Circulating miRNA 122-5p Expression Predicts Mortality and Cardiovascular Events in Chronic Hemodialysis Patients: A Multicentric, Pilot, Prospective Study.

BACKGROUND: Despite patients undergoing chronic hemodialysis (HD) being notoriously prone to adverse cardiovascular (CV) events, risk prediction in this population remains challenging. miRNA 122-5p, a short, non-coding RNA predominantly involved in lipid and carbohydrate metabolism, has recently been related to the onset and progression of CV disease. METHODS: We run a pilot, multicenter, longitudinal, observational study to evaluate the clinical significance and prognostic usefulness of circulating miRNA 122-5p in a multicentric cohort of 74 individuals on maintenance HD. RESULTS: Patients displayed lower circulating miRNA 122-5p as compared to healthy controls (p = 0.004). At correlation analyses, ALT (ß = 0.333; p = 0.02), E/e' (ß = 0.265; p = 0.02) and CRP (ß = -0.219; p = 0.041) were independent predictors of miRNA 122-5p levels. During a median follow-up of 22 months (range of 1-24), 30 subjects (40.5%) experienced a composite endpoint of all-cause mortality and fatal/non-fatal CV events. Baseline circulating miRNA 122-5p was higher in these subjects (p = 0.01) and it predicted a significantly higher risk of endpoint occurrence (Kaplan-Meier crude HR 3.192; 95% CI 1.529-6.663; p = 0.002; Cox regression adjusted HR 1.115; 95% CI 1.009-1.232; p = 0.03). CONCLUSIONS: Altered miRNA 122-5p levels in HD patients may reflect hepatic and CV damage and may impart important prognostic information for improving CV risk prediction in this particular setting.

A small circulating miRNAs signature predicts mortality and adverse cardiovascular outcomes in chronic hemodialysis patients.

Background: Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting. Methods: We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results: Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (P < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P = .05 to .02] while Kaplan-Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic-derived cut-off value (P ranging from .001 to <.0001; crude HRs 7.95 to 8.61). Conclusions: Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings.

Differences in the Profile of Circulating Immune Cell Subsets in Males with Type 2 Cardiorenal Syndrome versus CKD Patients without Established Cardiovascular Disease.

Maladaptive activation of the immune system plays a key role in the pathogenesis of chronic kidney disease (CKD). Our aim was to investigate differences in circulating immune cells between type 2 cardiorenal syndrome (CRS-2) patients and CKD patients without cardiovascular disease (CVD). CRS-2 patients were prospectively followed up, with the primary endpoint being all-cause and cardiovascular mortality. METHOD: A total of 39 stable males with CRS-2 and 24 male CKD patients matched for eGFR (CKD-EPI) were enrolled. A selected panel of immune cell subsets was measured by flow cytometry. RESULTS: Compared to CKD patients, CRS-2 patients displayed higher levels of proinflammatory CD14++CD16+ monocytes (p = 0.04) and T regulatory cells (Tregs) (p = 0.03), lower lymphocytes (p = 0.04), and lower natural killer cells (p = 0.001). Decreased lymphocytes, T-lymphocytes, CD4+ T-cells, CD8+ T-cells, Tregs, and increased CD14++CD16+ monocytes were associated with mortality at a median follow-up of 30 months (p < 0.05 for all). In a multivariate model including all six immune cell subsets, only CD4+ T-lymphocytes remained independent predictors of mortality (OR 0.66; 95% CI 0.50-0.87; p = 0.004). CONCLUSION: Patients with CRS-2 exhibit alterations in immune cell profile compared to CKD patients of similar kidney function but without CVD. In the CRS-2 cohort, CD4+ T-lymphocytes independently predicted fatal cardiovascular events.

Coronary microcirculation and left ventricular diastolic function but not myocardial deformation indices are impaired early in patients with chronic kidney disease.

