Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

BACKGROUND: Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. METHODS: The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). RESULTS: The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). CONCLUSIONS: Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Aortic Stiffness Can be Predicted From Different eGFR Formulas With Long Follow-Up in the Malmö Diet Cancer Study.

We studied the impact of estimated glomerular filtration rate (eGFR) based on either creatinine or cystatin C, or in combination, on vascular aging (aortic stiffness) and central hemodynamics (central systolic blood pressure) in a Swedish urban population with median 17 years of follow-up. Participants (n = 5049) from the population-based Malmö Diet and Cancer Study that underwent baseline examination and later participated in the prospective cardiovascular arm were selected. Of these, 2064 with measured carotid-femoral pulse wave velocity (cfPWV) and central blood pressure at follow-up were enrolled. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised (LMrev), and the European Kidney Function Consortium (EKFC) equations. Lower adjusted eGFRCR, but not eGFRCYS, were independently associated with higher cfPWV (P < .001, respectively). eGFR <60 mL/min/1.73 m2 determined higher cfPWV except when using the EKFC equation. Conversely, CAPA/LMrev and CAPA/EKFC ratios were not associated with aortic stiffness. Lower eGFRCR is associated with higher future aortic stiffness independently of age, sex, heart rate, mean blood pressure, body mass index, and antihypertensive treatment. The ratio of eGFRCYS and eGFRCR equations could not predict aortic stiffness at all.

Coronary artery calcification and aortic valve calcification in patients with kidney failure: a sex-disaggregated study.

BACKGROUND: Chronic kidney disease (CKD) is linked to an increased cardiovascular disease (CVD) burden. Albeit underappreciated, sex differences are evident in CKD with females being more prone to CKD development, but males progressing more rapidly to kidney failure (KF). Cardiovascular remodelling is a hallmark of CKD with increased arterial and valvular calcification contributing to CKD. However, little is known regarding sex differences in calcific cardiovascular remodelling in KF patients. Thus, we hypothesise that sex differences are present in coronary artery calcification (CAC) and aortic valve calcification (AVC) in patients with KF. METHODS: KF patients, males (n = 214) and females (n = 107), that had undergone computer tomography (CT) assessment for CAC and AVC were selected from three CKD cohorts. All patients underwent non-contrast multi-detector cardiac CT scanning, with CAC and AVC scoring based on the Agatston method. Baseline biochemical measurements were retrieved from cohort databases, including plasma analyses for inflammation markers (IL-6, TNF, hsCRP) and oxidative stress by skin autofluorescence measuring advanced glycation end-products (AGE), amongst other variables. RESULTS: Sex-disaggregated analyses revealed that CAC score was associated with age in both males and females (both p < 0.001). Age-adjusted analyses revealed that in males CAC was associated with diabetes mellitus (DM) (p = 0.018) and CVD (p = 0.011). Additionally, for females CAC associated with IL-6 (p = 0.005) and TNF (p = 0.004). In both females and males CAC associated with AGE (p = 0.042 and p = 0.05, respectively). CAC was associated with mortality for females (p = 0.015) independent of age. AVC in females was not reviewed due to low AVC-positive samples (n = 14). In males, in multivariable regression AVC was associated with age (p < 0.001) and inflammation, as measured by IL-6 (p = 0.010). CONCLUSIONS: In female KF patients inflammatory burden and oxidative stress were associated with CAC. Whereas in male KF patients oxidative stress and inflammation were associated with CAC and AVC, respectively. Our findings suggest a sex-specific biomarker signature for cardiovascular calcification that may affect the development of cardiovascular complications in males and females with KF.

Chronic kidney disease (CKD) is a condition that affects the kidneys and increases the risk of heart problems. Males and females may experience CKD differently, and our study aimed to understand the differences in the development of calcification in the blood vessels of the heart (coronary artery calcification, or CAC) and the heart valves (aortic valve calcification, or AVC) between males and females with CKD.We analysed 214 males and 107 females with CKD who had undergone a heart scan (computer tomography, or CT) to measure CAC and AVC. We collected information on age, diabetes, cardiovascular disease, and markers of inflammation and oxidative stress.Our results showed that in both males and females CAC was associated with age. In males, CAC was associated with diabetes and cardiovascular disease, while in females, it was linked to markers of inflammation. In females, CAC was also associated with mortality regardless of age. Unfortunately, we had insufficient samples of females with AVC for analysis. However, in males AVC was associated with age and inflammation.Overall, our study indicates sex-specific differences in the development of calcification in the blood vessels and heart valves of CKD patients. In females, inflammation and oxidative stress are associated with CAC, while in males, oxidative stress and inflammation are associated with CAC and AVC, respectively. These findings underscore the importance of considering these differences when assessing cardiovascular complications in CKD patients. It may help in developing personalised treatment approaches for both males and females with CKD.

