COVID-19 in patients with advanced stages of diabetic kidney disease: new onset renal replacement therapy as one of the predictors of adverse outcome

Background: patients with Diabetes Mellitus 2 (DM2) and advanced stages of Diabetic Kidney Disease (DKD) are at high risk for the lethal outcome of COVID-19. The causes of high mortality and the prognostic signifi cance of the new onset of renal replacement therapy (hemodialysis de novo, HD de novo) among these patients are still points of debate. Aim: the identifi cation of risk factors (RF) of lethal outcome in patients with DKD 4-5D stages and evaluation of the prognostic value of HD de novo in patients not receiving HD at the time of hospital admission. Methods: the patients with COVID-19 and advanced stages of DKD were included in a retrospective observational study from 04.01. to 10.30.2020. The endpoints were the outcome of hospitalization (discharge/death) and HD de novo initiation during the inpatient course. Several demographic, DM2, DKD, and COVID-19-associated signs and laboratory parameters were analyzed as independent variables. The subgroup of patients with HD de novo was selected from the general cohort. Results: 120 patients with DKD 4-5D stages were included, with a mean age of 69±10 y, females - 52%. Initially, the observation cohort was divided into subgroups: DKD 4-5 and DKD 5D on maintenance hemodialysis (MHD). The mortality among patients with DKD 4-5 was comparable with the patients on MHD (38,2% vs 38,5%, р=0,975). The independent predictors of lethal outcome in group DKD 4-5 were: age ≥65 y (OR 12,30;95% CI 1,40-33,5;р=0,009), initial prandial glycemia ≥10 mmol/l (OR 14,5;95% CI 3,7-55,4;р<0,001), albuminemia at admission ≤35 g/l (OR 5,17;95% CI 1,52-17,50;р=0,012), Charlson comorbidity index (CCI) ≥10 (OR 6,69;95% CI 1,95-23,00;р=0,002), News2 >4 at admission (OR 7,58;95% CI 2,18-26,37;р=0,001), lung damage CT 3-4 at admission (OR 3,39;95% CI 1,09-10,58;р=0,031). In subgroup DKD 5D the independent predictors of lethal outcome were prandial glycemia at admission ≥10 mmol/l (OR 28,5;95% CI 7,1-33,5;р<0,001), lung damage at admission CT 3-4 (OR 8,35;95% CI 2,64-26,40;р<0,001), CCI ≥10 (OR 6,00;95% CI 1,62-22,16;р=0,006). To determine the risk of lethal outcome predictive models were created using identifi ed risk factors and variables. The predictive value for DKD 4-5 group was 93%, and for DKD 5D was 88%. The assessment of the overall predictive value of these models was carried out using ROC analysis. The mortality among patients with DKD 4-5 without HD de novo was 21,6% vs 72,2% in patients with initiated HD de novo (р<0,001). The independent predictors of HD de novo during the inpatient course were: prandial glycemia at admission ≥10 mmol/l (OR 3,38;95% CI 1,04-10,98;р=0,050), albuminemia at admission ≤35 г/л (OR 3,41;95% CI 1,00-11,55;р=0,050), News2 >4 at admission (OR 5,60;95% CI 1,67-19,47;р=0,006), eGFR ≤20 ml/min/1,73 m2 at admission (OR 4,24;95% CI 1,29-13,99;р=0,020). HD de novo was identifi ed as an independent predictor of adverse outcomes (OR 9,42;95% CI 2,58-34,4;р=0,001). The analysis of cumulative survival demonstrated comparable results in DKD 4-5 without HD de novo group and DKD 5D group. The cumulative 55-day survival in the subgroup with HD de novo was only 10%. Conclusion: the need to start HD de novo is one of the most powerful predictors of adverse outcomes of COVID-19 in patients with advanced DKD. The comparable mortality rate in DKD 4-5 and DKD 5D groups is due to extremely high mortality in the subgroup with HD de novo. The strict control and correction of HD de novo risk factors could turn them into modifi able ones and thus improve the survival prognosis of patients with advanced stages of DKD. © 2023 JSC Vidal Rus. All rights reserved.

The application experience of focused ultrasound heart examination in patients with COVID-19 in Prone-position.

