PURPOSE: Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD. MATERIALS AND METHODS: We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. RESULTS: Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). CONCLUSIONS: In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.
PURPOSE: Increased serum concentrations of soluble Fas (sFas) have been reported in patients with chronic kidney disease (CKD). However, little is known about the renal clearance of sFas, whether sFas is reabsorbed in the renal tubules, or the behavior of sFas synthesis in CKD. MATERIALS AND METHODS: We studied 69 patients with CKD (60+/-15 years old, creatinine clearance 37+19 ml/min/1.73 m2) and 14 healthy subjects (61+/-17 years, creatinine clearance 79+/-24 ml/min/1.73 m2). ELISA was used to measure the levels of sFas (pg/mL) and retinol binding protein (RBP - mg/L). RT-PCR was used to quantify sFasmRNA of leukocytes. RESULTS: Serum sFas levels were significantly higher in patients with CKD (2781+/-1214 vs. 2196+/-773, p=0.02). The concentrations of sFas in 24-hour urine samples (23+/-27 vs. 40+/-17, p=0.006) and sFas Clearance (0.019+/-0.022 vs. 0.036+/-0.020, p=0.01) were significantly lower in patients with CKD. sFas clearance correlated with creatinine clearance (r=0.25, p=0.02). Urine concentrations of RBP correlated with sFas concentrations in the urine (r=0.80, p<0.001). sFasmRNA were higher in patients with CKD (3.9+/-1.8 vs. 2.5+/-0.9, p<0.001). CONCLUSIONS: In CKD patients, the decrease in renal function is followed by a decrease in sFas clearance and an increase in serum sFas. In patients with proximal tubule dysfunction (high urinary RBP concentrations), urinary sFas is also increased, suggesting that sFas is reabsorbed by the proximal tubule. It is possible that an increase in sFas synthesis also contributes to the increase of serum sFas concentrations in uremia.
Authors: Daniela Mendes Chiloff; Danilo Candido de Almeida; Maria A Dalboni; Maria Eugênia Canziani; Sunil K George; Alshaimaa Mahmoud Morsi; Nadia El-Akabawy; Christopher D Porada; Marcelino Souza Durao; Abolfazl Zarjou; Graca Almeida-Porada; Miguel Angelo Goes Journal: Am J Physiol Renal Physiol Date: 2020-01-31