The association between klotho and kidney and cardiovascular outcomes: a comprehensive systematic review and meta-analysis.

Background: Chronic kidney disease (CKD) and end-stage renal disease (ESKD) are significant global health challenges associated with progressive kidney dysfunction and numerous complications, including cardiovascular disease and mortality. This study aims to explore the potential association between plasma klotho levels and various prognostic outcomes in CKD and ESKD, including all-cause mortality, cardiovascular events, metabolic syndrome development and adverse renal events necessitating renal replacement therapies. Methods: A literature search was conducted through 3 June 2024 using the electronic databases Cochrane Library, Ovid MEDLINE, CINAHL, Web of Science, SCOPUS and PubMed. This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Fourteen studies were included. For all-cause mortality, comparing CKD patients with low versus high klotho levels showed a significant association {odds ratio [OR] 1.81 [95% confidence interval (CI) 1.34-2.44], P = .0001}, with substantial heterogeneity (I 2 = 69%). Excluding one study reduced heterogeneity (I 2 = 43%) while maintaining significance [OR 1.97 (95% CI 1.45-2.66), P < .0001]. Cardiovascular mortality was higher in patients with low klotho levels [OR 2.11 (95% CI 1.61-2.76), P < .00001], with low heterogeneity (I 2 = 25%). Excluding one study eliminated heterogeneity (I 2 = 0%) while maintaining significance [OR 2.39 (95% CI 1.83-3.12), P < .00001]. Composite cardiovascular events did not differ significantly between low and high klotho groups [OR 1.51 (95% CI 0.82-2.77), P = .18], but with high heterogeneity (I 2 = 72%). Patients with low klotho levels had a higher risk of adverse renal events [OR 2.36 (95% CI 1.37-4.08), P = .002], with moderate heterogeneity (I 2 = 61%). Sensitivity analysis reduced heterogeneity (I 2 = 0%) while maintaining significance [OR 3.08 (95% CI 1.96-4.85), P < .00001]. Specifically, for ESKD or kidney replacement therapy risk, low klotho levels were associated with an increased risk [OR 2.30 (95% CI 1.26-4.21), P = .007]. Similarly, CKD progression risk was higher in patients with lower klotho levels [OR 2.48 (95% CI 1.45-4.23), P = .0009]. Conclusion: Lower serum klotho levels serve as a significant predictor of adverse outcomes, including increased risks of all-cause mortality, cardiovascular mortality and progression to end-stage kidney disease among CKD patients.

Understanding the Role of Sex Hormones in Cardiovascular Kidney Metabolic Syndrome: Toward Personalized Therapeutic Approaches.

Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin-angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.

The Impact of Frailty and Severe Cognitive Impairment on Survival Time and Time to Initiate Dialysis in Older Adults With Advanced Chronic Kidney Disease: A Prospective Observational Cohort Study.

Background and objectives Frailty and cognitive impairment significantly impact survival time and time to initiate dialysis in older adults with advanced chronic kidney disease (CKD). This study aims to evaluate the effects of frailty and cognitive impairment on these outcomes and determine the most effective assessment tool for predicting early dialysis initiation and short survival time. Materials and methods This prospective observational cohort study involved 240 patients aged ≥65 years with stage 4 or 5 CKD, recruited from a nephrology outpatient department (ambulatory care) between March 2020 and March 2021. Frailty was assessed using the Physical Frailty Phenotype (PFP), PRISMA-7, Clinical Frailty Scale (CFS), and FRAIL scale. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). The primary outcomes were time to initiate dialysis and survival time, with secondary outcomes including hospitalization rates, length of stay, and mortality after dialysis initiation. Results Frail patients only showed significantly shorter time to dialysis initiation when identified by the PFP and FRAIL scale (28.3 months for frail vs. 31.2 months for non-frail, p = 0.028; 26.9 months for frail vs. 30.9 months for non-frail, p = 0.038). The PFP, FRAIL, and CFS tools indicated significantly shorter survival times for frail patients compared to non-frail patients (26.8 months for frail vs. 30.6 months for non-frail, p = 0.003). Frailty is strongly correlated with severe cognitive impairment, as 45.5% of frail patients (according to the FRAIL scale) have dementia compared to 15.1% of non-frail patients (p<0.001). However, cognitive impairment did not significantly affect the time to dialysis initiation or survival time. Hospitalization rates and length of stay in the hospital were significantly higher only for frail patients identified by PRISMA-7, with a median hospital length of stay of 9.15 days for frail patients vs 6.37 days for non-frail patients (p = 0.044). Overall, 37.5% of the patients did not survive during the study follow-up, with frail patients having a higher mortality rate. Conclusion Frailty, mainly when assessed by PFP and FRAIL, is a significant predictor of early dialysis initiation and reduced survival time in older adults with advanced CKD. Cognitive impairment, while prevalent, did not independently predict these outcomes. Regular frailty screening should be incorporated into CKD management to tailor interventions and improve patient outcomes.

Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum.

Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives.

Genotype-Phenotype Correlations in Alport Syndrome-A Single-Center Experience.

BACKGROUND: Alport syndrome (AS) is a common and heterogeneous genetic kidney disease, that often leads to end-stage kidney disease (ESKD). METHODS: This is a single-center, retrospective study that included 36 adults with type IV collagen (COL4) mutations. Our main scope was to describe how genetic features influence renal survival. RESULTS: A total of 24 different mutations were identified, of which eight had not been previously described. Mutations affecting each of the type IV collagen α chains were equally prevalent (33.3%). Most of the patients had pathogenic variants (61.1%). Most patients had a family history of kidney disease (71%). The most prevalent clinical picture was nephritic syndrome (64%). One-third of the subjects had extrarenal manifestations, 41.6% of patients had ESKD at referral, and another 8.3% developed ESKD during follow-up. The median renal survival was 42 years (95% CI, 29.98-54.01). The COL4A4 group displayed better renal survival than the COL4A3 group (p = 0.027). Patients with missense variants had higher renal survival (p = 0.023). Hearing loss was associated with lower renal survival (p < 0.001). CONCLUSIONS: Patients with COL4A4 variants and those with missense mutations had significantly better renal survival, whereas those with COL4A3 variants and those with hearing loss had worse prognoses.

Therapeutic Potential of Rituximab in Managing Hepatitis C-Associated Cryoglobulinemic Vasculitis: A Systematic Review.

(1) Background. Hepatitis C infection often leads to extrahepatic manifestations, including cryoglobulinemic vasculitis. This systematic review aimed to assess the efficacy and safety of rituximab in treating hepatitis C-associated cryoglobulinemic vasculitis. (2) Methods. Following PRISMA guidelines, databases were searched for relevant studies. Eligibility criteria included studies on hepatitis C-associated cryoglobulinemic vasculitis treated with rituximab. (3) Results. Nine studies met the eligibility criteria and were included in this analysis. Rituximab was commonly administered at 375 mg/m2 weekly for one month. The results consistently demonstrated the efficacy of rituximab, whether as a standalone treatment or as part of a therapeutic regimen. The combination of rituximab with Peg-IFN-α and ribavirin significantly increased the complete response rate compared to Peg-IFN-α and ribavirin alone (54.5% vs. 33.3%, p < 0.05). The 3-year sustained response rate was notably higher in the rituximab combination group (83.3% vs. 40%). In another trial, rituximab achieved remission in 83.3% of patients at 6 months, compared to only 8.3% in the control group. The efficacy of rituximab was supported by long-term experience, with clinical benefits in patients with severe cryoglobulinemic vasculitis, including those resistant to standard therapies. Mild adverse events were generally reported, with rare severe reactions in some studies. (4) Conclusions: In conclusion, rituximab appeared to be effective and safe in managing hepatitis C-associated cryoglobulinemic vasculitis, either alone or with antiviral therapy.

Intrauterine life to adulthood: a potential risk factor for chronic kidney disease.

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.

Non-Traditional Non-Immunological Risk Factors for Kidney Allograft Loss-Opinion.

Rates of late allograft loss have improved slowly in the last decades. Well described traditional risk factors that influence allograft survival include cardiovascular events, rejection, infections and post-transplant neoplasia. Here, we critically evaluate the influence of several non-immunological, non-traditional risk factors and describe their impact on allograft survival and cardiovascular health of kidney transplant recipients. We assessed the following risk factors: arterial stiffness, persistent arteriovenous access, mineral bone disease, immunosuppressive drugs residual levels variability, hypomagnesemia, glomerular pathological alterations not included in Banff criteria, persistent inflammation and metabolic acidosis.

Gut Microbiota in Chronic Kidney Disease: From Composition to Modulation towards Better Outcomes-A Systematic Review.

BACKGROUND: A bidirectional kidney-gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. MATERIALS AND METHODS: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. RESULTS: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. CONCLUSIONS: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Predictive Value of Collagen Biomarkers in Advanced Chronic Kidney Disease Patients.

