peritoneal Dialysis Patients: Review of 232 Consecutive Cases

BACKGROUND AND OBJECTIVES Coagulase-negative Staphylococcus species is the most common cause of peritoneal dialysis-related peritonitis; however, the optimal treatment strategy of coagulase-negative Staphylococcus species peritonitis remains controversial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All of the coagulase-negative Staphylococcus species peritonitis in a dialysis unit from 1995 to 2006 were reviewed. During this period, there were 2037 episodes of peritonitis recorded; 232 episodes (11.4%) in 155 patients were caused by coagulase-negative Staphylococcus species. RESULTS The overall primary response rate was 95.3%; the complete cure rate was 71.1%. Patients with a history of recent hospitalization or recent antibiotic therapy had a higher risk for developing methicillin-resistant strains. Episodes that were treated initially with cefazolin or vancomycin had similar primary response rate and complete cure rate. There were 33 (14.2%) episodes of relapse and 29 (12.5%) episodes of repeat peritonitis; 12 (60.6%) of the repeat episodes developed within 3 mo after completion of antibiotics. Relapse or repeat episodes had a significantly lower complete cure rate than the other episodes. For relapse or repeat episodes, treatment with effective antibiotics for 3 wk was associated with a significantly higher complete cure rate than the conventional 2-wk treatment. CONCLUSIONS Coagulase-negative Staphylococcus species peritonitis remains a common complication of peritoneal dialysis. Methicillin resistance is common, but the treatment outcome remains favorable when cefazolin is used as the first-line antibiotic. A 3-wk course of antibiotic can probably achieve a higher cure rate in relapse or repeat episodes.

Recurrent and relapsing peritonitis: causative organisms and response to treatment.

BACKGROUND The clinical behavior and optimal treatment of relapsing and recurrent peritonitis episodes in patients undergoing long-term peritoneal dialysis are poorly understood. STUDY DESIGN Retrospective study over 14 years. SETTING & PARTICIPANTS University dialysis unit; 157 relapsing episodes (same organism or culture-negative episode occurring within 4 weeks of completion of therapy for a prior episode), 125 recurrent episodes (different organism, occurs within 4 weeks of completion of therapy for a prior episode), and 764 control episodes (first peritonitis episode without relapse or recurrence). PREDICTORS Exit-site infection, empirical antibiotics. OUTCOME MEASURES Primary response (resolution of abdominal pain, clearing of dialysate, and peritoneal dialysis effluent neutrophil count < 100 cells/mL after 10 days of antibiotic therapy), complete cure (resolution by using antibiotics without relapse/recurrence), catheter removal (for any cause while on antibiotic therapy), and mortality. RESULTS Compared with the control group, more relapsing episodes were caused by Pseudomonas species (16.6% versus 9.4%) and were culture negative (29.9% versus 16.4%); recurrent infections commonly were caused by Enterococcus species (3.2% versus 1.2%) or other Gram-negative organisms (27.2% versus 11.1%) or had mixed bacterial growth (17.6% versus 12.7%). There were significant differences in primary response, complete cure, and mortality rates among groups (P < 0.001 for all comparisons). Compared with the control and relapsing groups, post hoc analysis showed that the recurrent group had a significantly lower primary response rate (86.4%, 88.5%, and 71.2%, respectively), lower complete cure rate (72.3%, 62.4%, and 42.4%, respectively), and higher mortality rate (7.7%, 7.0%, and 20.8%, respectively). LIMITATIONS Retrospective analysis. CONCLUSION Relapsing and recurrent peritonitis episodes are caused by different spectra of bacteria and probably represent 2 distinct clinical entities. Recurrent peritonitis episodes had a worse prognosis than relapsing ones.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients

Background:  Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial.

Endotoxemia is Associated with Better Clinical Outcome in Incident Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study

