Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKA) or direct anticoagulants (DOAC). Moreover, it remains unclear which is more effective and safer between them, because estimated creatinine clearance < 25-30 ml/min was an exclusion criterion of the randomized control trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint because they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC vs. OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in hemodialysis patients with AF and undergoing LAAC compared to patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient, to consider individual risks and benefits of each treatment option is underlined.

The Importance of Early Diagnosis and Intervention in Chronic Kidney Disease: Calls-to-Action from Nephrologists Based Mainly in Central/Eastern Europe.

BACKGROUND: Chronic kidney disease (CKD) has a global prevalence of 9.1-13.4%. Comorbidities are abundant and may cause and affect CKD. Cardiovascular disease strongly correlates with CKD, increasing the burden of both diseases. SUMMARY: As a group of 15 clinical nephrologists primarily practicing in 12 Central/Eastern European countries, as well as Israel and Kazakhstan, herein we review the significant unmet needs for patients with CKD and recommend several key calls-to-action. Early diagnosis and treatment are imperative to ensure optimal outcomes for patients with CKD, with the potential to greatly reduce both morbidity and mortality. Lack of awareness of CKD, substandard indicators of kidney function, suboptimal screening rates, and geographical disparities in reimbursement often hamper access to effective care. KEY MESSAGES: Our key calls-to-action to address these unmet needs, thus improving the standard of care for patients with CKD, are the following: increase disease awareness, such as through education; encourage provision of financial support for patients; develop screening algorithms; revisit primary care physician referral practices; and create epidemiological databases that rectify the paucity of data on early-stage disease. By focusing attention on early detection, diagnosis, and treatment of high-risk and early-stage CKD populations, we aim to reduce the burdens, progression, and mortality of CKD.

Glomerular hyperfiltration as a therapeutic target for CKD.

The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR) or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose cotransporter-2 inhibitors to tolvaptan, induced an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predates current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.

Updated Strategies in Non-Culprit Stenosis Management of Multivessel Coronary Disease-A Contemporary Review.

The prevalence of multivessel coronary artery disease (CAD) in acute coronary syndrome (ACS) patients underscores the need for optimal revascularization strategies. The ongoing debate surrounding percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), hybrid interventions, or medical-only management adds complexity to decision-making, particularly in specific angiographic scenarios. The article critically reviews existing literature, providing evidence-based perspectives on non-culprit lesion revascularization in ACS. Emphasis is placed on nuances such as the selection of revascularization methods, optimal timing for interventions, and the importance of achieving completeness in revascularization. The debate between culprit-only revascularization and complete revascularization is explored in detail, focusing on ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI), including patients with cardiogenic shock. Myocardial revascularization guidelines and recent clinical trials support complete revascularization strategies, either during the index primary PCI or within a short timeframe following the culprit lesion PCI (in both STEMI and NSTEMI). The article also addresses the complexities of decision-making in NSTEMI patients with multivessel CAD, advocating for immediate multivessel PCI unless complex coronary lesions require a staged revascularization approach. Finally, the article provided contemporary data on chronic total occlusion revascularization in ACS patients, highlighting the prognostic impact. In conclusion, the article addresses the evolving challenges of managing multivessel CAD in ACS patients, enhancing thoughtful integration into the clinical practice of recent data. We provided evidence-based, individualized approaches to optimize short- and long-term outcomes. The ongoing refinement of clinical and interventional strategies for non-culprit lesion management remains dynamic, necessitating careful consideration of patient characteristics, coronary stenosis complexity, and clinical context.

Cardiac Device Therapy in Patients with Chronic Kidney Disease: An Update.

Cardiovascular diseases (CVDs) and chronic kidney disease (CKD) are frequently interconnected and their association leads to an exponential increase in the risk of both fatal and non-fatal events. In addition, the burden of arrhythmias in CKD patients is increased. On the other hand, the presence of CKD is an important factor that influences the decision to pursue cardiac device therapy. Data on CKD patients with device therapy are scarce and mostly derives from observational studies and case reports. Cardiac resynchronization therapy (CRT) is associated with decreased mortality, reduced heart failure symptoms, and improved renal function in early stages of CKD. Implantable cardioverter defibrillators (ICDs) are associated with a significant reduction in the mortality of CKD patients only for the secondary prevention of sudden cardiac death. Cardiac resynchronization therapy with defibrillator (CRT-D) is preferred in patients who meet the established criteria. The need for cardiac pacing is increased three-fold in dialysis patients. CKD is an independent risk factor for infections associated with cardiac devices.

