Hypoxia-inducible factor 1 (HIF-1) as a biomarker of acute kidney injury in patients with acute decompensation of chronic heart failure.

Actuality. Impaired kidney function adversely influences both immediate and remote prognosis for patients with chronic heart failure (CHF). However, early detection and prediction of acute kidney injury (AKI) are understudied.The aim of study was to investigate hypoxia-inducible factor 1 (HIF-1) as a biomarker for early diagnosis of AKI and determining prognosis in patients with acute decompensated CHF (ADCHF). MATERIALS AND METHODS: 84 patients admitted for ADCHF (18 women; mean age, 61.4±7.1) were evaluated. ADCHF was diagnosed in accordance with SEHF guidelines for diagnosis and treatment of chronic heart failure (RCS, 2016). AKI was diagnosed according to KDIGO criteria (2012). HIF-1, N-terminal pro B-type natriuretic peptide (NТ-proBNP), and erythropoietin were measured in blood serum. The follow-up period lasted for 12 months. RESULTS: AKI was diagnosed in 27 (32.1 %) patients. Level of HIF-1 was 1.27±0.63 ng / ml; NТ-proBNP - 2469.6 (interquartile range (IQR), 1312.2; 3300.0) pg / ml; eryhthropoietin - 56.0 mIU / ml (IQR, 13.2; 68.1). No correlation was found between HIF-1 and glomerular filtration rate, NТ-proBNP, or erythropoietin. Differences in biomarker levels were not observed between patients with and without AKI; however, HIF-1 was higher in the group of deceased patients than in the group of survived patients (1.64±0.9 vs. 1.17±0.44 ng / ml, р=0.004), which was not observed for NТ-proBNP and erythropoietin. CONCLUSION: AKI was observed in every third patient with ADCHF. In ADCHF, HIF-1 was not correlated with the kidney function; however, a relationship was found between the HIF-1 level and prediction for patients with CHF.

[Causal relationships in stroke and kidney injury]. / Prichinno-sledstvennye vzaimootnosheniia pri insul'te i porazhenii pochek.

AIM: To assess the frequency, severity, and causes of acute kidney injury (AKI) in patients with stroke. SUBJECTS AND METHODS: 272 patients (143 men and 129 women) (mean age, 66.7±11.6 years) with stroke were examined. The 2008 European Stroke Organization (ESO) guidelines were used to diagnose stroke, to determine indications for and contraindications to thrombolytic therapy, and to evaluate its efficiency. Hemorrhagic and ischemic strokes (HS and IS) were diagnosed in 52 (19%) and 220 (81%) patients, respectively. AKI was diagnosed and classified according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: AKI was diagnosed in 89 (33%) patients: 19 (36.5%) with HS and 70 (31.8%) with IS. The relative risk of death in patients with AKI-associated stroke was 2.6 (95% confidence interval (CI) 1.6-4.0). A poor outcome (the combined endpoint of death or Rankin scale scores of 4-5) was noted in 56 (62.9%) patients with AKI and in 70 (38.2 %) without AKI (χ2=14.6; p=0.0002). The relative risk of a poor outcome in patients with AKI-associated with stroke was 1.64 (95% CI 1.3-2.0). Forty-five (50.6%) patients with stroke developed AKI in the prehospital period. CONCLUSION: AKI complicates stroke in every three patients and increases death rates. 50% of cases develop AKI in the prehospital period due to the common causes of stroke and AKI.

[Value of N-terminal pro brain natriuretic peptide in predicting acute kidney injury in patients with acute decompensated chronic heart failure]. / Znachenie N-kontsevogo predshestvennika mozgovogo natriiureticheskogo peptida v prognozirovanii ostrogo povrezhdeniya pochek u bol'nykh s ostroi dekompensatsiei khronicheskoi serdechnoi nedostatochnosti.

