Immunosuppression in Kidney Diseases and the 80-20 rule

When writing this article I felt a need to add more and more information, to be comprehensive.  I had a fear of leaving something out.

I need to stop.  The intention of BCNephro is not to be an encyclopedic nephrology resource.

The intention is to share my experiences in a way that makes topics in nephrology easy to understand.

This is where the 80-20 (Pareto) principle comes in.

What is the Pareto principle?

80% of outcomes come from 20% of causes

How does this apply to immunosuppression in kidney diseases?  If you know the following 5 immunosuppressive medications you will know the vast majority of treatments for glomerulonephritis and glomerulopathies (nephrotic syndrome).  After these 5 there are diminishing returns.

Immunosuppression:  The Big 5

• Glucocorticoids
• Cyclophosphamide
• Calcineurin inhibitors
• Rituximab
• Mycophenolate Mofetil

Glucocorticoids

Dosing:  Glucocorticoids are typically given in 2 ways

• IV: Pulse methylprednisolone.  1 gram daily x 3 days
• Oral: Prednisone.
  • High dose: (ie. 60 mg a day or 120 mg every other day) used in:
    • Taper post IV pulse
    • Single agent therapy
  • Low Dose: (ie. 15 mg day or ½ mg/kg every other day)
    • In conjunction with other immunosuppressants

Things to be Aware of:

When I Use:

My take:

• I will not use high dose prednisone for > 2 months. Patients will universally become Cushingnoid and often have severe complications.
• I prefer regimens with low dose steroids in combination with other immunosuppressants.

Cyclophosphamide

Dosing:  Cyclophosphamide also can be given IV or PO

• IV
  • 750 mg / m² monthly
  • 500 mg (flat dose) every 2 weeks
• Oral – 1.5-2 mg / kg

Things to be Aware of:

When I Use:

My Take:

• Avoid prolonged use (> 6 months oral or multiple IV courses).
• More likely to induce durable remission than other immunosuppressants (especially calcineurin inhibitors)
• Useful agent despite concerns of toxicities leading to preferential use of other agents
• Avoid use in elderly or frail patients
• Prefer to start with lower doses (ie 1.5 mg/kg/day oral). Decrease dose further with decreased eGFR or elderly

Calcineurin inhibitors: Cyclosporine and Tacrolimus

Dosing:

Oral:

• Cyclosporine:
  • 3-5 mg/kg/day divided in two daily doses (every 12 hrs)
  • Target Trough: 150-200
• Tacrolimus:
  • 05 – 0.10 mg/kg/ day – divided in two daily doses (every 12 hrs)
  • Target Trough: 4-7

Things to be Aware of:

When I Use:

My take:

• Frequent relapse when weaned.
• Prolonged course (1-2 years) with slow wean.
• Membranous Nephropathy: useful as bridge therapy with rituximab.
• FSGS: My preferred option with low dose steroids.

Rituximab

Dosing:

• IV: Typically given in 2 doses (1 gram separated by 2 weeks)
• Can also give 375 weekly x 4 (which is the standard lymphoma dose)
• Maintenance can be dosed every 6 months

Things to be Aware of:

When I Use:

My Take:

• Often preferred over cyclophosphamide (especially in elderly and frail patients). It is considered safer, but is by no means safe.
• Can follow CD 19 count to help decide timing of maintenance doses.

MMF:  Mycophenolate mofetil

Dosing:

• Oral: Target dose 1000 – 1500 mg twice a day.
• Often start at 500 mg twice a day with uptitration as tolerated.

Things to be Aware of:

When I Use:

My Take:

• Often preferred for in SLE nephritis (over cyclophosphamide) particularly when concerns of fertility in female patients.
• Sometimes used as an attempt in other refractory or relapsing glomerulopathies.

Summary

Familiarity of the dosing, complications and indications of these 5 immunosuppressive medications will provide one with the knowledge of the treatment of the vast majority of glomerulonephritis and nephrotic syndrome glomerulopathies.