Sadie van Esch

32 Years’ Experience of Peritoneal Dialysis-Related Peritonitis in a University Hospital

♦ Background: Peritonitis in peritoneal dialysis (PD) patients can lead to technique failure and contributes to infection-related mortality. Peritonitis prevention and optimization of treatment are therefore important in the care for PD patients. In the present study, we analyzed the incidence of peritonitis, causative pathogens, clinical outcomes, and trends in relation to three major treatment changes that occurred from 1979 onward: use of a disconnect system since 1988, daily mupirocin at the exit-site since 2001, and exclusive use of biocompatible dialysis solutions since 2004. ♦ Methods: In this analysis of prospectively collected data, we included peritonitis episodes from the start of PD at our center in August 1979 to July 2010. Incident PD patients were allocated to one of four groups: Group 1 - 182 patients experiencing 148 first peritonitis episodes between 1979 and 1987, before the introduction of the disconnect system; Group 2 - 352 patients experiencing 239 first episodes of peritonitis between 1988 and 2000, before implementation of daily mupirocin application at the catheter exit-site; Group 3 - 79 patients experiencing 50 first peritonitis episodes between 2001 and 2003, before the switch to biocompatible solutions; and Group 4-118 patients experiencing 91 first peritonitis episodes after 2004. Cephradine was used as initial antibiotic treatment. ♦ Results: In 32 years, 731 adult patients started PD, and 2234 episodes of peritonitis in total were diagnosed and treated. Of those episodes, 88% were cured with medical treatment only, and 10% resulted in catheter removal. In 3% of the episodes, the patient died during peritonitis. Median time to a first peritonitis episode increased from 40 days for group 1 to 150 for group 2, 269 for group 3, and 274 for group 4. The overall peritonitis rate and the gram-positive and gram-negative peritonitis rates showed a time-trend of decline. However, the duration of antibiotic treatment increased over time, with groups 3 and 4 having the longest duration of treatment, accompanied by a higher percentage of antibiotic switch. Increased resistance to cephradine was found for coagulase-negative Staphylococcus. ♦ Conclusions: Peritonitis rates declined significantly over the years because of several changes in PD treatment. However, the need to change the initial antibiotic increased because of diminished antibiotic susceptibility rates over time. Nevertheless, the cure rate was high and remained stable during the entire period analyzed, and the death rate remained low. Consequently, peritonitis is a manageable complication of PD that cannot be considered a contraindication to this mode of renal replacement therapy.

ISPD Catheter-Related Infection Recommendations: 2017 Update

Department of Medicine and Therapeutics,1 Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Department of Nephrology,2 University of Queensland at Princess Alexandra Hospital, Brisbane, Australia; Renal Electrolyte Division,3 University of Pittsburgh School of Medicine Pittsburgh, PA, USA; Renal Division,4 Department of Medicine, Peking University First Hospital, Beijing, China; Pontifícia Universidade Católica do Rio Grande do Sul,5 FAENFI, Porto Alegre, Brazil; Division of Nephrology,6 Nagoya University Graduate School of Medicine, Nagoya, Japan; Division of Nephrology,7 Bezmialem Vakif University, Medical Faculty, Istanbul, Turkey; Pontifícia Universidade Católica do Paraná,8 Curitiba, Brazil; Elisabeth Tweesteden Hospital,9 Nephrology Department and Internal Medicine, Tilburg, Netherlands; and Imperial College Renal and Transplant Centre,10 Hammersmith Hospital, London, UK ISPD GUIDELINES/RECOMMENDATIONS