AIM: To investigate abnormalities in myocardial strain and classic echocardiographic indices and coronary flow reserve (CFR), in younger versus older CKD patients. METHODS: Sixty consecutive CKD patients (<60 years old n = 30, ≥60 years old n = 30) and 30 healthy controls (age- and gender-matched with younger CKD patients) were recruited. An echocardiographic assessment including myocardial strain indices (i.e. global longitudinal strain -GLS -, TWIST, UNTWIST rate) was performed at baseline and following dipyridamole administration in all participants. RESULTS: Younger CKD patients had higher E/e', left ventricular mass index and relative wall thickness and lower E' (p < .005 for all) compared to healthy controls. Older CKD patients had lower E/A and E' (p < .05 for both) compared to younger CKD patients; these differences did not remain significant after adjustment for age. CFR was higher in healthy controls compared to younger and older CKD patients (p < .05 for both) without a significant difference between CKD groups. There were no significant differences in GLS, TWIST or UNTWIST values among the three groups of patients. Dipyridamole-induced changes did not differ significantly among the three groups. CONCLUSIONS: Compared to healthy controls, impaired coronary microcirculation and left ventricular diastolic function, but not myocardial strain abnormalities, are found in young CKD patients and deteriorate with aging.

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.

Validation of the International IgA Nephropathy Prediction Tool in the Greek Registry of IgA Nephropathy.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology. METHODS: We validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination ( R D 2 ) for model fit, and the regression coefficient of the linear predictor (ßPI), respectively. RESULTS: The study included 264 patients with a median age of 39 (30-51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The R D 2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported R D 2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (<16th, ~16 to <50th, ~50 to <84th, and >84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model. CONCLUSIONS: The two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

Circulating Omentin-1 levels and altered iron balance in chronic haemodialysis patients.

BACKGROUND: Iron deficiency is highly prevalent among patients undergoing chronic haemodialysis (HD) but its correct identification is often problematic as common biomarkers of iron status, such as transferrin saturation (TSAT) and ferritin, can be altered by inflammation or malnutrition. METHODS: In this pilot multicentre study, we aimed at evaluating circulating levels of Omentin-1, a novel fat depot-specific adipokine that is also involved in iron regulation, in a cohort of 85 chronic HD patients with relation to their iron status. RESULTS: Omentin-1 levels in HD were statistically higher than in healthy controls (P = 0.03) and there was a significant, growing trend in all iron parameters across Omentin-1 tertiles (P < 0.001). Compared with patients with optimal iron status, Omentin-1 levels were lower in subjects categorized according to TSAT ≤20% or serum ferritin ≤200 µg/L (both P < 0.001) and even more reduced in 19 patients (22%) simultaneously displaying low levels of both markers (P < 0.001). In this latter group, Omentin-1 levels increased in parallel to all other iron markers after iron correction by i.v. supplementation. At multivariate regression analyses, ferritin (ß = 0.71; P < 0.001) and TSAT (ß = 0.32; P = 0.03) remained the sole independent predictors of Omentin-1 levels. This biomarker also showed a remarkable diagnostic capacity at receiver operating characteristic analyses in identifying iron-depleted HD patients according to a criterion of TSAT ≤20% [area under the curve (AUC) 0.827], ferritin ≤200 µg/L (AUC 0.863) or low levels of both parameters (AUC 0.907). CONCLUSIONS: Findings obtained indicate that Omentin-1 is somewhat involved in iron balance regulation and might be a candidate biomarker for diagnosing and managing altered iron conditions in HD patients.

The Humoral Immune Response to BNT162b2 Vaccine Is Associated With Circulating CD19+ B Lymphocytes and the Naïve CD45RA to Memory CD45RO CD4+ T Helper Cells Ratio in Hemodialysis Patients and Kidney Transplant Recipients.

