Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n=15), gestational hypertension (GH) (n=14), and normotensive controls (NC) (n=44). Urinary markers of tubular injury, alpha-1 microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups, as an A1M/creatinine ratio >13 (66.7%, 8.3%, and 35%, respectively; p=0.01). Concentrations of C5b-9 were higher in the PE group than in GH and NC groups (medians 9.85 ng/mg, 0.05 ng/mg, and 0.28 ng/mg, respectively; p=0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7 and TIMP-2).