Response to corticosteroid therapy is not related to serum and urine NGAL concentration in nephrotic children

Aim of the study
Response to corticosteroids is a major factor determining the final outcome of nephrotic syndrome (NS) in children. There is no consensus in terms of specific biomarkers of steroid sensitivity. There are reports on the value of urine neutrophil gelatinase-associated lipocalin (uNGAL) as a marker of steroid sensitivity, although this has not been definitively established. Objectives: To evaluate serum (s) and urine (u) NGAL concentrations as markers of response to steroid therapy.

Material and methods
This was a retrospective study including 43 patients (1-17 years old) divided into two groups as follows: 1) children with steroid-resistant nephrotic syndrome (SRNS, n = 14) treated with additional immunosuppressive drugs, including cyclosporine A (CsA) and/or mycophenolate mofetil (MMF); and 2) steroid-sensitive nephrotic syndrome (SSNS, n = 29). The control group consisted of age-matched healthy children (HC, n = 59).

Results
Median sNGAL concentration was higher in nephrotic patients (83.0, 43.8-351 ng/ml) compared to HC (51.4, 12.1-193 ng/ml; p = 0.00). There was no difference in the sNGAL level between SRNS and SSNS patients (p = 0.34). Median uNGAL level was higher in the SRNS patients, compared to that in the SSNS group, although the difference was not significant (2.71 ng/ml, range: 0.02-62.8 ng/ml and 1.17 ng/ml, range: 0.02-99.3 ng/ml, respectively; p = 0.26). Median sNGAL was higher in children treated with triple-drug regimens including cyclosporine A (CsA) (82.6, 68.6-351 ng/ml) compared to the patients on double-drug regimen including mycophenolate mofetil (MMF) (p = 0.03). There was no correlation between sNGAL and CsA dose/blood concentration ratio. We found a negative correlation between sNGAL and renal function, reflected by the eGFR (r = –0.41, p = 0.01).

Conclusions
sNGAL concentration did not differ between steroid-resistant and steroid-sensitive nephrotic syndrome patients. The higher sNGAL concentration in patients on triple therapy (cyclosporine A + mycophenolate mofetil + prednisone – CsA + MMF + PRED) reflects inferior renal function in patients with the most severe clinical course of NS.