Figure 3.

Genetic deletion of RNLS associated with severe cisplatin-mediated AKI and CKD. RNLS KO mice and WT mice were given two intraperitoneal doses of cisplatin (15 mg/kg) administered two weeks apart. (A) Mouse body weight was measured five times a week for 4 weeks; the percentage of body weight loss was calculated as (body weight at day 0 − body weight)/(body weight at day 0)×100 and plotted, (**P<0.0005 at day 3, WT n=5, RNLS KO n=9). (B) Plasma creatinine level at baseline (day 0), 3 days post first CP dose (day 3), day 14 (before second dose), day 17 (3 days post second dose) and day 28 (at time of euthanization) (*P=0.029, n=6). (C) Survival of WT versus KO mice after cisplatin treatments. Data from (C) were analyzed using Kaplan–Meier curves and a log-rank test, ***P<0.0001. (D) UMAP plots from scRNA-seq, showing the renal cell populations in kidneys from the control and CP-induced CKD mice of WT and RNLS KO. (E and F) Percentage of PT and KIM-1 positive PT cells (E) and neutrophils, T cells, and macrophages (F) in kidneys of indicated mice. CP, cisplatin; PT, proximal tubule; tDL, thin descending limb; TAL, thick ascending limb; DCT, distal convoluted tubule; CNT, connecting tubule; CD, collecting duct; PC, principal cell; IC, intercalated cell; JGA, juxtaglomerular apparatus; VSMC, vascular smooth muscle cell; DC, dendritic cell.