Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus

Thrailkill, Kathryn M.; Moreau, Cynthia; Cockrell, Gael; Jo, Chan‐Hee; Bunn, R. Clay; Morales-Pozzo, Alba E.; Lumpkin, Charles K.; Fowlkes, John L.

doi:10.1007/s12020-010-9308-6

Cited by 67 publications

(68 citation statements)

References 39 publications

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“…Thraillkill et al [12] measured both urine MMP-9 and NGAL and found positive correlation with glycemic control and albuminuria. In our study we have not found any correlation between the MMP-9/NGAL ratio and serum albumin or urine protein/creatinine ratio.…”

Section: Discussionmentioning

confidence: 99%

Urinary MMP-9/NGAL Ratio as a Potential Marker of FSGS in Nephrotic Children

et al. 2013

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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.

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Section: Discussionmentioning

confidence: 99%

Urinary MMP-9/NGAL Ratio as a Potential Marker of FSGS in Nephrotic Children

et al. 2013

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“…9,19,20 Among them, neutrophil gelatinase-associated lipocalin (NGAL), which is a 178 amino acid 25 kDa protein, first purified and identified in 1993 by Kjeldsen et al, seems to be a promising biomarker. 9,19,21 It is mainly produced in renal tubules in response to structural kidney injury, 22 but also, to a lesser degree, in the lung, trachea, stomach, and colon, while it is excreted in the urine. 23 NGAL values may be influenced by renal diseases, hypertension, inflammatory conditions, hypoxia and malignancies.…”

Section: Introductionmentioning

confidence: 99%

NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up

Papadopoulou-Marketou¹,

Skevaki²,

Kosteria³

et al. 2014

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OBJECTIVE: Diabetic nephropathy constitutes a major long-term complication in patients with type 1 diabetes mellitus (T1D) and its diagnosis is based on microalbuminuria. The aim of this observational follow-up study was to explore the role of neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C in unravelling early diabetic nephropathy even in patients with normoalbuminuria. DESIGN: Fifty-six euthyroid patients with T1D, with mean age 13.1 (SD: 3.2) years, and 49 healthy controls with mean age 12.8 (SD: 6.6) were recruited. Besides standard blood chemistry and urinary albumin excretion, serum NGAL (ELISA) and cystatin C (nephelometry) were measured at enrollment and after 12-15 months. GFR was calculated with the bedside Schwartz formula (eGFR) and the Lund strategy formula (L-eGFR). RESULTS: At baseline, mean NGAL levels were not significantly different between children with diabetes and controls. At re-evaluation, mean NGAL value and mean eGFR value in patients with diabetes were increased (p=0.032 and p=0.003 respectively). At both baseline and reevaluation, NGAL was positively correlated with cystatin C (r=0.41, p<0.001), systolic arterial pressure z-score (r=0.3, p=0.031) and creatinine (r=0.32, p=0.010). NGAL correlated negatively with eGFR (r=-0.26, p=0.049) and L-eGFR (r=-0.33, p=0.010). Cystatin C had a negative correlation to eGFR (r=-0.29, p=0.025) and a positive one with creatinine (r=0.35, p=0.009) at reevaluation. No statistically significant correlation was found between cystatin C and microalbuminuria (p=0.736). CONCLUSIONS: NGAL and cystatin C, known markers of renal injury, correlate with renal function decline in T1D, suggesting that they may be used as supplementary tests to urine albumin excretion in order to unmask early renal dysfunction.

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“…Male patients affected by type 1 diabetes mellitus have increased urinary MMP-9 (29). Gender difference in MMP-9 concentration was also shown in experimental aortic aneurysm (30) and rat aortic smooth muscle cells (31).…”

Section: Discussionmentioning

confidence: 80%

Analysis of matrix metalloproteinase-9 gene polymorphism -1562 C/T in patients suffering from systemic sclerosis with and without ulcers

et al. 2011

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Abstract. The objective of this study was to determine whether the matrix metalloproteinase-9 (MMP-9) rs3918242 single nucleotide polymorphism may confer susceptibility to systemic sclerosis (SSc) with and without ulcers in an Italian caucasian population. The MMP-9 rs3918242 functional polymorphism was genotyped in 461 subjects of Italian caucasian origin: 228 patients with SSc (92 with and 136 without ulcers) and 233 unrelated healthy individuals. The SNP under study was in Hardy-Weinberg equilibrium in the control population. Genotype and allele distributions between SSc patients, with or without ulcers, were not statistically significant (P>0.05). A significant increase of the genotype C/T was observed in male SSc patients without ulcers when compared to patients with ulcers (P=0.04). The MMP-9 rs3918242 functional polymorphism is not associated with susceptibility to SSc. However, the presence of the polymorphism may have a protective effect on the development of ulcers in SSc male patients.

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Disease and gender-specific dysregulation of NGAL and MMP-9 in type 1 diabetes mellitus

Cited by 67 publications

References 39 publications

Urinary MMP-9/NGAL Ratio as a Potential Marker of FSGS in Nephrotic Children

Urinary MMP-9/NGAL Ratio as a Potential Marker of FSGS in Nephrotic Children

NGAL and cystatin C: two possible early markers of diabetic nephropathy in young patients with type 1 diabetes mellitus: one year follow up

Analysis of matrix metalloproteinase-9 gene polymorphism -1562 C/T in patients suffering from systemic sclerosis with and without ulcers

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