Urinary NGAL Measured after the First Year Post Kidney Transplantation Predicts Changes in Glomerular Filtration over One-Year Follow-Up.

Małgorzata Kielar,Barbara Maziarz,Piotr Ceranowicz,Agnieszka Gala-Błądzińska,Alina Będkowska-Prokop,Paulina Dumnicka,Beata Kuśnierz-Cabala,Ewa Ignacak

doi:10.3390/jcm10010043

Abstract

Currently, serum creatinine and estimated glomerular filtration rate (eGFR) together with albuminuria or proteinuria are laboratory markers used in long-term monitoring of kidney transplant recipients. There is a need for more sensitive markers that could serve as early warning signs of graft dysfunction. Our aim was to assess the urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of changes in kidney transplant function after the first year post-transplantation. We prospectively recruited 109 patients with functioning graft at least one year after the transplantation, with no acute conditions over the past three months, during their control visits in kidney transplant ambulatory. Urinary NGAL measured on recruitment was twice higher in patients with at least 10% decrease in eGFR over 1-year follow-up compared to those with stable or improving transplant function. Baseline NGAL significantly predicted the relative and absolute changes in eGFR and the mean eGFR during the follow-up independently of baseline eGFR and albuminuria. Moreover, baseline NGAL significantly predicted urinary tract infections during the follow-up, although the infections were not associated with decreasing eGFR. Additionally, we assessed urinary concentrations of matrix metalloproteinase 9—NGAL complex in a subgroup of 77 patients and found higher levels in patients who developed urinary tract infections during the follow-up but not in those with decreasing eGFR. High urinary NGAL in clinically stable kidney transplant recipients beyond the first year after transplantation may be interpreted as a warning and trigger the search for transient or chronic causes of graft dysfunction, or urinary tract infection.

Highlights

Renal transplantation is the best therapeutic option for patients with end-stage kidney disease
In September 2020, the follow-up data were collected based on medical records of the patients who remained in control in the kidney transplant recipients’ ambulatory, including the clinical course during the follow-up, the serum creatinine concentrations obtained during all control visits, and the results of laboratory tests performed at the last visit of a patient in the kidney transplant recipients’ ambulatory
We observed a significant increase in estimated glomerular filtration rate (eGFR) values in the subgroup with final eGFR >90% of baseline eGFR (p < 0.001; Figure 1B), resulting in a highly significant difference in final eGFR values between the studied subgroups: median final eGFR was 30 mL/min/1.73 m2 in patients with final eGFR ≤90% of the baseline values, and 56 mL/min/1.73 m2 in patients with final eGFR >90% baseline (p < 0.001)

Summary

Introduction

Renal transplantation is the best therapeutic option for patients with end-stage kidney disease Both donor—and recipient-related factors are associated with kidney graft function, including metabolic and immunological factors. Most centers only use graft biopsy in the patients with worsening renal function i.e., suspected acute kidney rejection episodes or a chronic elevation in creatinine and/or the onset of persistent proteinuria (indication or “for cause” biopsies), as recommended by the KDIGO guidelines [1]. This allows the diagnosis of kidney graft injury. The indication for graft biopsy based on the clinical assessment, including serum creatinine, eGFR, and albuminuria (proteinuria) may in some cases be controversial

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