Acute Kidney Injury (AKI)

Cisplatin induced dose-dependent acute kidney injury and systemic toxicity, as demonstrated by reduced survival and rapid increases in serum creatinine and BUN. The 30 mg/kg group showed the greatest mortality and an earlier deterioration in renal function.

Figure 1. Dose-dependent induction of acute kidney injury by cisplatin in mice.

 (A) Survival curves following a single intraperitoneal administration of vehicle or cisplatin at 20, 25, or 30 mg/kg. Survival decreased with increasing cisplatin dose, with the lowest survival observed in the 30 mg/kg group. (B) Serum creatinine (CREA) concentrations at 0, 24, 48, and 72 h after the first dose. (C) Blood urea nitrogen (BUN) concentrations at the indicated time points. Cisplatin treatment caused marked increases in serum CREA and BUN, indicating progressive renal dysfunction. Individual symbols represent individual animals, and lines connect group means. Group size: n = 4 for the vehicle group and n = 12 for each cisplatin group at study initiation. 

Cisplatin administration induced time-dependent renal tubular injury and pulmonary inflammation. Renal tubular damage became evident at 48 h and was severe by 72 h, accompanied by tubular protein accumulation. Inflammatory cell infiltration, including neutrophil accumulation, was also observed in the lung.

Figure 2. Histopathological evaluation of renal and pulmonary injury following cisplatin administration.

 (A) Semiquantitative renal tubular damage scores at 24, 48, and 72 h after a single intraperitoneal administration of vehicle or cisplatin at 20, 25, or 30 mg/kg. (B) Representative H&E-stained kidney sections at the indicated time points. Cisplatin-treated mice exhibited progressive tubular injury and tubular protein accumulation, indicated by green arrows. (C) Semiquantitative lung tissue inflammation scores at 24, 48, and 72 h after treatment. (D) Representative H&E-stained lung sections showing inflammatory cell infiltration and neutrophil accumulation, indicated by green arrows. Individual symbols represent individual animals, and bars are presented as mean ± SEM. N.A., not available.

Unilateral left renal ischemia–reperfusion injury caused sustained physiological and renal functional abnormalities in mice. Compared with sham-operated mice, IRI mice showed reduced body weight gain, increased daily and cumulative water intake, and significantly elevated terminal serum BUN and creatinine levels.

Figure 1. Physiological and renal functional changes following unilateral renal ischemia–reperfusion injury in mice.

(A) Longitudinal changes in body weight; (B) body weight change rate relative to Day 0; (C) daily water intake; (D) cumulative water intake; (E) terminal serum blood urea nitrogen (BUN) levels at Day 56; and (F) terminal serum creatinine (CREA) levels at Day 56. Groups were defined as G1 Sham and G2 IRI (left kidney). Data presented as mean ± SD (n = 10–15 per group). Individual symbols in panels E and F represent individual animals. ****p < 0.0001.

At Day 56, unilateral renal ischemia–reperfusion injury induced persistent renal fibrosis, macrophage infiltration, and tubular injury, as demonstrated by increased renal COL3A1, F4/80, and KIM-1 immunostaining compared with sham-operated mice.

Figure 2. Renal fibrosis, inflammation, and tubular injury following unilateral renal ischemia–reperfusion injury.

(A) Representative immunohistochemical staining for COL3A1 in kidney sections from G1 Sham and G2 IRI mice; (B) representative F4/80 immunohistochemical staining; (C) representative KIM-1 immunohistochemical staining; (D–F) semiquantitative scores for COL3A1, F4/80, and KIM-1 staining, respectively. Brown staining indicates positive immunoreactivity. Compared with the sham group, IRI mice showed increased COL3A1 deposition, F4/80-positive macrophage infiltration, and KIM-1 expression, indicating fibrotic remodeling, renal inflammation, and tubular injury. Scale bars: 200 μm in the upper-row images and 100 μm in the lower-row images. Data are presented as mean ± SD (n = 5 per group). Histological staining was graded according to the percentage of positive cells: 0, <5%; 1, 5%–<25%; 2, 25%–<50%; 3, 50%–<75%; and 4, ≥75%.