AIM: To investigate the prognostic value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in the development of acute kidney injury (AKI) in patients with acute decompensated chronic heart failure (ADCHF). SUBJECTS AND METHODS: Eighty-three patients (55 (66%) men and 28 (34%) women; mean age, 65±11 years) with ADCHF were examined. AKI was diagnosed and classified according to the 2012 Kidney Disease Improving Global Outcomes Clinical Practice guidelines. To rule out contrast-induced AKI, the investigation enrolled only patients in whom radiopague agents had not been injected 7 days before and during hospitalization. Enzyme immunoassay was used to determine serum NT-proBNP concentrations in all the patients upon hospital admission. RESULTS: AKI was diagnosed in 18 (22%) patients, 13 (16%) had Stage I, 4 (5%) had Stage II, and 1 (1%) had Stage III. The serum concentration of NT-proBNP was significantly higher in patients with AKI than that in the other patients [1512.1 (981.0; 2246.2) and 861.8 (499.0; 1383.6) pg/ml (p=0.008). The rise in NT-proBNP concentrations of more than 942 pg/ml was established to be associated with a considerable increase in the risk of AKI (relative risk (RR) was 4.3; 95% confidence interval (CI), 1.27-14.90; p=0.02). RОС analysis indicated that a NT-proBNP level of >942 pg/ml allows prediction of AKI with a sensitivity of 78% (52; 94) and a specificity of 55% (44; 69) (AUC=0.70; p=0.006). Four (5%) patients died in hospital. NT-proBNP levels in all the dead were greater than 942 pg/ml. Two of the 4 deceased patients had AKI. CONCLUSION: A high level of NT-proBNP in a patient with ADCHF during hospitalization can serve as a biomarker for high risk of AKI and for high mortality rates.

[Prognostic Significance of Erythropoietin in Patients With Acute Coronary Syndrome].

AIM: to investigate the prognostic role of erythropoietin (EPO) in patients with acute coronary syndrome (ACS). MATERIAL AND METHODS: Eighty-four patients (46 men, 38 women, mean age 63+/-11 years) with ACS were studied. Twenty-one patients had ST-elevation myocardial infarction (STEMI), 12 - non-ST-elevation myocardial infarction, 51 - unstable angina (UA). Ten patients with STEMI received thrombolytic therapy. Coronary angiography during hospitalization was criterion for exclusion from the study. Serum EPO was measured at hospital admission. RESULTS: In-hospital mortality was 5%. Median EPO serum level was higher among patients who died (78.1 [27.8-143.5] vs. 9.0 [6.4-14.1]I.U./ml, p=0.004). Acute kidney injury (AKI) was observed in 7 patients with myocardial infarction (21%) and only in 1 with UA.EPO >10.5 I.U./ml was a significant predictor of AKI development (area under curve 0.73; sensitivity 71%, specificity 67%). CONCLUSION: The results of the present study indicate that in patients with ACS admission serum level of EPO may be an important biomarker of development of AKI and in-hospital mortality.

[ACUTE KIDNEY INJURY AND IN-HOSPITAL MORTALITY IN PATIENTS WITH STROKE].

AIM: to estimate the frequency and severity of acute kidney injury (AKI) in patients with stroke and the influence of AKI on intra-hospital lethality. MATERIALS AND METHODS: 180 patients with stroke. 8 (4.4%) of them died within 24 hr after admission. It was impossible to diagnose AKI in these patients from serum creatinine dynamics. The development of AKI was followed up in the remaining 80 (47.1%) men and 91 (52.9%) women (mean age 66.6 ± 11.2 yr). AKI was diagnosed and classified as recommended by KDIGO (2012). RESULTS: AKI was documented in 47 (27.3%) patients including 13 (41.9%) and 34 (24.1%) with hemorrhagic and ischemic stroke respectively. Logistic regressive analysis revealed association of in-hospital lethality with AKI (relative risk 2.5; 95%, CI 1.7-3.8) regardless of sex, age, stroke type, duration of the disease prior to hospitalisation, arterial hypertension, and diabetes. CONCLUSION: stroke is complicated by AKI in every fourth patient; in combination, they significantly increase intra-hospital lethality.

