thymosin-beta(4) and Acute-Kidney-Injury

Thymosin β4 (Tβ4), a ubiquitous peptide, regulates several cellular processes that include cell morphology, wound healing, and inflammatory response. Administration of exogenous Tβ4 is protective in diabetic nephropathy and in a unilateral ureteral obstruction model. However, the role of endogenous Tβ4 in health and disease conditions remains unclear. To elucidate the pathophysiological role of endogenous Tβ4 in hypertension, we examined angiotensin-II (Ang-II)-induced renal and cardiac damage in Tβ4 knockout (Tβ4 KO) mice. Tβ4 KO and wild-type C57BL/6 mice were infused continuously for 6 weeks with either vehicle or Ang-II (980 ng/kg per minute). At baseline, Tβ4 deficiency did not affect renal and cardiac function. Systolic blood pressure in the Ang-II group was similar in wild-type and Tβ4 KO mice (wild-type Ang-II, 179.25±10.11 mm Hg; Tβ4 KO Ang-II, 169.81±6.54 mm Hg). Despite the similar systolic blood pressure after Ang-II infusion, Tβ4-deficient mice had dramatically increased albuminuria and decreased nephrin expression in the kidney (

Topics: Acute Kidney Injury; Angiotensin II; Animals; Blood Pressure; Cardiomyopathies; Hypertension; Infusions, Intravenous; Male; Mice; Mice, Knockout; Microfilament Proteins; Random Allocation; Rats; Thymosin

Sepsis is a systemic inflammatory response syndrome, associated with high risk of acute kidney injury (AKI) and in-hospital mortality. Thymosin beta-4 (Tβ4) is an actin-sequestering protein that can prevent inflammation in several tissues. Thus, we studied the role of Tβ4 in sepsis.. The Tβ4 concentrations were prospectively measured in 191 patients within 6 h of the intensive care units (ICU) admission with diagnosis of sepsis. The cohort was divided into Tβ4 concentration tertiles: 1.19-7.11 ng/ml (n = 64), 7.12-11.01 ng/ml (n = 64), and 11.02-28.10 ng/ml (n = 63).. Of 191 patients, 92 patients developed AKI, 24 of whom received continuous renal replacement therapy (CRRT), 29 patients died within 7 days, and 53 patients died within 28 days. Lower Tβ4 stages were correlated with poor prognosis, including AKI(odds ratio [OR], 2.102 per stage lower; 95% confidence interval [CI], 1.448 to 3.050; P < 0.001), CRRT(OR, 2.346 per stage lower; 95% CI, 1.287 to 4.276; P = 0.005), 7-day mortality(OR, 1.755 per stage lower; 95% CI, 1.050 to 2.935; P = 0.032), and 28-day mortality(OR, 1.821 per stage lower; 95% CI, 1.209 to 2.743; P = 0.004). Kaplan-Meier analysis also demonstrated that patients with lower Tβ4 stages had a high risk of AKI and death. In addition, the area under the curve (AUC) of Tβ4 for predicting AKI, CRRT, 7-day mortality, and 28-day mortality were, respectively, 0.702 (95% CI 0.628-0.776), 0.717 (95% CI 0.592-0.842), 0.694 (95% CI 0.579-0.808), and 0.682 (95% CI 0.598-0.767).. Lower Tβ4 stages are associated with higher odds of poor prognosis in ICU patients with sepsis.

Topics: Acute Kidney Injury; Aged; Biomarkers; Female; Hospital Mortality; Humans; Intensive Care Units; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Prospective Studies; Renal Replacement Therapy; Risk Assessment; Risk Factors; Sepsis; Thymosin