scholarly journals Effects of Mesenchymal Stem Cells Therapy on Cardiovascular Risk Factors in Experimental Diabetic Kidney Disease

2020 ◽  
Vol 7 ◽  
pp. 205435812095742
Author(s):  
Einas Nagib Hussein ◽  
Gehane M. Hamed ◽  
Ansam A. Seif ◽  
Mona A. Ahmed ◽  
Fatma Abd Elkarim Abu Zahra
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Risk ◽  
Blood Glucose ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Atherogenic Index ◽  
Diabetic Kidney

Background: Diabetic kidney disease (DKD) is a progressive kidney disease and a leading cause of end-stage renal disease (ESRD). Diabetic kidney disease has been strongly associated with increased risk of cardiovascular morbidity and mortality. Despite their susceptibility to cardiovascular diseases (CVDs), patients with DKD are less likely to receive appropriate cardiovascular risk modification as they are generally excluded from major cardiovascular trials. Awareness of vulnerability of these patients necessitates investigating potential interventions that would lessen their risk of adverse outcomes. Objectives: This study aimed to explore the effect of bone marrow–derived mesenchymal stem cells (MSCs) in modulating cardiovascular risk factors that develop with the progression of DKD. Methods: A total of 60 adult female albino rats were allocated into 3 groups: control group, untreated DKD group, and mesenchymal stem cells–treated diabetic kidney disease (MSCs-DKD) group. Blood pressure, blood glucose level, lipid profile, and atherogenic index were used to assess cardiovascular risk. All rats were killed and subjected to in vitro aortic reactivity studies 8 weeks after induction of diabetes. The MSCs-DKD rats received a single intravenous injection of MSCs 4 weeks after diabetes induction. Results: Mesenchymal stem cells injection significantly decreased blood pressure, atherogenic index, and blood glucose compared with untreated rats. The MSCs-DKD aorta also exhibited significant enhancement of vascular reactivity parameters despite absence of improvement in kidney function. These findings conformed to tracked MSCs, which were found residing in aortic and pancreatic tissues and absent in kidneys. Conclusions: Mesenchymal stem cells hold hope of improving cardiovascular risk and mortality in patients with DKD, particularly those deteriorating to ESRD.

Effect of Mesenchymal Stem Cells Therapy on Cardiovascular Risk in Experimental Diabetic Kidney Disease

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
E M Nagib ◽  
F A Abuzahra ◽  
A A Seif ◽  
M A Ahmed ◽  
G M Hamed
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Bone Marrow ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Atherogenic Index ◽  
Diabetic Patients ◽  
Disease Group ◽  
Diabetic Kidney

Abstract Background Bone Marrow-derived Mesenchymal stem cells (MSC)s were experimentally used in treating diabetes mellitus (DM) and its complications, particularly, diabetic kidney disease (DKD). Cardiovascular diseases are the leading cause of mortality in diabetic patients, which has been strongly associated with progression of DKD. Aim This study was designed to explore the effect of MSCs in modulating cardiovascular risk factors that develop with DKD. Study Design 60 adult female albino rats were allocated into three groups: control group, untreated diabetic kidney disease group (un-DKD) and MSCs treated diabetic kidney disease group (MSC-DKD). DM was induced by a single dose of Streptozotocin at a dose of 35mg/kg, then rats were sacrificed 8 weeks later. MSC-DKD rats were treated by IV injection of bone marrow-derived MSCs 4 weeks after DM induction. DKD establishment was confirmed by histopathological kidney changes and elevated plasma creatinine and urea in both un-DKD and MSC-DKD rats. Methods Blood Pressure and lipid profile were measured, and atherogenic index was calculated to assess cardiovascular risk accompanying the progression of the diabetic renal damage. Moreover, aortic reactivity studies were performed in vitro. Results A single MSCs injection to MSC-DKD rats resulted in significant decrease in final blood glucose, mean arterial blood pressure and atherogenic index, together with a significant increase in plasma HDL level compared to untreated rats, thus minimizing cardiovascular risk factors. MSC-DKD aortae also exhibited significant enhancement of vascular reactivity parameters, particularly vasorelaxation which could partially explain the improvement of blood pressure. On the other hand, DKD didn’t improve by MSCs therapy. These results conformed to tracking labelled MSCs which were found in abundance in both aortic and pancreatic tissues and absent in kidneys. Conclusion MSCs therapy holds hope of improving cardiovascular risk and mortality for diabetic patients with diabetic Kidney disease.