♦ Background: Endotoxemia is common in peritoneal dialysis (PD) patients; circulating lipopolysaccharide (LPS) level is related to the degree of systemic inflammation and atherosclerosis. We examine whether baseline plasma LPS level represents a prognostic marker in new PD patients. ♦ Methods: We studied 158 new Chinese PD patients (80 males). Baseline plasma LPS level at initiation of PD was measured. Patients were stratified into quartiles according to plasma LPS level: quartile I, <0.45 EU/mL; II, 0.45 – <0.70 EU/mL; III, 0.70 – <0.95 EU/mL; and IV, ≥0.95 EU/mL. The patients were then prospectively followed for the development of cardiovascular events. All-cause mortality and duration of hospitalization were also recorded. ♦ Results: Average age was 55.6 ± 14.7 years; average endotoxin concentration was 0.70 ± 0.30 EU/mL; average follow-up was 55.5 ± 36.9 months. At 60 months, event-free survival was 41.0%, 52.5%, 65.0%, and 61.5% for LPS level quartiles I, II, III, and IV, respectively (log rank test p = 0.066). By multivariate analysis with the Cox proportional hazard model to adjust for confounders, plasma LPS level had no independent effect. At 60 months, technique survival was 20.5%, 20.0%, 32.5%, and 51.3% for LPS level quartiles I, II, III, and IV, respectively (log rank test p = 0.0009). By Cox proportional hazard model, each higher quartile of LPS conferred 28.6% protection (95% confidence interval 15.6% – 40.3%, p = 0.0002) from developing technique failure. A higher plasma LPS level had a lower all-cause mortality (unadjusted hazard ratio 0.486, p = 0.046) and cardiovascular mortality (unadjusted hazard ratio 0.251, p = 0.025), but the result became insignificant after adjusting for potential confounders. ♦ Conclusion: A higher baseline plasma LPS level is an independent predictor of better technique survival in new Chinese PD patients, with an insignificant trend of fewer cardiovascular events. The observation seems to conform to the phenomenon of reverse epidemiology for other traditional cardiovascular risk factors in dialysis patients but the exact reason for this paradoxical phenomenon requires further investigation.

Longitudinal Changes of Cardiothoracic Ratio and Vascular Pedicle Width as Predictors of Volume Status during One Year in Chinese Peritoneal Dialysis Patients

Background: Volume overload is an important contributing factor of cardiovascular disease (CVD) in peritoneal dialysis (PD) patients. Vascular pedicle width (VPW) and cardiothoracic ratio (CTR) in routine chest radiograph are indicators of intravascular volume. Longitudinal changes of VPW and CTR may be important prognostic factors of PD patients. Method: We studied 212 PD patients. Longitudinal changes in VPW (ΔVPW) and CTR (ΔCTR) were calculated. The relationship between radiologic measurements and clinical outcome was analyzed. Results: During the 12 months prior to enrollment, VPW rose from 53.35 ± 5.66 to 55.40 ± 6.30 mm (p < 0.001) and CTR rose from 53.3 ± 7.1 to 56.0 ± 7.8% (p < 0.001). After adjusting for confounding variables by Cox regression model, ΔCTR is an independent predictor of hospitalization-free survival; 1% increase in CTR confers 2.9% higher risk of hospitalization (95% confidence interval 0.2–5.7%, p = 0.034). None of the radiologic measurements correlated with actuarial patient survival. Conclusions: In chronic PD patients, ΔCTR is an independent predictor of hospitalization-free survival. This simple radiological parameter may serve as an important parameter for the risk stratification of PD patients.

ARTERIAL PULSE WAVE VELOCITY AND PERITONEAL TRANSPORT CHARACTERISTICS INDEPENDENTLY PREDICT HOSPITALIZATION IN CHINESE PERITONEAL DIALYSIS PATIENTS

♦ Objective: Cardiovascular disease (CVD) is the most common cause of mortality in chronic peritoneal dialysis (PD) patients. Increased arterial stiffness may be related to a high peritoneal permeability resulting in fluid overload in PD patients. We studied the relations between arterial stiffness, peritoneal transport, and radiographic parameters of systemic fluid overload in a cohort of Chinese PD patients. ♦ Design: Prospective cohort study. ♦ Setting: University referral center. ♦ Patients: We studied 107 PD patients. Vascular pedicle width and cardiothoracic ratio were measured from a plain postero-anterior chest radiograph. Pulse wave velocity (PWV) was determined at carotid–femoral (C-F) and carotid–radial sites. Peritoneal transport was determined by the dialysate-to-plasma ratio (D/P) of creatinine at 4 hours of dwell. Patients were followed for 9.4 ± 4.6 months. ♦ Outcome Measures: Duration of hospitalization; actuarial and technique survival. ♦ Results: There were no relationships between radiographic measures, arterial PWV, and D/P creatinine. However, both C-F PWV and D/P creatinine were independent predictors of the number of hospitalizations for CVD. None of the parameters correlated with mortality in this study. ♦ Conclusions: There were no relationships between radiological parameters of fluid overload, peritoneal transport characteristics, and arterial PWV. Both C-F PWV and D/P creatinine were independent predictors of the number of hospitalizations for CVD. Our result suggests that arterial stiffness and high peritoneal transport each contribute to the development of CVD in this group of patients.

The relationship between bone morphogenic protein-7 and peritoneal transport characteristics

BACKGROUND After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. METHODS We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. RESULTS At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study.