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Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

ABSTRACT: BACKGROUND:Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death. METHODS:This study included new adult PD patients in Australia and New Zealand (ANZ; 1990-2010) or Scotland (2000-08) followed until 2012. Age, time on PD, primary renal disease, gender, data set and diabetic status were evaluated as predictors at the start of PD, then at 3 and 5 years after starting PD using flexible parametric competing risks models. RESULTS:In 17 396 patients (16 162 ANZ, 1234 Scotland), EPS was observed in 99 (0.57%) patients, less frequently in ANZ patients (n?=?65; 0.4%) than in Scottish patients (n?=?34; 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1 Kaplan-Meier?=?0.0126, cumulative incidence function?=?0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74-0.79) and this improved at 3 and 5?years after starting PD (C-statistic = 0.81-0.92). CONCLUSIONS:EPS risk estimates are lower when calculated using competing risk of death analyses. A patient's estimated risk of EPS is country-specific and can be predicted using age, primary renal disease and duration of PD.

SUBMITTER: Lambie M

PROVIDER: S-EPMC6735880 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

Lambie Mark M Teece Lucy L Johnson David W DW Petrie Michaela M Mactier Robert R Solis-Trapala Ivonne I Belcher John J Bekker Hilary L HL Wilkie Martin M Tupling Ken K Phillips-Darby Louise L Davies Simon J SJ

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20190901 9

<h4>Background</h4>Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death.<h4>Methods</h4>This study included new adult PD patients in Australia and New Z ...[more]

PMID: 30820552

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Project description:Encapsulating peritoneal sclerosis (EPS) is a life threatening complication of peritoneal dialysis (PD). Podoplanin is a glycoprotein expressed by mesothelial cells, lymphatic endothelial cells, and myofibroblasts in peritoneal biopsies from patients with EPS. To evaluate podoplanin as a marker of EPS we measured podoplanin mRNA and described the morphological patterns of podoplanin-positive cells in EPS. Included were 20 peritoneal biopsies from patients with the diagnosis of EPS (n = 5), patients on PD without signs of EPS (n = 5), and control patients (uremic patients not on PD, n = 5, non-uremic patients n = 5). EPS patient biopsies revealed significantly elevated levels of podoplanin mRNA (p<0.05). In 24 peritoneal biopsies from patients with EPS, podoplanin and smooth muscle actin (SMA) were localized by immunohistochemistry. Four patterns of podoplanin distribution were distinguishable. The most common pattern (8 of 24) consisted of organized, longitudinal layers of podoplanin-positive cells and vessels in the fibrotic zone ("organized" pattern). 7 of 24 biopsies demonstrated a diffuse distribution of podoplanin-positive cells, accompanied by occasional, dense clusters of podoplanin-positive cells. Five biopsies exhibited a mixed pattern, with some diffuse areas and some organized areas ("mixed"). These contained cuboidal podoplanin-positive cells within SMA-negative epithelial structures embedded in extracellular matrix. Less frequently observed was the complete absence of, or only focal accumulations of podoplanin-positive fibroblasts outside of lymphatic vessels (podoplanin "low", 4 of 24 biopsies). Patients in this group exhibited a lower index of systemic inflammation and a longer symptomatic period than in EPS patients with biopsies of the "mixed" type (p<0.05). In summary we confirm the increased expression of podoplanin in EPS, and distinguish EPS biopsies according to different podoplanin expression patterns which are associated with clinical parameters. Podoplanin might serve as a useful adjunct to the morphological workup of peritoneal biopsies.

Project description:Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value<0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment.