Aim of the study. To study the experience of using focused transthoracic echocardiography in patients with COVID-19 in prone position (fEchoPr) in intensive care units (ICU). Materials and methods. The retrospective observational study included 53 patients (period from 15 April to 31 December 2020). Inclusion criteria: confirmed diagnosis of COVID-19, availability of fEchoPr data, outcome certainty (discharge/death). We analyzed electronic medical records. The fEchoPr was performed in patients in the prone position with a bolster under the left side of the chest and left arm raised ('swimmer's position'). We assessed the systolic function of the right ventricle (RV) (tricuspid annular plane systolic excursion (TAPSE)), RV size, RV/LV ratio, systolic function of the left ventricle (LV) (left ventricular outflow tract velocity time integral. (LVOT VTI)), and pulmonary hypertension (PH) (tricuspid regurgitation peak gradient (PGTR). Depending on the results, the patients were divided into 2 groups: informative (+fEchoPr) and non-informative (-fEchoPr) examinations. Results. There was no statistically significant difference in the groups (+fEcho n = 35 vs -fEcho n = 18) by age (65.6 +/- 15.3 vs 60.2 +/- 15.8, p > 0.05), by gender (male: 23 (65.7%) vs 14 (77.8%), p > 0.05), by body mass index (31.3 +/- 5.3 kg/m2 vs 29.5 +/- 5.4 kg/m2, p > 0.05), by mechanical ventilation support (24 (68.6%) vs 17 (94.4%), p = 0.074), by NEWS scale indicators (6.9 +/- 3.7 vs 8.5 +/- 3.5 points), by mortality (82.8% vs 94.4%, p > 0.05). Correlation analysis revealed a moderate inverse relationship between being on mechanical ventilation and the informative value of the study (Spearman's r = -0.30 at p = 0.033). In the +fEchoPr group, the correct measurement of TAPSE and RV/LV was carried out in 100%: a decrease in RV systolic function was recorded in 5 patients (14%), expansion of the RV in 13 patients (37%). Signs of PH were detected in 11 patients (31%), PGTR could not be measured in 10 patients (28%). LV systolic dysfunction was detected in 7 patients (20%). No pathology was detected in 16 patients (46%). One patient was diagnosed with infective endocarditis of native mitral valve, which was later confirmed by autopsy. Conclusion. In 66% of cases, fEchoPr examinations were informative, especially in terms of assessing the state of the right heart. fEchoPr examination is an affordable, valid and reproducible method to assess and monitor the state of the heart in ICU patients.Copyright © 2021 VIDAR Publishing House. All Rights Reserved.

The application experience of focused ultrasound heart examination in patients with COVID-19 in Prone-position

Aim of the study. To study the experience of using focused transthoracic echocardiography in patients with COVID-19 in prone position (fEchoPr) in intensive care units (ICU). Materials and methods. The retrospective observational study included 53 patients (period from 15 April to 31 December 2020). Inclusion criteria: confirmed diagnosis of COVID-19, availability of fEchoPr data, outcome certainty (discharge/death). We analyzed electronic medical records. The fEchoPr was performed in patients in the prone position with a bolster under the left side of the chest and left arm raised ('swimmer's position'). We assessed the systolic function of the right ventricle (RV) (tricuspid annular plane systolic excursion (TAPSE)), RV size, RV/LV ratio, systolic function of the left ventricle (LV) (left ventricular outflow tract velocity time integral. (LVOT VTI)), and pulmonary hypertension (PH) (tricuspid regurgitation peak gradient (PGTR). Depending on the results, the patients were divided into 2 groups: informative (+fEchoPr) and non-informative (-fEchoPr) examinations. Results. There was no statistically significant difference in the groups (+fEcho n = 35 vs -fEcho n = 18) by age (65.6 ± 15.3 vs 60.2 ± 15.8, p >0.05), by gender (male: 23 (65.7%) vs 14 (77.8%), p >0.05), by body mass index (31.3 ± 5.3 kg/m2 vs 29.5 ± 5.4 kg/m2, p >0.05), by mechanical ventilation support (24 (68.6%) vs 17 (94.4%), p = 0.074), by NEWS scale indicators (6.9 ± 3.7 vs 8.5 ± 3.5 points), by mortality (82.8% vs 94.4%, p >0.05). Correlation analysis revealed a moderate inverse relationship between being on mechanical ventilation and the informative value of the study (Spearman's r = −0.30 at p = 0.033). In the +fEchoPr group, the correct measurement of TAPSE and RV/LV was carried out in 100%: a decrease in RV systolic function was recorded in 5 patients (14%), expansion of the RV in 13 patients (37%). Signs of PH were detected in 11 patients (31%), PGTR could not be measured in 10 patients (28%). LV systolic dysfunction was detected in 7 patients (20%). No pathology was detected in 16 patients (46%). One patient was diagnosed with infective endocarditis of native mitral valve, which was later confirmed by autopsy. Conclusion. In 66% of cases, fEchoPr examinations were informative, especially in terms of assessing the state of the right heart. fEchoPr examination is an affordable, valid and reproducible method to assess and monitor the state of the heart in ICU patients. © 2021 VIDAR Publishing House. All Rights Reserved.