Background: The humoral and cellular immune responses to SARS-COV-2 vaccination remain to be elucidated in hemodialysis (HD) patients and kidney transplant recipients (KTRs), considering their baseline immunosuppressed status. The aim of our study was to assess the associations of vaccine-induced antibody responses with circulating lymphocytes sub-populations and their respective patterns of alterations in maintenance HD patients and KTRs. Materials and Methods: We included 34 HD patients and 54 KTRs who received two doses of the mRNA-vaccine BNT162b2. Lymphocyte subpopulations were analyzed by flow cytometry before vaccination (T0), before the second vaccine dose (T1) and 2 weeks after the second dose (T2). The anti-SARS-CoV2 antibody response was assessed at T1 and at T2. Results: 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. HD patients who became seropositive following the first dose displayed higher CD19+ B lymphocytes compared to their seronegative HD counterparts. A positive correlation was established between CD19+ B cells counts and antibody titers at all time-points in both groups (p < 0.001). KTRs showed higher naïve CD4+CD45RA+ T helper cells compared to HD patients at baseline and T2 whereas HD patients displayed higher memory CD45RO+ T cells compared to KTRs at T2. The naïve CD4+CD45RA to memory CD4+CD45RO+ T helper cells fraction was negatively associated with antibody production in both groups. Conclusions: Our study provides a potential conceptual framework for monitoring vaccination efficacy in HD patients and KTRs considering the correlation established between CD19+ B cells, generation of memory CD4+ T helper cells and anti SARS-CoV2 antibody response to vaccination.

The Association of Circulating CD14++CD16+ Monocytes, Natural Killer Cells and Regulatory T Cells Subpopulations With Phenotypes of Cardiovascular Disease in a Cohort of Peritoneal Dialysis Patients.

The altered expression of immune cells including monocyte subsets, natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in end-stage kidney disease, affect the modulation of inflammation and immunity with significant clinical implications. The aim of this study was to investigate the profile of specific immune cells subpopulations and their correlations with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in peritoneal dialysis (PD) patients. Materials and Methods: 29 stable PD patients and 13 healthy volunteers were enrolled. Demographic, laboratory, bioimpedance measurements, lung ultrasound and echocardiography data were collected. The peripheral blood immune cell subsets analysis was performed using flow cytometry. Results: PD patients compared to normal controls had lower total lymphocytes (22.3 ± 6.28 vs. 31.3 ± 5.54%, p = <0.001) and B-lymphocytes (6.39 ± 3.75 vs. 9.72 ± 3.63%, p = 0.01) as well as higher CD14++CD16+ monocytes numbers (9.28 ± 6.36 vs. 4.75 ± 2.75%, p = 0.0002). PD patients with prevalent CAD had NK cells levels elevated above median values (85.7 vs. 40.9%, p = 0.04) and lower B cells counts (3.85 ± 2.46 vs. 7.2 ± 3.77%, p = 0.03). Patients with increased NK cells (>15.4%) had 3.8 times higher risk of CAD comparing with patients with lower NK cell levels (95% CI, 1.86 - 77.87; p = 0.034). B cells were inversely associated with the presence of CAD (increase of B-lymphocyte by 1% was associated with 30% less risk for presence of CAD (95% CI, -0.71 - 0.01; p = 0.05). Overhydrated patients had lower lymphocytes counts (18.3 ± 4.29% vs. 24.7 ± 6.18%, p = 0.006) and increased NK cells [20.5% (14.3, 23.6) vs. 13.21% (6.23, 19.2), p = 0.04)]. In multiple logistic regression analysis the CRP (OR 1.43; 95% CI, 1.00 - 2.05; p = 0.04)] and lymphocytes counts (OR 0.79; 95% CI, 0.63-0.99; p = 0.04)] were associated with the presence of lung comets. Patients with higher NK cells (>15.4%, n = 15) were more likely to be rapid transporters (D/P creatinine 0.76 ± 0.1 vs. 0.69 ± 0.08, p = 0.04). Patients displaying higher Tregs (>1.79%) were older (70.8 ± 10.7 years vs. 57.7 ± 14.7years, p = 0.011) and had higher nPCR (0.83 ± 0.14 vs. 0.91 ± 0.17, p = 0.09). Conclusion: Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients at the highest risk for complications and guide interventions.