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

BACKGROUND: The exact pathophysiological mechanisms of SGLT-2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT-2 inhibitors have potential anti-proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT-2 inhibitor drugs limit the generalizability of pre-clinical studies. METHODS: This is a narrative review discussing the potential anti-cancer effects of SGLT-2 inhibitors, an oral glucose-lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre-clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT-2 inhibitors in cancer treatment. RESULTS: Type II diabetes is linked to various comorbidities and malignancies, but some glucose-slowering medications may have a preventive role in cancer. The use of SGLT-2 inhibitors was associated with bladder cancer based on mice studies. However, meta-analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT-2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti-cancer effects of doxorubicin. Combining SGLT-2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT-2 inhibitors in various types of cancer. CONCLUSION: More large-scale pre-clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT-2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre-clinical and clinical data regarding the potential anti-cancer effects of SGLT-2 inhibitors including the hypothetical pathophysiological mechanisms.

Vitamin K supplementation impact in dialysis patients: a systematic review and meta-analysis of randomized trials.

Vitamin K supplementation has been considered recently as a potential treatment for addressing vascular calcification in chronic kidney disease patients. We conducted a systematic review and meta-analysis to summarize the impact of vitamin K supplementation in dialysis patients. Electronic databases were searched for clinical randomized trials among patients treated with vitamin K. Random effects models were performed and risk of bias was evaluated with Cochrane tools and the search was conducted until 15 of September 2023. Eleven trials comprising 830 patients (both adult and pediatric, mainly hemodialysis) compared vitamin K with different controls: lower doses of vitamin K, standard care or placebo. Vitamin K supplementation had no effect on mortality. Vitamin K administration improved vitamin K levels and led to lower levels of dp-uc-MGP and moderately increased calcium levels [0.18 (0.04-0.32)]. Vitamin K1 proved more potency in reducing dp-uc-MGP [SMD -1.64 (-2.05, -1.23) vs. -0.56 (-0.82, -0.31)] and also raised serum vitamin K levels in comparison with vitamin K2 [5.69 (3.43, 7.94) vs. 2.25 (-2.36, 6.87)]. While it did not have a proved benefit in changing calcification scores [-0.14 (-0.37 ± 0.09)], vitamin K proved to be a safe product. There was some concern with bias. Vitamin K supplementation has no impact on mortality and did not show significant benefit in reversing calcification scores. Vitamin K1 improved vitamin K deposits and lowered dp-uc-MGP, which is a calcification biomarker more than vitamin K2. As it proved to be a safe product, additional randomized well-powered studies with improved treatment regimens are needed to establish the true impact of vitamin K in dialysis patients.

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.

Renal Function Parameters in Distinctive Molecular Subtypes of Prostate Cancer.

Prostate cancer is a prevalent malignancy in male patients, having diverse clinical outcomes. The follow-up of patients diagnosed with prostate cancer involves the evaluation of renal function, because its impairment reduces patient survival rates and adds complexity to their treatment and clinical care. This study aimed to investigate the relationship between renal function parameters and distinctive molecular subtypes of prostate adenocarcinomas, defined by the immunoexpression of the SPINK1, ERG, HOXB13, and TFF3 markers. The study group comprised 72 patients with prostate cancer and associated chronic kidney disease (CKD) who underwent radical prostatectomy. Histopathological, molecular, and renal parameters were analyzed. Patients were categorized based on ERG/SPINK1 and HOXB13/TFF3 status, and correlations with renal function and prognostic grade groups were assessed. The ERG+/SPINK1+ subgroup exhibited significantly higher postoperative CKD stages and serum creatinine levels compared to the ERG+/SPINK1- subgroup. This suggests an intricate relationship between SPINK1 overexpression and renal function dynamics. The HOXB13-/TFF3+ subgroup displayed higher preoperative serum creatinine levels and CKD stages than the HOXB13-/TFF3- subgroup, aligning with TFF3's potential role in renal function. Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis.

Shared decision making in patients with kidney failure.