Vascular ageing: moving from bench towards bedside.

Prevention of cardiovascular disease (CVD) remains one of the largest public health challenges of our time. Identifying individuals at increased cardiovascular risk at an asymptomatic, sub-clinical stage is of paramount importance for minimizing disease progression as well as the substantial health and economic burden associated with overt CVD. Vascular ageing (VA) involves the deterioration in vascular structure and function over time and ultimately leads to damage in the heart, brain, kidney, and other organs. Vascular ageing encompasses the cumulative effect of all cardiovascular risk factors on the arterial wall over the life course and thus may help identify those at elevated cardiovascular risk, early in disease development. Although the concept of VA is gaining interest clinically, it is seldom measured in routine clinical practice due to lack of consensus on how to characterize VA as physiological vs. pathological and various practical issues. In this state-of-the-art review and as a network of scientists, clinicians, engineers, and industry partners with expertise in VA, we address six questions related to VA in an attempt to increase knowledge among the broader medical community and move the routine measurement of VA a little closer from bench towards bedside.

Vascular Aging and COVID-19.

Vascular age is determined by functional and structural changes in the arterial wall. When measured by its proxy, pulse wave velocity, it has been shown to predict cardiovascular and total mortality. Disconcordance between chronological and vascular age might represent better or worse vascular health. Cell senescence is caused by oxidative stress and sustained cell replication. Senescent cells acquire senescence-associated secretory phenotype. Oxidative stress, endothelial dysfunction, dysregulation of coagulation and leucocyte infiltration are observed in the aging endothelium. All of these mechanisms lead to increased vascular calcification and stiffness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can involve the vascular endothelium. It enters cells using angiotensin-converting enzyme 2 (ACE-2) receptors, which are abundant in endothelial cells. The damage this virus does to the endothelium can be direct or indirect. Indirect damage is caused by hyperinflammation. Direct damage results from effects on ACE-2 receptors. The reduction of ACE-2 levels seen during coronavirus disease 2019 (COVID-19) infection might cause vasoconstriction and oxidative stress. COVID-19 and vascular aging share some pathways. Due to the novelty of the virus, there is an urgent need for studies that investigate its long-term effects on vascular health.

Gender dimension in cardio-pulmonary continuum.

Cardio-pulmonary diseases, which were once regarded as a man's illness, have been one of the leading causes of morbidity and mortality for both men and women in many countries in recent years. Both gender and sex influence the functional and structural changes in the human body and therefore play an important role in disease clinical manifestation, treatment choice, and/or response to treatment and prognosis of health outcomes. The gender dimension integrates sex and gender analysis in health sciences and medical research, however, it is still relatively overlooked suggesting the need for empowerment in the medical research community. Latest advances in the field of cardiovascular research have provided supportive evidence that the application of biological variables of sex has led to the understanding that heart disease in females may have different pathophysiology compared to males, particularly in younger adults. It has also resulted in new diagnostic techniques and a better understanding of symptomatology, while gender analysis has informed more appropriate risk stratification and prevention strategies. The existing knowledge in the pulmonary field shows the higher prevalence of pulmonary disorders among females, however, the role of gender as a socio-cultural construct has yet to be explored for the implementation of targeted interventions. The purpose of this review is to introduce the concept of gender dimension and its importance for the cardiopulmonary continuum with a focus on shared pathophysiology and disease presentation in addition to interrelation with chronic kidney disease. The review presents basic knowledge of what gender dimension means, and the application of sex and gender aspects in cardiovascular medicine with a specific focus on early pulmonary development, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Early vascular aging and inflammation have been presented as a potential pathophysiological link, with further interactions between the cardiopulmonary continuum and chronic kidney disease. Finally, implications for potential future research have been provided to increase the impact of gender dimension on research excellence that would add value to everybody, foster toward precision medicine and ultimately improve human health.

