Most people are not focused on their kidneys.  From a consumer wellness perspective, kidney health isn’t a “thing” at all.  It probably should be, given the rapid growth of kidney disease in older populations.

Chronic Kidney Disease (CKD) currently affects 30 million American adults, (15% of US adults).  Adults with diabetes, high blood pressure or heart disease are at higher risk of developing CKD. African Americans, Hispanics, and American Indians tend to have a greater risk as well. The CDC 2017 Fact Sheet contains many helpful American statistics.

The kidneys serve as a filter for the bloodstream.  If the kidneys are not working well, harmful metabolites begin to accumulate in circulation in the blood. Dialysis can be used to filter and remove many of these compounds. Some compounds are particularly problematic because they cannot be removed by dialysis as they are bound to albumin and are very large. Two protein metabolites in particular are of particular concern: indoxyl sulfate (IS) and p-cresyl sulfate. Both of these compounds are produced in the gut and are broken down from amino acids in proteins (indoxyl sulfate is a tryptophan derivative and p-cresyl sulfate is a derivate of tyrosine and phenylalanine).

It is now widely recognized that the intestinal microbiota is a major source of this systemic inflammation and oxidative stress characteristic of chronic kidney disease (Lau & Vaziri 2017). The gut microbiome is markedly different in individuals with CKD compared to healthy adults. It is not clear, however, whether the kidneys or the intestinal tract causes or contributes to the inflammation and oxidative stress. Some research suggests that urea infiltrates the gut, increasing the production of ammonia and ammonium hydroxide, which causes damage to the intestinal gut barrier and promotes intestinal wall inflammation (Lau 2018).  Additional research suggests that the protein fermentation in the gut may initiate the process instead. In any case, this ‘gut-kidney axis’ is an area of active research.

Resistant starch and the kidneys

There are three major ways that resistant starch impacts the kidneys and can help maintain healthy kidney function:

(1) Resistant starch reduces toxic nitrogen-containing compounds in the blood plasma produced in the gut, notably indoxyl sulfate.

(2) Resistant starch reduces inflammation and oxidative stress.

(3) Resistant starch impacts Vitamin D metabolism.

(1) Resistant starch reduces plasma toxins by increasing fecal bulk. For every 1 gram of resistant starch consumed, approximately 1.6-2.6 gram of additional fecal mass was created, depending on the source and structure of the specific resistant starch (Cummings BJN 1996). This bacterial growth consumes nitrogen and is a “healthy” way to dispose of protein. Early research by Phillips and Birkett demonstrated that resistant starch reduced intestinal ammonia, phenol, cresol and total phenols. Animal studies have also shown that resistant starch reduces the protein fermentation by-products in the gut (Le Leu C 2007). In short, the fecal bulk removes protein-breakdown and nitrogen-based compounds from the body. Thus, the nitrogen-containing compounds are not absorbed into the body and do not have to be disposed of through the kidneys.

One of these nitrogen-containing compounds, Indoxyl sulfate, is a uremic toxin that induces inflammation and leukocyte activation.  It is associated with increased mortality in CKD patients. Two clinicals have shown that resistant starch reduces indoxyl sulfate and other compounds in the blood plasma of people with chronic kidney disease.

Dr. Timothy Meyer and his colleagues at Stanford University showed that 18 grams of resistant starch/day reduced indoxyl sulfate by 27% in 40 patients on hemodialysis in California, USA.  This study also showed a trend of 24% reduction of p-cresol sulfate, reduced plasma urea, nitrogen and plasma album, but these were not statistically significant. (Sirich 2014).

Dr. Denise Mafra and her colleagues at the Universidade Federal Fluminense in Rio de Janeiro, Brazil showed that 16 grams of resistant starch/day reduced indoxyl sulfate levels in 31 chronic kidney disease patients undergoing hemodialysis in Brazil (Esgalhado 2018). This study also showed reduced plasma levels of thiobarbituric acid reactive substances (TBARS) and IL-6 and a trend to reduced protein carbonyl levels.  There was no difference in plasma levels of p-cresyl sulfate.

Animal studies have also shown similar benefits (Chen BBB 2016, Kieffer AJPRP 2016)

(2) Resistant starch reduces inflammation.  Dr. Denise Mafra’s clinical trial in Brazil demonstrated reduced inflammation biomarkers, interleukin-6 (IL-6) and high-sensitive C-reactive protein (hs-CRP), and oxidative stress markers thiobarbituric acid reactive substances (TBARS). In addition, there was a trend to reduced protein carbonyl (p-0.06). (Esgalhado 2018)

A second clinical study also found reduced inflammation and oxidative stress biomarkers in hemodialysis patients.  Dr. Vaziri of UC Medical School in Irvine, California and his collaborators at the Tabriz University of Medical Sciences in Iran fed 46 hemodialysis patients 25 grams of resistant starch/day for 8 weeks and showed reduced TNF-a, IL-6 and malondialdehyde.  Serum urea and creatinine concentrations also significantly declined (Tayebi Khosroshahi 2018). There was no significant difference in hs-CRP, serum interleukin-1b and total antioxidant activity.  These participants also reported improvements in constipation.

A new animal study by Martin Kriegel and his colleagues at Yale University demonstrated that resistant starch improved the gut barrier and reduced the translocation of bacteria in mouse models of lupus. (Zegarra-Ruiz CHM 2018).  While the focus of this study is not kidney-related, it demonstrated that resistant starch restored the gut barrier. Loss of integrity of the gut barrier is a major contributor to systemic inflammation.  This mechanism could also be contributing to reducing inflammation and oxidative stress seen in clinical trials.

Dr. John Arthur and Dr. Boris Zybailov at the University of Arkansas are also working on the impact of resistant starch in kidney health. They just showing that resistant starch produces massive changes in proteins as well as the entire gut microbiome in animal models. They concluded that resistant starch shifted the microbiome from mucin degraders to butyrate producers (Zybaylov 2018). They speculated that the increased butyrate led to improvements of oxidative stress and inflammation as well as other biological processes. This team has also initiated a NIH-funded clinical trial with resistant starch in children and adults with stage 3 chronic kidney disease (Clinical Trials.gov Identifier NCT03356990).

Dr. Vaziri has published additional animal studies investigating various mechanisms related to resistant starch and kidney function.  (Kieffer 2016, Vaziri 2014)

(3) Resistant starch attenuated urinary loss of Vitamin D metabolites in animal models (Koh 2016, Smazal 2013, Koh 2014).  The kidneys activate 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. This research is still early, but it adds to the body of evidence demonstrating positive kidney health benefits following the dietary consumption of resistant starch.

There is now sufficient clinical evidence to conclude that dietary consumption of resistant starch helps maintain healthy kidneys and healthy kidney function.

Additional information is available in some excellent review articles: Lau & Vaziri Clinical Science 2018,  Moraes & Mafra European Journal of Nutrition 2016

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