'Elderly' is most commonly defined as an individual aged 65 years or older. However, this definition fails to account for the differences in genetics, lifestyle and overall health that contribute to significant heterogeneity among the elderly beyond chronological age. As the world population continues to age, the prevalence of chronic diseases, including chronic kidney disease (CKD), is increasing and CKD frequently progresses to kidney failure. Moreover, frailty represents a multidimensional clinical entity highly prevalent in this population, which needs to be adequately assessed to inform and support medical decisions. Selecting the optimal treatment pathway for the elderly and frail kidney failure population, be it hemodialysis, peritoneal dialysis, or conservative kidney management is complex, because of the presence of comorbidities associated with low survival rates and impaired quality of life. Management of these patients should involve a multidisciplinary approach including doctors from various specialties, nurses, psychologists, dieticians, and physiotherapists. Studies are mostly retrospective and observational, lacking adjustment for confounders or address selection and indication biases, making it difficult to use these data to guide treatment decisions. Throughout this review we discuss the difficulty of making a one-size-fits-all recommendation for the clinical needs of older patients with kidney failure. We advocate that a research agenda for optimization of the critical issues we present in this review be implemented. We recommend prospective studies that address these issues, and systematic reviews incorporating the complementary evidence of both observational and interventional studies. Furthermore, we strongly support a shared decision making process matching evidence with patient preferences to ensure that individualized choices are made regarding dialysis vs. conservative kidney management, dialysis modality, and optimal vascular access.

Efficacy and Safety of Ticagrelor versus Clopidogrel in Dialysis Patients with Coronary Syndromes: A Systematic Review and Meta-Analysis.

(1) Background: The optimal antiplatelet therapy for end-stage kidney disease (ESKD) patients on chronic dialysis presenting with acute or chronic coronary syndromes (ACS or CCS) remains uncertain. This meta-analysis aimed to compare the efficacy and safety endpoints of ticagrelor and clopidogrel in ESKD patients requiring dialysis and presenting with ACS or CCS. (2) Methods: Studies were included comparing ticagrelor and clopidogrel in ESKD patients on chronic dialysis with ACS or CCS. The primary composite efficacy outcome was a combination of all-cause and cardiovascular mortality, recurrent myocardial infarction or coronary revascularization, and ischemic or hemorrhagic stroke. The primary safety outcome was major and non-major bleeding events. (3) Results: Five observational studies met the eligibility criteria. The pooled analysis showed no significant difference in the primary composite efficacy outcome between ticagrelor and clopidogrel (p = 0.40). Similarly, the 2 groups had no significant differences in all-cause mortality (p = 0.82) or cardiovascular mortality (p = 0.79). Ticagrelor did not show a significantly different risk of coronary revascularization (p = 0.35) or recurrent myocardial infarction (p = 0.41) compared to clopidogrel. Also, the risk of stroke was similar (p = 0.21). The 2 groups had no significant difference in the primary composite safety outcome (p = 0.22) or major bleeding events (p = 0.27). (4) Conclusions: In ESKD patients on chronic dialysis with ACS or CCS, there was no significant difference in efficacy or safety outcomes between ticagrelor and clopidogrel. Further randomized controlled trials are needed to establish the optimal antiplatelet therapy in this population.

Special Issue: "Cardiovascular Complications in Renal Diseases".

The intricate interplay between cardiovascular (CV) pathology and chronic kidney disease (CKD) encompasses diagnostic protocols (both clinical and paraclinical), outcome assessments (such as mortality, morbidity, and costs), as well as advancements in new therapeutic approaches (including pharmacological, interventional, and surgical modalities) [...].

Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

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.

Clinical Implications and Risk Factors for Erectile Dysfunction in Kidney Transplant: A Single-Center Assessment.

BACKGROUND: Erectile dysfunction (ED) affects the great majority of people undergoing dialysis and also the majority of patients undergoing kidney transplantation. In this study, we investigated the degree of erectile dysfunction (ED), as well as its prevalence, contributory variables, and overall impact after renal transplant. METHODS: Adult male kidney transplant patients were the subject of an observational, non-interventional study that was conducted at a single center. Age, time and type of dialysis before transplantation, comorbidities, factors associated with cardiovascular risk, data on sexual history, physical examination, and laboratory results were among the clinical data we examined. In addition to gathering clinical and demographic characteristics, the International Index of Erectile Function (IIEF) questionnaire was used to evaluate sexual function. RESULTS: A total of 170 renal transplanted patients between 20 and 70 years old (mean age: 45.40±11.5) were included in this study. All of the patients had immunosuppressive treatment with a calcineurin inhibitor (cyclosporine or tacrolimus) and had a normal glomerular filtration rate (GFR). The prevalence of sexual dysfunction increased with age (42.6% of patients under 40, 47.4% of patients in the 40-60 age group, and 78.9% of patients over 60). Mild, moderate, and severe ED was noted in 33.5%, 20.6%, and 10.6% of cases, respectively, and 51 (30%) patients reported having a normal sexual function. While calcium channel blockers (122 cases) were the most commonly used antihypertensive medication and chronic glomerulosclerosis (55.3%) was the most common cause of chronic kidney disease (CKD) before transplantation, none of these variables appear to have affected the severity of erectile dysfunction. The only medications associated with sexual dysfunction were alpha-blockers and aspirin (75 mg) (p=0.026 and p=0.013, respectively). CONCLUSIONS: Although kidney transplantation has positive impacts on the quality of life, erectile dysfunction is a frequent condition among patients with renal transplants, and it has an increased frequency with age. In our study, it has been observed that only a small percentage of the research group had a normal sexual function, although most of the patients were young, and that alpha-blockers and aspirin (75 mg) are associated with erectile dysfunction.