Clusters of risk factors in metabolic syndrome and their influence on central blood pressure in a global study.

The effect of metabolic syndrome (MetS) and clusters of its components on central blood pressure (CBP) has not been well characterized. We aimed to describe the effect of MetS and clusters of its components on CBP in a large population and to identify whether this effect differs in men and women. We studied 15,609 volunteers (43% women) from 10 cohorts worldwide who participated in the Metabolic syndrome and Artery REsearch Consortium. MetS was defined according to the NCEP-ATP III criteria (GHTBW, glucose, high-density lipoprotein cholesterol, triglyceride, blood pressure, waist circumference). CBP was measured noninvasively and acquired from pulse wave analysis by applanation tonometry. MetS was associated with a 50% greater odds of having higher CSBP. After controlling for age, male sex, non HDL cholesterol, diabetes mellitus, and mean arterial pressure, only specific clusters of MetS components were associated with a higher CSBP; and some of them were significant in women but not in men. We identified "risky clusters" of MetS variables associated with high CSBP. Future studies are needed to confirm they identify subjects at high risk of accelerated arterial aging and, thus, need more intensive clinical management.

Increased fat mass index is associated with decreased glomerular filtration rate estimated from cystatin C. Data from Malmö Diet and Cancer cohort.

BACKGROUND: This study aims to describe associations of obesity and CKD in a Swedish urban population. The impact of fat mass, from bioimpedance analysis, on eGFR based on cystatin C and/or creatinine is studied. METHODS: 5049 participants from Malmö Diet and Cancer Study the cardiovascular arm (MDCS-CV) with available body mass composition (single frequency bioimpedance analysis) and cystatin C measured at baseline were selected. Body mass index (kg/m2) was used to define overweight/obesity. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Chronic Kidney Disease Epidemiology Collaboration 2012 (CKD-EPICR, CKD-EPICYS, CKD-EPICR-CYS), eGFRCYS based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised equation (LMrev), and Modified Full Age Spectrum creatinine-based equation (EKFCCR). Two different fat mass index (FMI) z-scores were calculated: FMI z-scoreLarsson and FMI z-scoreLee. RESULTS: Lower eGFRCYS and eGFRCR-CYS following multiple adjustments were prevalent in overweight/obese subjects. Increase in FMI z-scoreLarsson or FMI z-scoreLee was related to decrease in predicted CAPA, CKD-EPICYS, CKD-EPICR-CYS and CAPA-LMrev equation. CONCLUSION: eGFRCYS, in contrast to combined eGFRCR-CYS and eGFRCR, demonstrate the strongest association between FMI and kidney function.

Laser Doppler flowmetry evaluation of skin microvascular endothelial function in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is associated with high cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the MetS. Lifestyle changes and pharmacological intervention might partly restore endothelial function in MetS. Whereas an optimal non-invasive test for endothelial dysfunction is still being sought, the aim of this study was to assess the relationship between changes in skin microvascular endothelial function, detected by Laser Doppler flowmetry, and cardiovascular risk factors (CVRFs) of patients with MetS. DESIGN AND METHODS: 3081 patients (1865 women and 1216 men, mean age 53 ± 6 years) with MetS were enrolled in the study, which was conducted during the period of 2010-2014 at Vilnius University Hospital Santaros Klinikos. Skin microvascular endothelial function was evaluated using the Laser Doppler flowmetry in combination with the post-occlusive reactive hyperaemia test. The percentage change of flow from peak to the rest flow (PF-RF) was calculated and used as the main measure of endothelial function. RESULTS: The study showed that decrease in flow-mediated dilatation reflected by PF-RF was associated with increased triglycerides (p = 0.002), male sex (p < 0.001), and diabetes (p = 0.002). Patients with quite a few CVRFs (body mass index ≥25 kg/m2, smoking, diabetes, arterial hypertension, a positive history of dyslipidaemia) had significantly lower PF-RF score than patients only with one of these risk factors (p < 0.001). CONCLUSIONS: Changes in skin microvascular endothelial function are significantly associated with most CVRFs and depend on the number of CVRFs.

Blood-brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins.

Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood-brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.

Inflammaging and Vascular Function in Metabolic Syndrome: The Role of Hyperuricemia.

