The effectiveness of the Congo Red Dot paper test in hypertensive disorders of pregnancy: A systematic review and meta-analysis

Khaliq, Olive P.; Phoswa, Wendy N.; Moodley, Jagidesa

doi:10.3389/frph.2023.1120937

Cited by 5 publications

(3 citation statements)

References 41 publications

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“…The Congo red dot (CRD) test represents a non-invasive and low-cost alternative to other methods of assessing protein misfolding load associated with PE. The clinical applicability of the CRD test, which is based on the detection of urine congophilia, as established by our lab, has been examined in fourteen studies, including one randomized control trial and one meta-analysis ( [90,91,[204][205][206][207][208][209][210][211][212][213][214][215]). In one study, our lab evaluated the performance of the CRD test at measuring misfolded protein load in urine and serum against that of Thioflavin-T (ThT)-enhanced fluorescence, a benzothiazole dye that preferentially binds to amyloid fibrils [214].…”

Section: Early Prediction and Diagnosismentioning

confidence: 99%

“…In addition, the CRD test was not efficient at predicting PE in a term asymptomatic cohort (UK) and was determined to have low sensitivity at predicting impending MIDPE (within 28 days of initial assessment) in a randomized control trial, as well as low sensitivity at predicting adverse maternal and neonatal outcomes in women presenting with symptoms of suspected PE [205,206,210]. Finally, in a meta-analysis that included five studies, Khaliq et al concluded that the test is ineffective based on forest plot analysis [204]. Of note, the five studies compared in the meta-analysis comprised highly heterogeneous patient populations.…”

Section: Early Prediction and Diagnosismentioning

confidence: 99%

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Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Medegan Fagla,

Buhimschi

2024

Molecules

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Protein misfolding disorders are a group of diseases characterized by supra-physiologic accumulation and aggregation of pathogenic proteoforms resulting from improper protein folding and/or insufficiency in clearance mechanisms. Although these processes have been historically linked to neurodegenerative disorders, such as Alzheimer’s disease, evidence linking protein misfolding to other pathologies continues to emerge. Indeed, the deposition of toxic protein aggregates in the form of oligomers or large amyloid fibrils has been linked to type 2 diabetes, various types of cancer, and, in more recent years, to preeclampsia, a life-threatening pregnancy-specific disorder. While extensive physiological mechanisms are in place to maintain proteostasis, processes, such as aging, genetic factors, or environmental stress in the form of hypoxia, nutrient deprivation or xenobiotic exposures can induce failure in these systems. As such, pregnancy, a natural physical state that already places the maternal body under significant physiological stress, creates an environment with a lower threshold for aberrant aggregation. In this review, we set out to discuss current evidence of protein misfolding in pregnancy and potential mechanisms supporting a key role for this process in preeclampsia pathogenesis. Improving our understanding of this emerging pathophysiological process in preeclampsia can lead to vital discoveries that can be harnessed to create better diagnoses and treatment modalities for the disorder.

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Section: Early Prediction and Diagnosismentioning

confidence: 99%

Section: Early Prediction and Diagnosismentioning

confidence: 99%

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Medegan Fagla,

Buhimschi

2024

Molecules

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“…Thus, pregnant women with preexisting renal disease unrelated to pregnancy can yield positive results in the CRD tests. Conversely, when proteinuria is absent in cases of preeclampsia, the CRD test may also have reduced effectiveness, as evidenced by a recent meta-analysis [23].…”

Section: Plos Onementioning

confidence: 99%

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

Fedotov,

Khrabrova,

Vashukova

et al. 2024

PLoS ONE

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Preeclampsia is a disorder that can occur during pregnancy and is one of the leading causes of death among pregnant women. This disorder occurs after the 20th week of pregnancy and is characterized by arterial hypertension, proteinuria, fetoplacental, and multiple organ dysfunctions. Despite the long history of studying preeclampsia, its etiology and pathogenesis remain poorly understood, and therapy is symptomatic. One of the factors of the disorder is believed to be misfolded proteins that are prone to form amyloid aggregates. The CRD tests, utilizing the binding of the amyloid-specific dye Congo red to urine components, demonstrate high efficiency in diagnosing preeclampsia. However, these tests have also been found to be positive in other disorders with proteinuria, presumably associated with concomitant amyloidosis. To assess the limitations of the CRD tests, we examined urine congophilia and protein components mediating Congo red positivity in patients with proteinuria, including preeclampsia, amyloid and non-amyloid nephropathies. We stained the urine samples and calculated congophilia levels. We also assessed the contribution of large protein aggregates to congophilia values using ultracentrifugation and determined the molecular weights of congophilic urinary proteins using centrifugal concentrators. All proteinuric groups demonstrate positive results in the CRD tests and congophilia levels were more than two times higher compared with the control non-proteinuric groups (p <0.01). There was a strong correlation between urine protein excretion and congophilia in amyloid nephropathy (rs = 0.76), non-amyloid nephropathies (rs = 0.90), and preeclampsia (rs = 0.90). Removal of large aggregates from urine did not affect the congophilia levels. Separation of urine protein fractions revealed congophilic components in the range of 30–100 kDa, including monomeric serum albumin. Our results indicate limitations of CRD tests in preeclampsia diagnostics in women with renal disorders and underscore the need for further research on the mechanisms of Congo red binding with urine components.

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Predictive value of urine misfolded protein in preeclampsia in twin pregnancies

Liang,

Sun

2024

Arch Gynecol Obstet

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The effectiveness of the Congo Red Dot paper test in hypertensive disorders of pregnancy: A systematic review and meta-analysis

Cited by 5 publications

References 41 publications

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Protein Misfolding in Pregnancy: Current Insights, Potential Mechanisms, and Implications for the Pathogenesis of Preeclampsia

Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

Predictive value of urine misfolded protein in preeclampsia in twin pregnancies

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