BACKGROUND AND OBJECTIVES: Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured. RESULTS: Patients with preeclampsia had prominent characteristic glomerular lesions. The results showed that the number of podocytes per glomerulus did not differ significantly between the patients with preeclampsia and the control groups. However, preeclampsia was associated with a significant increase in intraglomerular cell proliferation (7.3% [SD 9.4] of the glomeruli of patients with preeclampsia had Ki-67-positive cells versus 1.6% [SD 3.3] of the glomeruli of hypertensive controls and 1.1% [SD 1.3] of nonpregnant controls; P=0.004) and activated parietal epithelial cells on a podocyte location (34% [SD 13.1] of the glomeruli of patients with preeclampsia versus 18.0% [SD 15.3] of pregnant controls, 11.9% [SD 13.2] of hypertensive controls, and 10.8% [SD 13.4] of nonpregnant controls; P=0.01). CONCLUSIONS: These findings suggest that the recently described mechanisms of podocyte replacement play a role in preeclampsia. These results provide key new insights into the pathogenesis of preeclamptic nephropathy, and they open new possibilities for developing therapeutic modalities.
BACKGROUND AND OBJECTIVES: Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured. RESULTS:Patients with preeclampsia had prominent characteristic glomerular lesions. The results showed that the number of podocytes per glomerulus did not differ significantly between the patients with preeclampsia and the control groups. However, preeclampsia was associated with a significant increase in intraglomerular cell proliferation (7.3% [SD 9.4] of the glomeruli of patients with preeclampsia had Ki-67-positive cells versus 1.6% [SD 3.3] of the glomeruli of hypertensive controls and 1.1% [SD 1.3] of nonpregnant controls; P=0.004) and activated parietal epithelial cells on a podocyte location (34% [SD 13.1] of the glomeruli of patients with preeclampsia versus 18.0% [SD 15.3] of pregnant controls, 11.9% [SD 13.2] of hypertensive controls, and 10.8% [SD 13.4] of nonpregnant controls; P=0.01). CONCLUSIONS: These findings suggest that the recently described mechanisms of podocyte replacement play a role in preeclampsia. These results provide key new insights into the pathogenesis of preeclamptic nephropathy, and they open new possibilities for developing therapeutic modalities.
Authors: S Ananth Karumanchi; Sharon E Maynard; Isaac E Stillman; Franklin H Epstein; Vikas P Sukhatme Journal: Kidney Int Date: 2005-06 Impact factor: 10.612
Authors: Vesna D Garovic; Steven J Wagner; Lydia M Petrovic; Catherine E Gray; Pauline Hall; Hikaru Sugimoto; Raghu Kalluri; Joseph P Grande Journal: Nephrol Dial Transplant Date: 2007-01-25 Impact factor: 5.992
Authors: Bart Smeets; Sandra Uhlig; Astrid Fuss; Fieke Mooren; Jack F M Wetzels; Jürgen Floege; Marcus J Moeller Journal: J Am Soc Nephrol Date: 2009-11-16 Impact factor: 10.121
Authors: Vesna D Garovic; Steven J Wagner; Stephen T Turner; David W Rosenthal; William J Watson; Brian C Brost; Carl H Rose; Larisa Gavrilova; Paula Craigo; Kent R Bailey; Johannes Achenbach; Mario Schiffer; Joseph P Grande Journal: Am J Obstet Gynecol Date: 2007-04 Impact factor: 8.661
Authors: Vera Eremina; J Ashley Jefferson; Jolanta Kowalewska; Howard Hochster; Mark Haas; Joseph Weisstuch; Catherine Richardson; Jeffrey B Kopp; M Golam Kabir; Peter H Backx; Hans-Peter Gerber; Napoleone Ferrara; Laura Barisoni; Charles E Alpers; Susan E Quaggin Journal: N Engl J Med Date: 2008-03-13 Impact factor: 91.245
Authors: M Casparie; A T M G Tiebosch; G Burger; H Blauwgeers; A van de Pol; J H J M van Krieken; G A Meijer Journal: Cell Oncol Date: 2007 Impact factor: 6.730
Authors: Fernanda Regina Giachini; Carlos Galaviz-Hernandez; Alicia E Damiano; Marta Viana; Angela Cadavid; Patricia Asturizaga; Enrique Teran; Sonia Clapes; Martin Alcala; Julio Bueno; María Calderón-Domínguez; María P Ramos; Victor Vitorino Lima; Martha Sosa-Macias; Nora Martinez; James M Roberts; Carlos Escudero Journal: Curr Hypertens Rep Date: 2017-10-06 Impact factor: 5.369
Authors: Cleo C L van Aanhold; Manon Bos; Katrina M Mirabito Colafella; Marie-Louise P van der Hoorn; Ron Wolterbeek; Jan A Bruijn; Kitty W M Bloemenkamp; Anton H van den Meiracker; A H Jan Danser; Hans J Baelde Journal: Sci Rep Date: 2021-03-11 Impact factor: 4.379