Concentration of selected liver enzymes across the stages of glomerular function: the associations with PFOA and PFOS

Kidney function/dysfunction may affect liver function/dysfunction and vice versa. Liver function is indicated by the observed concentrations of several liver enzymes. Kidney function is indicated by the glomerular filtration rate. Consequently, it is logical to study associations between liver enzymes and glomerular filtration rate indicted by the stages of glomerular function (GF). Thus, this study was undertaken to evaluate the associations between selected liver enzymes and the stages of GF for US adults aged >= 20 years. Data (N = 9523) for US adults for the years 2003-2014 from National Health and Nutrition Examination Survey were analyzed to estimate variabilities in concentrations associated with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (APH), and gamma-glutamyl transferase (GGT) across the stages of GF and to assess variabilities in associations that perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may have with these enzymes across the stages of GF. Those with eGFR > 90 mL/min/1.73 m(2) were defined as being in GF-1, those with eGFR between 60 and 89 mL/min/1.73 m(2) were defined as being in GF-2, those with eGFR between 45 and 59 mL/min/1.73 m(2) were defined as being in GF-3A, those with eGFR between 15 and 44 mL/min/1.73 m(2) were defined as being GF-3B/4. Regression models stratified by GF stages with ALT, AST, APH, and GGT as dependent variables were fitted to evaluate the associations of interest. Adjusted levels of ALT decreased with deteriorating kidney function from 25.3 IU/L at GF-1 to 20.9 IU/L at GF-3B/4 for obese adults and from 21.4 IU/L at GF-1 to 16.4 IU/L at GF-3B/4 for nonobese adults. Adjusted levels of AST followed inverted U-shaped distributions with increases from GF-1 to GF-2 followed by decreases from GF-2 to GF-3B/4. Adjusted levels of APH followed inverted U-shaped distributions with increases from GF-1 to GF-3A followed by decreases from GF-3A to GF-3B/4. Adjusted levels of GGT followed inverted U-shaped distribution among obese participants with point of inflection located at GF-3A. For the total population, obese had higher adjusted levels than nonobese at GF-1, GF-2, and GF-3A for ALT, APH, and GGT. Male-female differences in adjusted levels of ALT and GGT continued narrowing as kidney function deteriorated from GF-1 to GF-3B/4. The differences in ALT widened among non-obese smokers and nonsmokers as kidney function deteriorated. The concentrations of liver enzymes across GF stages varied by gender, race/ethnicity, smoking status, and obesity and more often than not, were indicated by inverted U-shaped curves with points of inflections located at G-2 or GF-3A. The associations between PFOA/ PFOS with liver enzymes varied in magnitude and/or direction by stages of GF as kidney function deteriorated.