Inflammation in Peritoneal Dialysis Patients: Effect of Obesity

Our study addresses the following research question: What is the role of obesity in modulating inflammation and innate immune function, as well as the overall responsiveness of innate immune cells (such as macrophages, neutrophils, and other peripheral leukocytes) in patients undergoing peritoneal dialysis?

The investigators hypothesize that obesity will lead to increased inflammation in patients undergoing peritoneal dialysis.

Study Overview

• Status: Withdrawn
• Conditions: Obesity; End-Stage Renal Disease; Renal Disease, End-Stage; Renal Failure, End-Stage

Detailed Description

Chronic inflammation is highly prevalent in ESRD and associated with adverse outcomes. For example, chronic exposure of the peritoneal cavity to PD solution leads to induction of cytokines and other inflammatory mediators, generating peritoneal membrane inflammation which results in functional decline of ultrafiltration. Obesity is characterized by a state of chronic low-grade systemic inflammation stemming from expanded adipose tissue mass. Animal studies from our group and others suggest that obesity is associated with exacerbated prolonged inflammatory responses in the peritoneal cavity. The shifting demographic characteristics of the ESRD population, with a rise in elderly patients and those with obesity, is as a significant challenge for management of dialysis patients. Specifically, a 2-fold increase in the percentage of obese patients in the ESRD population has been reported. The caloric burden of PD glucose-containing solutions adds an additional risk for development or exacerbation of obesity and diabetes in patients using this dialysis modality. Few studies have directly evaluated the association between degree of adiposity and inflammation in PD patients. Data obtained from the proposed experiments will help clarify the connection between obesity and risk factors for cardiovascular and infectious diseases in the PD population. These data will also further our knowledge of the basic pathophysiology of both obesity and ESRD and enhance our understanding of factors involved in successful delivery of PD. Results may lead to enhanced nutritional recommendations for PD patients and/or the use of low-glucose or non-glucose alternatives, with a resultant reduction in local and/or systemic inflammation and CVD and other risk factors.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing peritoneal dialysis

Description

Inclusion Criteria:

1. > 18 years; and
2. peritoneal dialysis (PD) > 6 months.

Exclusion Criteria:

1. infectious episode within 4 weeks; and
2. using immunosuppressive drugs

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma and dialysate levels of pro-inflammatory and anti-inflammatory molecules	Peritoneal dialysate effluent (PDE) and peripheral blood will be obtained from peritoneal dialysis (PD) subjects. Levels of pro- and anti-inflammatory cytokines, chemokines, adipokines, and acute-phase reactants will be evaluated in PDE and plasma. The ability of peripheral leukocytes to respond to microbial stimuli will be studied using whole blood cultures. We predict percentage of body fat will be significantly associated with higher levels of pro-inflammatory factors both systemically and locally and with reduced ability of peripheral leukocytes to respond to microbial stimuli.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peritoneal macrophage subphenotype	The composition of leukocytes from peritoneal dialysate effluent (PDE) will be analyzed to evaluate the absolute and relative amounts of leukocyte subclasses. The phenotype of peritoneal macrophages (pMac) will be evaluated by flow cytometry, by real time RT-PCR, and by measurement of mediators characteristic of each activation type following ex vivo culture. We predict that we will observe a significant shift from an anti- to a pro-inflammatory pMac phenotype as adiposity increases	24 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of adiposity/obesity	DXA (dual energy X-ray absorptiometry) will be conducted at UIC body composition laboratory using Hologic 4500 W Elite Scan. Values from DXA scans will be primary method for evaluation of adiposity. Height and weight will be measured by nurse to calculate body mass index (BMI).	24 hours

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Investigators: Principal Investigator: Jerrold S Levine, MD, UIC; Principal Investigator: Natalia Litbarg, MD, UIC; Principal Investigator: Giamila Fantuzzi, PhD, UIC

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: September 17, 2012
• First Submitted That Met QC Criteria: September 19, 2012
• First Posted (Estimate): September 24, 2012

Study Record Updates

• Last Update Posted (Actual): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Peritoneal dialysis; Macrophages; Innate immunity
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Renal Insufficiency; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Renal Insufficiency, Chronic; Kidney Diseases; Obesity; Inflammation; Kidney Failure, Chronic
• Other Study ID Numbers: 2012-0506 (Other Identifier: M D Anderson Cancer Center); Baxter/UIC Ref#2012-04881 (Other Identifier: Baxter)