Effects of Resistant Starch Diet on the Gut Microbiome in Chronic Kidney Disease

Chronic kidney disease (CKD), a progressive decline in kidney function, is a growing health problem: 13% of adults in the US have CKD. Among patients with CKD, the risk of progression to irreversible loss of kidney function (end-stage renal disease, ESRD) is about 1% per year. In addition, adjusted mortality is approximately four times greater among those with CKD compared to those without. For ESRD, apart from dialysis and kidney transplant, no treatment exists. CKD increases urea levels in bodily fluids leading to a dominance of urease-containing bacteria in the gut. Such dysbiosis results in decreased production of the short chain fatty acid, butyrate and decreased health of the colonic epithelial barrier. Consequently, bacterial toxins translocate into the bloodstream, promoting inflammation. Moreover, production of uremic toxins such as indoxyl and p-cresyl sulfates are also increased, resulting in further kidney injury.

CKD patients are prescribed a diet low in protein, fiber and symbiotic organisms, which reduces complications like hyperkalemia, but also contributes to the dysbiosis. Re-formulating the CKD diet may improve the clinical management of CKD. The investigators's overall hypothesis is that changes in the microbial diversity, xeno-proteins and xeno-metabolites correlate with CKD progression, and microbiome-directed therapies can be used to slow the disease. In this study, the investigators will determine the tolerability of supplemental resistant starch (RS). Secondary aims are to determine if a diet high in resistant starch changes fecal butyrate concentrations, the make-up of the gut microbiome and the concentrations in the blood of uremic toxins produced by the gut microbiome. This study will help in the design of a future study with the aim of understanding if a high resistant starch diet can slow the progression of chronic kidney disease.

Inclusion criteria

• Adult

• Between the ages of 18 and 85 years old
• Glomerular filtration rate estimated by creatinine clearance (eGFR Cr):between 59 and 30 ml/min for stage 3 CKD patients
• Urine protein < 1 gram per day by 24-hour protein collection or urine protein-to-creatinine ratio <1 gram/gram or urine microalbumin to creatinine concentration less than 1000 mg/g.
• Children

• Between the ages of 5 and 17 years
• eGFR Cr between 30 and 59 (stage 3 CKD) using the revised Schwartz equation.
• Urine protein < 1 gram per day by 24-hour protein collection or urine protein-to-creatinine ratio <1 gram/gram.

Exclusion criteria

Adult

• Age older than 85 years
• eGFR Cr > 59 ml/min or < 30 ml/min
• History of renal transplant
• Subject with diabetes (as defined by patient report, taking medications for the treatment of diabetes or as reported in the medical record)
• Use of antibiotics within 1 month
• Use of laxatives within 1 month
• Inflammatory bowel disease
• Irritable bowel syndrome
• Colorectal cancer
• Surgically removed bowel or presence of an ostomy
• Pregnancy
• Inability to obtain written informed consent
• Constipation
• Diarrhea

Children

• Age younger than 5 years
• eGFR > 59 ml/min and < 30 ml/min
• History of renal transplant
• Subject with diabetes (as defined by patient report, taking medications for the treatment of diabetes or as reported in the medical record)
• Use of antibiotics within 1 month
• Use of laxatives within 1 month
• Inflammatory bowel disease
• Surgically removed bowel or presence of an ostomy
• Pregnancy
• Constipation
• Diarrhea