Significance of acute kidney injury biomarkers in the treatment of refractory nephrotic syndrome with calcineurin inhibitors

Abstract

Objective To investigate the significance of acute kidney injury biomarkers with calcineurin inhi-bitors(CNI) related nephrotoxicity in the treatment of refractory nephritic syndrome. Methods Ninety-two patients were included with 59 males and 33 females with average age of (5.67±3.65) years old, who were diagnosed with nephrotic syndrome at Shanghai Children′s Hospital from March 2014 to December 2015.66 patients including 44 males and 22 females with mean age of (4.97±3.52) were treated by steroid as the control group and 26 patients including 15 males and 11 females with mean age of (6.59±3.95) were treated by steroid combined with CsA and FK506 as the observation group.The blood, urine samples were collected before drug treatment (0 d) and very early stage of treatment (3 d), early stage (1 month), middle and late stage (3 months and 6 months) as the different observation time points.The change level of neutrophil gelatinase associated lipocalin(NGAL), kidney injury molecular-1(KIM-1), fibronectin(FN) and tumor necrosis factor-alpha(TNF-α) in serum and urine were detected at different time points to compare with biomarkers such as retinol-binding protein(RBP), N-acetyl-β-D-glucosamccharase(NAG) in urine. Results The serum NGAL(sNAGL)level was more obvious after 6 months of CNI treatment in the observation group than in the control group[(138.00±32.49) μg/L vs.(46.54±11.41) μg/L, t=2.115, P<0.05]; the level of urine TNF-α(uTNF-α) was higher obviously after 6 months of CNI treatment in the observation group than in the control group with significant differences[(2.35±0.78) pg/μmol vs.(0.75±0.36) pg/μmol, t=1.840, P<0.05]; the level of urine KIM-1(uKIM-1)was lower in the observation group than the control group after 3 months treatment of the CNI[(0.15±0.03) ng/μmol vs.(0.33±0.07) ng/μmol, t=-2.077, P<0.05); the level of urine NGAL(uNGAL) was lower in the observation group than the control group after 3 months treatment of the CNI [(0.09±0.03) ng/μmol vs.(0.23±0.04) ng/μmol, t=-2.959, P<0.05]. But the serum TNF-α(sTNF-α), urine FN(uFN), urine RBP(uRBP)and urine NAG(uNAG)did not show any significant change before and after the CNI treatment. Conclusions Compared with other acute kidney injury biomarkers (uNGAL, KIM-1, FN, RBP, and NAG), sNAGL and uTNF-α may be more sensitive to the early evaluation of CNI related nephrotoxicity.The occurrence of CNI related kidney injury shall be watched out at the beginning of 6-month of CNI treatment. Key words: Calcineurin inhibitors; Kidney injury; Neutrophil gelatinize-associated lipocalin; Kidney injury molecule-1; Fibronectin; Tumor necrosis factor-alpha