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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: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.

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