Prediction of small-diameter arterial fibrosis in patients with hypertension and primary chronic glomerulonephritis

Aim. To study clinical, laboratory, and morphological risk factors for small-diameter renal arterial fibrosis in patients with hypertension (HTN) and primary chronic glomerulonephritis (CGN).Material and methods. The study included 102 patients with primary CGN. The first group consisted of 62 patients with small-diameter renal arterial fibrosis according to renal biopsy; the second group included 40 patients without vascular fibrosis. All patients signed informed consent.Results. A comparative analysis revealed the most significant differences between groups 1 and 2: mean systolic blood pressure (SBP) — 131,85±17,56 mm Hg and 119,65±22,2 mm Hg, respectively (p=0,0008); mean diastolic blood pressure (DBP) — 84,11±10,7 and 79,63±9,7 mm Hg (p=0,03), respectively; peak SBP — 158,61±23,76 mm Hg and 144,25±23,56 mm Hg (p=0,002), respectively; peak DBP — 95,66±10,33 mm Hg and 90,63±10,74 mm Hg (p=0,02), respectively; HTN stage — 1,85 [1; 3] and 1,38 [1; 3] (p=0,03), respectively; HTN grade — 1,73 [1; 3] and 1,13 [1; 3] (p=0,004), respectively; left ventricular hypertrophy — 15 patients and 2 patients (p=0,006), respectively; blood urea nitrogen — 8,98±7,31 and 6,42±4,02 mmol/L (p=0,03), respectively. Significant morphological differences between first and second groups were as follows: tubulointerstitial fibrosis — 56% and 21% (p<0,001), respectively; tubulointerstitial inflamemation — 44% and 16% (p=0,002), respectively; interstitial fibrosis — 24,9±20,5% and 9,89±19,8% (p=0,001), respectively.Conclusion. The presented analysis emphasizes a significant contribution of hemodynamics in small-diameter renal arterial fibrosis in patients with HTN and CGN. It manifested by a persistent increase of SBP and involvement of target organs. Systemic hemodynamic changes are fundamental in the development of small-diameter renal arterial fibrosis in patients with HTN and primary CGN, while the isolated progression of CGN does not significantly affect the structure of small-diameter renal arteries.

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Prediction of remodeling of arteries of kidneys of small diameter in patients with chronic glomerulonephritis

South Russian Journal of Therapeutic Practice ◽

10.21886/2712-8156-2021-2-2-44-55 ◽

2021 ◽

Vol 2 (2) ◽

pp. 44-55

Author(s):

E. S. Levickaja ◽

M. M. Batiushin ◽

E. A. Sinel’nik ◽

A. D. Bagmet ◽

A. A. Mokrushin ◽

...

Keyword(s):

Risk Factors ◽

Arterial Wall ◽

Clinical Laboratory ◽

Kidney Tissue ◽

Small Diameter ◽

Vascular Wall ◽

Renal Tissue ◽

Chronic Glomerulonephritis ◽

Target Organs ◽

Tubulointerstitial Inflammation

Objective: to determine the significance of clinical, laboratory and morphometric indicators of structural restructuring of kidney tissue in the prognosis of remodeling of small-diameter kidney arteries in patients with primary chronic glomerulonephritis. Materials and methods: the study included 97 patients with primary chronic glomerulonephritis and indications for puncture nephrobiopsy. In all patients, anamnestic and clinical and laboratory risk factors were recorded, and nephrobiopsy was performed. When performing morphometric analysis of nephrobiopsy, the state of the tissue and vessels of the kidneys of small diameter was studied. To achieve this goal, all patients were divided into two groups, the ranking of which was carried out according to the median wall thickness of the interlobular artery. Results: Among all the risk factors studied, a statistically significant effect of an increase in the stages of hypertension (χ2 criterion = 4.24, p = 0.03) and a decrease in GFR (χ2 criterion = 5.92, p = 0.015) on the risk of increasing the thickness of the interlobular artery was found. The indicators of structural reconstruction of the renal tissue did not have a statistically significant effect on the likelihood of remodeling of the arterial wall. However, a direct correlation of weak strength was found between the severity of tubulointerstitial inflammation and the thickness of the wall of the interlobular artery (r = 0.23, p = 0.02). Conclusions: this work shows the paramount importance of hypertension, accompanied by damage to target organs, as a marker of remodeling of the vascular wall of the interlobular artery in patients with chronic glomerulonephritis.

