Fibrotic remodeling of left ventricle in the murine remnant kidney model of chronic kidney disease is independent of arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kazakov ◽  
J Hermann ◽  
V Jankowski ◽  
T Speer ◽  
C Maack ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Bone Marrow ◽  
Kidney Disease ◽  
Left Ventricle ◽  
Arterial Hypertension ◽  
Sham Operation ◽  
Funding Source ◽  
Remnant Kidney

Abstract Background Cardiac fibrosis and arterial hypertension are common in patients with chronic kidney disease (CKD). We studied the mechanisms of cardiac fibrogenesis and the role of blood pressure in mice with CKD. Methods and results 10-week-old male C57/BL6N (BL6) and SV129 wildtype (WT) mice were underwent 5/6 nephrectomy (remnant kidney model, RKM) or sham operation for 10 weeks. RKM significantly elevated plasma creatinine and urea. RKM elicited both interstitial and replacement renal and left ventricular (LV) (BL6: SHAM 5.6±0.4%, RKM 7.3±0.7%, p=0.04; SV129: SHAM 6.0±0.5%, RKM 14±2%, p=0.001) fibrosis as assessed by picrosirius red staining. In parallel, the number of cardiac fibroblasts per mm2 (BL6: SHAM 36±4, RKM 85±13, p=0.001; SV129: SHAM 82±11, RKM 200±34, p=0.006) was increased in RKM mice. With regard to possible mechanisms, cardiac oxidative stress as shown by co-immunostaining for intracellular fibronectin and 8-hydroxyguanosine (BL6: SHAM 44±14%, RKM 60±24%, p=0.03; SV129: SHAM 51±6%, RKM 70±7%, p=0.04) and the percentage of CXCR4+ fibroblasts in the myocardium (BL6: SHAM 47±5%, RKM 62±4%, p=0.04; SV129: SHAM 63±5%, RKM 81±3%, p=0.005) were increased. Furthermore, the number of circulating CD45+ / collagen I+ fibrocytes (FACS) in the peripheral blood was increased by RKM in BL6 (SHAM 100±23%, RKM 443±252%, p=0.04) and diminished in SV129 (SHAM 100±19%, RKM 43±11%, p=0.01), while an opposite regulation was seen in the bone marrow. To further confirm the role of bone-marrow derived fibroblasts in renal and cardiac remodeling 10-week-old WT BL6 mice were subjected to transplantation of bone marrow from 10-week-old WT BL6 mice expressing green fluorescent protein (GFP)+ ubiquitously. 28 days later, RKM or SHAM-operation was performed. RKM significantly increased the number of GFP+ fibroblasts in kidney and LV-myocardium. CKD significantly decreased myocardial capillarization assessed by immunostaining for podocalyxin in both mouse lines. In parallel, myocardial protein expression of fibrosis regulators fibronectin, collagen I, CTGF and Hif1a were up-regulated and expression of the active form of eNOS (phospho-S1177) was reduced. As a possible confounder, tail-cuff blood pressure was moderately enhanced (Ø 30mmHg) 9 weeks after nephrectomy. In a control experiment using the vasodilator hydralazine (250 mg/L/day), peripheral blood pressure was equalized in all 4 experimental groups, but the extent of LV fibrosis and expression of the above-mentioned fibrosis markers remained unchanged. Conclusions Chronic kidney disease in the RKM model elicits left ventricle fibrosis by increasing myocardial protein expression of fibrosis regulators, reduction of myocardial capillarization and mobilization / recruitment of circulating fibroblasts, independently of blood pressure. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Deutsche Forschungsgemeinschaft

scholarly journals The Copenhagen chronic kidney disease echo study (COInCYDE)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Landler ◽  
S Bro ◽  
B Feldt-Rasmussen ◽  
D Hansen ◽  
A.L Kamper ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Kidney Disease ◽  
Cardiac Function ◽  
Left Ventricular ◽  
Funding Source ◽  
Ckd Stage ◽  
Significant Difference ◽  
Stage 1