Strategies to prevent SARS-CoV-2 transmission in hemodialysis centres across Europe-lessons for the future.

Background: Early reports on the pandemic nature of coronavirus disease 2019 (COVID-19) directed the nephrology community to develop infection prevention and control (IPC) guidance. We aimed to make an inventory of strategies that dialysis centres followed to prevent infection with COVID-19 in the first pandemic wave. Methods: We analyzed IPC measures taken by hemodialysis centres treating patients presenting with COVID-19 between 1 March 2020 and 31 July 2020 and that completed the European Renal Association COVID-19 Database centre questionnaire. Additionally, we made an inventory of guidelines published in European countries to prevent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dialysis centres. Results: Data from 73 dialysis units located in and bordering Europe were analyzed. All participating centres implemented IPC measures to mitigate the impact of SARS-CoV-2 during the first pandemic wave. Measures mentioned most often included triage with questions before entering the dialysis ward, measuring body temperature, hand disinfection, masking for all patients and staff, and personal protective equipment for staff members. These measures were also recommended in most of the 14 guidelines that were identified in the inventory of national guidelines and were also scored as being among the most important measures by the authors of this paper. Heterogeneity existed between centres and national guidelines regarding the minimal distance between dialysis chairs and recommendations regarding isolation and cohorting. Conclusions: Although variation existed, measures to prevent transmission of SARS-CoV-2 were relatively similar across centres and national guidelines. Further research is needed to assess causal relationships between measures taken and spread of SARS-CoV-2.

Connection between Cardiac Fibrosis Biomarkers and Echocardiography Parameters in Advanced Chronic Kidney Disease Patients.

BACKGROUND: Myocardial fibrosis represents a mainstay pathway in the pathophysiology of uremic cardiomyopathy. This process leads to structural and functional changes in the heart, which can be detected by echocardiography. The purpose of our study was to determine the association between four echocardiographic parameters (ejection fraction (EF), global longitudinal strain (GLS), mean E/e' ratio, and left atrial volume indexed) and biomarkers associated with cardiac fibrosis, such as procollagen type I carboxy-terminal propeptide (PICP), procollagen type III N-terminal peptide (P3NP), and galectin-3 (Gal-3) in patients with end-stage renal disease (ESRD). METHODS: 140 patients with ESRD were enrolled and investigated by echocardiography and the serum levels of the aforementioned biomarkers were determined at baseline. RESULTS: The mean EF was 53.63 ± 8%, the mean GLS was -10.2 ± 5.3%, the mean E/e' ratio was 9.8 ± 4.3, and the mean left atrial volume indexed (LAVI) was 45.8 ± 14.2 mL/m2. The average levels for PICP, P3NP, and Gal-3 were 457.2 ± 240 µg/L, 242 ± 199.9 µg/L, and 10.7 ± 3.7 ng/mL, respectively. In regression analysis, PICP was strongly associated with all four echocardiographic parameters (EF: p = 0.0002, R2 = 0.69; GLS: p = 0.00001, R2 = 0.81; mean E/e': p = 0.00002; R2 = 0.89; LAVI: p = 0.003; R2 = 0.73). P3NP and Gal-3 were only associated with the EF (p = 0.01, R2 = 0.31 and p = 0.02; R2 = 0.35, respectively). CONCLUSION: Our study evidenced that PICP, a collagen-derived biomarker, is associated with important echocardiography parameters, suggesting that it can serve as an indicator of the presence of subclinical systolic and diastolic dysfunction in patients with advanced CKD.

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.

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.