Shakhmatova OO, Komarov AL, Krivosheeva EN, Dobrovolsky AB, Titaeva EV, Amelyushkina VA, Gomyranova NV, Panchenko EP. Albuminuria as a marker of atherosclerosis burden and a possible predictor of adverse events in patients with polyvascular disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(9):763–768.
DOI: 10.26442/00403660.2023.09.202434
Альбуминурия у пациентов с мультифокальным атеросклерозом как маркер распространенности поражения и возможный предиктор прогноз-определяющих событий
Шахматова О.О., Комаров А.Л., Кривошеева Е.Н., Добровольский А.Б., Титаева Е.В., Амелюшкина В.А., Гомыранова Н.В., Панченко Е.П. Альбуминурия у пациентов с мультифокальным атеросклерозом как маркер распространенности поражения и возможный предиктор прогноз-определяющих событий. Терапевтический архив. 2023;95(9):763–768. DOI: 10.26442/00403660.2023.09.202434
Shakhmatova OO, Komarov AL, Krivosheeva EN, Dobrovolsky AB, Titaeva EV, Amelyushkina VA, Gomyranova NV, Panchenko EP. Albuminuria as a marker of atherosclerosis burden and a possible predictor of adverse events in patients with polyvascular disease. Terapevticheskii Arkhiv (Ter. Arkh.). 2023;95(9):763–768.
DOI: 10.26442/00403660.2023.09.202434
Обоснование. Значимость альбуминурии как маркера бремени атеросклероза, предиктора неблагоприятного прогноза у пациентов с мультифокальным атеросклерозом (МФА) практически не изучена. Цель. Оценить распространенность, связь с бременем атеросклероза и прогностическую ценность альбуминурии в отношении сердечно-сосудистых (ССО) и геморрагических осложнений у пациентов с МФА. Материалы и методы. В пилотное исследование включались участники проспективного регистра РЕГАТА-1 (NCT04347200). Включены 74 пациента c ишемической болезнью сердца и периферическим атеросклерозом, получающие ацетилсалициловую кислоту и ривароксабан 2,5 мг (75,7% – мужчины, медиана возраста – 67 [61–69] лет). Определялись соотношение альбумин-креатинин в разовой утренней порции мочи, расчетная скорость клубочковой фильтрации (рСКФ), уровень фактора Виллебранда. Результаты. Легкая альбуминурия (10–29 мг/г) выявлена у 45,9% пациентов, умеренная и выраженная (≥30 мг/г) – у 29,7%; рСКФ<60 мл/мин – у 21,7%, хроническая болезнь почек (ХБП) в соответствии с полными критериями KDIGO, учитывающими рСКФ и альбуминурию, – вдвое чаще (39,2%). Частота назначения нефропротективной терапии являлась недостаточной. Уровень альбуминурии не коррелировал с маркером эндотелиальной дисфункции фактора Виллебранда, однако связан с поражением 4–5 сосудистых бассейнов (ROC AUC 0,775; p=0,011). За 12 [8–18] мес зафиксировано 3 ССО и 11 кровотечений BARC 2–3. Ни альбуминурия, ни рСКФ не оказались предикторами ССО, кровотечений и суммы исходов. ХБП (KDIGO) также не ассоциировалась с геморрагическими осложнениями. У всех пациентов, перенесших ССО, имелась ХБП (KDIGO), связь сохранялась при многофакторном анализе методом множественной регрессии (β 0,097; p=0,0420), однако малое число конечных точек позволяет говорить лишь о гипотез-генерирующей тенденции. Имплементация ХБП (KDIGO) повысила ценность шкалы REACH в плане предсказания ССО. Заключение. Альбуминурия широко распространена у пациентов с МФА и является маркером бремени атеросклероза. ХБП, диагностированная с учетом уровня альбуминурии, может использоваться в комплексной оценке риска ССО у данной категории пациентов.
