How is lupus nephritis treated

How is lupus nephritis treated?

Although the clinical presentation (signs, symptoms, serologic and urine tests) is an important part of determining the therapy of lupus nephritis, the information gained from a kidney biopsy is the most useful determinant of a treatment decision for this disease.

The biopsy will differentiate severe active lupus nephritis (diffuse or segmental proliferative glomerulonephritis with or without membranous disease) from milder (mesangial glomerulonephritis) or inactive forms.

Treatment of severe active lupus nephritis is separated into an induction phase, of which the goal is to induce a remission, and a maintenance phase, of which the goal is to maintain remission and prevent relapse.

Because lupus nephritis is a rare and heterogeneous disease, a standard treatment algorithm does not exist, and treatment is currently individualized. However, based on evidence from clinical trials, the therapeutic options for the induction phase are high-dose prednisone coupled with cyclophosphamide or mycophenolate mofetil (MMF).

Cyclosporine is another option for induction, typically when membranous glomerulonephritis is present. To date, there is insufficient data to support the use of rituximab as initial induction therapy for severe lupus nephritis. However, rituximab may be effective in patients with severe lupus nephritis with refractory or relapsing disease.

Plasmapheresis has been proven to be ineffective when added to induction with cyclophosphamide and prednisone.

The length of induction depends on the method of administration and the response or side effects to the therapy but is typically from 2 to 12 months of therapy.

Therapeutic choices for the maintenance phase, which occurs after successful induction and lasts several years (perhaps for life), include MMF, azathioprine, or rarely cyclosporine. Low-dose prednisone is continued with goal of slowly tapering off or attaining the minimal dose required to control symptoms.

Immunomodulatory Treatment Options for Severe Lupus Nephritis

Induction

  • High-dose steroids (e.g., intravenous methylprednisolone initially or oral prednisone 1 mg/kg not to exceed 80 mg daily, tapering at 4–8 weeks depending on response) plus one of the following:
  • Oral cyclophosphamide 2 mg/kg daily (not to exceed 150 mg daily) for 6–12 weeks. Dose to be adjusted based on white blood cell count
  • High-dose IV cyclophosphamidea 0.5–1.0 g/m2 body surface area (BSA) monthly for 6 months. Dose to be adjusted based on white blood cell count
  • Low-dose IV cyclophosphamidea 500 mg every 2 weeks for six doses. Dose to be adjusted based on white blood cell count
  • Oral mycophenolate mofetil 2–3 g daily in two divided doses for 6 months

Maintenance

Choices of maintenance therapy are as follows:

Oral mycophenolate mofetil 0.5–2 g daily in two divided doses with prednisone taper

Oral azathioprine 1–3 mg/kg daily with prednisone taper

Cyclosporine dosed 2–4 mg/kg daily to keep trough levels 75–200 ng/mL with prednisone taper

Low-dose prednisone is continued with goal to slowly taper off or to attain the minimal dose required to control symptoms

Dose adjustment for kidney dysfunction is recommended.

Extrarenal manifestations and symptoms should be identified and treated appropriately.

Use of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to control blood pressure is essential. Managing sequelae of the nephrotic syndrome, such as hyperlipidemia and edema, can be achieved with lipid-lowering agents and diuretics coupled with a low-sodium diet.

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