Abstract Background The cardiovascular mortality of patients with chronic kidney disease (CKD) is 2–10 times higher than in the average population. Purpose To estimate the prevalence of abnormal cardiac function or structure across the stages CKD 1 to 5nonD. Method Prospective cohort study. Patients with CKD stage 1 to 5 not on dialysis, aged 30 to 75 (n=875) and age-/sex-matched controls (n=173) were enrolled consecutively. All participants underwent a health questionnaire, ECG, morphometric and blood pressure measurements. Blood and urine were analyzed. Echocardiography was performed. Left ventricle (LV) hypertrophy, dilatation, diastolic and systolic dysfunction were defined according to current ESC guidelines. Results 63% of participants were men. Mean age was 58 years (SD 12.6 years). Mean eGFR was 46.7 mL/min/1,73 m (SD 25.8) for patients and 82.3 mL/min/1,73 m (SD 13.4) for controls. The prevalence of elevated blood pressure at physical exam was 89% in patients vs. 53% in controls. Patients were more often smokers and obese. Left ventricular mass index (LVMI) was slightly, albeit insignificantly elevated at CKD stages 1 & 2 vs. in kontrols: 3.1 g/m2, CI: −0.4 to 6.75, p-value 0.08. There was no significant difference in LV-dilatation between patients and controls. Decreasing diastolic and systolic function was observed at CKD stage 3a and later: LVEF decreased 0.95% (CI: −1.5 to −0.2), GLS increased 0.5 (CI: 0.3 to 0.8), and OR for diastolic dysfunction increased 3.2 (CI 1.4 to 7.3) pr. increment CKD stage group. Conclusion In accordance to previous studies, we observe in the CPHCKD cohort study signs of early increase of LVMI in patients with CKD stage 1 & 2. Significant decline in systolic and diastolic cardiac function is apparent already at stage 3 CKD. Figure 1. Estimated GFR vs. GLS & histogram of GLS Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Capital Region of Denmark

The Role of Systemic Blood Pressure in the Progression of Chronic Kidney Disease

2015 ◽  
Vol 9 (5) ◽  
Author(s):  
Karen A Griffin ◽  
Krishna Pothugunta ◽  
Aaron J Polichnowski ◽  
Anil K Bidani
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Systemic Blood Pressure ◽  
Systemic Blood

scholarly journals Biochemical and Chemical Lipid Profile and Blood Pressure Assessment in Arterial Hypertension with Chronic Kidney Disease

2020 ◽  
Vol 71 (7) ◽  
pp. 425-435
Author(s):  
Teim Baaj ◽  
Ahmed Abu-Awwad ◽  
Mircea Botoca ◽  
Octavian Marius Cretu ◽  
Elena Ardeleanu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Hypertension ◽  
Lipid Profile ◽  
Blood Pressure Monitoring ◽  
Hdl Cholesterol ◽  
Night Time ◽  
Hypertensive Patients ◽  
Lipid Disorders

Accelerated atherosclerosis and cardiovascular diseases are frequent complications in hypertensive patients with chronic kidney disease (CKD), being mainly driven by cardiovascular risk factors as lipid disorders and an unfavorable blood pressure profile. The objectives of the study were to evaluate the lipid profile and to assess the characteristics of blood pressure (BP) in patients with primary arterial hypertension associating chronic kidney disease (CKD) in a primary care population in Timis County, Romania. Lipid disorders were highly prevalent in hypertensive patients with CKD, consisting in hyper LDL-cholesterolemia in 50.3%, hypertriglyceridemia in 52%, low HDL-cholesterol levels in 35.8%. More than 2 lipid abnormalities were present in 68.8% of CKD hypertensive. CKD hypertensive patients, compared with those without CKD, presented a BP profile with higher systolic and diastolic office BP. On ambulatory blood pressure monitoring they also registred higher systolic and diastolic BP, the systolic BP (SBP), both for 24 h SBP, day-time and night-time SBP being statistically significant higher than in hypertensive patients without CKD. The circadian 24 h BP profile demonstrated in the CKD hypertensive population an unfavourable nocturnal profile in 67%, consisting of a high prevalence of the non-dipping profile and of nocturnal riser pattern.

scholarly journals 435 Renal denervation in a patient with uncontrolled arterial hypertension secondary to polycystic kidney disease

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Maddalena Widmann ◽  
Simone Fezzi ◽  
Gianluca Castaldi ◽  
Domenico Tavella ◽  
Michele Pighi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Chronic Pain ◽  
Kidney Disease ◽  
Arterial Hypertension ◽  
Therapeutic Option ◽  
Renal Cysts ◽  
Secondary Hypertension ◽  
Polycystic Kidney ◽  
Loin Pain