Background and Objectives: Early vascular aging determines a more rapid course of age-related arterial changes. It may be induced by a proinflammatory state, caused by hyperuricemia and metabolic syndrome and their interrelationship. However, the impact of serum uric acid (SUA) on early arterial stiffening and vascular function remains uncertain. Materials and Methods: A total of 696 participants (439 women aged 50-65 and 257 men aged 40-55) from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program were enrolled in the study. They underwent anthropometric measurements and laboratory testing along with arterial parameters' evaluation. Quality carotid stiffness (QCS), carotid-radial pulse wave velocity (crPWV), carotid-femoral pulse wave velocity (cfPWV), flow-mediated dilatation (FMD), and carotid intima-media thickness (CIMT) were registered. Results: We found that hyperuricemia was significantly associated with inflammation, registered by high-sensitivity C-reactive protein in both sexes. A very weak but significant association was observed between cfPWV and SUA in men and in women, while, after adjusting for risk factors, it remained significant only in women. A positive, weak, but significant association was also observed for QCS, both right and left in women. No relationship was observed between crPWV, FMD, CIMT, and SUA.

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study.

BACKGROUND: Early life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46-67 years. METHODS: The study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age. RESULTS: In women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]). CONCLUSIONS: Lower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings.

Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality.

BACKGROUND: Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification-features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. METHODS: ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. RESULTS: Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). CONCLUSIONS: In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

Early Post-Transplant Leptin Concentration Changes in Kidney Transplant Recipients.

Background and Objectives: Kidney transplant recipients represent a unique population with metabolic abnormalities, altered nutritional and immune status, as well as an imbalanced regulation of adipocytokine metabolism. Leptin is a hormonally active protein mainly produced by fat tissue that modulates appetite, satiety, and influences growth, energy, and bone metabolism. There has been great interest in the role of this hormone in chronic kidney disease-related protein energy wasting; thus, a positive leptin correlation with body mass index and fat mass was confirmed. This study was designed to determine the association of pre and post-kidney transplant leptin concentration with nutritional status and body composition. Materials and Methods: We studied 65 kidney transplant recipients. Nutritional status was evaluated before kidney transplantation and 6 months later using three different malnutrition screening tools (Subjective Global Assessment Scale (SGA), Malnutrition Inflammation Score (MIS), and Geriatric Nutritional Risk Index (GNRI)), anthropometric measurements, and body composition (bioelectrical impedance analysis (BIA)). Demographic profile, serum leptin levels, and other biochemical nutritional markers were collected. Statistical analysis was performed with R software. Results: Median age of the studied patients was 45 years, 42% were females, and 12% had diabetes. Leptin change was associated with body weight (p < 0.001), waist circumference (p < 0.001), fat mass (p < 0.001) and body fat percentage (p < 0.001), decrease in parathyroid hormone (PTH) (p < 0.001) transferrin (p < 0.001), diabetes mellitus (p = 0.010), and residual renal function (p = 0.039), but not dependent on dialysis vintage, estimated glomerular filtration rate (eGFR), or delayed graft function at any time during the study. After adjustment for age and sex, body mass index (BMI) (p < 0.001), fat mass (p < 0.001), and body fat percentage (p < 0.001) were independent variables significantly associated with post-transplant leptin change. Lower leptin values were found both before and after kidney transplantation in the SGA B group. GNRI as a nutritional status tool was strongly positively related to changes in leptin within the 6-month follow-up period. Conclusions: Kidney transplant recipients experience change in leptin concentration mainly due to an increase in fat mass and loss of muscle mass. GNRI score as compared to SGA or MIS score identifies patients in whom leptin concentration is increasing alongside an accumulation of fat and decreasing muscle mass. Leptin concentration evaluation in combination with BIA, handgrip strength measurement, and GNRI assessment are tools of importance in defining nutrition status in the early post-kidney transplant period.

Arterial stiffness in regards to kidney function in middle-aged subjects with metabolic syndrome: Lithuanian high-risk cohort.