Project description:BackgroundEncapsulating peritoneal sclerosis (EPS) is a rare but serious complication of long-term peritoneal dialysis (PD). However, previous studies reported large variations in its mortality rates that may associate with a different degree of EPS severity. This study reports the incidence and outcomes of EPS and identifies the risk factors associated with severe EPS.MethodsWe retrospectively analyzed clinical data of EPS patients from 3 medical centers in Taiwan from January 1982 to September 2015, and classified patients as having mild/moderate or severe EPS. Patients with intractable intestinal obstruction/gut-related sepsis that needed surgical intervention or resulted in mortality were in severe EPS group. Follow-up for outcome was through December 31, 2015. Clinical characteristics, peritoneal dialysis (PD)-related parameters, biochemical and imaging results were analyzed and compared between groups.ResultsFifty-eight of 3202 patients undergoing PD during the study period had EPS (prevalence 1.8%). The incidence of EPS increased for patients on PD for >6-8 years (≤6 yrs. vs. >6-8 yrs., 0.0% vs. 1.8%, p = 0.001). Relative to those on PD for >6-8 years, the risk of EPS significantly increased with PD duration longer than 10 years (>10-12 years vs. >6-8 years: OR: 5.5, 95% CI: 1.7-17.1, p < 0.01). Twenty-three patients fulfilled the criteria for severe EPS. The overall mortality rate of EPS was 35% (20/58), and was 74% (17/23) in the severe EPS group. The average serum levels of C-reactive protein (CRP) and intact-parathyroid hormone (i-PTH), which were checked every 3~6 months within one year before diagnosis of EPS, were higher in severe EPS group than in mild/moderate group (p = 0.02, p = 0.08, respectively). Multivariate analysis revealed severe EPS was independently associated with bowel tethering (based on CT), presentation with bloody ascites, diagnosis of EPS after withdrawal from PD, and i-PTH ≥ 384 pg/mL. Receiver operating characteristic analysis indicated that presentation with 2 or more of the 5 risk factors (EPS diagnosis after PD withdrawal, bloody ascites, bowel tethering, CRP ≥ 29 mg/L, and i-PTH ≥ 384 pg/mL) had a good accuracy (AUC = 0.80, p = 0.001) for prediction of severe EPS.ConclusionsThe incidence of EPS increases with PD duration. Severe EPS has high mortality rate and is associated with bowel tethering, presentation of bloody ascites, diagnosis after PD withdrawal, and higher serum levels of i-PTH before EPS diagnosis. Having 2 or more of the 5 risk factors can provide a good accuracy for prediction of severe EPS.

Project description:ImportanceKidney failure risk prediction has implications for disease management, including advance care planning in adults with severe (ie, estimated glomerular filtration rate [eGFR] category 4, [G4]) chronic kidney disease (G4-CKD). Existing prediction tools do not account for the competing risk of death.ObjectiveTo compare predictions of kidney failure (defined as estimated glomerular filtration rate [eGFR] <10 mL/min/1.73 m2 or initiation of kidney replacement therapy) from models that do and do not account for the competing risk of death in adults with G4-CKD.Design, setting, and participantsThis prognostic study linked population-based laboratory and administrative data (2002-2017) from 2 Canadian provinces (Alberta and Manitoba) to compare 3 kidney risk models: the standard Cox regression, cause-specific Cox regression, and Fine-Gray subdistribution hazard model. Participants were adults with incident G4-CKD (eGFR 15-29 mL/min/1.73 m2). Data analysis occurred between July and December 2020.Main outcomes and measuresThe performance of kidney risk models at prespecified times and across categories of baseline characteristics, using calibration, reclassification, and discrimination (for competing risks). Predictive characteristics were age, sex, albuminuria, eGFR, diabetes, and cardiovascular disease.ResultsThe development and validation cohorts included 14 619 (7070 [48.4%] men; mean [SD] age, 74.1 [12.8] years) and 2295 (1152 [50.2] men; mean [SD] age, 71.9 [14.0] years) adults, respectively. The 3 models had comparable calibration up to 2 years from entry. Beyond 2 years, the standard Cox regression overestimated the risk of kidney failure. At 4 years, for example, risks predicted from standard Cox were 40% for people whose observed risks were less than 30%. At 2 years (risk cutoffs 10%-20%) and 5 years (risk cutoffs 15%-30%), 788 (5.4%) and 2162 (14.8%) people in the development cohort were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by standard Cox regression (the opposite was observed in 272 patients [1.9%] and 0 patients, respectively). In the validation cohort, 115 (5.0%) individuals and 389 (16.9%) individuals at 2 and 5 years, respectively, were correctly reclassified into lower- or higher-risk categories by the Fine-Gray model and incorrectly reclassified by the standard Cox regression; the opposite was observed in 98 (4.3%) individuals and 0 individuals, respectively. Differences in discrimination emerged at 4 to 5 years in the development cohort and at 1 to 2 years in the validation cohort (0.85 vs 0.86 and 0.78 vs 0.8, respectively). Performance differences were minimal during the entire follow-up in people at lower risk of death (ie, aged ≤65 years or without cardiovascular disease or diabetes) and greater in those with a higher risk of death. At 5 years, for example, in people aged 65 years or older, predicted risks from standard Cox were 50% where observed risks were less than 30%. Similar miscalibration was observed at 5 years in people with albuminuria greater than 30 mg/mmol, diabetes, or cardiovascular disease.Conclusions and relevanceIn this study, predictions about the risk of kidney failure were minimally affected by consideration of competing risks during the first 2 years after developing G4-CKD. However, traditional methods increasingly overestimated the risk of kidney failure with longer follow-up time, especially among older patients and those with more comorbidity.