Risk factors of adverse outcome of COVID-19 and experience of tocilizumab administration in patients on maintenance hemodialysis due to diabetic kidney disease

BACKGROUND: Patients with Type 2 Diabetes (T2DM) and patients on maintenance hemodialysis (MHD) are at a high risk of adverse clinical course of COVID-19. To date, the causes of high mortality in these groups are not fully understood. Data about peculiarity of clinical course and Tocilizumab (TCZ) administration in patients with T2DM receiving MHD due to outcome of diabetic kidney disease (DKD) are not yet highlighted in current publications. AIMS: Identification of risk factors (RF) of adverse COVID-19 outcome and evaluation of TCZ administration in patients with T2DM receiving MHD due to DKD. MATERIALS AND METHODS: The patients treated in Moscow City Hospital №52 were included in retrospective observational study. The observation period was from 04.15 to 07.30 2020. The study endpoints were the outcomes of hospitalization - discharge or lethal outcome. Data were collected from electronic medical database. The following independent variables were analysed: gender, age, body mass index, time from the onset of symptoms to hospital admission, cardiovascular and general comorbidity (Charlson Index, CCI), cardiovascular event (CVE) during hospitalization, treatment in ICU, mechanical ventilation (MV), degree of lung damage according to CT data, level of prandial glycemia at admission, MHD-associated parameters (vintage, type of vascular access, frequency of complications). The autopsy reports were evaluated for the purpose of lethal structure investigation. In a subgroup treated TCZ the time from symptoms onset to TCZ administration and number of laboratory indicators were evaluated. RESULTS: 53 patients were included, mean age 68 ±9 y, males - 49%. General mortality in observation cohort was 45%, mortality in ICU - 81%, mortality on MV - 95%. High cardiovascular and general comorbidity was revealed (mean CCI - 8,3 ±1,5 points). The causes of outcomes according to autopsy reports data: CVE 37,5% (among them - acute myocardial infarction during hospitalization), severe respiratory failure - 62,5%. The independent predictors of lethal outcome were: MV (OR 106;95% CI 11,5-984;р <0,001), 3-4 degree of lung damage according to CT data (ОR 6,2;95% CI 1,803-21,449;р = 0,005), CVE during hospitalization (ОR 18,9;95% CI 3,631-98,383;р <0,001);CCI ≥10 points (ОR 4,33;95% CI 1,001-18,767;р = 0,043), level of prandial glycemia at admission ≥10 mmol/l (ОR 10,4;95% CI 2,726-39,802;р <0,001). For risk identification of upcoming lethal outcome a predictive model was created with the use of discovered RF as variables. The predictive value of this model is 92,45% (positive prognostic value - 96,5%, negative prognostic value - 87,5%). In TCZ treated subgroup the laboratory markers of adverse outcome were detected with application of correlation analysis. Among them: increasing level of CPR 24-48 hours before lethal outcome (r = 0,82), the reduction of lymphocytes count after TCZ administration (r = -0,49), increasing of leukocytes and further reduction of lymphocytes count 24-48 hours before lethal outcome (r = 0,55 и r = -0,52, resp.)). CONCLUSIONS: The number of RF of adverse COVID-19 outcome in patients with T2DM receiving MHD due to DKD are identified. CVE is one of the leading causes of mortality in study cohort. According to our experience the preventive (instead of rescue) strategy of TCZ administration should be used.

