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Published on: April 28, 2013
Plasma neutrophil gelatinase-associated lipocalin and kidney graft outcome
Daan Kremer1, Adrian Post1, António W Gomes-Neto1
1Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Background:
Plasma neutrophil gelatinase-associated lipocalin (pNGAL) has been investigated extensively in acute kidney injury. This study investigated its pathophysiological significance and utility as marker for graft failure and mortality in stable kidney transplant recipients (KTR).
Methods:
Baseline pNGAL was measured in 698 KTR (58% male, age 53 ± 13 years, estimated glomerular filtration rate 52.4 ± 20.4 mL/min/1.73 m2) at median 5.4 (interquartile range 1.8-12.0) years after transplantation, enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study.
Results:
pNGAL concentrations were higher in males, younger patients, patients with a deceased-donor kidney and higher serum creatinine. Independent of these, pNGAL was positively associated with urinary protein excretion, systemic inflammation parameters and calcineurin inhibitor use. During median follow-up of 5.3 (4.5-6.0) years, death-censored graft failure rates were 3.9%, 7.3% and 25.0% across increasing tertiles of pNGAL (Plog-rank < 0.001). Cox-regression analyses showed no independent associations of pNGAL with mortality, but strong associations with graft failure (hazard ratio, per doubling 4.16; 95% confidence interval 3.03-5.71; P < 0.001), which remained independent of adjustment for confounders. These associations were present only in patients with pre-existent proteinuria and poor kidney function.
Conclusions:
pNGAL is associated with parameters of kidney graft damage and with graft failure. The latter association is particularly present in KTR with pre-existent poor kidney function and proteinuria. Trial Registration: ClinicalTrials.gov NCT02811835.
Insights
Plasma neutrophil gelatinase-associated lipocalin (pNGAL) predicts kidney transplant graft failure, especially in patients with existing proteinuria and poor kidney function. This biomarker is linked to graft damage but not mortality in stable recipients.
Area of Science:
- Nephrology
- Transplantation immunology
- Biomarker research
Background:
- Plasma neutrophil gelatinase-associated lipocalin (pNGAL) is recognized for its role in acute kidney injury.
- Its significance in stable kidney transplant recipients (KTR) requires further investigation.
- This study explores pNGAL's utility in predicting graft failure and mortality.
Purpose of the Study:
- To assess the pathophysiological significance of pNGAL in stable KTR.
- To evaluate pNGAL as a predictive marker for graft failure and mortality.
- To identify patient subgroups where pNGAL association is most pronounced.
Main Methods:
- Baseline pNGAL levels were measured in 698 KTR.
- Patients were enrolled in the prospective TransplantLines Food and Nutrition Biobank and Cohort Study.
- Median follow-up was 5.3 years, with analysis of graft failure and mortality.
Main Results:
- Higher pNGAL correlated with male sex, younger age, deceased-donor kidneys, and higher creatinine.
- pNGAL associated with urinary protein, inflammation, and calcineurin inhibitor use.
- Graft failure rates increased significantly with higher pNGAL tertiles (P < 0.001).
- pNGAL strongly predicted graft failure (HR 4.16) independent of confounders, particularly in patients with proteinuria and poor kidney function.
- No independent association was found between pNGAL and mortality.
Conclusions:
- pNGAL is linked to kidney graft damage and predicts graft failure in KTR.
- This association is most significant in KTR with pre-existing proteinuria and impaired kidney function.
- pNGAL may serve as a valuable prognostic marker in specific KTR populations.
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