OBJECTIVE: The current study aimed to check whether early vascular aging, measured as carotid-femoral pulse wave velocity (cfPWV), is related to kidney function, measured as creatinine-based estimated glomerular filtration (eGFR) and urinary albumin-to-creatinine ratio (UACR), in middle-aged subjects with metabolic syndrome. METHODS: Participants were recruited from Lithuanian high-risk cohort (LitHiR). The cohort consists of middle-aged individuals with high cardiovascular risk but without overt cardiovascular disease. Participants underwent baseline and second visit hemodynamics measurement, including aortic mean arterial pressure (MAP), cfPWV, crPWV, carotid-intima media thickness measurement (CIMT) and biochemical analysis and all fulfilled NCEP/ATPIII criteria for metabolic syndrome diagnosis. First of all, we had determined correlations among hemodynamic measurement and eGFR together with albuminuria, expressed as UACR. Then we compared subjects who experienced significant eGFR decline with the remaining population and determining factors influencing this. RESULTS: A total of 689 subject data were eligible for analysis. We observed relationship between cfPWV and MAP, crPWV, glucose, BMI, C-reactive protein, waist circumference except kidney function measured as eGFR at the baseline and at the second visit. eGFR was not associated with MAP or albuminuria. Baseline but not second visit UACR significantly positively correlated with cfPWV (r-spearman = 0.146, P = 0.003) and MAP (r-spearman = 0.142, P = 0.005). eGFR decline was mainly observed in subjects with higher baseline eGFR and was independently influenced by increase in cfPWV. CONCLUSION: In middle-aged subjects with prevalent metabolic syndrome eGFR decline is related to aortic and not peripheral arterial stiffening. Better baseline kidney function could be possibly an effect of glomerular hyperfiltration, and it allows us to conclude that this phenomenon indicates early vascular damage and it should be addressed seriously in metabolic syndrome patients with normal kidney function.

Successful laparoscopic living donor nephrectomy: first experience in Lithuania.

BACKGROUND: The aim of this paper is to share the initial results of LLDN in high-volume university centre that is performing laparoscopic nephrectomies for other indications. MATERIALS AND METHODS: During 2017, four LLDNs were performed. The transperitoneal approach was used in all cases and the kidney was removed using a suprapubic incision. All donors and recipients were prospectively analysed within six-month follow-up. The patients' clinical, laboratory, and operation-related data were collected from direct interviews with them and from medical records. All patients signed written informed consent. RESULTS: One male and three females donated their left kidneys by using the  LLDN technique. The mean age was 58 ±  9 years; two of them with a history of previous cholecystectomy. All donated kidneys had a single renal artery and renal vein. Pre-operative average eGFR was 94.2 ±  7.1 ml/min/1.73  m2, immediately after LLDN 57.5 ± 10.3 ml/min/1.73 m2, after one month 56.0 ± 9.1 ml/min/1.73 m2. There were no intraoperative complications; surgery duration was 223.75 ± 21.74 min, the cold ischemia time was 77.5 ± 28.77 min, and the warm ischemia time 6.37 ± 3.14 min. There was one postoperative donor complication, one case of acute kidney injury, and one case of prolonged postoperative abdominal pain. The only recipient complication was one case of acute kidney rejection; there were no cases of delayed graft function. CONCLUSIONS: Our initial experience confirms that LLDN is an approach that is easy to learn, especially in a high-volume university hospital with expertise in performing laparoscopic nephrectomies for other indications.

Should we calculate arterial stiffness gradient in middle-aged women with increased cardiovascular risk?

PURPOSE: The study was designed to evaluate clinical and laboratory determinants pulse wave velocity (PWV) ratio in women at the age of 50-65 years without overt cardiovascular disease but having elevated cardiovascular risk, such as hypertension, obesity, diabetes and hypercholesterolemia. MATERIALS AND METHODS: We analyzed data from 1170 women enrolled in the national-wide primary prevention program. Univariate and multivariate linear regression analysis was used to establish independent risk factors in groups based on clinical data, laboratory values, and comorbidities. Arterial stiffness was evaluated using applanation tonometry technique (SphygmoCor). The PWV ratio was calculated by dividing cfPWV to crPWV. RESULTS: In multivariate logistic regression analysis, age (OR = 1.109, p < .001), waist circumference (OR = 1.021, p = .001) and mean arterial pressure (OR = 1.031, p < .001) were found as independent clinical determinants of PWV ratio, while independent laboratory determinants were urine albumin to creatinine ratio (OR = 1.189, p = .010), triglycerides (OR = 1.161, p = .034), glucose (OR = 1.28, p = .001) and eGFR (OR = 0.998, p = .007). Diabetes (OR = 1.811, p = .029), hypertension (OR = 2.784, p = .042) and menopause (OR = 1.054, p = .018) were established as independent factors in comorbidities group. The analysis confirmed that PWV ratio (R2 = 0.0667, p < .001), as well as carotid radial (R2 = 0.0341, p < .001) and carotid femoral PWV (R2 = 0.1752, p < .001) is affected by mean arterial blood pressure. CONCLUSIONS: Age, abdominal obesity, blood pressure, triglycerides, glucose, kidney function parameters and menopause all are associated with PWV ratio. More importance to women with high cardiovascular risk should be given whilst screening and stratifying further progression of the disease.

