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- ItemSomente MetadadadosHigh serum levels of soluble Fas (sFas) in CKD patients: Effects of renal clearance, reabsorption and synthesis(Wichtig Editore, 2008-05-01) Dalboni, Maria Aparecida [UNIFESP]; Cenedeze, Marcos Antonio [UNIFESP]; Manfredi, Silvia Regina [UNIFESP]; Andreoli, Maria Claudia Cruz [UNIFESP]; Santos, Oscar Fernando Pavão dos [UNIFESP]; Canziani, Maria Eugênia Fernandes [UNIFESP]; Boim, Mirian Aparecida [UNIFESP]; Góes, Miguel Ângelo [UNIFESP]; Draibe, Sergio Antonio [UNIFESP]; Balakrishnan, V.; Cendoroglo Neto, Miguel [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Tufts Univ New England Med CtrPurpose: 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 m(2)) and 14 healthy subjects (61 +/- 17 years, creatinine clearance 79 +/- 24 ml/min/1.73 m(2)). 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.
- ItemSomente MetadadadosUrinary MCP-1 and RBP: Independent predictors of renal outcome in macroalbuminuric diabetic nephropathy(Elsevier B.V., 2012-11-01) Titan, S. M.; Vieira, J. M.; Dominguez, W. V.; Moreira, S. R. S. [UNIFESP]; Pereira, A. B. [UNIFESP]; Barros, R. T.; Zatz, R.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)Background: Albuminuria has been considered a sine qua non condition for the diagnosis of diabetic nephropathy (DN) and has been widely used as a surrogate outcome of chronic kidney disease (CKD). However, recent data suggest that albuminuria may fail as a biomarker in a subset of patients, and the search for novel markers is intense.Methods: We analyzed the role of urinary RBP and of serum and urinary cytokines (TGF-beta, MCP-1 and VEGF) as predictors of the risk of dialysis. doubling of serum creatinine or death (primary outcome. PO) in 56 type 2 diabetic patients with macroalbuminuric DN.Results: Mean follow-up time was 30.7 +/- 10 months. Urinary RBP and MCP-1 were significantly higher in patients presenting the PO, whereas no difference was shown for TGF-beta or VEGF. in the Cox regression, urinary RBP. MCP-1 and VEGF were positively associated and serum VEGF was inversely related to the risk of the PO. However, after adjustments for creatinine clearance, proteinuria, and blood pressure only urinary RBP (OR 11.6; 95% CI 2.7-49.2, p = 0.001 for log RBP) and urinary MCP-1 (OR 11.0; 95% CI 1.6-76.4, p = 0.02 for log MCP-1) remained as significant independent predictors of the PO.Conclusion: Urinary RBP and MCP-1 are independently related to the risk of CKD progression in patients with macroalbuminuric DN. Whether these biomarkers have a role in the setting of normoalbuminuria and microalbuminuria in DN should be further investigated. (C) 2012 Elsevier Inc. All rights reserved.