Background. The role of albuminuria as a marker of the atherosclerosis burden and a predictor of prognosis in patients with polyvascular disease (PD) has been little studied. Aim. To evaluate the prevalence, association with atherosclerosis burden, and prognostic value of albuminuria in relation to cardiovascular and bleeding complications in patients with PD. Materials and methods. The data was obtained from the prospective registry REGATA-1 (NCT04347200). Seventy four patients (75.7% males, median age 67 [61–69] years) with PD (CAD and peripheral arterial disease) were enrolled. All patients received aspirin and rivaroxaban
2.5 mg. The albumin-creatinine ratio in a single morning urine sample, estimated glomerular filtration rate (eGFR), and von Willebrand factor levels were determined. Results. Mild albuminuria (10–29 mg/g) was detected in 45.9% of patients, moderate and severe (≥30 mg/g) – in 29.7%; eGFR<60 ml/min – in 21.7%, chronic kidney disease (CKD) according to the full KDIGO criteria (eGFR and/or albuminuria ≥30 mg/g) – twice as often (39.2%). The frequency of nephroprotective therapy prescription was insufficient. The level of albuminuria did not correlate with von Willebrand factor (endothelial dysfunction marker), but was associated with affecting of 4–5 vascular beds (ROC AUC 0.775; p=0.011). During the follow-up (12 [8–18] months) 3 patients developed MACE, 11 – BARC 2–3 bleedings. Neither albuminuria nor eGFR were predictors of MACE, bleeding, or net clinical benefit. CKD (KDIGO) was also not associated with bleedings. CKD (KDIGO) was independent predictor of MACE (in significant multiple regression model beta – coefficient for CKD was 0.097; p=0.042), however, the small number of end points allows us to speak only of a hypothesis-generating trend. The implementation of CKD (KDIGO) has increased the predictive value of the REACH score. Conclusion. Albuminuria is highly prevalent in patients with PD. It is a marker of atherosclerosis burden. CKD, diagnosed taking into account the level of albuminuria, can be used in a comprehensive assessment of cardiovascular risk in this category of patients.
1. Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825-30.
DOI:10.7326/0003-4819-158-11-201306040-00007
2. Strain WD, Elyas S, Wedge N, et al. Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study. BMJ Open. 2021;11(9):e043253. DOI:10.1136/bmjopen-2020-043253
3. Matsushita K, Kwak L, Ballew SH, et al. Chronic kidney disease measures and the risk of abdominal aortic aneurysm. Atherosclerosis. 2018;279:107-113. DOI:10.1016/j.atherosclerosis.2018.08.043
4. Choi SW, Yun WJ, Kim HY, et al. Association between albuminuria, carotid atherosclerosis, arterial stiffness, and peripheral arterial disease in Korean type 2 diabetic patients. Kidney Blood Press Res. 2010;33(2):111-8. DOI:10.1159/000313594
5. Molnar AO, Bota SE, Garg AX, et al. The Risk of Major Hemorrhage with CKD. J Am Soc Nephrol. 2016;27(9):2825-32. DOI:10.1681/ASN.2015050535
6. Wilson PW, D'Agostino R Sr, Bhatt DL, et al. An international model to predict recurrent cardiovascular disease. Am J Med. 2012;125(7):695-703.e1. DOI:10.1016/j.amjmed.2012.01.014
7. Wang J, Wang Y, Li Y, et al. High Normal Urinary Albumin-Creatinine Ratio Is Associated With Hypertension, Type 2 Diabetes Mellitus, HTN With T2DM, Dyslipidemia, and Cardiovascular Diseases in the Chinese Population: A Report From the REACTION Study. Front Endocrinol (Lausanne). 2022;13:864562. DOI:10.3389/fendo.2022.864562
8. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1-S127. DOI:10.1016/j.kint.2022.06.008
9. Хроническая болезнь почек (ХБП). Клинические рекомендации 2021. Режим доступа: https://cr.minzdrav.gov.ru/recomend/469_2. Ссылка активна на 18.01.2023 [Khronicheskaia bolezn' pochek (KhBP). Klinicheskie rekomendatsii 2021. Available at: https://cr.minzdrav.gov.ru/ recomend/469_2. Accessed: 18.01.2023 (in Russian)].
10. Li MF, Tu YF, Li LX, et al. Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Cardiovasc Diabetol. 2013;12:110. DOI:10.1186/1475-2840-12-110
11. Kumar Jha P, Ete T, Malviya A, et al. Microalbuminuria: Correlation With Prevalence and Severity of Coronary Artery Disease in Non-Diabetics. J Clin Med Res. 2017;9(10):838-43. DOI:10.14740/jocmr2785w
12. Huang MJ, Wei RB, Zhao J, et al. Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease. Med Sci Monit. 2017;23:4447‑53. DOI:10.12659/msm.903660
13. Seliger SL, Salimi S, Pierre V, et al. Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults. BMC Nephrol. 2016;17(1):82.
DOI:10.1186/s12882-016-0303-x
14. Darmon A, Sorbets E, Ducrocq G, et al. Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients. J Am Coll Cardiol. 2019;73(25):3281-91. DOI:10.1016/j.jacc.2019.04.046
15. Matsushita K, Coresh J, Sang Y, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7):514‑25. DOI:10.1016/S2213-8587(15)00040-6
16. Shin JI, Grams ME, Coresh J, et al. Proteinuria and Risk of Lower-Extremity Amputation in Patients With Peripheral Artery Disease. Diabetes Care. 2019;42(9):e146-7. DOI:10.2337/dc19-0764
17. Tanaka K, Miwa K, Takagi M, et al. Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2. J Am Heart Assoc. 2022;11(6):e024749. DOI:10.1161/JAHA.121.024749
________________________________________________
1. Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med. 2013;158(11):825-30.
