All patients included in this study were enrolled in the Clinical Research Center (CRC) registry for ESRD, which is an ongoing observational prospective cohort study of patients with ESRD from 31 medical centers in Korea. The cohort was initiated in April 2009 and ended in April 2015. The cohort included adult (> 18 years of age) dialysis patients. A total of 598 patients incidentally undergoing PD were enrolled in this cohort. Patients with incomplete follow-up data or other missing values were excluded from this study. Finally, a total of 583 patients were enrolled.

Because our aim was to evaluate the impact of IRH on clinical outcomes after initiation of PD with a long-term follow-up period, we restricted the IRH group to PD patients who had been hospitalized for infection-related diseases within one year of the initiation of PD. IRHs were defined as an admission with an infection as a primary diagnosis according to the CRC for ESRD study classification system.

Demographic and clinical data were collected at the time of study enrollment. Dialysis characteristic were assessed and measurements were performed every six months until follow-up was completed. Dates and causes of death were reported throughout the follow-up period.

This study was approved by the Institutional Review Boards at each of the following centers (in alphabetical order): The Catholic University of Korea, Bucheon St. Mary’s Hospital; The Catholic University of Korea, Incheon St. Mary’s Hospital; the Catholic University of Korea, Seoul St. Mary’s Hospital; the Catholic University of Korea, Yeouido St. Mary’s Hospital; The Catholic University of Korea, St. Vincent’s Hospital; The Catholic University of Korea, Uijeongbu St. Mary’s Hospital; Cheju Halla General Hospital; Jeonbuk National University Hospital; Chonnam National University Hospital; Chung-Ang University Hospital; Chungbuk National University Hospital; Chungnam National University Hospital; Dong-A University Medical Center; Ehwa Womans University Medical Center; Fatima Hospital, Daegu; Gachon University Gil Medical Center; Inje University Busan Paik Hospital; Kyungpook National University Hospital; Kwandong University College of Medicine, Myongji Hospital; National Health Insurance Corporation Ilsan Hospital; National Medical Center; Pusan National University Hospital; Samsung Medical Center, Seoul; SMG-SNU Boramae Medical Center; Seoul National University Hospital; Seoul National University Bundang Hospital; Yeungnam University Medical Center; Yonsei University, Severance Hospital; Yonsei University, Gangnam Severance Hospital; Ulsan University Hospital; and Wonju Severance Christian Hospital. The study was performed in accordance with the tenets of the Declaration of Helsinki and written informed consent was collected from all patients before study inclusion.

In the CRC registry for ESRD, baseline demographic and clinical data including age, sex, body mass index (BMI), primary causes of ESRD, comorbidities, including cardiovascular disease with complications and diabetes mellitus (DM), laboratory values, and death rate were recorded. Cardiovascular disease was defined as the presence of coronary artery disease, congestive heart failure, peripheral vascular disease, cerebrovascular disease, or atrial fibrillation. Hemoglobin, serum albumin level, creatinine, calcium, phosphate, total CO₂ content (tCO₂), uric acid, total cholesterol, intact parathyroid hormone (iPTH), ferritin, and high-sensitivity C-reactive protein (hsCRP) were measured. Dialysis solute clearance was assessed based on the Kt/V parameter (amount of dialysis delivered: K, clearance of urea; t, time on dialysis; V, estimated total body water) using urea kinetic modeling. The adequacy of solute clearance was assessed based on the weekly total Kt/V (the sum of peritoneal Kt/V and renal Kt/V). Timed 24-hour urine collection was performed at the time of enrollment and urine volume was recorded at 24-hour intervals.

The clinical outcomes of this study were planned all-cause patient mortality as the primary outcome and technical survival of PD as the secondary outcome. For each death and drop-out from PD, the principal investigator at that given institution completed a form that included the cause of death and cause of drop-out according to the CRC registry for ESRD study classification. Follow-up of the patients was censored at the time of death, kidney transplantation, patient withdrawal from the study, or patient transfer to a nonparticipating hospital. The follow-up period was calculated after the initiation of PD.

Data with continuous variables and normal distributions are presented as mean ± standard deviation, while those without a normal distribution are presented as a median with range. Student’s t tests and Mann-Whitney U tests were used to determine the differences among continuous variables. Categorical variables were presented as percentages. Pearson’s chi-squared test was used to determine the differences in categorical variables.

Univariable and multivariable logistic regression analysis were used to assess the clinical factors associated with IRH in PD patients. Multivariable logistic regression analysis was adjusted for significant or nearly significant (P < 0.05) predictors of IRH in univariate logistic regression analysis, including DM, cardiovascular disease, systolic blood pressure (BP), and diastolic BP. To achieve an adequate confounder control, important covariates known to be influential based on previous studies and clinical insight were retained in the multivariable logistic regression model, regardless of their statistical significance. These covariates included age, sex, BMI, serum levels of albumin, calcium, phosphate, iPTH, ferritin, and hsCRP.

The survival curves were estimated using the Kaplan-Meier method and compared by log-rank tests between patients in the IRH and non-IRH groups. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with a 95% confidence interval (CI) for all-cause mortality. Analyses were adjusted for potential confounders including age, sex, DM, cardiovascular disease, systolic BP, and diastolic BP. A value of P < 0.05 was considered to be statistically significant. All statistical analyses were performed using the IBM SPSS 21.0 software program (IBM Corp., Armonk, NY, USA).

