Effects of High Dietary Fiber Supplementation on Uremic Retention Molecules and Inflammation in Diabetic Chronic Kidney Disease (CKD)

Loss of kidney function results in accumulation in the blood of molecules that are either excreted or metabolized by the kidney. Collectively, these molecules are termed Uremic Retention Molecules (URMs) or toxins. It is increasingly recognized that colonic bacterial metabolites like p-cresyl sulfate and indoxyl sulfate that are absorbed from the colon and excreted by the kidney may contribute to the pool of compounds implied in uremic toxicity. Indeed, these URMs have been linked to increased levels of inflammation markers, chronic kidney disease (CKD) progression, cardiovascular disease and overall mortality in CKD and/ or hemodialysis patients. Therefore, interventions that target the production or absorption of URMs from the gut might decrease inflammation and oxidative stress that are commonly seen in the uremic milieu. The National Health and Nutrition Examination Survey III (NHANES III) data show that high dietary fiber intake is associated with decreased serum levels of C-reactive protein (CRP) in those with and without CKD and these associations are much stronger in the CKD population. A possible explanation of this effect is that a high fiber diet in CKD patients modulates the bacterial production, intestinal absorption and finally the serum levels of URMs like p-cresyl sulfate and indoxyl sulfate, which in turn results in decrease in inflammation.

OBJECTIVES:

Hypothesis:

1. Higher serum levels of markers of inflammation such as high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF) -α seen in stage 4 CKD (estimated Glomerular Filtration Rate 15-29 ml/min/1.73 m2) compared to stage 2 CKD (estimated Glomerular Filtration Rate 60-89 ml/min/1.73 m2) is partly explained by the higher circulating levels of URMs (p-cresyl sulfate and indoxyl sulfate) in stage 4 CKD, and
2. Dietary supplementation in stage 4 CKD with 30g/d of a soluble fiber Psyllium (brand name-Metamucil TM) will decrease circulating URMs levels and thereby, decrease serum levels of inflammation markers and urinary levels of transforming growth factor (TGF)-β, a marker of kidney fibrosis.