Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

Nils E Magnusson, Mads Hornum, Kaj Anker Jørgensen, Jesper Melchior Hansen, Claus Bistrup, Bo Feldt-Rasmussen, Allan Flyvbjerg, Nils E Magnusson, Mads Hornum, Kaj Anker Jørgensen, Jesper Melchior Hansen, Claus Bistrup, Bo Feldt-Rasmussen, Allan Flyvbjerg

Abstract

Background: Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 healthy subjects matched for age, sex and body mass index (BMI). The kidney graft recipients were studied at baseline before transplantation and 3 and 12 months after transplantation and the uraemic group at baseline and after 12 months.

Methods: NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters.

Results: Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).

Conclusions: Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.

Figures

Figure 1
Figure 1
Relationship between serum creatinine and plasma NGAL levels in the kidney allograft recipients. Squares: before transplantation, circles: three months after transplantation, triangles: 12 months after transplantation. Insert: Three and 12 months after transplantation with expanded resolution.
Figure 2
Figure 2
Mean vs. absolute difference plot comparing the NGAL in-house assay with the commercial ELISA assay. Absolute differences were calculated as values obtained using the TRIFMA assay subtracted from values obtained using the ELISA assay. The 95% limits of agreement ( ± 1.96 SD) are ± 63 μg/L. SD is the standard deviation of the difference.
Figure 3
Figure 3
Scatter plot; TRIFMA assay NGAL levels vs. ELISA assay NGAL levels (linear regression: R = 0.96).

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