Longitudinal Assessment of Electrolyte Disorders in a Cohort of Chronic Stable Kidney Transplant Recipients.

BACKGROUND: Kidney transplantation is complicated by various electrolyte disturbances with variable reported prevalence and incidence and of multifactorial pathogenesis. The aim of our study was the retrospective longitudinal assessment of the serum electrolytes in a cohort of stable kidney transplant recipients (KTRs) and the possible associated parameters, including graft function and medications. METHODS: We included 93 stable KTRs under follow-up in our hospital's kidney transplant unit. Serum magnesium, calcium, phosphorus, potassium, sodium, and urine sodium levels were recorded retrospectively during 3 consecutive years. In addition, comorbidities, biochemical parameters, medications, and graft function (estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation and 24-hour urinary protein [uTpr]) were recorded. RESULTS: Mean age at baseline was 51 ± 11 years; 64 KTRs were men (68.8%), 17 (18.3%) had diabetes, 79 (85%) had hypertension, and 11 (11.8%) had cardiovascular disease. Mean eGFR and uTpr (mg/24 h) at study initiation were 47.1 ± 13.5 mL/min/1.73 m2 and 369.4 ± 404.2 mg/24 h, respectively. Hypomagnesemia was the most common disturbance observed in 21.7% of KTRs. Patients with hypomagnesemia displayed higher parathyroid hormone levels and more frequently had diabetes. Hypophosphatemia was recorded in 9.7% of KTRs during the first year. Hyperkalemia, hypokalemia, and hypercalcemia were rare (<5%). Mean serum and urine sodium concentration remained stable during the study, whereas urinary sodium levels showed a positive correlation with uTpr (P < .05). CONCLUSIONS: In our cohort of KTRs, there were no significant electrolyte disorders, either in terms of frequency or severity, with hypomagnesemia being the most prevalent disturbance. The identification of potential associated risk factors and clinical data correlations are pivotal for the development of individualized and evidence-based therapeutic approach and decisions.

Association between PCSK9 Levels and Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction in a Population of Nondialysis Chronic Kidney Disease Patients.

Proprotein convertase subtilisin/kexin 9 (PCSK9) plays an important role in lipid metabolism while available literature regarding its involvement in the pathogenesis of atherosclerosis and in the expression of genes associated with apoptosis and inflammation is constantly increasing. Patients with chronic kidney disease (CKD) experience disproportionately increased cardiovascular morbidity and mortality due to dyslipidemia, accelerated atherosclerosis, inflammation, oxidative stress, and other risk factors. In the present cross-sectional study, we investigated the possible association of serum PCSK9 levels with markers of inflammation, oxidative stress, and endothelial damage in patients with CKD. Patients and Methods. Ninety-two patients with CKD stages II-ΙV (eGFR CKD-EPI 47.3 ± 25.7 ml/min/1.73 m2, mean age 66 years, 51 men) were included in the study. Plasma PCSK9 levels were correlated with comorbidities (arterial hypertension, diabetes mellitus, and history of cardiovascular disease), renal function indices (eGFR, proteinuria-UPR/24 h), lipid parameters (LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), APO-A1, and APO-B), and soluble biomarkers of inflammation, oxidative stress, and endothelial damage (hs-CRP, fibrinogen, 8-epiPGF2a, ox-LDL, IL-6, TNF-α, sICAM-1, and sVCAM-1). Results. The mean plasma value of PCSK9 was 278.1 ng/ml. PCSK9 levels showed direct correlation with serum triglycerides (p = 0.03), Lp(a) (p = 0.01), and sICAM-1 levels (p = 0.03). There was no significant correlation between PCSK9 levels and indices of the renal function, other lipid profile parameters, inflammatory markers, or comorbidities. Multiple regression analysis showed a significant effect of Lp(a) on PCSK9 levels, and for each unit of higher Lp(a), an increase by 3.082 is expected (95% CI: 0.935-5.228, p = 0.006). At the same time, patients receiving statins are expected to have on average 63.8 ng/ml higher PCSK9 values compared to patients not receiving statins (95% CI: 14.6-113.5, p = 0.012). Conclusion. Plasma levels of PCSK9 in nondialysis CKD patients are correlated with endothelial dysfunction and lipid metabolism parameters. Statin intake increases PCSK9 levels significantly in this patient population. PCSK9 levels are not correlated with the severity of kidney disease. Major prospective studies are necessary to investigate the role of PCSK9 in the atherosclerotic cardiovascular outcome in CKD.

