Persistent inflammation underpins the accelerated atherosclerosis and increased prevalence of protein-energy wasting in maintenance hemodialysis (MHD) patients. However, the etiology of unprovoked inflammation in MHD patients remains unresolved. The human gut harbors 1014 bacteria, and gut microbial imbalance has been linked to inflammation, insulin resistance and atheroscleroisis. Prebiotic oligofructose enriched inulin (p-inulin) has been shown to restore gut microbial balance, thereby reducing endotoxin generation and inflammation. Pentoxifylline (PTX) blocks cytokine generation in response to endotoxemia at the tissue level, and hence complements the actions of p-inulin. In a two-by-two factorial clinical trial, we will randomize 120 MHD patients to receiv p-inulin/PTX/placebo daily for 12 months. First, we will demonstrate the feasibility of recruitment randomization, and retention of study participants in order to record endpoints in at least 90% of participants. Secondly, we will establish the safety and efficacy of p-inulin and PTX in reducing systemic inflammation. Finally, we propose to evaluate the effect of study intervention on selected exploratory clinical end-points: (a) Progression/regression of atherosclerosis will be determined using phase-sensitive dual inversion recovery magnetic resonance (MR) spectroscopy technique;(b) Alterations in muscle mass and visceral fat mass will be examined by MR imaging of thigh and abdomen;and (c) Changes in presence and severity of protein-energy wasting will be determined according to the International Society of Renal Nutrition and Metabolism criteria. This pilot study will prove the concept, establish feasibility and generate preliminary data to justify the launching of a full-clinical trial.

Public Health Relevance

Excess inflammation is associated with obesity, heart disease, and muscle wasting in hemodialysis patients. Toxins produced by the bacteria in the intestine may be an important cause of inflammation. We propose to use prebiotic inulin and pentoxifyllin to decrease inflammation, which we believe will decrease fat mass, increase muscle mass, and lower heart disease in hemodialysis patients.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-J (M1))
Program Officer
Kimmel, Paul
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
George Washington University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Amdur, Richard L; Feldman, Harold I; Gupta, Jayanta et al. (2016) Inflammation and Progression of CKD: The CRIC Study. Clin J Am Soc Nephrol 11:1546-56
Ramezani, Ali; Massy, Ziad A; Meijers, Björn et al. (2016) Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target. Am J Kidney Dis 67:483-98
Barrows, Ian R; Ramezani, Ali; Raj, Dominic S (2015) Gut Feeling in AKI: The Long Arm of Short-Chain Fatty Acids. J Am Soc Nephrol 26:1755-7
Ramezani, Ali; Barrows, Ian R; Raj, Dominic S (2015) Electroacupuncture therapy for muscle atrophy in CKD: is there a needle in the haystack? J Am Soc Nephrol 26:510-2
Velasquez, Manuel T; Ramezani, Ali; Raj, Dominic S (2015) Urea and protein carbamylation in ESRD: surrogate markers or partners in crime? Kidney Int 87:1092-4
Jose, Pedro A; Raj, Dominic (2015) Gut microbiota in hypertension. Curr Opin Nephrol Hypertens 24:403-9
Gupta, Jayanta; Dominic, Elizabeth A; Fink, Jeffrey C et al. (2015) Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study. PLoS One 10:e0124772
Poesen, Ruben; Ramezani, Ali; Claes, Kathleen et al. (2015) Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD. Clin J Am Soc Nephrol 10:1525-33
Ramezani, Ali; Devaney, Joseph M; Cohen, Scott et al. (2015) Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: a pilot study. Eur J Clin Invest 45:394-404
Rambod, Mehdi; Heine, Gunnar H; Seiler, Sarah et al. (2014) Association of vascular endothelial factors with cardiovascular outcome and mortality in chronic kidney disease patients: a 4-year cohort study. Atherosclerosis 236:360-5

Showing the most recent 10 out of 15 publications