The most likely diagnosis is anti–glomerular basement membrane (GBM) antibody disease. This 50-year-old patient has pulmonary-renal syndrome, including hemoptysis followed by hypoxic respiratory failure and kidney failure with an active urine sediment with protein, erythrocytes, and leukocytes, suggesting an underlying glomerulonephritis. The differential diagnosis of pulmonary-renal syndrome includes small-vessel vasculitis (ANCA associated), anti-GBM antibody disease (Goodpasture syndrome), and rarely, other autoimmune diseases such as cryoglobulinemic vasculitis, systemic lupus erythematosus, and IgA vasculitis. Anti-GBM antibody disease is an autoimmune disease caused by antibodies directed against the noncollagenous domain of type IV collagen that bind to the GBM, inciting an inflammatory response resulting in damage to the GBM and the formation of a proliferative and often crescentic glomerulonephritis. The same process occurs with the basement membrane of pulmonary capillaries, leading to pulmonary hemorrhage. Serologies show normal complement levels and elevated levels of anti-GBM antibodies in the serum. On kidney biopsy, there is a proliferative glomerulonephritis, often with many crescents (shown, top panel). There is linear deposition of immunoglobulin along the GBM by immunofluorescence, but no electron-dense deposits on electron microscopy (shown, bottom panel). Treatment is immunosuppressive therapy with cyclophosphamide and glucocorticoids, combined with daily plasmapheresis to remove circulating anti-GBM antibodies.

Although heart failure can be associated with pulmonary edema and hemoptysis with acute kidney injury (cardiorenal syndrome), such patients typically show signs of severe volume overload and normal urine sediment, unlike this patient.

Membranous nephropathy is associated with the nephrotic syndrome with a low serum albumin level, which is not seen in this patient. The nephrotic syndrome alone is not typically associated with pulmonary disease, although it can be complicated with venous thromboembolic manifestations such as pulmonary embolism. However, this patient's pulmonary presentation with significant hemoptysis and infiltrates on chest radiograph is not consistent with pulmonary emboli as the cause of his respiratory failure.

Microscopic polyangiitis is the most common cause of pulmonary-renal syndrome. However, in the absence of a serum ANCA level or evidence of peripheral vasculitic lesions (for example, palpable purpura), it is not possible to clinically differentiate this disease from anti-GBM antibody disease. A kidney biopsy is diagnostic, showing little or no immune deposits in microscopic polyangiitis (“pauci-immune glomerulonephritis”). In this patient, extensive linear deposition of IgG along the GBM is noted, which is classic of anti-GBM antibody disease.