Covid-19-associated cardiac damage in patients on maintenance hemodialysis. Case reports and review of the literature

A brief review of current publications about incidence, outcomes and mechanisms of cardiovascular complications in patients with the new coronaviral disease (COVID-19) is given. The possibility of direct deleterious viral effect on the myocardium, negative consequences of cytokine storm, the role of hypoxemia complicating acute respiratory distress syndrome (ARDS), myocardial infarction 1,2 type (MI 1, 2), hypercoagulation, systolic disfunction of right ventricle due to ARDS, recurrent pulmonary embolism (PE) and cardiotoxic effects of drug therapy is discussed. Three case reports of cardiac injury in patients on maintenance hemodialysis (MHD) with COVID-19 are presented. The first case demonstrated MI 2 type due to ischemic imbalance in a patient with severe ARDS in the absence of obstructive coronary arteries lesion. The second case represented coexistent affection of heart as a result of viral myocarditis and cardiotoxic effect of Azithromycin and Plaquenil co-administration. The viral myocarditis was proven by postmortem histological and immunohistochemical tests. The third case demonstrated the diagnostic quest in a patient with recurrent dyspnea due to sequential severe ARDS, viral hemorrhagic exudative pericarditis with cardiac tamponade and PE progression. Currently three basic phenotypes of cardiac injury are distinguished: permanent elevation of myocardial damage markers, MI 1, 2 Type and viral myo/pericarditis. Of note, the course of COVID-19 in patients on MHD is more complicated in comparison with the general population. The initial vulnerability of these patients is determined not only by severe co-morbidity. Some interconfounding pathophysiological processes same to COVID-19 are critically important for the understanding of the current state of the art. The crucial role of persistent chronic inflammation, coagulopathy, pulmonary hypertension, permanent hemodynamic stress and fluctuation of volemic status should also be taken into consideration. MHD by itself is a powerful risk factor which overburdens the course of COVID-19. Статья содержит краткий обзор текущих публикаций, касающихся распространенности, исходов и механизмов формирования сердечно-сосудистых осложнений у пациентов с новой коронавирусной инфекцией (COVID-19). Обсуждаются возможность прямого повреждающего действия вируса на миокард, негативные последствия цитокинового шторма, роль гипоксемии, осложняющей течение острого респираторного дистресс синдрома (ОРДС), развитие инфарктов миокарда 1 и 2 типов (ИМ 1, 2), гиперкоагуляции, систолической дисфункции правого желудочка на фоне ОРДС, рецидивирующей тромбоэмболии легочной артерии (ТЭЛА) и кардиотоксические эффекты медикаментозной терапии. Представлено описание трех клинических случаев поражения сердца у пациентов, находящихся на лечении программным гемодиализом (ПГД). В первом случае продемонстрировано развитие ИМ 2 типа вследствие ишемического дисбаланса у пациента с тяжелым ОРДС без обструктивного поражения коронарных артерий сердца. Во втором случае показано сочетанное поражение сердца у пациента с верифицированным вирусным миокардитом и кардиотоксическим эффектом совместного применения азитромицина и плаквенила. Вирусный миокардит был подтвержден при аутопсии с последующим проведением гистологического и иммунногистохимического исследований. Третий случай демонстрирует диагностический поиск причин рецидивирующего одышечного синдрома у пациента с последовательным развитием тяжелого ОРДС, вирусного геморрагического экссудативного перикардита, осложненного тампонадой сердца, и ТЭЛА. В обсуждении клинических случаев подчеркивается широкое распространение поражения сердца при COVID-19. Выделяется 3 основных фенотипа вовлечения сердца в патологический процесс: стойкое повышение концентрации маркеров повреждения миокарда, развитие ИМ 1, 2 типов и вирусные мио/перикардиты. Отмечается, что COVID-19 протекает значительно тяжелее у пациентов на ПГД по сравнению с общей популяцией. Стартовая уязвимость диализных пациентов для новой коронавирусной инфекции обусловлена не только исходно тяжелой коморбидностью. Крайне важным является наличие взаимоотягощающих патофизиологических процессов, синергичных таковым при COVID-19. Решающую роль играют персистирующие в диализной популяции процессы хронического воспаления, коагулопатия, легочная гипертензия, перманентный гемодинамический стресс и колебания волемического статуса. ПГД как таковой представляется мощным фактором риска, отягощающим течение COVID-19.

