Figure 4.

Pharmacologic treatment with megalin inhibitor cilastatin recapitulates AKI amelioration by proximal tubule-specific megalin deletion. (A) Experimental design. Cilastatin was administered immediately after glycerol. (B–D) In accordance with findings in iMegKO mice, cilastatin administration at the time of rhabdomyolysis induction resulted in increased urine output (B), increased acute proteinuria (C), and increased urine albumin (D), compared with vehicle. Cilastatin administration also prevented severe loss of GFR observed in vehicle-treated mice (E), and prevented the highly elevated serum urea nitrogen seen in vehicle-treated mice (F). Periodic acid–Schiff stained sections were also generally in accordance with findings in control and iMegKO mice (G), although histopathologic injury scoring was not different between cilastatin- and vehicle-treated mice. KIM-1 was elevated in both groups (H), but significantly reduced in cilastatin-treated mice compared with vehicle-treated mice. Scale bars are 100 µm. Statistical analysis presented is derived from the t test.