Abstract
BACKGROUND: The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. We hypothesized that matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin (MMP-9/NGAL) is a better marker of focal sclerosis in the glomerulus then matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) and matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 MMP2/TIMP-2.METHODS: The present study used a sample of 36 children and adolescents subdivided into two groups: I – 20 children with MCNS, subjected to examination twice: A – in relapse of nephrotic syndrome, before treatment and B – after regression of proteinuria; II – 16 children with FSGS. MMPs and TIMPs and NGAL levels were measured in the urine using ELISA kit. MMP-9/TIMP-1, MMP-2/TIMP-2 and MMP-9/NGAL ratios were calculated.RESULTS: Median NGAL/cr. was significantly higher in MCNS and FSGS patients when compared to healthy controls. Both, NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Contrary to FSGS children, in MCNS group, before treatment only NGAL/cr., but not MMP-9/cr. was increased. Urinary concentrations of NGAL and MMP-9 were highly associated with each other (NGAL/cr. vs. MMP-9/cr.,r= 0.485,p< 0.01). Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We also found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) – 9.0; confidence interval (CI) 1.97–41.07].CONCLUSION: MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children.
Highlights
Childhood nephrotic syndrome is most commonly caused by one of two idiopathic diseases: minimalchange nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS)
Our study describes for the first time the urinary Matrix metalloproteinases (MMPs)-9/neutrophil gelatinase-associated lipocalin (NGAL) ratio, as a marker of FSGS in children with nephrotic syndrome
We did not find any significant differences in MMP-9/tissue inhibitors of metalloproteinases (TIMPs)-1 ratio and MMP-2/TIMP-2 ratio in minimal change nephrotic syndrome (MCNS) children, before cyclosporine treatment
Summary
Childhood nephrotic syndrome is most commonly caused by one of two idiopathic diseases: minimalchange nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS). It is important to develop a noninvasive alternative to biopsy which would decrease the likelihood of complications We undertook this pilot study to develop potential new markers for diagnosis of FSGS in nephrotic patients. The study was undertaken to develop a potential new markers for distinguishing minimal change nephrotic syndrome (MCNS) and focal segmental glomerulosclerosis (FSGS) in children. NGAL and MMP-9 urinary levels were significantly elevated in FSGS subjects, as compared with control subjects. Median urine MMP-9/NGAL ratio in FSGS patients was significantly higher than in patients with MCNS. We found that significant increase in MMP-9/NGAL was associated with FSGS [odds ratio (OR) – 9.0; confidence interval (CI) 1.97–41.07]. CONCLUSION: MMP-9/NGAL ratio may serve as differentiation marker between MCNS and FSGS in nephrotic children
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