scholarly journals Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 18 (3) ◽  
pp. 17-25
Author(s):  
Stoiţă Marcel ◽  
Popa Amorin Remus
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Significant Positive Association ◽  
Diabetic Kidney

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p <0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p <0.01).

scholarly journals Novel Cardiovascular Risk Factors in Patients with Diabetic Kidney Disease

2021 ◽  
Vol 22 (20) ◽  
pp. 11196
Author(s):  
Christodoula Kourtidou ◽  
Maria Stangou ◽  
Smaragdi Marinaki ◽  
Konstantinos Tziomalos
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Risk Stratification ◽  
Cardiovascular Risk Factors ◽  
Cardiovascular Events ◽  
Diabetic Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Diabetic Kidney ◽  
Increased Risk

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.

scholarly journals Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan

2020 ◽  
Vol 8 (1) ◽  
pp. e000902 ◽  
Author(s):  
Yui Yoshida ◽  
Kosuke Kashiwabara ◽  
Yosuke Hirakawa ◽  
Tetsuhiro Tanaka ◽  
Shinsuke Noso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Diabetic Kidney Disease ◽  
Cross Sectional ◽  
Diabetic Kidney ◽  
Patients With Diabetes

ObjectiveGlomerular filtration rate (GFR) decreases without or prior to the development of albuminuria in many patients with diabetes. Therefore, albuminuria and/or a low GFR in patients with diabetes is referred to as diabetic kidney disease (DKD). A certain proportion of patients with diabetes show a rapid progressive decline in renal function in a unidirectional manner and are termed early decliners. This study aimed to elucidate the prevalence of DKD and early decliners and clarify their risk factors.Research design and methodsThis combination cross-sectional and cohort study included 2385 patients with diabetes from 15 hospitals. We defined DKD as a urinary albumin to creatinine ratio (ACR) ≥30 mg/gCr and/or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². We classified patients into four groups based on the presence or absence of albuminuria and a decrease in eGFR to reveal the risk factors for DKD. We also performed a trajectory analysis and specified the prevalence and risk factors of early decliners with sequential eGFR data of 1955 patients in five facilities.ResultsOf our cohort, 52% had DKD. Above all, 12% with a low eGFR but no albuminuria had no traditional risk factors, such as elevated glycated hemoglobin, elevated blood pressure, or diabetic retinopathy in contrast to patients with albuminuria but normal eGFR. Additionally, 14% of our patients were early decliners. Older age, higher basal eGFR, higher ACR, and higher systolic blood pressure were significantly associated with early decliners.ConclusionsThe prevalence of DKD in this cohort was larger than ever reported. By testing eGFR yearly and identifying risk factors in the early phase of diabetes, we can identify patients at high risk of developing end-stage renal disease.

scholarly journals Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

2021 ◽  
Vol 22 (4) ◽  
pp. 1546
Author(s):  
Christian Sávio-Silva ◽  
Poliana E. Soinski-Sousa ◽  
Antônio Simplício-Filho ◽  
Rosana M. C. Bastos ◽  
Stephany Beyerstedt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Diabetic Kidney ◽  
Ros Accumulation

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs’ biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

scholarly journals Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ferdinando Carlo Sasso ◽  
Pia Clara Pafundi ◽  
Vittorio Simeon ◽  
Luca De Nicola ◽  
Paolo Chiodini ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Trial ◽  
Cardiovascular Risk ◽  
Kidney Disease ◽  
Primary Endpoint ◽  
Diabetic Kidney Disease ◽  
Multifactorial Intervention ◽  
Diabetic Kidney

Abstract Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure < 130/80 mmHg, glycated haemoglobin < 7%, LDL, HDL and total cholesterol < 100 mg/dL, > 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925

Investigation of the prevalence of cardiovascular risk factors in obese patients diagnosed with metabolic syndrome in childhood and examination of left ventricular function by echocardiography

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Güzin Özden ◽  
Ayşe Esin Kibar Gül ◽  
Eda Mengen ◽  
Ahmet Ucaktürk ◽  
Hazım Alper Gürsu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Left Ventricular ◽  
Atherogenic Index ◽  
Volume Index ◽  
Common Component

