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Chapter 33: Lupus Nephritis

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A 23-year-old woman with a 3-year history of SLE and biopsy-proven Class IV Diffuse Proliferative LN (high-activity index, low-chronicity index) received induction therapy with pulse cyclophosphamide monthly for 6 months and then switched to mycophenolate mofetil 1 g twice daily and low dose prednisone as maintenance therapy. Extrarenal disease remitted and lupus serologies and kidney function had normalized by the 1 year follow-up visit. Despite excellent compliance with the treatment regimen, between months 12 and 16 proteinuria steadily rose from a nadir, partial-remission value of 0.6–5.6 g/day and creatinine increased from a nadir value of 1.3–2.4 mg/dL. Urinalysis showed minimal hematuria along with granular, broad and waxy casts. Anti-DNA and complement that had normalized during induction therapy remained unchanged.

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Which of the following would represent the best approach to the escalating proteinuria and deteriorating renal function?

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A. Consider that the latest clinical scenario represents a flare of Class IV LN and reinstitute the previously successful induction regimen

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B. Consider that the new clinical scenario might represent a change in class of LN and proceed to a repeat kidney biopsy to gather evidence that will determine the need for possible change in therapies

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C. Consider that the patient has failed the best available therapies and prepare the patient for the inevitable need for end-stage renal failure therapies

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D. Switch to a completely different therapeutic approach to the flare using a combination of calcineurin inhibitor and rituximab

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The answer is B. There is rather broad experience showing that proteinuric flares can arise during maintenance therapy. In cases such as this, the renal pathology may reflect attenuated expression (related to the ongoing immunosuppression) of flares arising from the same original class of proliferative disease. Quite often, proteinuric flares in such cases may represent transition to class V lupus membranous nephropathy, or a combination of mixed membranous and proliferative LN. Renal biopsy is usually needed to distinguish these pathways, to assess the degree of cumulative damage, and to redirect therapies.

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A 25-year-old woman with inactive SLE seeks your counsel about the implications of starting a family. She had a 3-year history, starting at age 21, of active SLE, including Class IV Diffuse Proliferative LN. Induction therapy comprised of pulse methylprednisolone, prednisone, and 3 g/day of mycophenolate was very effective. She achieved complete clinical remission which has been sustained for the past year. Her maintenance treatment includes low-dose prednisone and 1.5 g/day of mycophenolate, along with lisinopril and birth control pills. Serum creatinine concentration is 1.4 mg/dL, C3, and C4 are normal; anti-DNA has improved during induction but has persisted at low titers.

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Which of the following approaches would represent sound ...

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