Wendy M White

Publications (6)28.8 Total impact

• Article: Podocyturia Predates Proteinuria and Clinical Features of Preeclampsia: Longitudinal Prospective Study.

  Iasmina M Craici, Steven J Wagner, Kent R Bailey, Patrick D Fitz-Gibbon, Christina M Wood-Wentz, Stephen T Turner, Suzanne R Hayman, Wendy M White, Brian C Brost, Carl H Rose, Joseph P Grande, Vesna D Garovic
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  ABSTRACT: Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.
  Hypertension 03/2013; · 6.21 Impact Factor
• Article: Obstetric Nephrology: Lupus and Lupus Nephritis in Pregnancy.

  Todd J Stanhope, Wendy M White, Kevin G Moder, Andrew Smyth, Vesna D Garovic
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  ABSTRACT: SLE is a multi-organ autoimmune disease that affects women of childbearing age. Renal involvement in the form of either active lupus nephritis (LN) at the time of conception, or a LN new onset or flare during pregnancy increases the risks of preterm delivery, pre-eclampsia, maternal mortality, fetal/neonatal demise, and intrauterine growth restriction. Consequently, current recommendations advise that the affected woman achieve a stable remission of her renal disease for at least 6 months before conception. Hormonal and immune system changes in pregnancy may affect disease activity and progression, and published evidence suggests that there is an increased risk for a LN flare during pregnancy. The major goal of immunosuppressive therapy in pregnancy is control of disease activity with medications that are relatively safe for a growing fetus. Therefore, the use of mycophenolate mofetil, due to increasing evidence supporting its teratogenicity, is contraindicated during pregnancy. Worsening proteinuria, which commonly occurs in proteinuric renal diseases toward the end of pregnancy, should be differentiated from a LN flare and/or pre-eclampsia, a pregnancy-specific condition clinically characterized by hypertension and proteinuria. These considerations present challenges that underscore the importance of a multidisciplinary team approach when caring for these patients, including a nephrologist, rheumatologist, and obstetrician who have experience with these pregnancy-related complications. This review discusses the pathogenesis, maternal and fetal risks, and management pertinent to SLE patients with new onset or a history of LN predating pregnancy.
  Clinical Journal of the American Society of Nephrology 08/2012; · 5.23 Impact Factor
• Article: Normal early pregnancy: a transient state of epigenetic change favoring hypomethylation.

  Wendy M White, Brian C Brost, Zhifu Sun, Carl Rose, Iasmina Craici, Steven J Wagner, Stephen Turner, Vesna D Garovic
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  ABSTRACT: The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age and body mass index matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n = 14), in the same women postpartum (n = 14), and in nulligravid women (n = 14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared with both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared with non-pregnant states; there is no apparent permanent methylation imprint after a normal term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy.
  Epigenetics: official journal of the DNA Methylation Society 07/2012; 7(7):729-34. · 4.58 Impact Factor
• Article: Mass spectrometry as a novel method for detection of podocyturia in pre-eclampsia.

  Vesna D Garovic, Iasmina M Craici, Steven J Wagner, Wendy M White, Brian C Brost, Carl H Rose, Joseph P Grande, David R Barnidge
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  ABSTRACT: BACKGROUND: Podocyturia, i.e. urinary loss of viable podocytes, may serve as a diagnostic tool for pre-eclampsia and as a marker of active renal disease. The current method to detect podocyturia is technically complex, lengthy and requires a high level of expertise for interpretation. The aim of this study was to develop a new technique for the identification of urinary podocytes, based on the detection of podocyte-specific tryptic peptides by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), which will provide an operator-independent and highly reproducible method.Methods and RESULTS: The diagnosis of pre-eclampsia was confirmed in the presence of hypertension (>140/90 mmHg) and proteinuria >0.3 g/24 h urine. The diagnosis of HELLP was confirmed based on the accepted clinical criteria of hemolysis, elevated liver enzymes and low platelet count.Random urine samples within 24 h prior to delivery were collected and centrifuged. One half of the sediment was cultured for 24 h to select for viable cells and then stained with a podocin antibody, followed by a secondary fluorescein isothiocyanate-labeled antibody to identify podocytes. The second half of the pellet was solubilized, digested and analyzed by LC-MS/MS using an internal standard. We have recruited 13 patients with pre-eclampsia and 6 patients with pre-eclampsia/HELLP syndrome. The presence of podocytes was confirmed in all patients by the podocyte culture method. In the respective samples, the presence of a podocin-specific tryptic peptide was confirmed with LC-MS/MS technology.CONCLUSION: The LC-MS/MS method is a reliable technology for the identification of urinary podocytes, based on the presence of podocyte-specific proteins in the urine.
  Nephrology Dialysis Transplantation 04/2012; · 3.40 Impact Factor
• Source

  Available from: Jean-Pierre A Kocher

  Article: Batch effect correction for genome-wide methylation data with Illumina Infinium platform.

