American Journal of Physiology - Renal Physiology
American Journal of Physiology - Renal Physiology
5 years ago

Accumulation of Uremic Solutes in the Cerebrospinal Fluid in Experimental Acute Renal Failure

Robert DeWolfe Mair, Huy Nguyen, Ting-Ting Huang, Natalie S. Plummer, Tammy L Sirich, Timothy W. Meyer
The accumulation of uremic solutes in kidney failure may impair mental function. This study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 hours after sham operation (control, n=10) or bilateral nephrectomy (nephrectomy, n=10) and analyzed using an established metabolomic platform. 248 solutes were identified as uremic based on their accumulation in plasma ultrafiltrate of nephrectomized compared to control rats. CSF levels of 124 of these solutes were sufficient to allow calculation of CSF/plasma ultrafiltrate concentration ratios. Levels of many of the uremic solutes were normally lower in the CSF than in the plasma ultrafiltrate indicating exclusion of these solutes from the brain. CSF levels of the great majority of the uremic solutes increased in renal failure. The increase in the CSF was however relatively less than in the plasma ultrafiltrate for most solutes. In particular, for the 31 uremic solutes with CSF to plasma ultrafiltrate ratios less than 0.25 in control rats, the average CSF to plasma ultrafiltrate ratio decreased from 0.13 ± 0.07 in control rats to 0.09 ± 0.06 in nephrectomized rats revealing sustained ability to exclude these solutes from the brain. In summary, levels of many uremic solutes are normally kept lower in the CSF than in the plasma ultrafiltrate by the action of the blood-brain and blood-CSF barriers. These barriers remain functional but cannot prevent accumulation of uremic solutes in the CSF when the kidneys fail.

Publisher URL: https://physiology.org/doi/abs/10.1152/ajprenal.00100.2019

DOI: 10.1152/ajprenal.00100.2019

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