[Endogenous erythropoietin, acute kidney injury, and prognosis in patients with acute coronary syndrome].

AIM: To investigate the prognostic value of serum endogenous erythropoietin (EPO) in patients with acute coronary syndrome (ACS), including that in the development of acute kidney injury (AKI). SUBJECTS AND METHODS: Eighty-four patients (46 men, 38 women; mean age 63 ± 11 years) with ACS were examined. Twenty-one (25%) patents were diagnosed with ECG ST-segment elevation acute myocardial infarction (STSEAMI), 12 (14%) had ECG non-STSEAMI, and 51 (61%) had unstable angina. Thrombolytic therapy was performed in 10 (48%) patients with STSEAMI. The patients whom had not undergone coronarography were included in the investigation to exclude the nephrotoxic effect of X-ray contrast agents. RESULTS: AKI was observed in 7 of the patients with acute myocardial infarction and in only 1 of those with unstable angina. Four (5%) patients died during hospitalization. The EPO level of > 10.5 IU/ml predicted the development of AKI in the ACS patients with a sensitivity of 71% and a specificity of 67%. That of > 13.7 IU/ml was associated with hospital death in the ACS patients with a sensitivity of 100% and a specificity of 75% (AUC = 0.93%). CONCLUSION: High serum EPO levels in an ACS patent during his hospital stay may serve as a biomarker for a high risk for AKI and high death rates.

[Type of Thrombolytic Agent and Rate of Acute Kidney Injury in Patients With Myocardial Infarction].

Aim of this study was to assess incidence and severity of acute kidney injury (AKI) in patients with ST-elevation (STE) myocardial infarction (MI) after thrombolytic therapy with alteplase or streptokinase. Among 292 included patients (227 men, 65 women, mean age 58 ± 11 years) 170 received streptokinase, 122 - alteplase. Coronary angiography in acute stage of MI was an exclusion criterion. Thrombolysis was effective in 213 (73%) patients. There was no statistically significant difference in effectiveness of thrombolysis among streptokinase or alteplase treated patients. Incidence of AKI in patients with STEMI was 25%. Both incidence and severity of AKI were higher in streptokinase treated patients. Only stage II-III AKI was significantly associated with higher in-hospital mortality.

[TREATMENT COMPLIANCE IN PATIENTS WITH CHRONIC HEART FAILURE AND COMORBIDITIES].

UNLABELLED: Treatment compliance determines to a large degree the effectiveness of therapy of chronic heart failure (CHF). However; individual characteristics of a patient, such as comorbidities and personality status are frequently disregarded. This work was aimed to study clinical and psychological peculiarities of patients with CHF determining treatment compliance taking account of comorbidity. MATERIALS AND METHODS: The study included 203 patients (130 men and 73 women) of mean age 61.8 ± 9.6 yr. The following features were evaluated: comorbidity psychological status, compliance with medicamental and non-medicamental treatment of CHF. RESULTS: Charlson comorbidity index corrected for age was 5.0 ± 2.1. Compliance with non-medicamental (recommendations on self-control and changes in the lifestyle) and medicamental therapy was documented in 37 (18.2%) and 61 (30%) patients respectively. Patients with poor compliance were characterised by disadaptive type of responsiveness, emotional lability and indecisiveness (p < 0.04). CONCLUSION: Poor treatment compliance is to a large extent determined by peculiarities of the personality status.

[Type of Thrombolytic Agent and Rate of Acute Kidney Injury in Patients With Myocardial Infarction].

Aim of this study was to assess incidence and severity of acute kidney injury (AKI) in patients with ST-elevation (STE) myocardial infarction (MI) after thrombolytic therapy with alteplase or streptokinase. Among 292 included patients (227 men, 65 women, mean age 58+/-11 years) 170 received streptokinase, 122 - alteplase. Coronary angiography in acute stage of MI was an exclusion criterion. Thrombolysis was effective in 213 (73%) patients. There was no statistically significant difference in effectiveness of thrombolysis among streptokinase or alteplase treated patients. Incidence of AKI in patients with STEMI was 25%. Both incidence and severity of AKI were higher in streptokinase treated patients. Only stage II-III AKI was significantly associated with higher in-hospital mortality.

