Quantitative Polymerase Chain Reaction–Based Analysis of Podocyturia Is a Feasible Diagnostic Tool in Preeclampsia

Kelder, Tim P.; Penning, Marlies E.; Uh, Hae‐Won; Cohen, Daniëlle; Bloemenkamp, Kitty W. M.; Bruijn, Jan A.; Scherjon, Sicco A.; Baelde, Hans J.

doi:10.1161/hypertensionaha.112.201681

Cited by 40 publications

(42 citation statements)

References 31 publications

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“…Our group and others recently reported significantly higher numbers of podocytes in the urine (i.e., podocyturia) of women with preeclampsia compared with pregnant controls (5,6). This podocyturia remained in the patients with preeclampsia up to 1 month after delivery, although their proteinuria resolved (7).…”

Section: Introductionsupporting

confidence: 51%

Association of Preeclampsia with Podocyte Turnover

Penning¹,

Bloemenkamp

Zon³

et al. 2014

Clinical Journal of the American Society of Nephrology

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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.

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Section: Introductionsupporting

confidence: 51%

Association of Preeclampsia with Podocyte Turnover

Penning¹,

Bloemenkamp

Zon³

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Structural alterations with downregulation of podocyte function-specific proteins as well as podocytopenia occur in DN [26][27][28][29][30][31] . The detection of podocytes or associated markers in urine as an index of podocyte damage has been described in glomerulopathies including DN, pre-eclampsia and other diseases [18,19,[32][33][34][35][36] .…”

Section: Discussionmentioning

confidence: 99%

Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes

Lioudaki

Stylianou²,

Petrakis³

et al. 2015

Nephron

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Background: Podocyte injury plays a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). We investigated whether patients with diabetes mellitus (DM) without overt DN present podocyte markers in urine suggestive of early podocyte injury. Methods: We studied 71 patients with DM type 2 and normal urine albumin excretion (UAE) and 39 non-diabetic controls. The mRNA abundance of 3 podocyte-specific markers in urinary sediment (nephrin, podocin and synaptopodin) was measured with real-time quantitative PCR. All the subjects were categorized according to their urinary podocyte marker profile into 2 groups, those with only synaptopodin mRNA presence (synaptopodin only group) and those with nephrin and/or podocin mRNA presence in addition to synaptopodin in their urine (nephrin and/or podocin group). Results: Synaptopodin mRNA was detected in the urine of all the diabetics and controls. The presence of nephrin and/or podocin mRNA in urine was more frequent among DM patients compared to controls (53.5 vs. 30.8%, respectively; p = 0.022). Binary logistic regression analysis revealed that the only significant predictor of the presence of nephrin and/or podocin mRNA in urine was the presence of DM (OR 2.59, 95% CI 1.14-5.91, p = 0.024, adjusted for all risk factors). A strong correlation between nephrin and podocin urinary mRNA levels was noted (r = +0.796, p < 0.001). Conclusion: This study demonstrated that urinary podocyte markers are more prevalent in diabetic patients with normal UAE compared to controls, and this may reflect early podocyte injury. DM is the only significant determinant of the presence of nephrin and/or podocin mRNA in urine in this population. Therefore, urinary podocyte markers may emerge as a valuable tool in the early diagnosis of DN.

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“…Significantly elevated mRNA levels of nephrin, podocin, and VEGF were detected in preeclamptic women compared with healthy controls [65] .…”

Section: Podocyturiamentioning

confidence: 92%

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

Müller-Deile

Schiffer

2014

WJN

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Proteinuria is a frequently detected symptom, found in 20% of pregnancies. A common reason for proteinuria in pregnancy is preeclampsia. To diagnose preeclampsia clinically and to get new insights into the pathophysiology of the disease it is at first essential to be familiar with conditions in normal pregnancy. Animal models and biomarkers can help to learn more about disease conditions and to find new treatment strategies. In this article we review the changes in kidney function during normal pregnancy and the differential diagnosis of proteinuria in pregnancy. We summarize different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. We describe the current animal models and give a broad overview of different biomarkers that were reported to predict preeclampsia or have a prognostic value in preeclampsia cases. We end with a summary of treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia. Most of these novel biomarkers for preeclampsia are not yet implemented in clinical use. Therefore, we recommend using proteinuria (measured by UPC ratio) as a screening parameter for preeclampsia. Delivery is the only curative treatment for preeclampsia. In early preeclampsia the primary therapy goal is to prolong pregnancy until a state were the child has an acceptable chance of survival after delivery.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Preeclampsia; Pregnancy; Proteinuria; Biomarkers; Treatment Core tip: This review summarises different pathophysiological theories of preeclampsia with a special focus on the renal facets of the disease. In this context current animal models are presented. The reader gets a broad overview about different biomarkers for preeclampsia. Furthermore, the article discusses treatment options for preeclampsia related symptoms including the use of plasmapheresis as a rescue therapy for so far refractory preeclampsia.Müller-Deile J, Schiffer M. Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy. World

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Quantitative Polymerase Chain Reaction–Based Analysis of Podocyturia Is a Feasible Diagnostic Tool in Preeclampsia

Cited by 40 publications

References 31 publications

Association of Preeclampsia with Podocyte Turnover

Association of Preeclampsia with Podocyte Turnover

Increased Urinary Excretion of Podocyte Markers in Normoalbuminuric Patients with Diabetes

Preeclampsia from a renal point of view: Insides into disease models, biomarkers and therapy

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