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

Abstract

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 ( = 15), gestational hypertension (GH; = 14), and normotensive controls (NC; = 44). Urinary markers of tubular injury, α1-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, = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, = 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).

Subclinical First Trimester Renal Abnormalities Are Associated With Preeclampsia in Normoalbuminuric Women With Type 1 Diabetes

“…Two other studies addressed urinary KIM-1 in relation to PE. In one, KIM-1 showed no predictive ability for PE when measured at the second trimester in a general population cohort (41). In the other, KIM-1 was measured at term and was increased in women with versus without PE, but its predictive value was not addressed (42).…”

Systemic Outcomes of (Pyr1)-Apelin-13 Infusion at Mid-Late Pregnancy in a Rat Model with Preeclamptic Features

“…Furthermore, preeclampsia can be associated with proteinuria, glomerular and tubular changes 48,49 . Apelin treatment attenuated glomerulosclerosis and interstitial fibrosis in agreement with reduced total renal collagen deposition in TGA-PE rats.…”

Protective effect of dexmedetomidine on kidney injury of parturients with preeclampsia undergoing cesarean section: a randomized controlled study

“…Cr and urinary protein contents are critical indicators for clinical diagnosis of kidney injury and their enhancements in expression are considered to be closely correlated to the extent of renal trauma [22]. In addition, another study attested that the levels of urinary KIM-1 and β2-MG in PE parturients were significantly higher than those in normal parturients, suggesting that the level of β2-MG and KIM-1 in the urine play a vital role in preeclamptic kidney damage [23]. Liang et al applied dexmedetomidine in cisplatin-based cancer chemotherapy and it was found that apart from promote to keep calm and dexmedetomidine can also exert protective effects in kidney damage induced by cisplatin.…”