[Neutrophil gelatinase-associated lipocain as a predictor of acute renal lesion in patients with acute coronary syndrome].

AIM: To estimate the possibility of using neutrophil gelatinase-associated lipocain (NGAL) as a predictor of acute renal lesion (ARL) in patients with acute coronary syndrome (ACS). Only those patients were included in whom coronarography was found to be impracticable which allowed to exclude the development of contrast-induced ARL. A total of 122 patients with ACS (69 men and 53 women, mean age 64 +/- 11 yr) were available for examination. 18 (15%) patients had acute myocardial infarction without ST elevation, 73 (60%) presented with unstable angina. ARL was diagnosed and classified following KDIGO recommendations (2012). Serum creatinine level was determined at admission. (Urine NGAL level was measured by an immunoenzyme assay. ARL was diagnosed in 27 (22%) patients (stage 1 in 26%. stage 2 in 1%). NGAL level above 82 ng/ml was a highly specific (99%) predictor of ARL in patients with ACS, but its sensitivity did not exceed 20%. It is concluded that urinary NGAL is a moderate predictor of ARL in patients with ACS whose specificity increases with increasing urinary level.

[Problems in the diagnosis of acute kidney injury in patients with ST-segment elevation myocardial infarction].

AIM: To estimate the frequency and severity of acute kidney injury (AKI) in patients with ST-segment elevation acute myocardial infarction (STSEAMI), to specify whether the changes in diuresis and serum creatinine levels are equally sensitive diagnostic criteria for AKI, and to define their prognostic value. SUBJECTS AND METHODS: Three hundred and nineteen patients (249 (78%) men and 70 (22%) women; age 58 +/- 10 years) with STSEAMI who received thrombolytic therapy (TLT) were examined. The diagnosis of STSEAMI, indications for and contraindications to TLT, evaluation of its efficiency were made in accordance with the All-Russian Scientific Society of Cardiology guidelines (2007). AKI was diagnosed and classified using the KDIGO guidelines (2012). RESULTS: AKI was diagnosed in terms of diuresis, calculated creatinine levels, and creatinine level changes in 107 (34%), 73 (23%), and 68 (22%) patients, respectively. Among the patients with AKI diagnosed in view of diuresis, in-hospital death rates were higher than in those without AKI (chi2 = 25.46; p < 0.001); the similar pattern was seen in patients with AKI diagnosed in terms of calculated creatinine levels (chi2 = 3.99; p = 0.045). Logistic regression analysis indicated that regardless of gender, age, and time interval between onset of clinical manifestation and hospital admission, the in-hospital death rates were associated with the presence of AKI in view of diuresis (relative risk 14; 95% confidence interval, 4.03 to 52.08; p < 0.001). CONCLUSION: The STSEAMI patents receiving TLT exhibited a high rate of AKI. The major problem in the early detection of AKI is associated with difficulties in the differential diagnosis of AKI and chronic kidney disease. AKI diagnosed in view of diuresis is of greater prognostic value for in-hospital mortality than that diagnosed in terms of creatinine levels. The diagnosis of renal dysfunction in view of basal creatinine levels is prognostically important despite the fact that this cannot differentiate AKI from chronic kidney disease in the early stage.

[S24-hour arterial pressure monitoring in patients with chronic cardiac failure and the state of renal function].

