Markers for Lupus Nephritis

Hemapriya Gopal Reddy and others from Ascension St. John in Detroit, Michigan, described a case of diffuse class 4 lupus nephritis with normal complement levels at the National Kidney Foundation Spring Clinical Meetings.

A 35-year-old female presented with lower extremity swelling that was gradually worsening. The patient’s medical history included significant hypertension, diabetes, hyperlipidemia, and lupus nephritis treated with cyclophosphamide. She was receiving a maintenance dose of mycophenolate mofetil 1000 mg twice a day and prednisone for the previous 6 months.

The patient’s eVitals were stable, and a physical examination demonstrated lower extremity edema. Her laboratory results were 142.00 sodium, 4.70 potassium, 22.00 bicarbonate, 20.00 BUN, and 0.74 creatinine. Her hemoglobin was 12.6, white blood cell count 5.8, and platelets 234.0.

Low total complement hemolytic activity and decreased C3 and C4 levels are characteristic of lupus nephritis. This patient’s complements were normal: C3, 119 and C4, 28. ANA was positive, and C-ANCA and P-ANCA were negative (proteinase-3 antibody <0.2, myeloperoxidase antibody <0.2). Urinalysis showed protein of 500.0 mg/dl and a urine protein-to-creatinine ratio of 3.6 g/g.

A biopsy found widespread endocapillary hypercellularity and cellular and fibrocellular crescents in 6/25 glomeruli. Immunofluorescence revealed granular deposits of C1q, C3, IgA, IgG, and IgM along the capillary walls in the mesangium. The biopsy indicated diffuse class 4 lupus nephritis. The patient was given methylprednisolone 500 mg intravenously for 3 days and rituximab 1 g twice daily; she also continued mycophenolate mofetil 1500 mg twice daily. After beginning therapy, she showed 0.5 g/g improvement in proteinuria.

Decreased complements are considered a reliable marker for disease activity in lupus nephritis. However, as this case shows, a patient may present with normal creatinine and normal complements but still have highly active disease requiring therapy. Clinicians should be aware of this and readily conduct a biopsy of patients with lupus even if they are seemingly stable.

Source: Reddy HG, Topf JM, Henderson H. A case of diffuse class 4 lupus nephritis with normal complement levels. Presented at the National Kidney Foundation Spring Clinical Meetings 2024; May 14-18, 2024; Long Beach, California.