Association of Preeclampsia with Podocyte Turnover

Abstract

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] 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.

Podocyte Regeneration Driven by Renal Progenitors Determines Glomerular Disease Remission and Can Be Pharmacologically Enhanced

“…Several previous studies support the possibility that RPC differentiation into podocytes may be involved in remission of different types of diseases, including proliferative glomerulonephritis ( Rizzo et al., 2013 ), gestational pre-eclampsia ( Penning et al., 2014 ), and diabetic nephropathy ( Pichaiwong et al., 2013 ). In addition, drugs that are already used in clinical practice to delay disease progression, such as renin-angiotensin-aldosterone system blockers, not only prevent progressive renal damage but also promote the regression of glomerulosclerosis in several models of CKD ( Remuzzi et al., 2006 ), suggesting that they may also exert their beneficial effects by promoting RPC differentiation into podocytes ( Benigni et al., 2011 ).…”

Classical Complement Pathway Activation in the Kidneys of Women With Preeclampsia

“…27 In brief, for the preeclamptic women, the median age was 32.5 years (interquartile range: 29–36), median gestational age was 35.7 weeks (interquartile range: 34–39), mean parity was 0.6 children, and median proteinuria was 0.36 g/24 hours (interquartile range: 0.3–6.1). The hypertensive control group was significantly older than the other two study groups ( p <0.05), and the preeclamptic women had significantly higher systolic and diastolic blood pressure ( p <0.05) than pregnant controls; no other significant differences were observed with respect to the remaining clinical characteristics.…”

“…27 In brief, the majority (82%) of preeclamptic women had prominent glomerular lesions, including various degrees of endotheliosis, podocyte swelling, and tram tracking (i.e., double contours of the glomerular basement membrane). The prevalence of endotheliosis in the preeclamptic women (55%) was higher than in the pregnant (12%; p <0.05) and hypertensive controls (15%; p <0.05).…”

Updates in Diagnosis and Management of Preeclampsia in Women with CKD

“…When kidney biopsy has been performed for historical or research purposes, the predominant change is increased glomerular volume and endothelial cell swelling (endotheliosis), leading to narrowing and occlusion of glomerular capillaries. Although mild endotheliosis has been described in normal pregnancies, mesangial interposition distinguishes hypertensive women (38,39). Duplication of the glomerular basement membrane may be evident in severe disease.…”