Patients with chronic kidney disease have an increased risk of all-cause death. The value of collagen biomarkers such as procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III N-terminal peptide (P3NP), in end-stage renal disease (ESRD), has not yet been defined (in the literature and in clinics). The purpose of this study was to determine the potential value of these new biomarkers in the prediction of mortality in this population. Plasma PICP and P3NP levels were determined in 140 patients with ESRD, not yet on dialysis, who were followed up for 36 ± 5.3 months. During follow-up, 58 deaths were recorded (41.4%), with the majority of them being cardiovascular deaths (43, 74.13%). Using the ROC curve, the cut-off value for the prediction of mortality for PICP was 297.31 µg/L, while for P3NP, the cut-off value was 126.67 µg/L. In univariate analysis, a value of PICP above the cut-off point was associated with a fivefold increased risk of mortality (hazard ratio (HR) 5.071, 95% confidence interval 1.935-13.29, p = 0.001) and a value of P3NP above the cut-off point was associated with a twofold increased risk of mortality (HR 2.089, 95% CI 1.044-4.178, p = 0.002). In a multivariable Cox proportional hazards model, PICP values remained independent predictors of mortality (HR 1.22, 95% CI 1.1-1.31, p < 0.0001). Our data suggest that the collagen biomarker PICP is an independent predictor of mortality in ESRD patients who are not yet on dialysis.

An update review on hemodynamic instability in renal replacement therapy patients.

BACKGROUND: Hemodynamic instability in patients undergoing kidney replacement therapy (KRT) is one of the most common and essential factors influencing mortality, morbidity, and the quality of life in this patient population. METHOD: Decreased cardiac preload, reduced systemic vascular resistance, redistribution of fluids, fluid overload, inflammatory factors, and changes in plasma osmolality have all been implicated in the pathophysiology of hemodynamic instability associated with KRT. RESULT: A cascade of these detrimental mechanisms may ultimately cause intra-dialytic hypotension, reduced tissue perfusion, and impaired kidney rehabilitation. Multiple parameters, including dialysate composition, temperature, posture during dialysis sessions, physical activity, fluid administrations, dialysis timing, and specific pharmacologic agents, have been studied as possible management modalities. Nevertheless, a clear consensus is not reached. CONCLUSION: This review includes a thorough investigation of the literature on hemodynamic instability in KRT patients, providing insight on interventions that may potentially minimize factors leading to hemodynamic instability.

The impact of renal transplantation on sexual function in males with end-stage kidney disease: a systematic review and meta-analysis.

INTRODUCTION: Patients with end-stage kidney disease (ESKD) on dialysis have a special profile, including constant uremic status and frequent comorbidities, such as diabetes mellitus, arterial hypertension and coronary artery disease, as well as complications related to dialysis. All listed factors can influence or be the cause of sexual dysfunction in both men and women. There is a high incidence (70%) and prevalence (82%) of erectile dysfunction in men with CKD. PURPOSE: In this meta-analysis, we aimed to evaluate the impact of renal transplantation in patients with end-stage chronic kidney disease and erectile dysfunction, using the same study population before and after transplantation. DATA SOURCES: we searched MEDLINE (PubMed), Embase, Scopus and Cochrane Library (Inception to August 2022) and clinicaltrials.gov (Inception to August 2022) without language restrictions. STUDY SELECTION: eligible studies evaluated the same patients with end-stage kidney disease before and after renal transplantation using IEEF questionnaire. DATA EXTRACTION: reviewers working independently and in duplicate extracted data and assessed the risk of bias. DATA SYNTHESIS: the final analysis included 28 cohort studies, comprising 2252 participants. RESULTS: Our results showed improvement in erectile function after renal transplantation. Our study shows a 13% improvement in erectile dysfunction after renal transplantation. CONCLUSIONS: The results of this meta-analysis would suggest improvement in erectile dysfunction after renal transplantation.

Predicting Renal Denervation Response in Resistant High Blood Pressure by Arterial Stiffness Assessment: A Systematic Review.

Background: Accurately selecting hypertensive candidates for renal denervation (RDN) therapy is required, as one-third of patients who undergo RDN are non-responders. We aimed to systematically review the literature on RDN response prediction using arterial stiffness assessment, optimizing the selection of patients referred for interventional blood pressure lowering procedures. Methods: A literature search was performed in MEDLINE, Embase, Scopus, and Cochrane databases to retrieve potential eligible studies from the inception to 30 June 2022. Results: Ten studies were finally included in this systematic review. Studies consistently documented that invasive pulse wave velocity (PWV) was correlated with RDN's significant success. Nevertheless, non-invasive ambulatory arterial stiffness index and PWV derived from ambulatory blood pressure monitoring were independent predictors of blood pressure response (p = 0.04 and p < 0.0001). In some studies, magnetic resonance imaging parameters of arterial stiffness (ascending aortic distensibility, total arterial compliance) were correlated with blood pressure reduction (AUC = 0.828, p = 0.006). Conclusions: Assessing arterial stiffness prior to RDN predicted procedural success, since stiffness parameters were strongly correlated with a significant blood pressure response. Our endeavor should be tackled as a step forward in selecting appropriate hypertensive patients scheduled for RDN therapy. Non-invasive measurements could be an alternative to invasive parameters for response prediction.

The Usefulness of Assessing Heart Rate Variability in Patients with Acute Myocardial Infarction (HeaRt-V-AMI).

