Neurologic Problems in Acute Renal Failure

Basic Pathophysiology of the Brain in Acute Renal Failure

In the intensive care unit (ICU) setting, the patient may be admitted with acute renal failure (ARF), or ARF may develop during the course of the patient's stay in the ICU. A majority of patients will experience additional aspects of organ failure other than ARF, and sepsis, trauma, and surgery also will have an impact on cerebral function. In ARF cerebral blood flow often is reduced, with alterations in the blood-brain barrier leading to localized areas of increased permeability with astrocyte swelling. In part, these changes are compensatory as a result of the changes in plasma osmolality, owing to the retention of urea and other osmolytes, and accompanying acidosis. Neurotransmitter regulation is affected, with inhibition of the GABA-ergic inhibitory system, and activation of the excitatory N -methyl- d -aspartate system. These changes can be exacerbated by other conditions; for example, in severe sepsis without direct central nervous system infection, cerebral perfusion is decreased, with increased blood-brain barrier permeability and an influx of glutamate and other amino acids, resulting in increased elaboration of neurotransmitters. Postmortem examination has shown various anatomic changes including astrocyte and glial cell swelling in the cortex, cerebral micro- and macroinfarcts, multiple small white matter hemorrhages, central pontine myelinosis, and disseminated microabscesses.

In clinical practice, neurologic assessment may be difficult, especially when patients are sedated and paralyzed. Glial cells (astrocytes, microglia, and oligodendrocytes) play a major role in coordinating the response to brain injury with neurons. Astrocyte reactivity or astrogliosis in response to brain injury is characterized by three key features: hypertrophy, increased expression of intermediate filaments (glial-fibrillary acidic protein [GFAP]), nestin and vimentin. In addition, S-100β protein, a calcium-binding protein found predominantly in astrocytes, and neuron-specific enolase, an intracytoplasmic glycolytic enolase located in neurons and Schwann cells, have been proposed as biomarkers of brain injury, with increasing levels when the blood-brain barrier is disrupted with underlying brain injury. Myelin-basic protein (MBP) is a specific marker of oligodendrocytes and can be detected in blood, indicating potential disruption in myelin, leading to axonal injury. However, the role of these biomarkers in clinical practice remains to be established.

Infections Causing Acute Renal Failure and Cerebral Dysfunction

Acute uremia and systemic sepsis can cause delirium. With ARF resulting from sepsis, it often is difficult to exclude underlying structural brain abnormalities, such as abscesses, in patients who are confused and unable to fully cooperate in the acute setting. Circulating cytokines can cross the blood-brain barrier at the base of the third ventricle resulting from the fenestration of the capillaries in the median eminence, and as such confusion and delirium are common complications of severe generalized sepsis. All patients admitted to the ICU with renal failure and sepsis should have an ultrasound examination of the urinary tract to exclude renal obstruction.

Although ARF can develop in patients admitted to the ICU with severe sepsis of any cause, some infections typically cause acute cerebral involvement and renal dysfunction. Cerebral involvement may be due to direct infection of the brain and meninges, causing encephalitis and meningitis, or confusion resulting from toxin release or a vasculopathy resulting from infection-induced vasculitis or local thrombosis ( Table 106.1 ). The key to clinical management is to recognize when ARF is not due to simple renal hypoperfusion consequent to sepsis—for example, acute proliferative or crescentic nephritis after staphylococcal infection resolves more quickly with steroid therapy once the infection has been treated appropriately with antibiotics. Thus an essential component of evaluation is dipstick testing of urine for blood and protein, along with standard microscopy and culture, as well as cytologic examination of the urine.

In immunocompromised patients such as renal transplant recipients and other patients who have received solid organ transplants, ARF may occur readily in systemic sepsis. The scope of the differential diagnosis widens, owing to the possibility of Listeria monocytogenes meningitis, cerebral toxoplasmosis, fungal meningitis, viral encephalitis, human immunodeficiency virus (HIV), and cerebral lymphoma resulting from posttransplantation lymphoproliferative disease.