Case Presentation: A 48-year-old Hispanic man with no medical history presented with two weeks of bilateral extremity edema and gross hematuria. He was febrile and hypertensive with non-pitting edema of all extremities and right knee pain but no rashes or ulcers. Urinalysis showed 3+ blood and 200 mg/dL protein. Laboratory studies revealed hypoalbuminemia, normocytic anemia (Hgb 10–11 g/dL), thrombocytopenia (40–50K), positive direct antiglobulin test, low C3/C4, and elevated CRP; hepatitis serologies, infectious workup, rheumatoid factor, and cryoglobulins were negative.Nephritic syndrome with cytopenias raised concern for lupus nephritis, cryoglobulinemia, or thrombotic microangiopathy (TMA) (Thrombotic Thrombocytopenic Purpura [TTP], Hemolytic Uremic Syndrome [HUS]). ANA 1:80 (homogeneous) supported systemic lupus erythematosus (SLE), though anti–dsDNA, anti-Smith, antiphospholipid panel, and ADAMTS13 were negative. Renal function rapidly worsened, producing an RPGN-like picture. Methylprednisolone (500 mg twice daily for 3 days) with rituximab were initiated, followed by prednisone (40 mg daily) and mycophenolate.Renal biopsy showed endothelial injury (swelling, fenestration loss, capillary wall duplication, mesangiolysis, subendothelial remodeling) with podocyte effacement and no immune-complex deposition on immunofluorescence, consistent with SLE-associated renal TMA. Factor H antibody, genetic testing for atypical HUS, lymphoma workup, and CT imaging were unrevealing. His creatinine improved to 1.5 mg/dL by day 7 and subsequently normalized to 0.8 mg/dL in outpatient follow-up. Findings supported TMA secondary to SLE rather than TTP, HUS, or atypical HUS.
Discussion: SLE predominantly affects young women and presents with a combination of arthritis, cutaneous rash, Raynaud, leucopenia and renal disease [1]. In contrast, TMA is an uncommon but life-threatening complication in SLE occurring in only < 1-9% of cases of SLE and with a 31.9% mortality risk [2,3]. It can mimic HUS, TTP, or other causes of rapidly progressive glomerulonephritis [4]. While no standardized care for SLE complicated by TMA exists, some evidence points towards rituximab and eculizumab having promising effects in acquired TMA [5–9]. This case demonstrates an unusual first presentation of SLE in a middle-aged Hispanic man without features classically associated with early-onset SLE nor pulmonary involvement or serositis typically associated with late-onset SLE [10,11].The biopsy pattern of diffuse endothelial injury with minimal deposits initially suggested a primary TMA. However, the combination of hypocomplementemia, Coombs-positive anemia, thrombocytopenia, and ANA positivity strongly supported SLE-associated TMA. Recognizing that lupus-driven TMA may show limited hemolysis and early preserved creatinine is essential, as misclassification can delay immunosuppression. Early kidney biopsy and broad autoimmune evaluation were critical in establishing the diagnosis and guiding treatment.
Conclusions: SLE-associated renal TMA should be considered in patients presenting with nephritic syndrome, cytopenias, and hypocomplementemia even when classical SLE features are absent and immune-complex deposition is minimal. For hospitalists, maintaining diagnostic vigilance, pursuing early renal biopsy, and coordinating multidisciplinary evaluation can expedite immunosuppression and prevent irreversible kidney injury.
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