Prognostic Factors for Peritonitis Outcome

Despite advances in treatment and prevention, peritonitis remains a major problem in peritoneal dialysis (PD) patients with often technique failure as a consequence. The last decades the focus of PD peritonitis has changed from lowering peritonitis incidence to improvement of peritonitis outcome. Prognostic factors for peritonitis outcome can influence decision making during the treatment of peritonitis, for example to take out the PD catheter early in the time course of peritonitis and prevent further damage to the peritoneal membrane. In this paper, we give a review of the literature about prognostic factors for peritonitis outcome. In most studies, age, gender, diabetes, time on PD, a precursor of calcitonin:procalcitonin, IL-6 and albumin did not show a significant effect on peritonitis outcome. The following factors have been associated with poor outcome of peritonitis: Gram-negative organisms, Mycobacterium species, fungal peritonitis, polymicrobial peritonitis, concurrent exit site or tunnel infection, Caucasian race, low residual GFR, persistently elevated peritoneal dialysate white cell count, CRP, and low levels of slCAM-1 and hyaluronan at the end of peritonitis treatment. In fungal peritonitis, abdominal pain, bowel obstruction, the catheter remaining in situ and Candidaparapsilosis are factors associated with higher mortality rate and a greater risk of technique failure. Recent antibiotic therapy and peritonitis are associated with poor treatment response in culture-negative peritonitis. Recurrent peritonitis episodes have a poor therapeutic response and high mortality and have a worse prognosis than relapsing ones. Older age, long PD duration and continuous elevated serum CRP levels are predictors of adverse outcomes in PD patients after peritonitis-related catheter removal. Peritonitis remains a serious complication of PD with marked morbidity. It is a common cause of technique failure. The rate of PD-related peritonitis has decreased over the last decades due to advances in treatment and prevention. Nowadays, the focus moved from lowering peritonitis incidence towards improving peritonitis outcome. It is useful to have prognostic factors for peritonitis outcome, because they can influence decision-making during the treatment of peritonitis, for example to take out the PD catheter early in the time course of peritonitis and prevent further damage to the peritoneal membrane. In the last decades, many publications appeared about prognostic factors for peritonitis outcome. This article summarizes those prognostic factors, based on an extensive review of the literature.

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

♦ Objective: Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection. ♦ Participants: We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared. ♦ Main outcome measurements: SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes. ♦ Results: Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04. ♦ Conclusions: The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state.

The Mutual Relationship Between Peritonitis and Peritoneal Transport

♦ Background: Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Methods: Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ Results: At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Conclusions: Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.

THE NATURAL TIME COURSE OF MEMBRANE ALTERATIONS DURING PERITONEAL DIALYSIS IS PARTLY ALTERED BY PERITONITIS

♦ Background: The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis—representing the natural course—and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ Methods: This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990–2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis (“no-peritonitis group”) were compared with the results obtained in patients who experienced 1 or more peritonitis episodes (“peritonitis group”) during a follow-up of 4 years. ♦ Results: The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ Conclusions: On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport—especially the transport of solute-free water. Those modifications increase the risk for overhydration.

The Association Between Glucose Exposure and the Risk of Peritonitis in Peritoneal Dialysis Patients.

♦ Background and objective: Little or no clinical evidence is available on the association between glucose exposure and peritoneal host defense in peritoneal dialysis (PD) patients. The objective of the present study was to quantify the exposure to glucose during the first year on PD and investigate the association with subsequent peritonitis. ♦ Methods: We analyzed prospectively collected demographic and peritonitis data from incident adult PD patients between 1990 and 2010. For the present study, we conducted a review of both in- and outpatient medical records of all patients to obtain their day-to-day dialysis schemes during the first year on PD. From these data, the average exposure to glucose was quantified. The exposure was stratified into low- and high-glucose groups based on the median, analyzed per standard deviation and in quartiles. Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HRs) and 95% confidence intervals for the association between glucose exposure and peritonitis. Adjustments were made for age, sex, primary kidney disease, diabetes mellitus, Davies comorbidity score and the treatment period. ♦ Results: In total, 230 patients were included in the study of whom 151 (66%) experienced a first peritonitis episode. The median follow-up time was 2.6 years (interquartile range [IQR]: 1.9 – 3.8) in the low-glucose group and 3.1 (IQR: 2.1 – 4.2) in the high-glucose group. After adjustment for confounding factors, no association between high glucose exposure and the risk of peritonitis was found (HR: 0.81; 0.55 – 1.17). No association was present when glucose exposure was analyzed per standard deviation (SD) (HR: 0.98; 0.79 – 1.21) or patient quartiles were applied. No association was identified between glucose exposure and severe peritonitis, Staphylococcus aureus peritonitis, or a peritonitis episode that lasted more than 14 days. ♦ Conclusions: Exposure to glucose is not associated with an increased risk of peritonitis. The equilibrium between glycemic harm to peritoneal host defense and detrimental effects of glucose on invading microorganisms may determine the susceptibility to peritoneal infection.