  Zhifu Sun, High Seng Chai, Yanhong Wu, Wendy M White, Krishna V Donkena, Christopher J Klein, Vesna D Garovic, Terry M Therneau, Jean-Pierre A Kocher
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  ABSTRACT: Genome-wide methylation profiling has led to more comprehensive insights into gene regulation mechanisms and potential therapeutic targets. Illumina Human Methylation BeadChip is one of the most commonly used genome-wide methylation platforms. Similar to other microarray experiments, methylation data is susceptible to various technical artifacts, particularly batch effects. To date, little attention has been given to issues related to normalization and batch effect correction for this kind of data. We evaluated three common normalization approaches and investigated their performance in batch effect removal using three datasets with different degrees of batch effects generated from HumanMethylation27 platform: quantile normalization at average β value (QNβ); two step quantile normalization at probe signals implemented in "lumi" package of R (lumi); and quantile normalization of A and B signal separately (ABnorm). Subsequent Empirical Bayes (EB) batch adjustment was also evaluated. Each normalization could remove a portion of batch effects and their effectiveness differed depending on the severity of batch effects in a dataset. For the dataset with minor batch effects (Dataset 1), normalization alone appeared adequate and "lumi" showed the best performance. However, all methods left substantial batch effects intact in the datasets with obvious batch effects and further correction was necessary. Without any correction, 50 and 66 percent of CpGs were associated with batch effects in Dataset 2 and 3, respectively. After QNβ, lumi or ABnorm, the number of CpGs associated with batch effects were reduced to 24, 32, and 26 percent for Dataset 2; and 37, 46, and 35 percent for Dataset 3, respectively. Additional EB correction effectively removed such remaining non-biological effects. More importantly, the two-step procedure almost tripled the numbers of CpGs associated with the outcome of interest for the two datasets. Genome-wide methylation data from Infinium Methylation BeadChip can be susceptible to batch effects with profound impacts on downstream analyses and conclusions. Normalization can reduce part but not all batch effects. EB correction along with normalization is recommended for effective batch effect removal.
  BMC Medical Genomics 12/2011; 4:84. · 3.69 Impact Factor
• Article: Posterior reversible encephalopathy syndrome and eclampsia: pressing the case for more aggressive blood pressure control.

  Steven J Wagner, Letitia A Acquah, E Paul Lindell, Iasmina M Craici, Majken T Wingo, Carl H Rose, Wendy M White, Phyllis August, Vesna D Garovic
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  ABSTRACT: To assess the prevalence, clinical presentations, and neuroimaging abnormalities in a series of patients treated for eclampsia at Mayo Clinic in Rochester, MN. We reviewed the records of all pregnant patients diagnosed as having eclampsia at Mayo Clinic in Rochester, MN, between January 1, 2001, and December 31, 2008. All patients who underwent neuroimaging were identified, and all studies were reviewed by an independent neuroradiologist. Comparisons were made between groups who did and did not undergo imaging to identify differentiating clinical or laboratory variables. Thirteen cases of eclampsia were found, with neuroimaging studies available for 7: magnetic resonance imaging (n=6) and computed tomography (n=1). All 7 patients developed eclamptic seizures, and 2 of 7 patients had severe hypertension, with recorded systolic blood pressures exceeding 180 mm Hg. Neuroimaging showed characteristic changes of posterior reversible encephalopathy syndrome (PRES) in all patients. Follow-up imaging showed resolution in 2 of 3 patients; 1 patient had residual neuroimaging abnormalities. Our results suggest that the clinical syndrome of eclampsia is associated with an anatomical substrate that is recognizable by neuroimaging as PRES. The levels of blood pressure elevation are lower than those reported in cases of PRES because of hypertensive encephalopathy. Further studies are needed to determine whether more aggressive blood pressure control and early neuroimaging may have a role in the management of these patients.
  Mayo Clinic Proceedings 09/2011; 86(9):851-6. · 5.70 Impact Factor