Abstract Aims Autosomal dominant polycystic kidney disease (ADPKD) represents the most common inherited cause of chronic kidney disease. Typical manifestations of this condition include secondary hypertension, abdominal pain, haematuria and urinary tract infections. Despite the progressive increase in the use of antihypertensive therapy in patients with ADPKD in the last decades, reaching blood pressure target is often difficult in this setting due to the complex physiopathology of arterial hypertension in ADPKD. Catheter-based renal sympathetic denervation (RDN) represents nowadays a therapeutic strategy to approach resistant hypertension. Based on consistent results of several sham-controlled clinical trials, the evidence of safety and efficacy of this procedure is increasing, also in patients with multiple comorbidities including chronic kidney disease. Patients with ADPKD often develop chronic severe kidney-related pain, caused by distension of the renal capsule due to the expansion of the cysts. RDN was proposed to be an effective therapeutic option able to relieve loin pain. Methods A 49-year-old man affected by ADPKD was referred to our centre for resistant uncontrolled arterial hypertension, despite combined therapy with five antihypertensive drugs. He also complained about intense loin pain and 3 years earlier underwent two surgical interventions to remove voluminous renal cysts, that did not relieve chronic pain. His kidney function was moderately decreased at presentation, with progressive decline in the previous years. After a multi-disciplinary discussion with a nephrologist and algologist, the patient was proposed for RDN with the aim of lowering blood pressure and reducing pain. He was treated in July 2018, and after the procedure, was observed a better control of blood pressure but no benefits on pain. Because of the persistence of intractable loin pain, the patient was submitted to a second RDN in December 2018. Also, after this procedure, blood pressure declined remarkably, decreasing his need for antihypertensive medications without a significant worsening of kidney function. Unfortunately, no benefit on chronic pain was observed. Results ADPKD is characterized by the progressive bilateral development of focal renal cysts. Cardiovascular complications, mainly related to hypertension, are a major cause of morbidity and mortality for these patients. RDN could be a valid and safe therapeutic option for the treatment of secondary hypertension in this setting.

scholarly journals The functions and geometry of the left ventricle in patients with chronic glomerulonephritis

2012 ◽  
Vol 93 (2) ◽  
pp. 204-207
Author(s):  
O N Sigitova ◽  
A G Shcherbakova
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Left Ventricle ◽  
Arterial Hypertension ◽  
Kidney Function ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Left Ventricular ◽  
Chronic Glomerulonephritis ◽  
Stage 1

Aim. To study the functions and the geometry of the left ventricle in patients with chronic glomerulonephritis at different stages of chronic kidney disease, depending on the presence of arterial hypertension and dyslipidemia. Methods. Observed were 156 patients with chronic glomerulonephritis (80 men and 76 women, mean age 40.23±1.1 years), including 91 people with arterial hypertension (observation group), 65 patients without arterial hypertension (comparison group). The observation and comparison groups were divided into subgroups depending on the stage of chronic kidney disease: the first subgroup - stage 1-2, the second subgroup - stage 3-4, the third subgroup - stage 5. The control group consisted of 30 healthy people. Conducted were general clinical, laboratory and instrumental investigations. Results. Left ventricular hypertrophy was formed at stage 1-2 of chronic kidney disease in 52.5% of patients with chronic glomerulonephritis with arterial hypertension, at stage 3-4 - in 69.2%, at stage 5 - in 80.0%. The dominant type of hypertrophy was concentric; with the decrease in kidney function the frequency of eccentric hypertrophy increased. In the early stages of chronic kidney disease the incidence of left ventricular dysfunction was almost similar in arterial hypertension (62.5%) and normal blood pressure (60.0%). With the decline of the kidney function in the presence of arterial hypertension the incidence of left ventricular dysfunction reached up to 84.6% at stage 3-4 and up to 88.0% - at stage 5 of chronic kidney disease. No influence of the lipid profile on the function and the geometry of the left ventricle were found. Conclusion. In patients with chronic glomerulonephritis with arterial hypertension with the decrease in kidney function increases the frequency of left ventricular hypertrophy; in the early stages of chronic kidney disease the incidence of left ventricular dysfunction is the same in patients with and without hypertension, increasing with the decline in renal function in patients with hypertension.

scholarly journals Chronic kidney disease and cardiovascular events: a focus on central blood pressure

2017 ◽  
Vol 14 (1) ◽  
pp. 58-60
Author(s):  
I T Murkamilov ◽  
K A Aitbaev ◽  
I S Sabirov ◽  
V V Fomin ◽  
F A Yusupov
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Arterial Stiffness ◽  
Renal Dysfunction ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Vascular Wall ◽  
Cardio Vascular

The purpose of the review - to present the literature on the role of central arterial pressure (CAP) and arterial stiffness progression cardio-vascular complications (CVC) and renal dysfunction in patients with chronic kidney disease (CKD). The main provisions. In this review we discuss the pathogenetic questions damaging effect of increasing CAP and arterial stiffness on the vascular wall, the development of arteriosclerosis, atherosclerosis and destabilization of atherosclerotic plaque in the blood vessels of the kidneys. All this is the direct cause of the CVC and renal dysfunction in CKD.

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