A 37-year-old woman comes to the office due to worsening leg swelling for the past 2 months. She has also felt excessively tired and has had achy pain in her hands during this time. The patient reports occasional respiratory illness and minor "aches and pains." She has no chronic medical conditions and takes no medications. She occasionally drinks 1 or 2 glasses of wine during social gatherings but does not use tobacco or illicit drugs. Temperature is 37.3 C (99 F), blood pressure is 156/92 mm Hg, and pulse is 86/min. Physical examination shows normal jugular venous pressure, dullness and decreased breath sounds at the left lung base, normal heart sounds, and no abdominal organomegaly. There is 3+ bilateral lower extremity pitting edema. Bilateral finger joints and wrists are mildly swollen and tender to palpation. Laboratory studies reveal a hemoglobin of 9.1 g/dL, platelet count of 102,000/mm³, and serum creatinine level of 2.1 mg/dL. A peripheral blood smear is normal. Urinalysis is positive for proteinuria and hematuria. Which of the following is most likely involved in the pathogenesis of this patient's renal disease?

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Explanation: 11ec25c8_d500_350e_bc81_3b1742258123_MD0003_00 This patient's hypertension, proteinuria, hematuria, elevated serum creatinine, and significant lower extremity edema raise strong suspicion for glomerulonephritis. The concurrent presence of fatigue, inflammatory arthritis (swollen, tender joints), anemia, and thrombocytopenia suggests the underlying cause is systemic lupus erythematosus (SLE). Lupus nephritis is seen in most patients with SLE and is usually caused by the deposition of anti-double-stranded DNA immune complexes in the glomerulus. Depending on the location and severity of immune complex deposition, patients can develop subclinical (eg, microscopic hematuria, proteinuria) or clinically significant disease, including the following: Glomerulonephritis - immune complexes are deposited above the glomerular basement membrane, which triggers neutrophil and macrophage recruitment from the bloodstream. This results in significant glomerular inflammation, leading to an active urine sediment (eg, hematuria, cellular/granular casts), proteinuria, and renal insufficiency. Nephrotic syndrome - immune complexes are deposited below the glomerular basement membrane (separated from the vasculature) so immune cell recruitment does not occur. This results in nephrotic syndrome with a bland urine sediment (eg, no hematuria). Because lupus nephritis often causes significant urinary protein loss, patients frequently develop low serum albumin with subsequent lower extremity edema and pleural effusions (ie, dullness to percussion and decreased breath sounds). Risk of lupus nephritis is greatest in those with higher serum anti-double-stranded DNA antibody titers. (Choice A) Multiple myeloma is associated with the production of monoclonal immunoglobulin, which can deposit in the renal tubules and cause renal insufficiency. This generally leads to proteinuria and the presence of granular casts but no hematuria. In addition, myeloma is uncommon in young patients, and arthritis is not a typical manifestation. (Choice C) Poststreptococcal glomerulonephritis arises after infection with nephrogenic strains of group A beta-hemolytic Streptococcus. Although it is also a glomerulonephritis caused by immune complex deposition, most cases arise in children and are not associated with inflammatory arthritis or cytopenias. (Choice D) Sickle cell disease can lead to ischemia and infarction of the renal medulla due to occlusion of the vasa recta capillaries with sickled red cells. Over time, this often leads to impaired renal function and hypertension. However, this patient's normal peripheral blood smear makes sickle cell disease unlikely. (Choice E) Microthrombotic occlusion of the renal vasculature can be seen in hemolytic uremic syndrome or thrombotic thrombocytopenic purpura. Although patients often have elevated creatinine, anemia, and thrombocytopenia, peripheral blood smear would show signs of red blood cell shearing (eg, schistocytes). Educational objective: Lupus nephritis is caused by deposition of anti-double-stranded DNA immune complexes in the glomerulus, which leads to glomerulonephritis (eg, hematuria, proteinuria, renal insufficiency, hypertension, peripheral edema) or nephrotic syndrome. Serum anti-double-stranded DNA antibody titers correlate with risk of nephritis. References: The pathogenesis of lupus nephritis. (http://www.ncbi.nlm.nih.gov/pubmed/23929771)

A 37-Year-Old Woman Comes to the Office Due to Worsening