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

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 [1]. 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 [1-3,7-9]. 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 [7-16]. 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. As discussed in the relevant research of
the mentor section, Dr. Beddhu and his colleagues found in the National Health and Nutrition
Examination Survey III (NHANES III) data 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. Similarly, high fiber intake was
associated with lower mortality in the CKD population than in the non-CKD population [4-6].
The reasons for these observed effect modification by CKD of the associations of dietary
fiber intake with inflammation and mortality are unclear. A possible explanation 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 (eGFR 15-29 ml/min/1.73 m2) compared to stage 2 CKD (eGFR 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.