DOI:10.7326/0003-4819-158-11-201306040-00007
2. Strain WD, Elyas S, Wedge N, et al. Evaluation of microalbuminuria as a prognostic indicator after a TIA or minor stroke in an outpatient setting: the prognostic role of microalbuminuria in TIA evolution (ProMOTE) study. BMJ Open. 2021;11(9):e043253. DOI:10.1136/bmjopen-2020-043253
3. Matsushita K, Kwak L, Ballew SH, et al. Chronic kidney disease measures and the risk of abdominal aortic aneurysm. Atherosclerosis. 2018;279:107-113. DOI:10.1016/j.atherosclerosis.2018.08.043
4. Choi SW, Yun WJ, Kim HY, et al. Association between albuminuria, carotid atherosclerosis, arterial stiffness, and peripheral arterial disease in Korean type 2 diabetic patients. Kidney Blood Press Res. 2010;33(2):111-8. DOI:10.1159/000313594
5. Molnar AO, Bota SE, Garg AX, et al. The Risk of Major Hemorrhage with CKD. J Am Soc Nephrol. 2016;27(9):2825-32. DOI:10.1681/ASN.2015050535
6. Wilson PW, D'Agostino R Sr, Bhatt DL, et al. An international model to predict recurrent cardiovascular disease. Am J Med. 2012;125(7):695-703.e1. DOI:10.1016/j.amjmed.2012.01.014
7. Wang J, Wang Y, Li Y, et al. High Normal Urinary Albumin-Creatinine Ratio Is Associated With Hypertension, Type 2 Diabetes Mellitus, HTN With T2DM, Dyslipidemia, and Cardiovascular Diseases in the Chinese Population: A Report From the REACTION Study. Front Endocrinol (Lausanne). 2022;13:864562. DOI:10.3389/fendo.2022.864562
8. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1-S127. DOI:10.1016/j.kint.2022.06.008
9. Khronicheskaia bolezn' pochek (KhBP). Klinicheskie rekomendatsii 2021. Available at: https://cr.minzdrav.gov.ru/ recomend/469_2. Accessed: 18.01.2023 (in Russian).
10. Li MF, Tu YF, Li LX, et al. Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Cardiovasc Diabetol. 2013;12:110. DOI:10.1186/1475-2840-12-110
11. Kumar Jha P, Ete T, Malviya A, et al. Microalbuminuria: Correlation With Prevalence and Severity of Coronary Artery Disease in Non-Diabetics. J Clin Med Res. 2017;9(10):838-43. DOI:10.14740/jocmr2785w
12. Huang MJ, Wei RB, Zhao J, et al. Albuminuria and Endothelial Dysfunction in Patients with Non-Diabetic Chronic Kidney Disease. Med Sci Monit. 2017;23:4447‑53. DOI:10.12659/msm.903660
13. Seliger SL, Salimi S, Pierre V, et al. Microvascular endothelial dysfunction is associated with albuminuria and CKD in older adults. BMC Nephrol. 2016;17(1):82.
DOI:10.1186/s12882-016-0303-x
14. Darmon A, Sorbets E, Ducrocq G, et al. Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients. J Am Coll Cardiol. 2019;73(25):3281-91. DOI:10.1016/j.jacc.2019.04.046
15. Matsushita K, Coresh J, Sang Y, et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2015;3(7):514‑25. DOI:10.1016/S2213-8587(15)00040-6
16. Shin JI, Grams ME, Coresh J, et al. Proteinuria and Risk of Lower-Extremity Amputation in Patients With Peripheral Artery Disease. Diabetes Care. 2019;42(9):e146-7. DOI:10.2337/dc19-0764
17. Tanaka K, Miwa K, Takagi M, et al. Increased Cerebral Small Vessel Disease Burden With Renal Dysfunction and Albuminuria in Patients Taking Antithrombotic Agents: The Bleeding With Antithrombotic Therapy 2. J Am Heart Assoc. 2022;11(6):e024749. DOI:10.1161/JAHA.121.024749
ФГБУ «Национальный медицинский исследовательский центр кардиологии им. акад. Е.И. Чазова» Минздрава России, Москва, Россия
*olga.shahmatova@gmail.com
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Olga O. Shakhmatova*, Andrey L. Komarov, Elena N. Krivosheeva, Anatoly B. Dobrovolsky, Elena V. Titaeva, Vera A. Amelyushkina, Nataliya V. Gomyranova, Elizaveta P. Panchenko