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.
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.
| Charytan, David M; Himmelfarb, Jonathan; Ikizler, T Alp et al. (2018) Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): a randomized, placebo-controlled, multiple dosage trial. Kidney Int : |
| Roumelioti, Maria-Eleni; Glew, Robert H; Khitan, Zeid J et al. (2018) Fluid balance concepts in medicine: Principles and practice. World J Nephrol 7:1-28 |
| Muralidharan, Jagdeesan; Ramezani, Ali; Hubal, Monica et al. (2017) Extracellular microRNA signature in chronic kidney disease. Am J Physiol Renal Physiol 312:F982-F991 |
| Alaini, Ahmed; Malhotra, Deepak; Rondon-Berrios, Helbert et al. (2017) Establishing the presence or absence of chronic kidney disease: Uses and limitations of formulas estimating the glomerular filtration rate. World J Methodol 7:73-92 |
| Nallu, Anitha; Sharma, Shailendra; Ramezani, Ali et al. (2017) Gut microbiome in chronic kidney disease: challenges and opportunities. Transl Res 179:24-37 |
| Chang, Tara I; Reboussin, David M; Chertow, Glenn M et al. (2017) Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial). Hypertension 70:751-758 |
| Velasquez, Manuel T; Beddhu, Srinivasan; Nobakht, Ehsan et al. (2016) Ambulatory Blood Pressure in Chronic Kidney Disease: Ready for Prime Time? Kidney Int Rep 1:94-104 |
| 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 |
| 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 |
Showing the most recent 10 out of 22 publications