Risk factors of adverse prognosis in patients on maintenance hemodialysis with Covid-19. Focus on cardivascular comorbidity. Single center experience

Background: patients on maintenance hemodialysis (MHD) are at high risk of adverse clinical course of COVID-19. Study objective: analysis and evaluation of heart condition and risk factors of adverse clinical course of COVID-19 in patients on MHD. Materials and methods: 85 patients were included in retrospective observational hospital-based study in Moscow City Hospital 52 from 04.15 to 06.02.2020. The endpoints were results of hospitalization: discharge or lethal outcome. Several demographic, anamnestic, clinical and instrumental indicators were analyzed. Among them: gender, age, general and cardiovascular comorbidity (Charlson index, CCI), the type of vascular dialysis access, the etiology of ESKD, dialysis vintage, body mass index (BMI), cardiovascular events (CVE) in the course of hospital stay (myocardial infarction, MI, pulmonary embolism, PE, and others), ICU admission, mechanical ventilation (MV), the results of echocardiography and lung computed tomography (CT). Odds ratio (OR) was calculated and logistic regression with step-by-step algorithm was applied to assess risk factors of adverse outcomes of COVID-19 in cohort under study. Results: The mean age was 65±13 years (59%, males). Mortality in whole cohort was 43.5% (75%, in ICU patients, and 89% in patient on MV). The concomitant diseases were hypertension (92%), ischemic heart disease (54%), recent MI (19%), chronic heart failure (55%), permanent atrial fibrillation (20%) and diabetes (45%). Mean CCI was 6.6±2.4. Obesity was observed in 33% of cases. No statistical confidence was found in CCI (6.3±2.4 points (survivors) vs 7.0±2.3 points, p>0.05), BMI (26.8±5.3 kg/m2 vs 27.1±5.8 kg/m2, p>0.05). The total number of CVE - 20 (4 vs 16, p=0.019), MI - 10%, PE - 6%. No statistically significant difference was found in LV myocardial mass index - average index 140±33 g/m2 (138±36 g/m2 vs 143±30 g/m2, p>0.05), LA volume index - median 35 (33;40) ml/m2 - 35 (33;40) ml/m2 vs 36 (35;38) ml/m2, p>0.05. In 35% systolic disfunction of right ventricle was observed with no difference between groups. The average index of left ventricle ejection fraction (LVEF) was 53±9% (54±6% vs 50±10%, p=0.019). The median of pulmonary artery systolic pressure - 40 mm Hg (30;53) (38 (30;52) mm Hg vs 42 mm (34;53) Hg, p>0.05). The highest OR was calculated for following parameters: MV (OR=31.95% CI 18-121, p=0.0001), CVE (OR=8.3, 95% CI=2.5-2.8, p=0.0001), CCI ≥6 (OR=4.8, CI=1.6-11.2, p=0.002) and LVEF ≤45% (OR=3-8, 95%, CI=1.3-11,3, p=0.018). Regression logistic analysis demonstrated a strong relationship of lethal outcome with MV (OR=18.0) and CVE (OR=8.5), the moderate relationship with male gender (OR=2.1) and CCI (OR=1.25). Conclusion: the predictors of adverse outcome of COVID-19 in patients on MHD are the need for MV, CVE, CCI ≥6, decline of LVEF ≤45%, male gender. Введение: пациенты на программном гемодиализе (ПГД) формируют группу высокого риска неблагоприятного течения COVID-19. Цель исследования: анализ структурно-функциональных особенностей сердца и факторов риска (ФР) неблагоприятного исхода COVID-19 у пациентов на ПГД. Материалы и методы: в ретроспективное наблюдательное исследование с 15.04 по 02.06.20 г. включено 85 пациентов. Конечные точки исследования - исходы госпитализации (выписка/летальный исход). Сбор данных осуществлялся путем анализа электронных историй болезни. Независимые переменные: пол, возраст, сердечно-сосудистая, общая коморбидность (индекс Charlson, ССI), тип сосудистого доступа, причина тПН, винтаж