Survival of Peritoneal Membrane Function on Biocompatible Dialysis Solutions in a Peritoneal Dialysis Cohort Assessed by a Novel Test.

BACKGROUND: Longitudinal surveillance of peritoneal membrane function is crucial in defining patients with a risk of ultrafiltration failure. Long PD is associated with increased low molecular weight solute transport and decreased ultrafiltration and free water transport. Classic PET test only provides information about low molecular solute transport, and the vast majority of longitudinal studies are based on this test and include patients using conventional dialysates. Our aim was to prospectively analyze longitudinal data on peritoneal function in patients on biocompatible solutions using a novel test. METHODS: Membrane function data were collected based on uni-PET (a combination of modified and mini PET). A total of 85 patients (age 61.1 ± 15.1 years) with at least one test/year were included. RESULTS: The median follow up was 36 months (21.3, 67.2). A total of 219 PETs were performed. One-way repeated measures ANOVA showed that there were no statistically significant differences over time in ultrafiltration, free water transport, ultrafiltration through small pores, sodium removal, D/D0 and D/PCre in repeated PET-tests. Twenty-three tests revealed ultrafiltration failure in 16 (18.8%) patients. Those patients were longer on PD, had higher D/P creatinine ratios, lower ultrafiltration at one hour with lower free water transport and higher urine volume at baseline. Multivariate analysis revealed that the variation of ultrafiltration over repeated PET-tests independently correlated only with D/Pcreatinine, free water transport and ultrafiltration through small pores. CONCLUSIONS: Uni-PET is a combination of two tests that provides more information on the function of the membrane compared with PET. Our study on a PD cohort using only biocompatible solutions revealed that function membrane parameters remained stable over a long time. Ultrafiltration failure was correlated with increased D/P creatinine and decreased free water transport and ultrafiltration through small pores.

The Endothelial Glycocalyx as a Target of Ischemia and Reperfusion Injury in Kidney Transplantation-Where Have We Gone So Far?

The damage of the endothelial glycocalyx as a consequence of ischemia and/or reperfusion injury (IRI) following kidney transplantation has come at the spotlight of research due to potential associations with delayed graft function, acute rejection as well as long-term allograft dysfunction. The disintegration of the endothelial glycocalyx induced by IRI is the crucial event which exposes the denuded endothelial cells to further inflammatory and oxidative damage. The aim of our review is to present the currently available data regarding complex links between shedding of the glycocalyx components, like syndecan-1, hyaluronan, heparan sulphate, and CD44 with the activation of intricate immune system responses, including toll-like receptors, cytokines and pro-inflammatory transcription factors. Evidence on modes of protection of the endothelial glycocalyx and subsequently maintenance of endothelial permeability as well as novel nephroprotective molecules such as sphingosine-1 phosphate (S1P), are also depicted. Although advances in technology are making the visualization and the analysis of the endothelial glycocalyx possible, currently available evidence is mostly experimental. Ongoing progress in understanding the complex impact of IRI on the endothelial glycocalyx, opens up a new era of research in the field of organ transplantation and clinical studies are of utmost importance for the future.