BACKGROUND: Heart rate variability (HRV) could have independent and critical prognostic values in patients admitted for ST segment elevation myocardial infarction (STEMI). There are limited data in the literature regarding HRV assessment in STEMI setting. Thus, we aim to investigate the potential correlations between HRV and adverse outcomes in a contemporary cohort of patients presenting with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: We will perform a prospective, observational cohort study in a single healthcare center. Adult patients aged ≥18 years presenting with STEMI in sinus rhythm will be enrolled for primary PCI within 12 h from symptoms onset. Time domain, frequency domain, and nonlinear HRV parameters will be measured using a medically approved wrist-wearable device for 5 min segments during myocardial revascularization by primary PCI. Additional HRV measurements will be performed one and six months from the index event. The primary composite outcome will include all-cause mortality and major adverse cardiovascular events (during the hospital stay, one month, and one year following admission). Several secondary outcomes will be analyzed: individual components of the primary composite outcome, target lesion revascularization, hospitalizations for heart failure, ventricular arrhythmias, left ventricular ejection fraction, and left ventricular diastolic function. CONCLUSIONS: Our study will enlighten the reliability and usefulness of HRV evaluation as a prognostic marker in contemporary patients with STEMI. The potential validation of HRV as a risk marker for adverse outcomes following STEMI will ensure a background for including HRV parameters in future risk scores and guidelines.

Epidemiology of biopsy-proven glomerulonephritis in the past 25 years in the North-Eastern area of Romania.

PURPOSE: The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. METHODS: We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. RESULTS: During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994-2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. CONCLUSION: The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.

Evaluation of cardiovascular risk factors in patients with familial hypercholesterolemia from the North-Eastern area of Romania.

BACKGROUND: Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. METHODS: This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. RESULTS: Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: "possible" FH identified in 39.4%, "probable" FH in 45.9% and "definite" FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. CONCLUSIONS: In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

Multi-modality cardiac imaging in advanced chronic kidney disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is particularly frequent among those with severe renal impairment. Early diagnosis and therapeutic intervention may help alleviate the burden of cardiovascular complication within this population. In the last years, advances have been made toward developing noninvasive imaging techniques that could offer better insight into the cardiac involvement in end-stage renal disease (ESRD). Conventional transthoracic echocardiography remains the first-line investigation used to assess cardiac function, but encompassing in our daily practice, the newer approaches such as speckle-tracking imaging, cardiac computed tomography, or cardiac magnetic resonance can guide us to a more comprehensive understanding of CVD in ESRD. Given that patients with chronic kidney disease may not present with typical CVD symptoms, the amount of information brought by newer imaging techniques is crucial for an accurate diagnosis, risk stratification, and further management. The purpose of this review is to briefly summarize the specific applications of standard cardiac imaging techniques in patients with ESRD and to offer insight into the novel imaging modalities, highlighting the newest research in this field. By doing so, we aim to identify the most important imaging predictors of clinical outcomes in this population.

A comprehensive review on apolipoproteins as nontraditional cardiovascular risk factors in end-stage renal disease: current evidence and perspectives.

PURPOSE: Nontraditional cardiovascular risk factors such as lipoprotein(a) (Lp(a)), the genetic polymorphisms of apolipoprotein(a), apolipoprotein E (ApoE), and apolipoprotein B (ApoB) increase the prevalence of atherosclerosis in end-stage renal disease (ESRD) through quantitative and qualitative alterations. Given the high burden of cardiovascular fatal events in ESRD, this review aims to gather studies depicting apolipoproteins' changes in ESRD, to describe current evidence and to explore potential lipid-lowering therapies. METHODS: We searched the electronic database of PubMed, SCOPUS, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins in ESRD. Randomized controlled trials, observational studies (including case-control, prospective, or retrospective cohort), and reviews/meta-analysis were included if reference was made to apolipoproteins and cardiovascular consequences in ESRD. RESULTS: 21 studies met the inclusion criteria. We found a significant correlation between Lp(a) plasma concentrations and atherosclerosis. Lp(a) levels were independent risk factors for atherothrombosis and cardiovascular mortality. LMW apo(a) phenotype proved to be the best predictor for coronary events in ESRD. Single nucleotide polymorphisms in ApoE gene affected the expression and function of the protein, increasing the risk of cardiovascular events. ApoB had a significant correlation with the value of carotid intima-media thickness and vascular stiffness. CONCLUSIONS: The picture of "lipid milieu" in ESRD has not been clearly described. Novel studies show that specific apolipoproteins suffer modifications in uremic patients, being correlated with cardiovascular events. Probably in the next years, the treatment of dyslipidemia in ESRD will not merely target LDL or total cholesterol, but specific isoforms of apolipoproteins which seem to become the central part of the problem.