Metabolite Retention in Kidney Failure Associated With Cognitive Impairment

A metabolite that is usually excreted in urine is associated with impaired cognitive function in patients with kidney failure, according to a new study.

“Retention of metabolites normally excreted by the kidney have long been thought to be a cause of cognitive impairment in patients with kidney failure, but the responsible metabolite(s) have remained unknown,” said study lead author Manjula K. Tamura, MD, at the Division of Nephrology at Stanford University School of Medicine.

The researchers performed metabolic profiling on predialysis blood samples from a cohort of 141 patients with kidney failure. They assessed cognitive function with the Trail Making Test Part B and the Digit Symbol Substitution test, and they defined impaired cognitive function as a score of 2 or more standard deviations below normative values.

The researchers found 4 metabolites–4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline–to be associated with impaired cognitive function.

The associations remained statistically significant after adjustment for demographic and clinical characteristics.

The researchers replicated the association between 4-hydroxyphenylacetate and impaired cognitive function in a second cohort of patients with kidney failure, whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort.

“These metabolites are not efficiently removed by conventional hemodialysis, and their blood levels are poorly correlated with blood urea nitrogen,” Dr Tamura said.

One of the study authors is investigating whether dietary approaches, such as increased intake of fiber, or changes to the dialysis prescription can lower levels of these metabolites.

—Mike Bederka

Reference:
Tamura MK, Chertow GM, Depner TA, et al; FHN Study. Metabolic profiling of impaired cognitive function in patients receiving dialysis [published online July 20, 2016]. J Am Soc Nephrol. doi:10.1681/ASN.2016010039.