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Disorganization of intercalated discs in dilated cardiomyopathy

Scientific Reports ◽

10.1038/s41598-021-90502-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yukinobu Ito ◽

Makoto Yoshida ◽

Hirotake Masuda ◽

Daichi Maeda ◽

Yukitsugu Kudo-Asabe ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Pathological Diagnosis ◽

Control Group ◽

Failure Group ◽

Intercalated Discs ◽

Group Reduction ◽

Group A ◽

Morphological Differences

AbstractDilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in the intercalated discs (ICDs) between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 22 autopsy cases, including five DCM cases, nine CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized ICDs, clearly illustrated by N-cadherin immunostaining in the DCM group. “Reduction of N-cadherin immunostaining intensity” and “ICD scattering” was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM.

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Overweight female rats selectively breed for low aerobic capacity exhibit increased myocardial fibrosis and diastolic dysfunction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01027.2011 ◽

2012 ◽

Vol 302 (8) ◽

pp. H1667-H1682 ◽

Cited By ~ 19

Author(s):

Vincent G. DeMarco ◽

Megan S. Johnson ◽

Lixin Ma ◽

Lakshmi Pulakat ◽

Irina Mugerfeld ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Diastolic Dysfunction ◽

Aerobic Capacity ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Female Rats ◽

Normal Blood ◽

Omental Fat ◽

Fat Pads

The statistical association between endurance exercise capacity and cardiovascular disease suggests that impaired aerobic metabolism underlies the cardiovascular disease risk in men and women. To explore this connection, we applied divergent artificial selection in rats to develop low-capacity runner (LCR) and high-capacity runner (HCR) rats and found that disease risks segregated strongly with low running capacity. Here, we tested if inborn low aerobic capacity promotes differential sex-related cardiovascular effects. Compared with HCR males (HCR-M), LCR males (LCR-M) were overweight by 34% and had heavier retroperitoneal, epididymal, and omental fat pads; LCR females (LCR-F) were 20% heavier than HCR females (HCR-F), and their retroperitoneal, but not perireproductive or omental, fat pads were heavier as well. Unlike HCR-M, blood pressure was elevated in LCR-M, and this was accompanied by left ventricular (LV) hypertrophy. Like HCR-F, LCR-F exhibited normal blood pressure and LV weight as well as increased spontaneous cage activity compared with males. Despite normal blood pressures, LCR-F exhibited increased myocardial interstitial fibrosis and diastolic dysfunction, as indicated by increased LV stiffness, a decrease in the initial filling rate, and an increase in diastolic relaxation time. Although females exhibited increased arterial stiffness, ejection fraction was normal. Increased interstitial fibrosis and diastolic dysfunction in LCR-F was accompanied by the lowest protein levels of phosphorylated AMP-actived protein kinase [phospho-AMPK (Thr172)] and silent information regulator 1. Thus, the combination of risk factors, including female sex, intrinsic low aerobic capacity, and overweightness, promote myocardial stiffness/fibrosis sufficient to induce diastolic dysfunction in the absence of hypertension and LV hypertrophy.

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Disorganization of Intercalated Discs in Dilated Cardiomyopathy

10.21203/rs.3.rs-153597/v1 ◽

2021 ◽

Author(s):

Yukinobu Ito ◽

Makoto Yoshida ◽

Hirotake Masuda ◽

Daichi Maeda ◽

Yukitsugu Kudo-Asabe ◽

...

