Kidney Disease and Epilepsy

Introduction

Seizures refer to abnormal neurological functions marked by uncontrolled, spontaneous electrical activity in the brain. These fits tend to bring a sudden change in one’s behavior, movement, actions, or even feelings. One may experience two or more seizures within a day when suffering from epilepsy. It is important to note the incidence of seizures in patients with chronic kidney disease. The nephrologists often find it challenging to manage the epileptic incidents while simultaneously keeping the kidney disease in check. It may be possible for the person to be epileptic before the occurrence of kidney disease. However, many times, kidney-related etiologies such as uremic encephalopathy, dialysis, and hyponatremia may also be held responsible for the incidence of seizures. The use of anti-epileptic drugs needs to be cautiously monitored in patients with chronic kidney disease. This article aims to highlight this neglected problem in patients with kidney disease and discusses ways to manage seizure episodes.

How Are Chronic Kidney Disease (CKD) and Seizures Related?

Seizures are not a disease but a symptom of a pre-existing disorder. Data suggests that ten percent of the world's population will suffer from a seizure at least once in their lifetime, out of which one percent will be deemed epileptic. The incidence of seizures in patients with chronic kidney disease accounts for ten percent. About one-third of patients with uremic encephalopathy develop seizures. There are two main categories of people when it comes to establishing a link between CKD and seizures:

1. People who develop provoked seizures are encountered during or due to CKD.

2. People who are already epileptic and develop CKD later.

Recognizing the seizures and managing them effectively can be a serious challenge for clinicians, especially non-neurologists. There are varied types of seizures that one may suffer from. The seizure may be focal or generalized depending on the origin and level of motor movement involved. These include:

• Myoclonic Seizures: These are seizures characterized by lightning-fast, sudden muscular movements. These seizures can be potentially harmful if they occur during mid-activities, such as driving or carrying something heavy.

• Focal Aware Seizures: These are also referred to as focal onset seizures. These happen when a person is fully aware of his or her conscious self and surroundings. There can be slight alterations in the movements and feelings observed. However, the seizure is quite short-lived, mostly two minutes.

• Absence Seizures: These seizures are marked by short, sudden lapses of the conscious state. The person experiencing this seizure may appear zoned out during the time of the seizure and may return to the alert state post-seizure. These seizures do not cause any potential harm to the patient.

• Generalized Tonic-Clonic Seizures: A person experiencing a generalized tonic-clonic seizure loses consciousness and experiences muscular stiffness and jerks. Typically, these seizures begin on both sides of the brain and are generalized.

• Convulsive or Non-Convulsive Status Epilepticus (NCSE): Depending on the type of seizure, different temporal thresholds apply to characterize unusually protracted seizures. This lasts five minutes for convulsive status epilepticus. The threshold for NCSE is ten minutes, where NCSE is defined as status epilepticus without noticeable motor signs.

What Are the Causes of Seizures in Uremia?

Seizures associated with uremic encephalopathy are also quite commonly seen. There is a vast array of reasons proposed that explain the cause of these seizures in uremia patients.

1. Rapid Accumulation of Uremic Toxins: It has been suggested that the build-up of guanidino compounds throughout uremia activates excitatory N-methyl-D-aspartate (NMDA) receptors and inhibits inhibitory GABA receptors, perhaps leading to myoclonus and seizures.

2. Enhanced Cortical Excitability: A key component of how the human brain functions is cortical excitability, defined as the strength of a cortical neuron's reaction to a particular stimulus. This property represents neuron reactivity and response specificity. Increased cortical excitability may be the underlying cause of epilepsies and the tendency to experience seizures.

3. Electrolyte Disbalance: Seizures may be the only presenting symptom of acute or severe electrolyte abnormalities. Patients with hypocalcemia, hypomagnesemia, and salt disorders—particularly hyponatremia—are more likely to experience seizures.

4. Dialysis Disequilibrium Syndrome: Dialysis disequilibrium syndrome is the term used to describe neurological symptoms and indications that occur during or soon after dialysis. The osmotic fluid shift following hemodialysis is linked to the change in urea level. It is likely due to the quick removal of compounds like urea that build up in the blood. This may cause an imbalance in the fluid content of the brain's cells, which may result in swelling and symptoms including headache, nausea, restlessness, confusion, or, in extreme situations, seizures, coma, and even death.

5. Other Causes: Air embolism, sepsis, antibiotic usage, subdural hematomas, higher incidence of stroke, and Posterior Reversible Encephalopathy Syndrome (PRES) are some of the other reasons that may contribute to the occurrence of seizures in patients with chronic kidney disease.

What Are the Effects of Anti-Epileptic Drugs on the Kidney?

The seizures encountered in a kidney disease patient are managed by administering anti-epileptic drugs (AEDs). The drugs, however, pose a set of consequences that are borne by the kidney. These are:

• Nephrolithiasis: This is the term given to kidney stones that may be small or large and cause immense pain during the passage of urine.

• Interstitial Nephritis: This disease causes swelling (inflammation) in the gaps between the renal tubules. This may result in issues with renal function.

• Drug-Induced Lupus Nephritis: The effect of drugs can cause kidney inflammation to aggravate into lupus. The cessation of the drug is advised in such cases.

• Hyponatremia: Low levels of sodium in blood result from improperly administered AEDs.

• Hypokalemia and Hypomagnesemia: An electrolyte imbalance can be observed with AED administration that is not supervised or monitored according to the needs of the CKD patient.

• Peripheral Edema: AED may occasionally result in fluid accumulation, leading to swelling in lower limbs.

Conclusion

Seizures affect approximately ten percent of patients with end-stage renal failure. Using a low threshold, measuring seizures in people with encephalopathy is recommended. It is strongly advised to keep a neurologist informed about any neurological symptoms a renal disease patient may be experiencing. Before starting any other form of treatment, the seizure's primary cause should always be addressed. When giving AEDs to patients with CKD and epilepsy, caution is required.