Two years of maintenance hemodialysis has a pronounced effect on arterial stiffness progression.

BACKGROUND: The change of aortic stiffness, but not the particular baseline value, plays a crucial role in estimating the patient risk with end-stage renal disease. Therefore, we aimed to analyze the evolution of central and peripheral arterial stiffness in hemodialysis population without previous cardiovascular events during a 2-year follow-up. METHODS: 60 hemodialysis patients (mean age 57.61 ± 13.01 years) were prospectively interviewed, and they underwent blood tests, chest X-ray for aortic calcification evaluation and pulse wave velocity (PWV) measurements at the baseline, after 6 months and after 2 years of observation period. RESULTS: We found significant progression of aortic PWV (12.73 vs. 14.24 m/s, p = 0.032) and regression of brachial PWV (11.53 vs. 8.85 m/s, p < 0.001). CRP increase influenced evolution of aortic PWV (ß = 0.331, p = 0.031, R2 = 0.599). Higher ß2-microglobulin values was related to the progression of aortic PWV (ß = 0.219, p = 0.022, R2 = 0.568). Mean arterial blood pressure had influence only on the short-term arterial stiffness evolution. CONCLUSIONS: Patients on maintenance hemodialysis experience pronounced changes of arterial stiffness during the 2-year follow-up period. The progression of aortic stiffness is related to inflammatory response and particularly is influenced by ß2-microglobulin concentration and aortic calcification.

Histopathological Classification-A Prognostic Tool for Rapidly Progressive Glomerulonephritis.

Background: Recently proposed histopathological classification may predict patient outcome in pauci-immune glomerulonephritis. This study sought to prove that the prognostic effect could be extended to all types of rapidly progressive glomerulonephritis. Methods: Retrospective analysis of patients diagnosed with rapidly progressive glomerulonephritis between April 1999 and August 2015 was performed. Epidemiological and clinical data were collected from medical records. The descriptions of renal biopsies were reviewed and classified into focal, sclerotic, crescentic and mixed class according to classification proposed by Berden et al. The study end points were end stage renal disease (ESRD) or death. Survival analyses were modelled using Cox regression. Results: 73 renal biopsies with diagnosis of rapidly progressive glomerulonephritis were included in the study. 25 (34.2%), 16 (21.9%), 24 (32.9%) and 8 (11%) patients were assigned to focal, crescentic, mixed and sclerotic class, respectively. Thirty-two (42.5%) patients were anti-neutrophil cytoplasmic antibody (ANCA) negative, of which eight (10.9%) were anti⁻glomerular basement membrane antibody (anti⁻GBM) positive and 24 (32.8%) were negative for autoimmune antibodies. Six (8.2%) patients died within one year. Among patients who survived, median change in estimated glomerular filtration rate (eGFR) values were: -10.5 mL/min in focal, 4.2 mL/min in crescentic, -4.3 mL/min in mixed and 4.1 mL/min in sclerotic group, p > 0.05. In the Cox regression model, there was no significant predictor of patient survival whereas the sclerotic group (HR 3.679, 95% CI, 1.164⁻11.628, p < 0.05) and baseline eGFR of <15 mL/min (HR 4.832, 95% CI, 1.55⁻15.08, p < 0.01) had an unfavorable effect for renal survival. Conclusions: Predominant glomerular sclerosis and low eGFR at baseline are associated with higher risk of ESRD in cases with crescentic glomerulonephritis. Therefore, despite the origin of injury, histological classification might aid in prediction of patient outcomes in rapidly progressive glomerulonephritis.