Annexin V in children with idiopathic nephrotic syndrome treated with cyclosporine A.

BACKGROUND: Treatment with cyclosporine A (CsA), a calcineurin inhibitor, is effective in children with difficult idiopathic nephrotic syndrome (INS). Prolonged CsA treatment can result in several adverse effects, the most significant being nephrotoxicity (CsAN). The plasma and urine levels of the proteins annexin V (AnV) and uromodulin (UM) were investigated in order to assess their usefulness as indicators of early-stage CsAN. Uromodulin is considered a distal tubular damage marker. Annnexin V is present in the distal tubules. OBJECTIVES: To measure AnV in children with INS receiving CsA treatment and to assess the usefulness of this biomarker for monitoring CsAN and as an indicator of changes in the distal tubules of the nephron. MATERIAL AND METHODS: The prospective study included 30 patients with INS and 22 controls. Plasma and urinary AnV levels were measured 3 times: before CsA treatment, and after 6 and 12 months of therapy. The AnV levels were compared to those of UM. RESULTS: The urinary AnV and UM levels were significantly higher in the INS patients before CsA therapy in comparison to the reference group. A progressive increase of urinary AnV was observed after 6 and 12 months of therapy. Urinary UM only increased after 6 months. No significant correlations were found between plasma and urinary concentrations of the proteins studied. CONCLUSIONS: The increased urinary excretion of AnV in children with INS receiving CsA treatment may suggest its usefulness as an early marker of subclinical CsAN. Annexin V seems to be a more sensitive indicator of tubular damage in the course of CsA therapy than UM, though large, multicenter studies are needed.

Proteomic identification of early urinary-biomarkers of acute kidney injury in preterm infants.

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.

Urinary annexin V in children with nephrotic syndrome: a new prognostic marker?

Annexin V has a molecular weight of 32-35 kDa and has been reported to possess anticoagulant activity, inhibition of phospholipase A(2), regulation of membrane transport, proliferation and signal transduction. It is reported that urinary annexin V concentration may be an indicator of apoptosis and acute renal injury related to the urinary protein level. The aim of this study was to define the role of urinary annexin V excretion and serum annexin V concentrations as new prognostic tools and follow-up criteria in children with steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS). Annexin V concentrations were measured in serum and 24-h urine samples in 23 SSNS patients in both relapse and remission periods of each patient and in 22 SRNS patients and 22 healthy controls. Total protein, albumin, blood urea nitrogen (BUN), creatinine, total cholesterol concentrations, and 24-h urinary excretion of protein and creatinine were also measured in each patient. In the SRNS group, median 24-h urinary annexin V levels were significantly higher than for all other groups (5,048.8 ng/g creatinine vs. 2,839.5 ng/g creatinine in SSNS relapse group; 2,500.0 ng/g creatinine in SSNS remission group, and 2,018.3 ng/g creatinine in healthy control group). No significant correlation was found between urinary protein excretion and 24-h urinary annexin V levels in all subjects. Twenty-four-hour urinary annexin V excretion may be a predictor in children with SRNS, and it may be a prognostic marker in children with NS.

Measurement of urinary annexin V by ELISA and its significance as a new urinary-marker of kidney disease.

To confirm the significance of excretion of annexin V into the urine and the change of urinary annexin V concentration in kidney disease, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed using two monoclonal antibodies. Urinary annexin V concentration was measured in healthy individuals and patients with kidney and other diseases. Urinary annexin V did not change over a range of pH between 5.0 and 8.0, and was stable during the course of the study for 24 h at room temperature and for 8 days at 4 degrees C. The mean urinary annexin V concentration in 105 normal healthy individuals was 1.5+/-1.5 ng/ml, while that in patients with nephrotic syndrome and systemic lupus erythematosis (SLE) nephritis was 9.3+/-9.1 and 6.6+/-6.7 ng/ml, respectively, and that in IgA nephropathy and chronic renal failure was 2.6+/-2.1 and 1.3+/-0.7 ng/ml, respectively. Annexin level correlated with urinary protein concentration (r=0. 717), but not the serum creatinine concentration, blood urea nitrogen (BUN) and 24-h creatinine clearance. Mean urinary annexin V concentration in patients with ischemic heart disease, hypertension, and diabetes mellitus was 1.4+/-1.0, 1.4+/-1.1, and 1.7+/-1.3 ng/ml, respectively. In one case of relapsing nephrotic syndrome, the urinary annexin V concentration was markedly increased in the early phase after admission and then decreased. This patient later required hemodialysis. These results suggest that a high urinary annexin V concentration may be an indicator of acute renal injury related to the urinary protein level.