A 20-year-old woman comes to the office due to intermittent pain and swelling of both knees over the past 3 months. She has no fever, chills, or abnormal vaginal discharge. The patient has no other medical conditions and is not sexually active. Temperature is 37.2 C (99 F), blood pressure is 150/90 mm Hg, and pulse is 78/min. Small, nontender oral ulcers are present. Examination shows mild tenderness of the knee joints but no effusion. The remainder of the examination shows no abnormalities. Laboratory results reveal anemia, thrombocytopenia, and elevated serum creatinine. Urinalysis shows proteinuria and red blood cell casts. Which of the following pathogenic mechanisms is most likely responsible for this patient's renal disease?
This young woman with hypertension, elevated serum creatinine, proteinuria, and red blood cells casts on urinalysis has glomerulonephritis. In association with the transient arthralgias, oral ulcers, and cytopenia, this presentation suggests systemic lupus erythematosus (SLE) complicated by lupus nephritis. SLE is an autoimmune disease that occurs due to the formation of autoantibodies against cell surface and nuclear antigens. Disease manifestations result from direct tissue injury by the autoantibodies or from the formation of circulating immune complexes that deposit in tissues.
Lupus nephritis occurs primarily due to deposition of DNA/anti-DNA immune complexes within the glomerulus (eg, mesangium, subendothelial or subepithelial space). This results in the activation of complement and the recruitment of inflammatory cells (type III hypersensitivity), leading to glomerular injury and reduced renal function. Elevated levels of anti-DNA antibodies often precede clinically apparent renal disease and can be used to monitor disease activity.
(Choice A) Activation of CD4+ and CD8+ T lymphocytes by donor histocompatibility antigens occurs during acute cellular rejection of a renal allograft. CD8+ T cells do not play a prominent role in the pathogenesis of lupus nephritis.
(Choice B) Poststreptococcal glomerulonephritis is another cause of nephritic syndrome and results from glomerular deposition of immune complexes involving streptococcal antigens. However, it typically occurs 1-4 weeks after an infection (eg, impetigo, pharyngitis) and is far more common in young children. In addition, it is not associated with oral ulcers or cytopenias.
(Choice D) Multiple myeloma can cause anemia and bone pain; kidney injury occurs due to monoclonal free light-chain deposition in the renal tubules. However, urinalysis would be expected to demonstrate waxy casts composed of Bence Jones proteins, not red blood cell casts. In addition, multiple myeloma does not cause oral ulcers and is extremely uncommon in young patients.
(Choice E) Autoantibodies against podocyte antigens occurs in membranous nephropathy. Although membranous nephropathy can occur in SLE, it results in nephrotic syndrome characterized by massive proteinuria and edema. Red blood cell casts are unexpected.
Educational objective:
Systemic lupus erythematosus is an autoimmune disease characterized by the formation of antinuclear antibodies (eg, anti-DNA antibodies). Lupus nephritis occurs primarily due to the formation of immune complexes containing DNA and anti-DNA in the circulation. These are deposited in the glomerulus where they result in complement activation, recruitment of inflammatory cells, and renal injury (type III hypersensitivity).