Acute Kidney Injury: The USMLE Step 1 Guide

Answer: B. In systemic lupus erythematosus (SLE), anti-dsDNA and other autoantibodies form immune complexes with nuclear antigens released from apoptotic cells. These immune complexes deposit in the glomeruli and activate the classical complement pathway: C1q binds the Fc regions of IgG (and IgM) within the complexes, sequentially activating C1r, C1s, C4, and C2 to generate C3 convertase, driving consumption of C3 and C4. Low C3 and C4 therefore indicate active classical pathway consumption and correlate with lupus nephritis activity. 'Full house' immunofluorescence (IgG, IgA, IgM, C3, C1q) is pathognomonic for lupus nephritis. The alternative pathway (option A) consumes C3 without C4 reduction; isolated low C3 with normal C4 suggests MPGN type II or C3 glomerulopathy rather than lupus.

Answer: C. Fabry disease is an X-linked lysosomal storage disorder caused by deficient alpha-galactosidase A activity, which normally degrades globotriaosylceramide (Gb3) and related glycosphingolipids; progressive lysosomal accumulation of these glycosphingolipids within vascular endothelium and other tissues produces the characteristic acroparesthesias, angiokeratomas, corneal opacities, and progressive renal and cardiac disease, and the X-linked inheritance pattern explains why affected males (like the uncle) transmit disease risk through unaffected or mildly symptomatic carrier female relatives (like the mother), rather than the recessive pattern that would require two mutant alleles in females. Option A incorrectly proposes autosomal recessive inheritance, which does not match the pedigree pattern described. Option B incorrectly substitutes the glucocerebroside/Gaucher disease mechanism. Option D incorrectly proposes autosomal dominant inheritance with full penetrance in all carriers, which does not reflect the X-linked pattern with typically milder or absent symptoms in heterozygous females. Option E incorrectly dismisses the well-established, defining renal and cardiac manifestations of this disease.

Answer: A. In primary hyperaldosteronism due to an aldosterone-producing adenoma, autonomous aldosterone secretion causes renal sodium and water retention, expanding extracellular fluid volume and increasing renal perfusion pressure; this volume expansion suppresses renin release from the juxtaglomerular apparatus through normal negative feedback, independent of the classic renin-angiotensin-aldosterone cascade that would otherwise drive aldosterone secretion. This combination of high aldosterone with suppressed renin is the key biochemical signature distinguishing primary from secondary hyperaldosteronism, the latter of which, as in renal artery stenosis, would show elevated renin. ACE inhibitors increase, rather than decrease, renin release by interrupting angiotensin II-mediated negative feedback, the opposite of what is described in one distractor option.