Acidosis, cognitive dysfunction and motor impairments in patients with kidney disease

Abstract

Metabolic acidosis, defined as a plasma or serum bicarbonate concentration <22 mmol/L, is a frequent consequence of chronic kidney disease (CKD) and occurs in ~10-30% of patients with advanced stages of CKD. Likewise, in patients with a kidney transplant, prevalence rates of metabolic acidosis range from 20% to 50%. CKD has recently been associated with cognitive dysfunction, including mild cognitive impairment with memory and attention deficits, reduced executive functions and morphological damage detectable with imaging. Also, impaired motor functions and loss of muscle strength are often found in patients with advanced CKD, which in part may be attributed to altered central nervous system (CNS) functions. While the exact mechanisms of how CKD may cause cognitive dysfunction and reduced motor functions are still debated, recent data point towards the possibility that acidosis is one modifiable contributor to cognitive dysfunction. This review summarizes recent evidence for an association between acidosis and cognitive dysfunction in patients with CKD and discusses potential mechanisms by which acidosis may impact CNS functions. The review also identifies important open questions to be answered to improve prevention and therapy of cognitive dysfunction in the setting of metabolic acidosis in patients with CKD.

Aphasia Associated With Acute on Chronic Kidney Failure in an Adolescent

“…Another proposed mechanism for our patient’s aphasia is uremic encephalopathy. The accumulation of uremic toxins, organic acids, and development of metabolic acidosis in CKD has been linked to the development of cognitive dysfunction [ 12 ]. The metabolic acidosis may lead to increased blood-brain barrier permeability and affect local metabolism to alter cognition [ 12 ].…”

“…The accumulation of uremic toxins, organic acids, and development of metabolic acidosis in CKD has been linked to the development of cognitive dysfunction [ 12 ]. The metabolic acidosis may lead to increased blood-brain barrier permeability and affect local metabolism to alter cognition [ 12 ]. A study on MRI findings in 10 patients with acute or chronic renal failure and predominately motor symptoms and dysarthria demonstrated diffusion imaging consistent with vasogenic or cytotoxic edema particularly affecting the basal ganglia and cerebral cortex [ 13 ].…”

State-of-the-Art Evaluation of Acute Adult Disorders of Consciousness for the General Intensivist

“…Patients with acute DoC due to uremic encephalopathy should undergo either IHD or CRRT to achieve metabolic clearance and neurologic reevaluation (51, 102). Patients taking valproic acid, or those with acute hepatic failure, may manifest hyperammonemia and benefit from gastrointestinal tract catharsis (i.e., lactulose) and luminal antibacterial therapy (i.e., rifaximin) to reduce potentially culpable metabolites (103, 104).…”

Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment

“…Moreover, it is possible that the metabolic acidosis that characterizes patients with CKD has an effect on cognitive ability, although there are currently few studies on this subject [42]. What is surprising, however, is the lack of correlation between the prevalence of MCI and that of metabolic acidosis, especially in the later stages of CKD [43]. The central nervous system might therefore operate an effective buffering system that prevents large changes in pH and mitigates the latter's cellular effects.…”