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DOI: http://dx.doi.org/10.20534/ESR-17-1.2-120-123
Sabirov Maksud Atabaevich, PhD, head of Department of therapeutic directions № 2 of Tashkent State Dental Institute Senior Researcher of Tashkent Pediatric Medical Institute
Tashkent, Uzbekistan
Remodeling the left heart chambers in patients with arterial hypertension and chronic kidney disease
Abstract: The objective of the research is to study the structural and functional condition of the left heart chambers in patients with chronic kidney disease (CKD). The research involved 254 patients; the main group consisted of 214 CKD patients and the control group included 40 people to compare. The patients in the main group suffered from CKD of the third stage (eGFR with 30-59 ml/min/m 2). The arterial hypertension and the decrease of eGFR were the criteria to enroll the patients in the study. The present research has shown that in case of CKD, the left heart chambers remodeling is observed that manifests by disturbance of early diastolic filling, myocardium hypertrophy, dilatation of the cavities and the tendency to decrease systolic LV functions correlating with a decrease in filtration functions of the kidneys and intensity of secondary hyperparathyroidism.
Keywords: Chronic kidney diseases, arterial hypertension, left ventricular hypertrophy.
Aim: The objective of the research is to study the structural and functional condition of the left heart chambers in patients with chronic kidney disease (CKD).
Material and Methods
The research involved 254 patients; the main group consisted of 214 CKD patients and the control group included 40 people to compare. The patients in the main group suffered from CKD of the third stage (eGFR with 30-59 ml/min/m 2). The arterial hypertension and the decrease of eGFR were the criteria to enroll the patients in the study. According to etiology, chronic glomerulonephritis was diagnosed in 178 patients of the main group, chronic pyelonephritis was diagnosed in 26 patients; the etiologic diagnosis was not made to the rest 10 patients. Diabetes and other endocrinological diseases, systemic vasculitis, valve lesions and congenital heart defects, non-sinusoid pace maker (imposed rhythm, fibrillation, idioventricular rhythm), neoplasia, acute infectious diseases, diseases of the central nervous system, and the refusal of the patient to participate were the criteria of exclusion of the patients from the research.
The clinical picture in patients with CKD consisted of classical symptoms: arterial hypertension was found out in 100% of patients, edema — in 167 patients (78.04%), skin itching and peripheral neuropathy — in 72 patients (33.64%). Such impairment of the central nervous system as encephalopathy, tremor, muscles cramps and im-potency was observed in 115 patients (53.74%); the reduction of muscle mass and arthropathy were found in 53 patients (24.77%). The GIS impairment manifested as nausea, anorexia, pancreatitis were observed in 119 patients (55.61%). The impairment of the
cardiovascular system like angina pectoris, cardiac arrhythmia and pericarditis were diagnosed in 160 patients (74.77%), the blood system impairment in the form of anemia and thrombocytopenic purpura were found in 172 patients (80.72%).
The comparison group consisted of two cohorts of patients: the ones with arterial hypertension (AH) without any kidneys damage (the AH group of 20 patients) and healthy volunteers with the healthy kidneys and cardiovascular system (the CG of 20 people).
The groups differed in the age of the members: the representatives of the AH group were significantly elder than the ones from the CKD and CG groups (<0.001 for both comparison groups) which did not differ from each other. According to the level ofAP, SAP and DAP, the AH group significantly (p<0.001) exceeded the index characteristic for the CG. In the CKD group, AP significantly exceeded not only the average value in the CG group (p<0.001), but also in the AH group (p<0.01). The filtering function of the kidneys was preserved and comparable in the AH and CG. It was diminished in the CKD group (p<0.001 in comparison with both groups) that was a criterion to include the patients in the research. All the patients with CKD have taken the standard basic therapy for at least three months before the start of the research, though AP was not completely controlled. The basic therapy [1] consisted ofvalsartan, i. e. angiotensin receptor blocker II of type 1 in the dose of 160 mg a day, aspirin, i. e. antiagregant in the dose of 100 mg a day, and according to the indication: loop diuretics (in edema syndrome), carvedilol, i. e. beta-adrenoblocker (in tachycardia and other rhythm disorders), atorvastatin (in dislipidemia), allopurinol (in hyperuricemia over
Remodeling the left heart chambers in patients with arterial hypertension and chronic kidney disease
800 mg/dl). All the patients were also recommended to keep diet (low-salt, hypoproteinemic one in proteinuria and microalbuminuria), avoid physical activities (sparing regime, obligatory day rest in a horizontal position) and weight-control [2].
At the time of enrollment in the research all patients had the documented diagnosis of CKD S3 made on the basis of eGFR determined by the serum concentration of creatinine calculated using the CKD-EPI formula of2009, in modification of 2011 (the on-line calculator was used at http://nefrosovet.ru/).
When the patients were included in the research, the serum concentration of creatinine and the serum level of cystatin, the universal marker of the kidney function, were determined in all the patients; simultaneous eGFR calculation based on cystatin were made: GFR=90.63, cystatin S-1.192 (Hojs R. et al. Clin Nephrol 2008; 70 [1]: 10-7.).
