The impact of calcineurin inhibitors on neutrophil gelatinase‐associated lipocalin and fibroblast growth factor 23 in long‐term kidney transplant patients

Background Neutrophil gelatinase‐associated lipocalin ( NGAL ), a protein with bacteriostatic functions rapidly excreted from stimulated or damaged epithelial cells, is elevated in acute and chronic kidney disease. A calcineurin dependent signaling pathway for fibroblast growth factor 23 ( FGF 23) has been revealed, but the effect of calcineurin inhibitors ( CNI s) on the levels of NGAL and markers of mineral metabolism in long‐term kidney transplant patients has not been explored. Methods In a cross‐sectional study, 39 patients who received a first kidney transplant more than 10 years ago were split into two groups based on whether (n=28) or not (n=11) they used CNI s. Only patients with well‐functioning grafts defined as an estimated glomerular filtration rate ≥45 mL/min per 1.73 m 2 were included. Results The median levels of NGAL , intact parathyroid hormone (iPTH), and iFGF 23 were significantly higher in CNI users vs CNI nonusers, 167.0 (134.0‐235.0) ng/mL vs 105.0 (91.3‐117.0) ng/mL, P <.001, 13.8 (10.0‐17.3) pmol/L vs 8.4 (6.4‐9.9) pmol/L, P =.003, and 81.6 (56.4‐116.5) pg/mL vs 61.8 (43.3‐72.1) pg/mL, P =.04 respectively. Conclusions The median levels of iFGF 23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF 23 resistance in the parathyroid. The net result of CNI s side effects needs to be further explored.