Project description:Expression data from peritoneal biopsies of patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first implantation of a peritoneal dialysis catheter (PD), and patients undergoing abdominal surgery for non-peritoneal conditions (controls) We used microarrays to determine the transcriptional profiles of peritoneal membrane in patients with encapsulating peritoneal sclerosis (EPS), patients undergoing first insertion of a peritoneal dialysis cathetier (PD), and uremic patients without history of PD or EPS, undergoing abdominal surgery for non-peritoneal problems (CON) Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD), characterized by marked inflammation and severe fibrosis of the peritoneum, and associated with high morbidity and mortality. EPS can occur years after termination of PD and, in severe cases, leads to intestinal obstruction and ileus requiring surgical intervention. Despite ongoing research, the pathogenesis of EPS remains unclear. We performed a global transcriptome analysis of peritoneal tissue specimens from EPS patients, PD patients without EPS, and uremic patients without history of PD or EPS (Uremic). Unsupervised and supervised bioinformatics analysis revealed distinct transcriptional patterns that discriminated these three clinical groups. The analysis identified a signature of 219 genes expressed differentially in EPS as compared to PD and Uremic groups. Canonical pathway analysis of differentially expressed genes showed enrichment in several pathways, including antigen presentation, dendritic cell maturation, B cell development, chemokine signaling and humoral and cellular immunity (P value <0.05). Further interactive network analysis depicted effects of EPS-associated genes on networks linked to inflammation, immunological response, and cell proliferation. Gene expression changes were confirmed by qRT-PCR for a subset of the differentially expressed genes. EPS patient tissues exhibited elevated expression of genes encoding sulfatase1, thrombospondin 1, fibronectin 1 and alpha smooth muscle actin, among many others, while in EPS and PD tissues mRNAs encoding leptin and retinol-binding protein 4 were markedly down-regulated, compared to Uremic group patients. Immunolocalization of Collagen 1 alpha 1 revealed that Col1a1 protein was predominantly expressed in the submesothelial compact zone of EPS patient peritoneal samples, whereas PD patient peritoneal samples exhibited homogenous Col1a1 staining throughout the tissue samples. The results are compatible with the hypothesis that encapsulating peritoneal sclerosis is a distinct pathological process from the simple peritoneal fibrosis that accompanies all PD treatment. Total RNA was isolated from frozen peritoneal biopsy specimens obtained at time of surgery. RNA was hybridized to Affymetrix arrays, and analyzed. Select transcripts were subjected to validation by rt-pcr and by immunodetection.

Dataset Information

Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

Publications

Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

Similar Datasets

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