Keyword(s):

Dilated Cardiomyopathy ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Pathological Diagnosis ◽

Control Group ◽

Failure Group ◽

Intercalated Discs ◽

Group Reduction ◽

Group A ◽

Morphological Differences

Abstract Dilated cardiomyopathy (DCM) is a primary myocardial disease, the pathology of which is left ventricular or biventricular dilation and impaired myocardial contractility. The clinical and pathological diagnosis of DCM is difficult, and other cardiac diseases must be ruled out. Several studies have reported pathological findings that are characteristic of DCM, including cardiomyocyte atrophy, nuclear pleomorphism, and interstitial fibrosis, but none of these findings are DCM-specific. In this study, we examined the morphological differences in ICDs between three groups of patients, a DCM group, a chronic heart failure group, and a control group. A total of 21 autopsy cases, including five DCM cases, eight CHF cases and eight control cases, were retrieved from the archives of the Department of Pathology at Akita University, Japan. The morphological differences were examined using multiple methods: macroscopic examination, light microscopy, immunohistochemistry, electron microscopy, and gene expression analyses. We observed disorganized intercalated discs (ICDs), clearly illustrated by N-cadherin immunostaining in the DCM group. “Reduction of N-cadherin immunostaining intensity” and “ICD scattering” was DCM-specific. The results suggest that disorganized ICDs contribute to the development of DCM, and that N-cadherin immunostaining is useful for determining the presence of disorganized ICDs and for the pathological diagnosis of DCM.

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Abstract 3003: Central or Peripheral Systolic or Pulse Pressure: Which Best Predicts Target-Organ Damage and Mortality?

Circulation ◽

10.1161/circ.118.suppl_18.s_804 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Kang-Ling Wang ◽

Hao-Min Cheng ◽

Shao-Yuan Chuang ◽

Harold A Spurgeon ◽

Chih-Tai Ting ◽

...

Keyword(s):

Blood Pressure ◽

Pulse Pressure ◽

Target Organ Damage ◽

Univariate Analysis ◽

Density Lipoprotein ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Left Ventricular ◽

Cholesterol Ratio ◽

Target Organs

Background : Pulse pressure (PP) and systolic blood pressure (SBP), in central and peripheral arteries, may contribute differently to predictions of damage to different target organs and mortality. Method : We examined the relations of PP and SBP in central (calibrated tonometric carotid pulse) and peripheral (brachial, mercury sphygmomanometer) arteries to left ventricular mass index (LVMI), carotid intima-media thickness (IMT), glomerular filtration rate (GFR), and 10-year all-cause and cardiovascular (CV) mortality in 1272 participants (47% women, aged 30 –79 years) from a community of homogeneous Chinese. Result : LVMI was more strongly related to SBP (r = 0.420 and 0.379 for central and brachial arteries, respectively) than PP (r = 0.374 and 0.285, correspondingly). In contrast, IMT and GFR were more strongly related to central PP and SBP (r = 0.265 and 0.252 for IMT, and r = −0.256 and −0.218 for GFR, respectively) than brachial PP and SBP. A total of 130 participants died, 37 from CV causes. In univariate analysis, all four blood pressure variables significantly predicted all-cause and CV mortality. After adjustment for age, sex, current smoking, glucose, cholesterol/high-density-lipoprotein-cholesterol ratio, carotid-femoral pulse wave velocity, LVMI, IMT, and GFR, none of the blood pressure variables predicted all-cause mortality (Figure 1A ). Only central SBP independently predicted CV mortality (Hazards ratio = 1.21 per 10 mmHg) in multivariate analysis (Figure 1B ). Conclusion : PP and SBP contribute differently to damage to different target organs. Central SBP is more valuable than other blood pressure variables in predicting CV mortality.

