Correct answer: Percutaneous kidney biopsy

Discussion

This patient has the acute nephritic syndrome with depressed kidney function, hypertension, and tea-colored urine with acanthocytes. This is sufficient clinical information to pursue a kidney biopsy. Although CT imaging of the kidneys could likely be done quickly, this presentation is not consistent with a urologic source of hematuria with casts and noted proteinuria; therefore, a CT scan would not be warranted.

Question 2 of 10

Diffuse proliferative (class 4) lupus nephritis

Discussion

When patients with lupus present with the acute nephritic syndrome, the types of lupus nephritis (LN) to consider are class 3 and class 4. The difference between the two is based on how many glomeruli are involved with endocapillary proliferation (class 3 <50%, class 4 >50%), with class 4 typically having more severe symptoms.¹ In this patient, 75% of the glomeruli had proliferative lesions. As a group, patients with class 4 LN will have a more severe degree of kidney dysfunction, hypertension, and proteinuria (including nephrotic range) than class 3 LN. Despite this, differentiating class 3 from class 4 LN is not possible clinically because some patients with class 3 LN will have more severe disease if the number of glomeruli involved approaches 50%. Likewise, occasionally a patient with class 4 LN can present without hypertension or kidney dysfunction. Option B is incorrect because this patient is not nephrotic clinically and proteinuria is not in the nephrotic range, making class 5 LN very unlikely. Option E is not correct as the platelet count, although a bit lower, is not low enough to suggest and thrombotic microangiopathy.

Question 3 of 10

Correct answer: mycophenolate mofetil and IV cyclophosphamide

Discussion

High-dose mycophenolate mofetil (MMF) at a dose of 1000-1500 mg twice daily in addition to high-dose corticosteroids is the first-line therapy for proliferative LN because of its favorable side effect profile compared with cyclophosphamide. A regimen of low-dose IV cyclophosphamide (Eurolupus protocol) has been shown to have similar efficacy as MMF and a similar side effect profile.^2,3 Thus, both MMF and IV cyclophosphamide are considered first-line therapies. However, consideration should be made for specific side effect profiles when choosing a regimen. In particular, the risk of infertility would need to be reviewed in-depth with a female patient of child-bearing age. The Eurolupus protocol³ is used more frequently in Europe than in the United States, where, in general, MMF is often the first-line therapy. This preference is noted in the American Society of Rheumatology guidelines.² None of the other medications would be considered first-line therapy for lupus nephritis.^4-7 Recently, a new calcineurin inhibitor, voclosporin (Lupkynis), was FDA approved for use with MMF and corticosteroids in patients with LN. The AURORA phase 3 clinical trial showed this combination resulted in higher renal response rates with a similar side effect profile.⁸ This has not yet been officially determined to be a first-line regimen.

Question 4 of 10

Correct answer: C3, C4, and dsDNA Ab levels

Discussion

Measuring the therapeutic response of systemic lupus symptoms, kidney function, and proteinuria are considered key clinical factors in determining whether remission is achieved. However, depressed C3 and C4 levels and elevated dsDNA levels are hallmarks of a lupus nephritis flare. These abnormalities will trend back to or close to normal ranges as remission is induced. None of the other lab values fluctuate with disease activity.^1,2

Question 5 of 10

Correct answer: Complement-mediated thrombotic microangiopathy

Discussion

All of the above can develop in a patient with active lupus and cause anemia and thrombocytopenia; however, this patient’s blood pressure is not high enough to cause a thrombotic microangiopathy.⁹ In studies, patients with malignant hypertension-associated thrombotic microangiopathy (thrombotic microangiopathy resolved only after controlling blood pressure) had a mean arterial pressure of 159 mm Hg (range 123-189 mm Hg)¹⁰ or mean blood pressure of 262/160 mm Hg¹¹ with more severe kidney dysfunction (mean serum creatinine 5.2 mg/dL) than patients with “primary” thrombotic microangiopathy.¹⁰ This patient’s mean arterial pressure was 107 mm Hg, which is not in a range expected to cause a thrombotic microangiopathy.

Case continued

Two months after starting therapy with prednisone and MMF, the patient develops a viral gastroenteritis with fevers, chills, nausea, and vomiting that turns into abdominal bloating and diarrhea. She notifies you a week later that she feels better except for persistence of the diarrhea and abdominal bloating.

Question 6 of 10

Correct answer: decrease MMF dose

Discussion

The major dose-limiting side effects of MMF are gastrointestinal (GI) side effects (abdominal pain and diarrhea) and leukopenia. GI side effects will often be dose-dependent, in which patients will tolerate lower doses but not higher ones. They can also contribute to persistence of diarrhea from another cause even when that cause has resolved. In these cases, decreasing the MMF dose or even holding it for up to a week may be needed for the diarrhea to resolve¹²

Question 7 of 10

Correct answer: Male sex

Discussion

Although lupus nephritis is more common in females, males are at higher risk for progression of kidney disease, as are nonwhite race, lower socioeconomic status, onset in children, frequent relapses, or failure to reach complete remission and proteinuria levels above 4 grams/24 hours at presentation.¹³

Case continued

After 1 month on MMF and a tapering dose of prednisone, the patient’s lupus symptoms have resolved. Lab study results show serum creatinine 1.1 mg/dL, C3 65 mg/dL, C4 28 mg/dL, and urine protein: creatinine ratio of 0.8 g/g.

Question 8 of 10

Correct answer: no changes

Discussion

The standard course of MMF induction therapy is 4 to 6 months. After that, the dose can be reduced to 500 to 750 mg twice/day.^1,4

Question 9 of 10

Correct answer: Pneumocystis jirovecii

Discussion

The use of mycophenolate mofetil alone does not warrant Pneumocystis jirovecii prophylaxis, but use of high-dose prednisone is a potential risk factor for resurfacing of Pneumocystis jirovecii infections. As such, it is common practice to use prophylactic antibiotics in such patients, especially for prednisone doses larger than 20 mg/day.¹⁴ It is not recommended that prophylactic regimens be used for any of the other infections listed in the answers.

Question 10 of 10

Correct answer: At least 2 years

Discussion

Although the optimal timeframe has not been established, the minimum time a patient should receive immunosuppressive therapy for lupus nephritis is 24 months, with some sources quoting up to 5 years.^1,9

KEY POINTS

• Lupus nephritis is a common complication of systemic lupus erythematosus, and will often occur earlier in the course of disease.
• Presentation with the nephritic or nephrotic syndrome warrants urgent referral for a kidney biopsy.
• Classes 3, 4, and 5 lupus nephritis most often require therapy.
• Standard first-line therapy for lupus nephritis includes high-dose corticosteroids and high-dose mycophenolate mofetil.
• Induction therapy is used for 4 to 6 months after which long-term lower-dose maintenance therapy is prescribed.