What is the best approach to manage seizures in a patient with Focal Segmental Glomerulosclerosis (FSGS)?

Management of Seizures in Patients with FSGS

Seizures in FSGS patients are not a direct manifestation of the glomerular disease itself but rather a complication requiring standard neurological management while carefully considering the patient's underlying kidney disease and immunosuppressive therapy.

Understanding the Clinical Context

Seizures occurring in FSGS patients typically arise from:

• Metabolic derangements related to nephrotic syndrome (severe hyponatremia from diuretic overuse, hypocalcemia, hypomagnesemia) 1
• Hypertensive encephalopathy from uncontrolled blood pressure in the setting of kidney disease 1
• Drug toxicity from calcineurin inhibitors (cyclosporine or tacrolimus), which can cause neurotoxicity and lower seizure threshold 1, 2
• Genetic syndromes where FSGS occurs alongside neurological manifestations (rare autosomal recessive forms with psychomotor retardation, microcephaly, and seizures) 3

Immediate Seizure Management Algorithm

Step 1: Stabilize and identify the cause

• Obtain immediate serum electrolytes (sodium, calcium, magnesium), glucose, and renal function 1
• Measure blood pressure urgently to exclude hypertensive emergency 1
• If on cyclosporine or tacrolimus, obtain trough levels immediately 1, 2
• Perform neuroimaging (CT or MRI) to exclude structural lesions or posterior reversible encephalopathy syndrome (PRES) 1

Step 2: Treat the seizure with standard anticonvulsants

• Use benzodiazepines (lorazepam or diazepam) for acute seizure termination, with dose adjustment for renal function 1
• Initiate maintenance anticonvulsant therapy based on standard neurological protocols, selecting agents with minimal renal excretion if kidney function is impaired 1

Step 3: Address the underlying cause

• If hyponatremia: Correct slowly (no faster than 8-10 mEq/L per 24 hours) to avoid osmotic demyelination 1
• If hypertensive emergency: Lower blood pressure gradually with IV agents, targeting systolic BP ≤125/80 mmHg as recommended for nephrotic syndrome 1, 4
• If calcineurin inhibitor toxicity: Reduce or temporarily discontinue cyclosporine/tacrolimus and consider alternative immunosuppression 1, 2
• If hypocalcemia/hypomagnesemia: Replete cautiously with IV supplementation 1

Adjusting FSGS Treatment in Context of Seizures

Corticosteroid considerations:

• High-dose corticosteroids (prednisone 1 mg/kg/day up to 80 mg or 2 mg/kg alternate day up to 120 mg) remain first-line for primary FSGS with nephrotic syndrome, but may worsen seizure control through electrolyte disturbances 1, 5
• Monitor sodium and glucose closely, as steroids can cause hyponatremia and hyperglycemia 1

Calcineurin inhibitor management:

• If seizures are CNI-related: Cyclosporine and tacrolimus both cause neurotoxicity, with risk increasing at higher trough levels 1, 2
• Target lower cyclosporine trough levels (100-125 ng/mL rather than 125-175 ng/mL) or tacrolimus levels (4-6 ng/mL rather than 5-10 ng/mL) if neurotoxicity suspected 1
• Consider switching from cyclosporine to alternative agents (MMF, rituximab) if seizures persist despite dose reduction 2

In elderly patients with seizures:

• Strongly consider calcineurin inhibitors as first-line rather than high-dose corticosteroids due to better side effect profile, but use lower target levels given seizure history 4
• Ensure infection prophylaxis (trimethoprim-sulfamethoxazole, vaccinations) as immunosuppression increases CNS infection risk 4

Critical Monitoring Parameters

• Weekly electrolytes during the first month of immunosuppression, then monthly 1
• Blood pressure monitoring at every visit, targeting ≤125/80 mmHg with ACE inhibitor or ARB at maximally tolerated dose 1, 4
• CNI trough levels every 2 weeks initially, then monthly once stable 1
• Neurological examination at each follow-up to detect early signs of encephalopathy 1

Common Pitfalls to Avoid

• Do not attribute all seizures to FSGS itself—this is a glomerular disease and seizures require separate neurological evaluation 3, 6
• Do not continue full-dose CNIs if neurotoxicity is suspected; dose reduction or discontinuation takes priority over maintaining immunosuppression 1, 2
• Do not correct hyponatremia rapidly in nephrotic patients on diuretics, as this causes more harm than the hyponatremia itself 1
• Do not withhold immunosuppression entirely unless seizures are clearly drug-related; untreated nephrotic syndrome from primary FSGS leads to ESRD in 50% of cases within 5-10 years 2, 7, 6

When Genetic FSGS with Neurological Syndrome is Suspected

• Consider genetic testing if patient presents with FSGS plus seizures, psychomotor retardation, microcephaly, or dysmorphic features 3
• Do not use immunosuppression in confirmed genetic FSGS, as it provides no benefit and only adds toxicity 1, 6
• Focus on supportive care with ACE inhibitors/ARBs and blood pressure control 8, 6