Department of Obstetrics and Gynecology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Complications of Diabetes Unit, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Nephrol Dial Transplant. 2022 May 25;37(6):1109-1117. doi: 10.1093/ndt/gfab175.
Pre-eclampsia has a major impact on renal function as shown by the development of proteinuria and podocyturia. How the systemic, soluble Fms-like tyrosine kinase-1 (sFlt-1)-driven inhibition of vascular endothelial growth factor (VEGF) activity detected in pre-eclampsia directly affects renal function remains unknown. The aim of the study was to clarify whether a non-canonical, renal-centred escape from VEGF inhibition in the case of pre-eclamptic pregnancy might have a direct impact on renal function.
We evaluated plasma and urinary VEGF and placental growth factor (PlGF), plasma sFlt-1 and carbonic anhydrase IX (CAIX), albuminuria and podocyturia in 18 women with uncomplicated pregnancy, 21 with pre-eclampsia and 18 non-pregnant. The three groups were matched for age and the pregnant groups also for gestational age at enrolment.
Plasma VEGF was reduced in uncomplicated (P = 0.001) and pre-eclamptic (P = 0.0003) pregnancies when compared with controls. In uncomplicated pregnancy, the dysfunction was balanced by an increase (P = 0.009) of plasma PlGF. Increased (P = 0.0001) plasma CAIX in pre-eclampsia was in line with hypoxia. Pre-eclampsia resulted in a paradoxical increase (P = 0.0004) of urinary excretion of VEGF. Urinary concentrations of VEGF and podocytes were correlated to each other (r2 = 0.48, P < 0.0005) but also to plasma sFlt-1 (r2 = 0.56, P < 0.0001 and r2 = 0.23, P = 0.03, respectively).
In the case of pre-eclampsia, the systemic VEGF inhibition leads the kidney, possibly the podocyte, to increase the VEGF synthesis. The mechanisms leading to local VEGF overproduction or the overproduced VEGF itself are reasonably involved in the pathogenesis of podocyturia and, as a consequence, renal dysfunction in pre-eclampsia.
子痫前期会导致肾功能受损，表现为蛋白尿和足细胞尿的发生。目前尚不清楚子痫前期患者体内系统性、可溶性 Fms 样酪氨酸激酶-1（sFlt-1）驱动的血管内皮生长因子（VEGF）活性抑制如何直接影响肾功能。本研究旨在阐明子痫前期妊娠中是否存在非经典的、以肾脏为中心的 VEGF 抑制逃逸，这是否会直接影响肾功能。
我们评估了 18 名正常妊娠妇女、21 名子痫前期妇女和 18 名非妊娠妇女的血浆和尿液 VEGF 和胎盘生长因子（PlGF）、血浆 sFlt-1 和碳酸酐酶 IX（CAIX）、白蛋白尿和足细胞尿。这三组按年龄匹配，妊娠组也按入组时的孕周匹配。
与对照组相比，正常妊娠（P=0.001）和子痫前期（P=0.0003）孕妇的血浆 VEGF 降低。在正常妊娠中，这种功能障碍通过血浆 PlGF 的增加（P=0.009）得到平衡。子痫前期中增加的（P=0.0001）血浆 CAIX 与缺氧一致。子痫前期导致尿 VEGF 排泄的反常增加（P=0.0004）。尿 VEGF 和足细胞的浓度相互相关（r2=0.48，P<0.0005），也与血浆 sFlt-1 相关（r2=0.56，P<0.0001 和 r2=0.23，P=0.03）。
在子痫前期中，全身性的 VEGF 抑制会导致肾脏（可能是足细胞）增加 VEGF 的合成。导致局部 VEGF 过度产生或产生的 VEGF 本身很可能参与了子痫前期中足细胞尿和肾功能障碍的发病机制。