The research included determination of the osteoporosis marker, i. e. parathyroid hormone and the parameters of central hemody-namics using Echo CG.
The kidney filtration function was determined by the clearance of endogenous creatinine calculating the rate of glomerular filtration using SKD-EPI formula, 2009, in modification of 2011 (the on-line calculator was used at http/nefrosovet.ru/). The concentration of creatinine was evaluated in the blood taken from the cubital vein. The blood was taken at 8-11 a. m. on empty stomach when the patient was sitting or lying. In the previous day the patients were recommended to avoid physical activities and food rich with protein. The blood was centrifuged to obtain the serum in which the concentration of creatinine was determined by Yaffe's modified method of[3]. This method is based on measuring the optic density of the painted creatinine complex with picric acid.
The second method to determine the kidney filtration function is calculation of GFR using the serum concentration of cystatin.
The marker was determined in the same blood specimen as creatinine. After centrifugation and serum separation, ELISA assay was used. It was followed by calculation of the GFR = 90.63 x cystatin C — 1.192 (Hojs R et al. Clin Nephrol. 2008; 70 (1):10-7.).
Osteoporosis markers were determined in peripheral blood plasma [4]; the samples were taken on an empty stomach at 8-11 a. m. in the sitting or laying position after 30-minute rest. It was recommended to avoid excessive physical activity and alcohol in the day before and the day of blood sampling as well as smoking for an hour before blood sampling.
The parathyroid hormone concentration was determined by electrochemiluminescence ELISA using Cobase 601 (Roche) [5].
EchoCG was made by an ultrasonic scanner with the phased detector at 3.5-5 mHz frequency. The examination was made when the patient was lying on his back or left side. The study was conducted in the standard positions: left parasternal one on the long axis of the left and right ventricle, on the short axis at the level of the ends of the aortal valve shutters, the ends of the mitral valve shutters, heads of papillary muscles, the left ventricle apex, as well as apical two-, three-, four- and five-chamber, subcostal and suprasternal positions.
The following indicators were registered [6]: the structural parameters (the parasternal position on the long axis of the left ventricle), the front-back size of the left atrium (LA), end-diastolic and end-systolic diameters (EDD and ESD) of the left atrium with calculation of end-diastolic and systolic volumes of the left atrium by Teich-golz formula because the geometry of the left atrium was preserved. In addition, the thickness of the left atrium walls (IVS and LVPW) was determined. The LV myocardium mass was calculated by Penn's method with subsequent indexation to the area of the body surface.
To determine the LV systolic function the fraction of LV ejection was calculated by the standard formula (LV EF = (EDV-ESV)/EDV • 100%).
To study LV diastolic function the duration of the phase of LV isometric relaxation (LV IRP) and the maximum speed of early and late diastolic filling (E and A) were registered and their correlation (E/A) was calculated. The obtained findings were used to determine the types of diastolic filling and diastolic dysfunction.
After termination of the observation period the entire collected information was tabulated into Excel's spreadsheets for statistical processing. The mean arithmetic values, mean standard error, reliability of intergroup difference were calculated using Student's criterion for paired and unpaired differences. For multiple comparisons, Bonferroni correction was used. The qualitative signs were evaluated by the frequency of occurrence in the groups with calculation of intergroup differences using the Chi-square criterion. The correlation analysis was made using Pearson correlation coefficient and its significance was determined by the reliability tables.
Results of the research and discussion
EchoCG revealed significantly thicker LV walls (p<0.001 in diastolic thickness of the IVS and LVPW) in AH patients in comparison with the CG; it resulted in an increase in LVMMI (p<0.01). This occurs due to LV heavier afterload which characterizes the pathogenesis of remodelling heart under the conditions of arterial hypertension. The LV diastolic function determined by transmitral diastolic flow was characterized by a significant increase in the duration of the isovolumic relaxations phase (p<0.01) and reduction of the correlation of the maximum speeds of early and atrium filling phases (p<0.01). The LV systolic function characterized by LV EF in AH patients was not disordered (Table 1).
In the CKD patients, all EchoCG indicators were comparable to the parameters characteristic for AH because the remodelling processes are triggered by the same mechanisms: an increase in afterload due to raised AP and activation of the renin-angiotensin-aldosteron system (RAAS). The additional factor is liquid retention and an increase in the volume of circulating blood that resulted in an increase in preload of the heart that manifested, besides hypertrophy (an increase in IVS thickness by 29.67% and LVPW by 35.23% and LVMMI by 125.54% in comparison with the CG; p <0.001 for all three indicators), by dilatation of the chambers: LA by 12.35% and LV by 19.21% (p<0.01 reliability of the LA difference in the CKD and CG groups and p <0.001 reliability of LV EDD difference). A greater than in AH increase in RAA.S activity, including the tissue one, leads to calcium myocardiocyte resetting and mitochondria deficiency. The first manifestation of this process is an increase in rigidity of the myocardium and disorder of the processes of active diastolic relaxation (an IRP increase by 37.50%, p <0.001 compared with the CG) and a compensatory increase in the contribution of atrium filling (reduction of E/A correlation by 29.75%, p <0.001 compared with the CG) and development of hypertrophic type of diastolic dysfunctions. Subsequently, calcium resetting and activation of local RAAS and also cavities dilatation due to the preload lead to reduced contractile function of myocardiocytes. Our research recorded a relative decrease in LV EF in the CKD group in comparison with the CG (p <0.05) though the absolute value remains within the nominal norm. The additional contribution to disorder of systolic and diastolic functions is made by impairment of the mineral exchange and vascular and metastatic calcification and endothelium dysfunction leading to myocardium hypoxia and increased energy deficiency.
