Protecting Kidney Disease Patients from Intestinal-Renal Syndrome

When I asked several nephrologists to define intestinal-renal syndrome or explain the significance of the severe imbalance of gut microbes seen with progressive uremia, the question mostly drew a blank expression. After I read papers by Nick Vaziri, MD, professor emeritus of nephrology, medicine and bio-engineering at University of California, Irvine, that defined intestinal renal syndrome, a concept that was new to me, I recognized the importance of applying lessons learned to improve the health of our kidney patients.

When I was editing my book on kidney disease, I sought Dr. Vaziri’s constructive criticism. In our communications, we discussed the importance of a healthy gut microbiome in patients with kidney disease. The consequences of the imbalance of the trillions of bacteria residing in the colon of patients with various stages of chronic kidney is called “intestinal-renal syndrome.”

During the last 10 years, many health-conscience people have become aware of the importance of maintaining a healthy balance of intestinal bacteria. This impacts the immune system’s ability to fight disease, reduce inflammation and promote the synthesis of serotonin, the neurotransmitter that helps regulate mood and more. As a result, many consumers are presently ingesting probiotics to supply the appropriate bacteria to create the proper balance. In addition, many are increasing their consumption of fruits and vegetables in order to provide the right amount of nutrients or prebiotics to maintain the delicate microbiome.

Patients experiencing various stages of chronic kidney disease are particularly prone to an imbalance of their intestinal biome. Frequently during the course of their disease, they are given antibiotics to either prevent or treat infection in a vascular access, created for delivering future hemodialysis. The result is the reduction of important and healthful bacteria that dwell in the gut. In addition, kidney patients are urged to avoid foods that contain potassium, which is found in healthful fruits and vegetables. The deficiency of prebiotic fiber also reduces the population of healthful organisms, which can lead to increased deleterious inflammation and acceleration of chronic renal failure.

Dr. Vaziri claims to be the first scientist to demonstrate that uremia disrupts the composition of the gut microbiome. In an article published in Kidney International, Vaziri and colleagues state that “The large community of microbes residing in the intestinal tract constitutes a dynamic and symbiotic, ecosystem that is in constant interaction with the host metabolism. Under normal conditions, the gut microbiome provides trophic and protective functions.” However, uremia can profoundly modify the biochemical milieu of the gut via heavy influx of urea into the gastrointestinal tract.

What are the physiologic consequences of imbalance of the gut biome in kidney patients? The tight junctions normally found in healthy colon cells develop leaks that enable luminal antigens and other noxious substances to enter the systemic circulation. This disruption of the colonic tight junction results in inflammation throughout the colon with histologic evidence of chronic enterocolitis in dialysis patients. It is well known that chronic inflammation is an important factor in the genesis of cardiovascular disease. Cardiovascular disease still remains the leading cause of mortality in end-stage kidney patients who are maintained on dialysis! Thus, by restoring the balance of bacteria in the colon of kidney patients, inflammatory colitis may be prevented, and the resultant reduction of inflammation may slow cardiovascular disease in our patients.

Dr. Vaziri and his colleagues have studied the effects of a form of fiber—high-amylose maize resistant starch type 2 (HAM-RS2)—on CKD animals. HAM-RS2 is able to pass undigested into the colon, where it provides the substrate for the growth of beneficial bacteria, lowers fecal nitrogen excretion and lowers plasma urea. In studies of hemodialysis patients, inflammatory markers improved and patients had fewer gastrointestinal symptoms, such as bloating and gas.

Maintaining a balance of bacteria may be beneficial for all of us, but especially valuable for patients with various stages of chronic kidney disease. Judicious use of antibiotics is advised. If antibiotics are given, then probiotics can be administered to prevent imbalance of the intestinal biome. However, the probiotic will not likely arrive intact to the target organ, the intestinal tract, because a large percentage of the capsule containing the probiotic may be destroyed by stomach acid. Hao Zhang and colleagues are developing an acid resistant gel that can house the probiotic and prevent gastric acid from killing the enclosed dose of friendly bacteria.

The judicious use of foods rich in fiber may maintain a normal balance of intestinal flora. In ongoing studies, Dr. Vaziri and colleagues in Tehran are feeding high-amylose maize to dialysis patients, looking to see if the balance of the gut microbiome is restored, the inflammatory process abates and the general clinical outcome improves (i.e., gastrointestinal bloating and gas diminishes). Other variables being studied are whether fiber that reaches the gut can slow the rate of loss of kidney function.

In summary, evidence to date suggests that a reduction in the use of antibiotics and the inclusion of fiber in the diet of patients with CKD may slow the progression of kidney disease, reduce the dangerous inflammation of the bowel that is associated with accelerated cardiovascular disease, improve general immune function and improve patient mood. The mechanism is simply restoring the balance of the human microbiome. Once the results of studies, such as the one in Tehran on amylose resistant starch, are available, nephrologists can use the information to help improve the health of patients with kidney disease.