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High salt intake induces left ventricular interstitial fibrosis by a blood pressure and angiotensin II type 1 receptor‐independent mechanism

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.626.9 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Daniele Nunes Ferreira ◽

Isis A. Katayama ◽

Ivone B. Oliveira ◽

Kaleizu T. Rosa ◽

Michella S. Coelho ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Salt Intake ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

High Salt ◽

High Salt Intake ◽

Independent Mechanism

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Influence of angiotensin-converting enzyme inhibitor ramipril on indicators of tubular kidney lesion in patients with chronic glomerulonephritis

Current Issues in Pharmacy and Medical Sciences ◽

10.2478/cipms-2020-0005 ◽

2020 ◽

Vol 33 (1) ◽

pp. 17-20

Author(s):

Mariia O. Dolinna ◽

Oleksandr O. Svyntozelskyi

Keyword(s):

Ace Inhibitor ◽

Clinical Laboratory ◽

Enzyme Inhibitor ◽

Interstitial Fibrosis ◽

Morphological Data ◽

Chronic Glomerulonephritis ◽

Renal Tubules ◽

Diagnostic Efficiency ◽

Entire Treatment Period ◽

Kidney Lesion

AbstractTo research and deepen the understanding of the links between morphological tubular kidney lesion parameters and serum markers – neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18), in patients with chronic glomerulonephritis (CGN) with saved renal function, as well as to estimate therapeutic correction of identified changes using ACE inhibitor ramipril. The diagnosis of “chronic glomerulonephritis” was verified based on clinical, laboratory and morphological data. Patients were divided into 2 clinical groups: patients with CGN and arterial hypertension (AH) and without AH. We used the data of renal biopsies to analyze the indicators of tubular kidney lesion in patients with CGN. Levels of serum NGAL and IL-18 were measured by means of ELISA kits. Treatment of patients was carried out over 24 weeks using the ACE inhibitor ramipril. The average daily dose of ramipril for the entire treatment period for patients with AH was 12.8±5.6 mg, patients of the second group – without AH, were treated with ramipril at a dose of 2.5 mg. On the basis of rank correlation analysis, we demonstrated that the level of serum NGAL is directly correlated with interstitial fibrosis (r=0.65; p<0.05), serum IL-18 – with dystrophic changes in the epithelium of renal tubules (r=0.81; p<0.05).Conclusion. Serum levels of NGAL and IL-18 are one of the most sensitive markers of tubular kidney lesion and have diagnostic efficiency up to 97%. A 24-week treatment with ACE inhibitor ramipril in patients with CGN with and without AH leads to a decrease in the levels of tubular kidney lesion markers.

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Abstract 550: Large Blood Pressure Variability Aggravates Arteriolosclerosis and Ischemic Changes in the Kidney in Hypertensive Rats

Hypertension ◽

10.1161/hyp.62.suppl_1.a550 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Yuji Aoki ◽

Hisashi Kai ◽

Hidemi Kajimoto ◽

Hiroshi Kudo ◽

Narimasa Takayama ◽

...

Keyword(s):

Blood Pressure ◽

Interstitial Fibrosis ◽

Target Organ Damage ◽

Organ Damage ◽

Left Ventricular ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Matrix Deposition ◽