Table 1. - EchoCG indicators in patients with AH and CKD
Healthy Healthy, statistical error AH, statistical error CKD, statistical error Healthy- AH Healthy-CKD AH-CKD
LA 3,32±0,11 3,52±0,16 3,73±0,07 not sig. P<0,01 not sig.
LV EDD 4,53±0,14 4,96±0,24 5,40±0,09 not sig. P<0,001 not sig.
IVSd 0,91±0,03 1,22±0,06 1,18±0,03 P<0,001 P<0,001 not sig.
LVPWd 0,88±0,03 1,20±0,06 1,19±0,03 P<0,001 P<0,001 not sig.
LV EF 64,60±1,94 64,25±2,05 58,34±1,01 not sig. P<0,05 not sig.
E MV 0,74±0,04 0,81±0,04 0,89±0,03 not sig. P<0,01 not sig.
A MV 0,50±0,04 0,86±0,04 0,96±0,03 not sig. P<0,01 not sig.
E/A 1,21±0,12 0,87±0,10 0,85±0,08 P<0,01 P<0,001 not sig.
IRP 71,25±2,98 88,95±4,01 97,97±1,94 P<0,01 P<0,001 not sig.
LVMMi 82,08±6,83 152,27±21,37 185,12±9,31 P<0,01 P<0,001 not sig.
Distribution of the patients by the types of diastolic dysfunctions has revealed (Figure 1) the comparable number of patients with hypertrophic type of LV diastolic dysfunctions in the AH and CKD groups (over 80%) and reliable prevalence of people with
normal diastolic function in the CG group (Chi-square 3x2=53.46, p <0.001). Pseudo-normal and restrictive types of diastolic functions were found in none of the groups.
Figure 1. Distribution of controls and patients with AH and CKD depending on diastolic dysfunction types
Figure 2. Coefficients of correlation between eGFRsyc and EchoCG indicators Note: reliability of all the indicated Pearson's correlation coefficients is p<0.001.
The correlation analysis in the CKD group (Figure 2) has found out a significant positive relation of eGFRsyc with indicators of the LV systolic function (LV EF) and early diastolic filling (E and E/A).
To evaluate the contribution of various factors in LV remodelling we have studied the interrelations between the EchoCG parameters and serum concentration of parathyroid hormone and the AP
level. Reliable positive relations of parathyroid hormone concentration with structural indicators of the left chambers of the heart were revealed and negative ones with the systolic function and parameters of early diastolic filling (Figure 3) reliable relation between EchoCG parameters and AP level wasn't found out.
Post-Stroke Seizures in Children: incidence and clinical features depending on the type of stroke
Figure 3. Coefficients of correlation between the parathyroid hormone serum concentration and EchoCG indicators
Note: reliability of all indicated Pearson's correlation coefficients is p <0.001.
Thus, the present research has shown that in case of CKD, the left heart chambers remodeling is observed that manifests by disturbance of early diastolic filling, myocardium hypertrophy, dilatation
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DOI: http://dx.doi.org/10.20534/ESR-17-1.2-123-126
Samadov Furkatjon Nosibjanovich, Assistant of Pediatric neurology Department, Tashkent Institute of Postgraduate Medical education E-mail: [email protected] Saidazizova Shahlo Hibziddinovna, Associate professor of Pediatric neurology Department, Tashkent Institute of Postgraduate Medical education E-mail: [email protected] Gulyamova Maktuba Kamalovna, Associate professor of Pediatric neurology Department, Tashkent Institute of Postgraduate Medical education E-mail: [email protected]
Post-Stroke Seizures in Children: incidence and clinical features depending on the type of stroke
Abstract: A total of 157 children with stroke were included in this study. Early post-stroke seizure were seen in 68 (43.3%) of patients. 52 of 122 (42.6%) patients with hemorrhagic stroke and 16 of 35 (45.7%) ischemic stroke patients had seizures as presenting. Most commonly witnessed seizure type was partial seizure in 50 (51.5%) of patients while 47 (48.5%) had generalized seizures. Analysis of generalized and partial seizure type between hemorrhagic and ischemic stroke patients showed no statistically significant difference (p>0.612; p>0.315).
Keywords: seizures, epilepsy, risk factors, stroke, children.