The 24-hr AP profiles were obtained in 194 patients with chronic cardiac failure (CCF) depending on the glomerular filtration rate (GFR). It was shown that 24-hour arterial pressure monitoring markedly improves detection of potentially dangerous changes of AP The target AP was achieved in 42.9 and 18.4% of the patients with GFR < or = 45.1 and > or = 69.8 ml/min/1.73 m2 respectively. Episodes of systolic arterial hypotony were diagnosed in 51.0 and 26.5% of the patients with GFR < or = 45.1 and 69.8 ml/min/1.73 m' respectively; episodes of diastolic arterial hypotony in 71.4 and 61.2% of the patients with GFR < or = 45.1 and > or = 69.8 ml/min/1.73 m2 respectively. Duration of systolic and diastolic arterial hypotony during 24 hr correlated with the level of glycemia and the age of the patients respectively.

[Acute kidney injury in patients with myocardial infarction and efficacy of thrombolytic therapy].

Aim of the study was to assess rate and severity of acute kidney injury (AKJ) (RIFLE and AKIN criteria) in patients with ST-elevation myocardial infarction (STEMI), to determine relationship between AKJ, mortality and effectiveness of thrombolytic therapy (TLT). We examined 146 patients (117 men, 29 women, mean age 56.7+/-10.8 ) with STEMI subjected to TLT with streptokinase. AKJ was diagnosed and classified according to RIFLE and AKIN criteria by creatinine (RIFLECr, AKINCr) and diuresis (RIFLEou, AKINou). TLT was effective in 104(71%) patients. AKJ was found in 74 (51%) according to RIFLECr and in 86 (59%) - AKINCr, in 51 (35%) - RIFLEou and AKINou criteria. Eight patients 8 (5%) died. Results of logistic regression analysis showed that AKJ according to RIFLEou or AKINou irrespective of sex, age, and time after appearance of symptoms to hospitalization, was associated with mortality (relative risk [RR] 12.9, 95% confidence interval [95%CI] 1.45-115,58, p=0.002). Thus more than 50% of STEMI patients have AKJ according to RIFLECr AKINCr criteria. Frequency of AKJ according to RIFLEou and AKINou was by 40% and one third less than that according to AKINCr and RIFLECr, respectively. Presence of AKJ was associated with TLT inefficacy and elevation of mortality.

[Total body water and recurrent atrial fibrillation].

AIM: To specify the relationship between content of total body water and recurrent atrial fibrillation (AF) of non-valvular etiology. MATERIAL AND METHODS: Pharmacological amiodaron cardioversion followed by amiodaron supportive anti-arrhythmic therapy was made in 76 patients (47 males, 29 females, mean age 58 +/- 8 years) with persistent AF of non-valvular etiology. Measurements were made of the height, body mass, arm circumference, thickness of the lipocutaneous fold above the biceps. Body mass index (BMI) and arm muscular circumference were estimated. Body composition was calculated according to Watson formula. RESULTS: Fifty three (70%) patients with recurrent AF had overweight or obesity. Body fat mass in patients with frequent (1 recurrence and more for 3 months) and rare AF recurrences did not significantly differ (24.4 +/- 10.6 and 30.0 +/- 13.8 kg, respectively; p = 0.064). Total body water was significantly less (36.8 +/- 5.2 and 42.7 +/- 5.4 kg, respectively; p = 0.0009) in patients with frequent AF recurrences. Multifactor regression analysis showed that content of total body water, irrespective of gender and age, inversely correlates with an early AF recurrence (R2 = 0.24; beta = -0.49; p = 0.0003). CONCLUSION: Low content of body water is associated with a risk of early AF recurrence.

[Effect of acute normobaric hypoxia on electrical stability of the myocardium in healthy people]. / Vliianie ostroi normobaricheskoi gipoksii na élektricheskuiu stabil'nost' miokarda u zdorovykh liudei.

We studied the impact of acute 10-min normobaric hypoxia on myocardial electrical stability, systolic and diastolic cardiac functions in 10 young healthy men. Hypoxia induced a decrease of ejection fraction and left ventricular early peak filling velocity. The QTc interval was prolonged during normobaric hypoxia without QT dispersion increase. Electrocardiographic investigation with assessment of QT-interval must be mandatory before normobaric hypoxic therapy is started. Prolonged QT interval is contraindication to normobaric hypoxic therapy.