M. J. Kennedy, H. J. Rozycki; Virginia Commonwealth University, Richmond, VA

BACKGROUND: AGs are an important cause of neonatal AKI. Megalin, an endocytic receptor, is responsible for AG uptake into proximal tubular cells and polymorphisms in the megalin gene may influence AKI susceptibility. The objective of this pilot, case-control study was to investigate associations between candidate megalin SNPs and AKI in AG-treated newborns.
METHODS: Waste blood was collected from AG-treated neonates (n=49) and genotyping performed for 7 candidate megalin SNPs. Change in serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were calculated using pre- and post-AG SCr. Modified pRIFLE criteria previously applied in neonatal AKI studies (> 25% eGFR decrease or > 1.5-fold SCr increase) were used to identify AKI. Demographics were compared via Mann-Whitney U and t-tests. Genotype and allele frequencies were compared via Fisher’s exact.
RESULTS: rs 3944004 genotype was associated with AKI. Demographics and genotype frequencies are presented in the Table.
CONCLUSION: These preliminary data suggest the megalin rs 3944004 genotype is associated with AKI in AG-treated newborns. Altered AG uptake into proximal tubular cells in infants with variant genotypes may influence AKI susceptibility and studies to test this hypothesis are planned.
AKI (n=9)No AKI (n=40)p
Gestational age [weeks, (median, IQR)]32 (7.5)35 (5.8)0.3
Birth weight [grams, (mean (SD)]1982 (840)2416 (989)0.2
Gentamicin dose [mg/kg/day (median, IQR)]3.1 (1)4.0 (0.8)0.06
Treatment duration [days (median, IQR)]3 (0)7 (4)0.004
Pre-treatment SCr [mg/dL (median, IQR)]0.7 (0.2)0.8 (0.2)0.07
Pre-treatment eGFR [ml/min/1.73m2 (median, IQR)]20 (12)19 (11)0.85
rs 3944004 TT genotype (frequency, n)0.22 (2)0.60 (24)
rs 3944004 TG/GG genotype (frequency, n)0.78 (7)0.40 (16)0.04OR: 5.395% CI: 0.98, 27