Luminal Narrowing ◽

Extracellular Matrix Deposition

Background: Increased blood pressure (BP) variability (BPV) is a characteristic feature of hypertensive patients. Large BPV aggravates hypertensive target organ damage, such as left ventricular hypertrophy, carotid atherosclerosis, and microalbuminuria. We have shown that angiotensin II (AngII)-mediated inflammation plays a role in the aggravation of hypertensive cardiac remodeling in spontaneously hypertensive rats (SHR) with large BPV. However, little was known regarding renal damages induced by large BPV. The aims of this study were to investigate pathological changes of the kidney and to examine whether candesartan would prevent the renal damages in SHR with large BPV. Methods and Results: A model of a combination of hypertension and large BPV was created by bilateral sino-aortic denervation (SAD) in SHR at 12 weeks old. SAD increased BPV without changes in mean BP. At 19 weeks old, SAD induced patchy cortical interstitial lesions associated with ischemic changes of glomeruli and tubules and interstitial fibrosis. The interlobular or afferent arterioles around ischemic lesions showed remarkable arteriolosclerotic changes characterized by vascular smooth muscle cell proliferation and extracellular matrix deposition, leading to the luminal narrowing and occlusion (Figure). Chronic treatment with a subdepressor dose of candesartan prevented not only arteriolosclerotic changes but also interstitial fibrosis and ischemic changes in SHR with SAD. Conclusion: Large BPV aggravates renal arteriolosclerosis, which results in the cortical ischemic changes and fibrosis in the kidney of hypertensive rats through angII-mediated mechanisms.

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Indicators of ambulatory blood pressure monitoring in patients with essential hypertension of the 2-nd stage depending on the type of 24-hours blood pressure profile, the state of the left ventricular diastolic filling and endothelial function of vessels

Reports of Vinnytsia National Medical University ◽

10.31393/reports-vnmedical-2021-25(4)-11 ◽

2021 ◽

Vol 25 (4) ◽

pp. 577-583

Author(s):

T. Yu. Niushko ◽

E. S. Osiadla

Keyword(s):

Blood Pressure ◽

Brachial Artery ◽

Blood Pressure Monitoring ◽

Pressure Profile ◽

Left Ventricular ◽

Diastolic Filling ◽

Pressure Monitoring ◽

Blood Pressure Profile ◽

Target Organs ◽

Left Ventricular Diastolic Filling

Annotation. Arterial hypertension (AH) is one of the most important risk factors for the development of cardiovascular complications and mortality in the world and it has become a medical and social problem. The prevalence of hypertension will increase to 1.56 billion by 2025, making the disease a very serious problem. The severity of clinical manifestations and prognosis in patients with hypertension are determined not only by the degree of increase in blood pressure (BP) but also the damage to target organs. The load on the cardiovascular system caused by elevated BP leads to structural remodelling of the heart and vessels. The aim – to evaluate peculiarities of indicators of ambulatory blood pressure monitoring in patients with essential hypertension of the 2nd stage depending on the type of 24-hours blood pressure profile, the state of the left ventricular diastolic filling and endothelial function of the vessels and determine independent clinical and instrumental criteria of the 24-hours profile “dipper” and “non-dipper”. The study involved 110 patients (40 men and 70 women) with hypertension of the II-nd stage, hypertensive heart, chronic heart failure of the 0-I stage (average age was 54.19±0.89 years). The patients underwent 24-hour blood pressure monitoring, echocardiography and determination the thickness of the intima-media complex (IMCT) of the brachial artery, endothelium-dependent (EDVD) and endothelium-independent (EIVD) vasodilatation. For statistical analysis, arithmetic means (M), errors of mean values (m), t - Student's t test for paired measurements were calculated. Correlation ratios were evaluated by the method of linear correlation for parametric data and the method of Spearman’s rank correlation for nonparametric data. Paired group comparisons were performed by the nonparametric Mann-Whitney method. Wilcoxon test was used in the analysis of dependent samples. Step-by-step multifactor regression was used to identify independent criteria for daily blood pressure profiles. Two types of 24-hours profile of blood pressure – “dipper” and “non-dipper” were detected. The left ventricle diastolic dysfunction (LVDD) by type of relaxation disorder was observed in all “non-dipper” patients and most “dipper” patients. Patients with DD had higher levels of BP per 24-hours, day, night, corresponding the time indexes, the magnitude of the morning increase of systolic and diastolic blood pressure, more pronounced structural changes of the heart and vessels compared with patients with preserved diastolic filling of the LV(р<0,01). The duration of the hypertensive anamnesis (p=0.0002), the thickness of the posterior wall of the LV (p=0.002), the maximum speed of early diastolic filling of the LV (E) (p<0.0001), the LV ejection fraction (p=0.001), the index of the left atrium (p=0.008), the thickness of the intima-media complex of the brachial artery (p=0.013), increase of the diameter of the brachial artery in 90 s after compression (EDVD) (p<0.0001) and in 5 min after taking of nitroglycerin (EIVD) (p=0.009) were determined as independent clinical and instrumental criteria of the “dipper” and “non-dipper” profile. Insufficient the degree of the nightly decrease of the BP, higher magnitude of the morning increase of systolic and diastolic BP cause more hemodynamic pressure on target organs and lead to more significant pathological remodeling of the LV and vessels, disorders of the LV relaxation processes and endothelial dysfunction.