Abstract Objectives The objective of this study is to investigate the cardiovascular risk factors associated with metabolic syndrome (MetS), which is increasingly becoming prevalent in childhood obesity. Methods A total of 113 patients, 76 of whom were between the ages of 10 and 17 (mean age: 14.5 ± 1.8 years) and diagnosed with obesity (30 non-MetS and 46 MetS using IDF) and 37 of whom constituted the control group, participated in the study. Echocardiographic examination and atherogenicity parameters (Atherogenic index of plasma [AIP: logTG/HDL], total cholesterol/HDL, and TG/HDL ratio and non-HDL) were evaluated. Results The most common component accompanying obese MetS was found to be hypertension and low HDL. While obesity duration, body mass index (BMI), blood pressure, fasting insulin, insulin resistance, atherogenicity parameters were determined to be significantly higher in the obese-MetS group. Echocardiography showed that while the thickness, volume, and diameter of LV end-diastolic wall, left ventricular mass (LVM), LVM index (LVMI g/m2) and relative wall thickness (RWT) were significantly high in the MetS group, however, mitral E/A ratio was significantly lower (p<0.05). Change in LV geometry consistent with concentric remodeling (increased RWT, normal LVMI) was visible in obese groups. LVM were positively significantly related to BMI, waist circumference, insulin resistance, blood pressure, LDL level, and negative to mitral E/A ratio. In the obese-MetS group, LVMI was positively correlated to office systolic BP, left atrium end-diastolic volume/index. Conclusions LVMI and atherogenicity parameters that were found to be significantly higher in obese MetS exhibit increased cardiovascular risk in childhood.

scholarly journals Vascular inflammation, atherosclerosis, and lipid metabolism and the occurrence of non-high albuminuria diabetic kidney disease: A cross-sectional study

2021 ◽  
Vol 18 (1) ◽  
pp. 147916412199252
Author(s):  
Yuwei Yang ◽  
Peng Xu ◽  
Yan Liu ◽  
Xiaohong Chen ◽  
Yiyang He ◽  
...  
Keyword(s):  
Risk Factors ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Density Lipoprotein ◽  
Endothelial Damage ◽  
Lipid Metabolism Disorder ◽  
Cross Sectional ◽  
Diabetic Kidney ◽  
Significant Difference

Aim: Atherosclerosis involves vascular endothelial damage and lipid metabolism disorder, which is closely related to the occurrence and development of diabetic kidney disease (DKD). However, studies on non-high albuminuria DKD (NHADKD) with an albumin to creatinine ratio (ACR) <30 mg/g are rare. This study is to investigate the relationship between atherogenic factors and the occurrence of NHADKD. Methods: Serum lipid indicators, lipoprotein-associated phospholipase A2 (Lip-PLA2) and homocysteine levels were measured in 1116 subjects to analyze their relationship with NHADKD. Results: Among all subjects, Lip-PLA2 had the closest but relatively weak correlation with ACR ( r = 0.297, p < 0.001) and only homocysteine was moderately correlated with eGFR ( r = −0.465, p < 0.001). However, in patients with NHADKD, these atherosclerotic factors were weakly correlated or uncorrelated with eGFR (max. | r| = 0.247). Stratified risk analysis showed that when ACR was <10 mg/g, homocysteine [OR = 6.97(4.07–11.95)], total cholesterol (total-Chol) [OR = 6.04(3.03–12.04)], and high-density lipoprotein cholesterol (HDL-Chol) [OR = 5.09(2.99–8.64)] were risk factors for NHADKD. There was no significant difference of OR between these three factors ( Z = 0.430–1.044, all p > 0.05). When ACR was ⩾10mg/g, homocysteine [OR = 17.26(9.67–30.82)] and total-Chol [OR = 5.63(2.95–10.76)] were risk factors for NHADKD, and ORhomocysteine was significantly higher than ORtotal-Chol ( Z = 3.023, p < 0.05). Conclusions: The occurrence of NHADKD may be related to the levels of homocysteine, total-Chol, HDL-Chol, and Lip-PLA2 in blood. Among them, homocysteine may be most closely related to NHADKD.

Sign in / Sign up

Export Citation Format

Share Document