диализа, индекс массы тела (ИМТ), кардиоваскулярное событие (КВС) в ходе госпитализации (острый инфаркт миокарда (ИМ), тромбоэмболия легочной артерии (ТЭЛА) и др.), лечение пациента в ОРИТ, проведение ИВЛ, данные МСКТ ОГК и эхокардиографического исследования. Для оценки ФР неблагоприятного исхода рассчитывалось отношение шансов (ОШ), построена модель логистической регрессии с пошаговым алгоритмом включения и исключения предикторов. Результаты: средний возраст 65±13 лет, мужчины - 59%. Общая летальность - 43,5%, среди пациентов ОРИТ - 75%, на ИВЛ - 89%. Сопутствующие заболевания: артериальная гипертензия (92%), ишемическая болезнь сердца (54%), постинфарктный кардиосклероз (19%), хроническая сердечная недостаточность (55%), постоянная форма фибрилляции предсердий (20%), сахарный диабет (45%). Средний CCI - 6,6±2,4 баллов, ИМТ >30 кг/м2 - у 33%. Не выявлено статистически значимой разницы в группах исхода по ССI (6,3±2,4 балла (выжившие) vs 7,0±2,3 балла, p>0,05), ИМТ (26,8±5,3 кг/м2 vs 27,1 ±5,8 кг/м2, p>0,05). Общее количество КВС - 20 (4 vs 16, p=0,019), ОИМ - в 10% случаев, ТЭЛА - в 6%. Не выявлено статистически значимой разницы в группах исхода по индексу массы миокарда ЛЖ (средний показатель 140±33 г/м2 (138±36 г/м2 vs 143±30 г/м2, p>0,05), индексу объема левого предсердия - медиана 35 (33;40) мл/м2 (35 (33;40) мл/м2 vs 36 (35;38) мл/м2, p>0,05). У 35% выявлена систолическая дисфункция правого желудочка. Средние показатели % фракции выброса ЛЖ (ФВЛЖ) - 53±9%, (54±6% vs 50±10%, p=0,019). Медиана систолического давления в легочной артерии - 40 mm Hg (30;53), с тенденцией к более высоким показателям в группе летальных исходов - 38 (30;52) mm Hg vs 42 (34;53) mm Hg, p>0,05. Получены следующие отношения шансов (ОШ): ИВЛ (ОШ 31;95% ДИ 8-121;p=0,0001), КВС (ОШ 8,3;95% ДИ 2,5-2,8;p=0,0001), CCI ≥6 баллов (ОШ 4,8;95% ДИ 1,6-11,2;p=0,002), ФВЛЖ ≤45% (ОШ 3,8;95% ДИ 1,3-11,3;p=0,018). Регрессионный логистический анализ выявил сильную связь летального исхода с пребыванием на ИВЛ (ОШ 18,0) и с КВС (ОШ 8,5), умеренную - с мужским полом (ОШ 2,1) и CCI (ОШ 1,25). Выводы: предикторами неблагоприятного течения COVID-19 у пациентов на ПГД являются: потребность в ИВЛ, КВС в ходе госпитализации, CCI ≥6 баллов, ФВЛЖ ≤45%, мужской пол.

Stress-induced cardiomyopathy in a patient with a fulminant course of COVID-19 early after a kidney allotransplantation

The article provides a brief review of the literature on Takotsubo syndrome (TS) in a pandemic of a new coronavirus infection. A clinical case of TS development in a young patient with COVID-19 who received immunosuppressive therapy early after allotransplantation of a cadaveric kidney is described. The diagnosis of TS was established on the basis of clinical, echocardiographic and ECG data. In the present observation, the course of COVID-19 was extremely unfavorable and ended in death. An autopsy followed by histological examination of the myocardium confirmed the diagnosis of TS by eliminating other probable causes of acute myocardial injury. В статье представлен краткий обзор литературы, посвященной синдрому Такоцубо (СТ) в условиях пандемии новой коронавирусной инфекции. Описан клинический случай развития СТ у молодой пациентки с covid-19, получавшей иммуносупрессивную терапию в ранние сроки после аллотрансплантации трупной почки. Диагноз СТ был установлен на основании клинических, эхокардиографических и экг-данных. в настоящем наблюдении течение covid-19 было крайне неблагоприятным и закончилось летальным исходом. Аутопсия с последующим гистологическим исследованием миокарда подтвердила диагноз СТ методом исключения других вероятных причин острого повреждения миокарда.