Renal tubular secretion in chronic kidney disease: description, determinants, and outcomes

Thesis (Ph.D.)--University of Washington, 2014Background The presence and severity of chronic kidney disease are currently assessed by glomerular filtration rate and urinary albumin excretion. Other kidney functions, such as proximal tubular secretion, are not typically quantified. Tubular secretion is capable of clearing metabolites from the blood more efficiently than filtration, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and prediction of adverse outcomes. Methods We developed and validated mass spectrometry assays to measure hippurate and cinnamoylglycine, which are primarily cleared by renal tubular secretion. We estimated secretion function in a prospective cohort study of 298 CKD patients using timed urinary clearance of these molecules. We examined associations between renal secretion and estimated filtration (average of creatinine and urea clearance), related clinical characteristics, and mortality. Results Tubular secretion correlated with glomerular filtration, but considerable residual variability remained. Tubular secretion was significantly greater among men. For a given level of filtration function, diminished hippurate clearance was associated with increased risk of death (hazard ratio comparing low to high secretion groups: 2.3, 95% confidence interval: 1.1-4.7). Diminished cinnamoylglycine clearance, for a given level of filtration, was associated with increased risk of starting dialysis (hazard ratio comparing low to high secretion groups: 4.5, 95% confidence interval: 1.4-14.4). Conclusion Proximal tubular secretion function comprises a measurement of kidney function that modestly correlates with filtration function and may be associated with mortality and starting dialysis