TY - JOUR

T1 - Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations

AU - Федотов, Сергей Александрович

AU - Храброва, Мария Сергеевна

AU - Вашукова, Елена Сергеевна

AU - Глотов, Андрей Сергеевич

AU - Анпилова, Анастасия Олеговна

AU - Добронравов, Владимир Александрович

AU - Велижанина, Мария Евгеньевна

AU - Рубель, Александр Анатольевич

N1 - Fedotov SA, Khrabrova MS, Vashukova ES, Glotov AS, Anpilova AO, Dobronravov VA, et al. (2024) Diagnostics of preeclampsia based on Congo red binding to urinary components: Rationales and limitations. PLoS ONE 19(1): e0297144. https://doi.org/10.1371/journal.pone.0297144

PY - 2024/1/19

Y1 - 2024/1/19

N2 - 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.

AB - 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.

KW - преэклампсия

KW - Тест CRD

KW - протеинурия

KW - амилоидозы

KW - нефропатия

KW - Humans

KW - Female

KW - Pregnancy

KW - Pre-Eclampsia/metabolism

KW - Congo Red

KW - Hypertension

KW - Amyloid/metabolism

KW - Amyloidogenic Proteins

KW - Amyloidosis/pathology

KW - Proteinuria/diagnosis

UR - https://www.mendeley.com/catalogue/5c05a950-2d44-39e5-9a7c-202a9250a505/

U2 - 10.1371/journal.pone.0297144

DO - 10.1371/journal.pone.0297144

M3 - Article

C2 - 38241324

VL - 19

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 1

M1 - e0297144

ER -