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Identification of ethnogenetic differences in genetic markers in the clinical course and damage to target organs in arterial hypertension in Russians and Buryats

Patologiya krovoobrashcheniya i kardiokhirurgiya ◽

10.21688/1681-3472-2020-4-103-113 ◽

2020 ◽

Vol 24 (4) ◽

pp. 103

Author(s):

A. Ya. Kovaleva ◽

N. V. Kokh ◽

E. N. Voronina ◽

O. S. Donirova ◽

E. M. Zelenskаyа ◽

...

Keyword(s):

Blood Pressure ◽

Genetic Markers ◽

High Blood Pressure ◽

Conflict Of Interest ◽

Basic Research ◽

Left Ventricular ◽

Target Organs ◽

Data Collection And Analysis ◽

Genetic Features ◽

Basic Research Project

Аim. To study the influence of genetic factors on the severity of essential аrteriаl hypertension (AH) clinical outcomes in patients of Russian and Buryаt ethnicity.Methods. Our study included 206 patients with а diagnosis of essential AH: 136 patients were of Russiаn аnd 70 patients were of Buryаt ethnicity. Pаtients were evаluаted for the following genotype markers; АCE, АDRB1, АDRB2, АDRB3, NOS3, АGT, EDN1, GNB3, and STK39.Results. Allele T of GNB3 was аssociаted with high blood pressure in Russiаn аnd Buryаt patients. In Buryat patients, locus rs934379 of EDN1 was аssociаted with high blood pressure, whereas allele G of the same marker was associated with increased heart damage risk. In Russians, allele I of ACE was protective towards the development of left ventricular hypertrophy.Conclusion. Our data revealed ethnogenetic differences in the genetic features of essential AH. We identified the patients severe hypertension among two etnhic group. Studying ethnic genetic markers for essential AH facilitates a greater understanding of the genetic predisposition underlying this condition.Received 2 July 2020. Revised 31 August 2020. Accepted 9 September 2020.Funding: The work is supported by grant of the Russian Foundation for Basic Research (project No. 19-315-80032).Conflict of interest: Authors declare no conflict of interest.Author contributions Conception and design: N.V. Kokh, .M. Zelenskаyа, G.I. Lifshits Data collection and analysis: A.Yа. Kovаlevа, N.V. Kokh, E.N. Voroninа, O.S. Donirovа, E.M. Zelenskаyа, A.A. Slepukhina, G.I. Lifshits Statistical analysis: N.V. Kokh Drafting the article: A.Yа. Kovаlevа, N.V. Kokh, E.N. Voroninа, O.S. Donirovа, E.M. Zelenskаyа, A.A. Slepukhina, G.I. Lifshits Critical revision of the article: A.Yа. Kovаlevа, N.V. Kokh, E.N. Voroninа, O.S. Donirovа, E.M. Zelenskаyа, A.A. Slepukhina, G.I. Lifshits Final approval of the version to be published: A.Yа. Kovаlevа, N.V. Kokh, E.N. Voroninа, O.S. Donirovа, E.M. Zelenskаyа, A.A. Slepukhina, G.I. Lifshits

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