The Innate Immune System and Cardiovascular Disease in ESKD: Monocytes and Natural Killer Cells.

Adverse innate immune responses have been implicated in several disease processes, including cardiovascular disease (CVD) and chronic kidney disease (CKD). The monocyte subsets natural killer (NK) cells and natural killer T (NKT) cells are involved in innate immunity. Monocytes subsets are key in atherogenesis and the inflammatory cascade occurring in heart failure. Upregulated activity and counts of proinflammatory CD16+ monocyte subsets are associated with clinical indices of atherosclerosis, heart failure syndromes and CKD. Advanced CKD is a complex state of persistent systemic inflammation characterized by elevated expression of proinflammatory and pro-atherogenic CD14++CD16+ monocytes, which are associated with cardiovascular events and death both in the general population and among patients with CKD. Diminished NK cells and NKT cells counts and aberrant activity are observed in both coronary artery disease and end-stage kidney disease. However, evidence of the roles of NK cells and NKT cells in atherogenesis in advanced CKD is circumstantial and remains to be clarified. This review describes the available evidence regarding the roles of specific immune cell subsets in the pathogenesis of CVD in patients with CKD. Future research is expected to further uncover the links between CKD associated innate immune system dysregulation and accelerated CVD and will ideally be translated into therapeutic targets.

Incretin based therapies and SGLT-2 inhibitors in kidney transplant recipients with diabetes: A systematic review and meta-analysis.

AIMS: We aimed to conduct a systematic review and meta-analysis regarding the use of incretin-based therapies including dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists as well as sodium-glucose co-transporter-2 (SGLT2) inhibitorsin persons with posttransplantation diabetes mellitus (PTDM) so as to assess both their efficacy and safety. METHODS: We searched for publications on Kidney/Renal Transplantation and DPP-4 inhibitors, GLP-1-receptor agonists and SGLT-2 inhibitors and included every study using these antidiabetics. A p-value < 0.05 was considered statistical significant. RESULTS: Sixteen studies and 310 individuals with a mean age of 55.98 ± 8.81 years were included in the analysis. Participants received DPP-4 inhibitors in 8 studies, SGLT-2 inhibitors in 6 studies and GLP-1 receptor agonists in 2 studies, with a mean follow-up of 22.03 ± 14.95 weeks. Hemoglobin A1c (HbA1c) reduction was demonstrated in 10 studies (mean +/- standard deviation (MD) = - 0.38%, I2 = 45%). MD of HbA1c was -0.3741 and -0.4596 mg/dl for DPP-4 inhibitors and SGLT-2 inhibitors respectively. Nine studies demonstrated differences in fasting plasma glucose (FPG) (MD = - 25,76) and 5 studies in post-prandial glucose (PPG) (MD = - 6.61) before and following treatment. Most studies did not show adverse effects on the glomerular filtration rate (GFR) and hepatic function. CONCLUSIONS: DPP-4 inhibitors and SGLT2 inhibitors appear both efficacious and safe in renal transplant recipients. More high-quality studies are required to guide therapeutic choices for PTDM.

Coronary microcirculation and left ventricular diastolic function: comparison between patients on hemodialysis and peritoneal dialysis.

