How to manage coordination issues in a patient with minimal change disease (MCD) who is receiving immunosuppressive therapy, such as corticosteroids (e.g. prednisone) or calcineurin inhibitors (e.g. cyclosporine or tacrolimus)?

Management of Coordination Issues in Minimal Change Disease Patients on Immunosuppressive Therapy

Critical Recognition: Coordination Issues Are Not a Direct Feature of MCD or Standard Immunosuppressive Therapy

Coordination problems are not a recognized adverse effect of corticosteroids, cyclosporine, or tacrolimus in minimal change disease treatment, and their presence should trigger immediate evaluation for alternative neurological causes rather than being attributed to MCD therapy. 1

Immediate Diagnostic Approach

When a patient with MCD on immunosuppressive therapy develops coordination issues, you must systematically exclude:

• Calcineurin inhibitor neurotoxicity: While CNIs can cause tremor, headache, and rarely posterior reversible encephalopathy syndrome (PRES), frank coordination problems are uncommon and suggest toxicity requiring immediate drug level assessment 1
• Severe hypoalbuminemia complications: MCD-related nephrotic syndrome can cause cerebral venous thrombosis presenting with neurological deficits—check albumin levels and consider neuroimaging if albumin <2.0 g/dL 2
• Steroid-induced complications: High-dose corticosteroids (≥30 mg daily) can cause psychiatric symptoms and myopathy but not typically coordination deficits 3, 4
• Infection in immunosuppressed state: Progressive multifocal leukoencephalopathy or other CNS infections must be excluded in patients on combination immunosuppression 1

Specific Management Based on Immunosuppressive Agent

If Patient is on Calcineurin Inhibitors (Cyclosporine or Tacrolimus)

Immediately check CNI trough levels and serum creatinine:

• For cyclosporine: Target trough 60-150 ng/mL; levels >200 ng/mL increase neurotoxicity risk 1
• For tacrolimus: Target trough 5-10 ng/mL; aim for lowest level maintaining remission 1
• If creatinine elevated >30% above baseline: Reduce CNI dose by 25-50% immediately 1, 5
• If coordination issues persist after dose reduction: Discontinue CNI and obtain urgent brain MRI to exclude PRES or other structural lesions 1

If Patient is on High-Dose Corticosteroids

Assess for steroid myopathy versus CNS complications:

• Proximal muscle weakness (difficulty rising from chair, climbing stairs) suggests steroid myopathy—this is distinct from coordination problems 4
• True ataxia or coordination deficits are not typical steroid effects and warrant neuroimaging 4
• Consider transition to steroid-sparing agents if patient requires prolonged high-dose therapy (>16 weeks at 1 mg/kg daily) to minimize cumulative toxicity 1

Therapeutic Adjustments for MCD Management

Transition Strategy When CNI Must Be Discontinued

If CNI-related neurotoxicity is confirmed, switch to alternative steroid-sparing agents:

• Cyclophosphamide: 2 mg/kg/day for 8-12 weeks achieves durable remission in 68% of patients but carries gonadal toxicity risk 5, 6
• Mycophenolate mofetil: Reserve for patients intolerant of both cyclophosphamide and CNIs, though evidence quality is lower 5
• Rituximab: Consider in refractory cases, though should ideally be administered within clinical trial context 1

Monitoring Requirements During Continued Immunosuppression

For patients continuing CNI therapy after coordination issues resolve:

• Check serum creatinine every 2-4 weeks and maintain <30% above baseline 1, 5
• Obtain repeat renal biopsy at 12-24 months if creatinine remains elevated or maintenance dose >3.5 mg/kg/day to assess for CNI nephrotoxicity 1, 5
• Monitor CNI levels monthly to maintain therapeutic range while minimizing toxicity 1

Critical Pitfalls to Avoid

• Do not attribute neurological symptoms to MCD itself: MCD does not cause coordination problems; this represents either drug toxicity, thrombotic complication, or unrelated neurological disease 2
• Do not continue CNI at same dose if neurotoxicity suspected: Immediate dose reduction or discontinuation is mandatory to prevent irreversible damage 1
• Do not delay neuroimaging: If coordination issues persist despite CNI adjustment, urgent MRI is required to exclude PRES, stroke, or infection 1
• Do not abruptly stop all immunosuppression: MCD will relapse; transition to alternative agent while investigating neurological symptoms 5, 6

Long-Term Prognosis Considerations

MCD patients who respond to immunosuppression have excellent long-term kidney survival (<5% progress to ESRD), but neurological complications from therapy can cause significant morbidity requiring aggressive management. 2, 7