A total of 583 patients with incident PD from the CRC were included in this study. The mean dialysis duration of all patients was 29 months (interquartile range, 16 to 42 months). A total of 73 patients (12.5%) were included in the IRH group, whereas 510 patients were included in the non-IRH group. The median period from the initiation of PD to the IRH event in the IRH group was 4 months (interquartile range, 1 to 8 months). The baseline characteristics of the study population are shown in Table 1. The IRH group had more underlying comorbidities such as cardiovascular diseases and DM compared with the non-IRH group. Systolic and diastolic BP were significantly increased in the IRH group compared with the non-IRH group. There were no significant differences in age, sex, BMI, hemoglobin level, serum levels of creatinine, albumin, alkaline phosphatase, calcium, phosphate, uric acid, iPTH, total cholesterol, tCO₂, ferritin, hsCRP, 24-hour urine volume, or residual renal function between the IRH and non-IRH groups.

Next, we evaluated the clinical parameters to predict IRH. Table 2 shows the clinical and laboratory risk factors that influence the IRH in the entire patient cohort. In the univariable logistic regression analysis, DM (odds ratio [OR], 1.68; 95% CI, 1.12 to 5.29; P = 0.031), cardiovascular disease (OR, 1.88; 95% CI, 1.11 to 3.19; P = 0.019), systolic BP (OR, 1.02; 95% CI, 1.00 to 1.03; P = 0.006), and diastolic BP (OR, 1.03; 95% CI, 1.01 to 1.04; P = 0.008) significantly influenced the prevalence of IRH. In the multivariable logistic analysis, DM was a significant independent risk factor for IRH in model 1 (OR, 2.26; 95% CI, 1.08 to 4.72; P = 0.031) as well as model 2 (OR, 2.43; 95% CI, 1.12 to 5.29; P = 0.007). Model 1 was adjusted for age, sex and significant factors found in univariate analysis such as DM, cardiovascular diseases, systolic BP and diastolic BP and model 2 was adjusted for the factors included in model 1 and BMI, serum levels of albumin, calcium, phosphate, iPTH, ferritin, and hsCRP.

Table 3 shows the distribution of causative infectious diseases in the IRH group. The most common cause of IRH was peritonitis (63.0%) and the second leading cause of IRH was respiratory tract infections, including pneumonia and bronchitis (9.6%). Other causes identified included skin and soft tissue infection, abscess, urinary tract infection, gastrointestinal tract infection, military tuberculosis, fungal infection, and viral infections.

During the median follow-up period of 29 months, nine patients died in the IRH group (12.3%) and 21 deaths occurred in the non-IRH group (4.1%). The median period from the event of IRH to a death in the IRH group was 23 months (interquartile rage, 13 to 37 months). The causes of death in the study population are shown in Table 4. Cardiovascular disease was the most common cause of death (36.7% of all death), followed by infectious diseases (30.0% of all deaths).

We determined the association between IRH and all-cause mortality in this study cohort. Fig. 1A shows the Kaplan-Meier survival curve for all-cause mortality. The log-rank test showed that all-cause mortality was significantly increased in the IRH group compared to the non-IRH group (P = 0.007).

Univariable and multivariable Cox proportional hazards model analysis of all-cause mortality are shown in Table 5. In the crude model, the HR for all-cause mortality of the IRH group was 2.81 (95% CI, 1.29 to 6.14; P = 0.010) using the non-IRH group as the reference category. In multivariable Cox regression analysis, the IRH group had a significantly higher risk for all-cause mortality in model 1 (HR, 2.79; 95% CI, 1.28 to 6.09; P = 0.010) and model 2 (HR, 2.51; 95% CI, 1.12 to 5.62; P = 0.026). These findings indicate that the predictive power of the IRH for all-cause mortality was independent of the potential confounders, including age, sex, DM, cardiovascular diseases, systolic BP, and diastolic BP, and the IRH group had a 2.5-fold higher risk of death compared with the non-IRH group.

During the follow-up period, 12.7% of enrolled patients in this study cohort (n = 74 of 583 patients) changed the modality of dialysis to HD from PD due to technical failure. Technical failure rates of PD in the IRH group and the non-IRH group were 30.1% (n = 22 of 73 patients) and 10.2% (n = 52 of 510 patients), respectively. The median period from the IRH event to a technical failure in the IRH group was 20 months (interquartile rage, 9 to 31 months).

A Kaplan-Meier plot showed that the cumulative survival rate from technical failure was significantly lower in the IRH group compared with the non-IRH group (P < 0.001 by log-rank test) (Fig. 1B). Table 5 shows the results of univariable and multivariable Cox regression analysis for technical failure. In the crude model, the HR for technical failure in the IRH group was 3.11 (95% CI, 1.89 to 5.12; P < 0.001) using the non-IRH group as the reference category. In multivariable Cox regression analysis, the IRH group had a significantly independent higher risk for technical failure even after adjusting for demographics, laboratory data, and comorbid conditions (model 1: HR, 3.14; 95% CI, 1.90 to 5.18; P < 0.001; model 2: HR, 3.23; 95% CI, 1.90 to 5.51; P < 0.001).