BACKGROUND: End-stage renal disease is considered to influence coronary microcirculation and left ventricular (LV) diastolic function. We investigated whether differences exist in LV diastolic function indices and coronary flow reserve (CFR) between patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: A complete transthoracic echocardiographic study was performed on 21 HD and 22 PD patients and LV diastolic function was evaluated. CFR was estimated using transthoracic Doppler echocardiography on the left anterior descending artery, during high-dose dypiridamole infusion. RESULTS: HD and PD groups did not differ regarding Doppler-derived diastolic indices, but they significantly differed in the frequency of severe LV hypertrophy (38.1% in HD vs 4.5% in PD group, p = 0.009) and grade II diastolic dysfunction (42.9% in HD vs 4.5% in PD group, p = 0.004). No patient had restrictive filling pattern. There was no difference in the prevalence of arterial hypertension and diabetes mellitus in patients with grade II vs less than grade II dysfunction. Mean CFR was similar in the HD and PD groups (2.25 ± 0.65 vs 2.36 ± 0.76, p = 0.635) and lower in patients with grade II diastolic dysfunction (1.87 ± 0.43 vs 2.44 ± 0.72, p = 0.023) and diabetes (1.70 ± 0.59 vs 2.39 ± 0.68, p = 0.04). LV mass index was negatively associated with CFR (r = - 0.308, p = 0.045). CONCLUSION: Patients on HD had more advanced diastolic dysfunction compared to PD, independently of the presence of hypertension and diabetes. CFR did not differ between HD and PD patients, but it was significantly lower in diabetics and in patients with more advanced diastolic dysfunction.

Hypertension in Chronic Kidney Disease: Novel Insights.

Management of arterial hypertension in patients with chronic kidney disease (CKD) remains a major challenge due to its high prevalence and associations with cardiovascular disease (CVD) and CKD progression. Several clinical trials and meta-analyses have demonstrated that aggressive treatment of hypertension in patients with and without CKD lowers the risk of CVD and all-cause mortality, nevertheless the effects of blood pressure (BP) lowering in terms of renal protection or harm remain controversial. Both home and ambulatory BP estimation have shown that patients with CKD display abnormal BP patterns outside of the office and further investigation is required, so as to compare the association of ambulatory versus office BP measurements with hard outcomes and adjust treatment strategies accordingly. Although renin-angiotensin system blockade appears to be beneficial in patients with advanced CKD, especially in the setting of proteinuria, discontinuation of renin-angiotensin system inhibition should be considered in the setting of frequent episodes of acute kidney injury or hypotension while awaiting the results of ongoing trials. In light of the new evidence in favor of renal denervation in arterial hypertension, the indications and benefits of its application in individuals with CKD need to be clarified by future studies. Moreover, the clinical utility of the novel players in the pathophysiology of arterial hypertension and CKD, such as microRNAs and the gut microbiota, either as markers of disease or as therapeutic targets, remains a subject of intensive research.

The prognostic role of myocardial strain indices and dipyridamole stress test in renal transplantation patients.

INTRODUCTION: Renal transplantation (RT) increases survival in end-stage kidney disease patients but cardiovascular diseases remain the leading cause of morbidity and mortality. We evaluated the role of myocardial strain (2DSTE) indices and dipyridamole-induced (DIPSE) changes in echocardiographic parameters at baseline for the prediction of clinical events and echocardiographically assessed deterioration of cardiac function in a RT population. METHODS: Forty-five RT patients underwent an echocardiographic study at baseline including 2DSTE and DIPSE. If no cardiovascular/renal event occurred, patients were investigated at 3-year follow-up; eight patients presented a clinical event while 37 patients were re-evaluated. RESULTS: Coronary flow reserve (CFR) was abnormal in 24% of the population. DIPSE induced improvements in classic and 2DSTE systolic and diastolic echocardiographic indices including TWIST, UNTWIST, global longitudinal strain (GLS), and circumferential strain (P < .05 for all). Compared to baseline, deteriorations in E/E', LVEF, E', and TWIST were observed at follow-up (P < .05 for all). DIPSE-induced changes in GLS, global radial strain, and LVEF were associated with changes in these indices at follow-up (P < .05 for all). Higher LV mass index, E/E', and lower MAPSE, E', and CFR at baseline were associated with the occurrence of clinical events at follow-up (P < .05 for all). CONCLUSIONS: In RT patients, coronary vascular dysfunction (ie, low CFR) was associated with the occurrence of adverse events. DIPSE-induced changes in myocardial strain and classic echocardiographic indices could identify individuals with a subclinical deterioration in cardiac function at follow-up. This may indicate that DIPSE could serve as a means to assess myocardial reserve in this population.