Immunofluorescence study to demonstrate the presence of S100A8/A9-positive cells in the kidney from an acute kidney injury model.

<p>Immunofluorescence study for neutrophils (CD15), monocytes/macrophages (CD68), and S100A8/A9-staining cells in an acute kidney injury model demonstrating that S100A8/A9, CD15, and CD69 staining were found frequently in the CDDP group which might reflect the inflammatory damage in this group. S100A8/A9 staining appeared to correlate with areas of CD15 (a) and CD68 staining (b). These findings also suggest that increased S100A8/A9 expression reflects the infiltration of inflammatory cells in intrinsic AKI. Magnification, × 400 in (a) and (b)</p

Serum and urinary Klotho, S100A8/A9, and Neutrophil gelatinase-associated lipocalin (NGAL) concentrations in an acute kidney injury model.

<p>(a) Urinary Klotho and urinary Klotho/creatinine (Cr) decreased significantly in the volume depletion (VD) group. (b) Serum and urinary S100A8/A9 and urinary S100A8/A9/Cr increased significantly in the cisplatin (CDDP) group. (c) Serum and urinary NGAL showed no significant difference between the VD and CDDP groups. Data are given as means±SD. (<i>n</i> = 6 for each group). *, p < 0.05, vs. the control group; †, p < 0.05, vs. the VD group.</p

Semiquantitative immunoblotting and immunohistochemistry of the kidney from the acute kidney injury model.

<p>(a) Renal Klotho abundance was reduced in the volume depletion (VD) group (48%) versus the control (100%) and cisplatin (CDDP) groups (74%). Immunohistochemical analysis also showed decreased renal Klotho labeling in kidneys from VD group. (b) S100A8/A9 abundance was increased in the CDDP group (220%) versus the control (100%) and VD groups (83%). Immunohistochemical analysis also showed increased renal S100A8/A9 labeling in kidneys from CDDP group. (c) Neutrophil gelatinase-associated lipocalin (NGAL) abundance and labeling showed no significant difference between the VD and CDDP groups. Data are given as means±SD. *, p < 0.05, vs. the control group; †, p < 0.05, vs. the VD group; magnification, × 200.</p

Experimental scheme.

<p>A volume-depleted pre-renal AKI model (VD) was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model (CDDP), animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection.</p

Representative hematoxylin and eosin (H&E) staining and renal pathological score of the acute kidney injury model.

<p>(a) H&E staining showed near normal or mild brush border loss in the volume depletion (VD) group. On the other hand, the cisplatin (CDDP) group shows loss of brush border membranes, obvious dilation of many tubules, and interstitial inflammatory infiltration. (b) Renal pathological score was significantly higher in the CDDP group than control and VD groups. Data are given as means±SD. (n = 4 for each group). *, p < 0.05, vs. the control group; †, p < 0.05, vs. the VD group; magnification, × 400.</p

Baseline characteristics of study participants (before after propensity score 1∶1 matching).

<p>BMI: body mass index;</p><p>CVD: cardiovascular disease;</p><p>PUD: peptic ulcer disease;</p><p>eGFR: estimated glomerular filtration rate;</p><p>HDL: high-density lipoprotein;</p><p>RAAS: renin-angiotensin-aldosterone system;</p><p>CCB: calcium channel blocker.</p><p><i>Note:</i> Conversion factors for units were as follows: hemoglobin in g/dl to g/l, ×10; white blood cell in ×10³/µl to ×10⁹/l, equal; platelets in ×10³/µl to ×10⁹/l, equal; albumin in mg/dl to g/l,×10; cholesterol in mg/dl to mmol/l,×0.02586; triglycerides in mg/dl to mmol/l,×0.01129; HDL-cholesterol in mg/dl to mmol/l,×0.02586; calcium in mg/dl to mmol/l, ×0.2495; phosphorus in mg/dl to mmol/l, ×0.3229; uric acid in mg/dl to µmol/l, ×59.48.</p

Cohort formation.

<p>Cohort formation.</p

Laboratory parameters of the study patients.

<p>Laboratory parameters of the study patients.</p

Association of aspirin use and cardiovascular disease in subgroups of the matched cohort.

<p>Association of aspirin use and cardiovascular disease in subgroups of the matched cohort.</p

The event-free survival for (A) composite bleeding, (B) all-cause death, (C) a doubling of baseline serum creatinine, and (D) renal death according to treatment group in the matched cohort.

<p>There were no significant differences in the incidence of composite bleeding and the cumulative overall survival rate between aspirin users and non-users. Aspirin users showed a higher incidence of doubling of baseline serum creatinine and an increased renal death rate compared with non-users.</p