Urine NGAL and KIM-1: tubular injury markers in acute lymphoblastic leukemia survivors

Abstract

Introduction Nephrotoxicity is a potential adverse effect of anticancer treatment in childhood. Cytostatics, abdominal radiotherapy, total body irradiation (TBI) and some agents used in supportive care may induce acute kidney injury (AKI) or lead to chronic kidney disease (CKD). The aim of this study was to test the hypothesis whether urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are increased in acute lymphoblastic leukemia (ALL) survivors. Method The study cohort consisted of 86 patients (42 females) previously treated for ALL. The median time after cessation of treatment was 6.55 (IQR: 1.96–9.93) years and median age at the time of study: 12 (IQR: 6.76–16.00). The control group included 53 healthy peers. Immunoenzymatic ELISA commercial kits were used to measure urine KIM-1 and NGAL levels. Results The median levels of urine uNGAL (p < 0.05), uNGAL/creatinine (cr.) ratio (p < 0.0001) and uKIM-1/creatinine ratio (p < 0.0001) were significantly higher in ALL survivors in comparison with healthy controls. Female patients had significantly higher levels of NGAL and NGAL/cr. than males (mean 8.42 ± 7.1 vs. 4.59 ± 4.5 ng/mL and 86.57 ± 77 vs. 37.7 ± 37 ng/mg, respectively; p < 0.01). Of all the study participants, 11 (13%) presented eGFR below 90 mL/min/1.73 m2. The NGAL/cr. ratio seemed to be the best predictor of decreased eGFR (AUC = 0.65). The cumulative dose of methotrexate and cyclophosphamide did not predict the values of the urine NGAL, NGAL/cr., KIM-1/cr. and eGFR. Five years after the end of treatment, the patients had higher levels of uKIM-1 (1.02 ± 0.8 vs. 0.62 ± 0.6 ng/mL, p < 0.01), uNGAL (7.9 ± 6.7 vs. 4.6 ± 5 ng/mL, p < 0.01) and lower eGFR (114 ± 29 vs. 134 ± 35 mL/min/1.73 m2, p < 0.01) in comparison with ALL survivors with the observation period of less than 5 years. Conclusion We demonstrated that ALL survivors have higher levels of urine NGAL, NGAL/cr. and uKIM-1/cr. ratio as compared to the control group. Further long-term follow-up studies are necessary to assess the significance of the NGAL and KIM-1 and their relationship to kidney damage after anticancer treatment in childhood.

Urine NGAL and KIM-1—Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study

“…These conditions included acute lymphoblastic leukemia (ALL), CKD, glomerulonephritis, autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy, and pediatric systemic lupus erythematosus. Moreover, they suggest that NGAL (serum and urine) may be a good predictor of CKD progression to end-stage kidney disease [ 14 , 21 , 25 , 26 ]. Similar observations were reported in research assessing the usefulness of KIM-1 and NGAL in children with congenital hydronephrosis.…”

“…Therefore, the authors focused mainly on the analysis of the effect of particular cytostatic agents rather than the specific types of tumors. Thirdly, in the current study the same reference group was used as in our previous study for acute leukemia survivors [ 14 ]. Finally, the size of the study group was relatively small, which may influence the final results.…”

“…The control group consisted of 53 age-matched healthy peers (24 males, 29 females) who were offspring of the department’s employees and healthy school pupils recruited form the OLAF study [ 13 ]. This group of healthy individuals has already been used in our previous research on biomarkers of kidney damage carried out in a cohort of acute lymphoblastic leukemia patients [ 14 ].…”

Low-Dose Aspirin Prevents Kidney Damage in LPS-Induced Preeclampsia by Inhibiting the WNT5A and NF-κB Signaling Pathways

“…To further evaluate the rescue effect of ASP in tubule injury, we detected the expression of NGAL (neutrophil gelatinase-associated lipocalin) and KIM-1 (kidney-injury molecule-1) in the kidneys of each group. The two molecules are important markers of tubular injury and chronic kidney disease (39)(40)(41). Immunohistochemical staining revealed that administration of ASP significantly reduced the up-regulation of NGAL in the damaged tubules of mice treated with LPS ( Figure 3A, a, b and c).…”

Clinical Proteomics of Biofluids in Haematological Malignancies

“…In haematological malignancies, the urinary proteome has been probed to detect diagnostic and prognostic biomarkers as well as markers of nephrotoxicity [ 99 , 153 , 154 ]. A well-establish method of assessment of MM or other plasma cell dyscrasias is the detection of paraproteins in serum or urine by protein electrophoresis or immunofixation [ 99 ].…”