Low LCAT activity is linked to acute decompensated heart failure and mortality in patients with CKD.

Chronic kidney disease (CKD) is often associated with decreased activity of lecithin-cholesterol acyltransferase (LCAT), an enzyme essential for HDL maturation. This reduction in LCAT activity may potentially contribute to an increased risk of cardiovascular mortality in patients with CKD. The objective of this study was to investigate the association between LCAT activity in patients with CKD and the risk of adverse outcomes. We measured serum LCAT activity and characterized lipoprotein profiles using nuclear magnetic resonance spectroscopy in 453 non-dialysis CKD patients from the CARE FOR HOMe study. LCAT activity correlated directly with smaller HDL particle size, a type of HDL potentially linked to greater cardiovascular protection. Over a mean follow-up of 5.0 ± 2.2 years, baseline LCAT activity was inversely associated with risk of death (standardized HR 0.62, 95% CI 0.50-0.76; P < 0.001) and acute decompensated heart failure (ADHF) (standardized HR 0.67, 95% CI 0.52-0.85; P = 0.001). These associations remained significant even after adjusting for other risk factors. Interestingly, LCAT activity was not associated with the incidence of atherosclerotic cardiovascular events or kidney function decline during the follow-up. To conclude, our findings demonstrate that low LCAT activity is independently associated with all-cause mortality and ADHF in patients with CKD, and is directly linked to smaller, potentially more protective HDL subclasses.

Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease represents one of the strongest risk factors for cardiovascular diseases, and particularly for heart failure. Despite improved pharmaceutical treatments, mortality remains high. Recently, experimental studies demonstrated that mosaic loss of Y chromosome (LOY) associates with cardiac fibrosis in male mice. Since diffuse cardiac fibrosis is the common denominator for progression of all forms of heart failure, we determined the association of LOY on mortality and cardiovascular disease outcomes in patients with chronic kidney disease. METHODS: LOY was quantified in men with stable chronic kidney disease (CARE for HOMe study, n=279) and dialysis patients (4D study, n=544). The association between LOY and mortality, combined cardiovascular and heart failure-specific end points, and echocardiographic measures was assessed. RESULTS: In CARE for HOMe, the frequency of LOY increased with age. LOY >17% was associated with increased mortality (heart rate, 2.58 [95% CI, 1.33-5.03]) and risk for cardiac decompensation or death (heart rate, 2.30 [95% CI, 1.23-4.27]). Patients with LOY >17% showed a significant decline of ejection fraction and an increase of E/E' within 5 years. Consistently, in the 4D study, LOY >17% was significantly associated with increased mortality (heart rate, 2.76 [95% CI, 1.83-4.16]), higher risk of death due to heart failure and sudden cardiac death (heart rate, 4.11 [95% CI, 2.09-8.08]), but not atherosclerotic events. Patients with LOY >17% showed significantly higher plasma levels of soluble interleukin 1 receptor-like 1, a biomarker for myocardial fibrosis. Mechanistically, intermediate monocytes from patients with LOY >17% showed significantly higher C-C chemokine receptor type 2 expression and higher plasma levels of the C-C chemokine receptor type 2 chemokine (C-C motif) ligand 2, which may have contributed to increased heart failure events. CONCLUSIONS: LOY identifies male patients with chronic kidney disease at high risk for mortality and heart failure events.

Plasma Concentrations of Trimethylamine-N-Oxide, Choline, and Betaine in Patients With Moderate to Advanced Chronic Kidney Disease and Their Relation to Cardiovascular and Renal Outcomes.

OBJECTIVES: Trimethylamine N-oxide (TMAO) is a gut bacteria-mediated liver metabolite of dietary betaine, choline, and carnitine, which is excreted by glomerular filtration. We studied whether TMAO is excreted by cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). METHODS: Among 478 patients with CKD stage G2 (n = 104), G3a (n = 163), G3b (n = 123), and G4 (n = 88), we studied the association between fasting plasma concentrations of TMAO, choline, or betaine at baseline and kidney function, prevalent CVD, and future renal outcomes during a mean follow-up of 5.1 years. RESULTS: Decreased glomerular filtration rate was associated with higher plasma concentrations of TMAO, choline, and betaine. Baseline concentrations of TMAO were higher in participants with preexisting CVD compared to those without CVD (8.4 [10.1] vs. 7.8 [8.0] µmol/L; P = .047), but the difference was not significant after adjusting for confounders. During the follow-up, 147 participants experienced CVD or died, and 144 reached the predefined renal endpoint. In the adjusted regression analyses, TMAO or choline concentrations in the upper three quartiles (vs. the lowest quartile) were not associated with any of the study's clinical endpoints. In contrast, the adjusted hazard ratio of plasma betaine in the highest quartile versus the lowest quartile was 2.14 (1.32, 3.47) for the CVD endpoint and 1.64 (1.00, 2.67) for the renal endpoint. CONCLUSIONS: Elevated plasma TMAO concentrations were explained by impaired kidney function. Elevated plasma concentrations of betaine, but not those of TMAO or choline, constituted a risk factor for adverse outcomes. TMAO might not be an appropriate target to reduce CVD or renal outcomes in patients with preexisting CKD.

Percutaneous interventional thrombectomy of an endovascular AV-fistula, a case report.

Dialysis access thrombosis is a common complication in the process of care. With the introduction of endovascular AV-fistulas [AVF]s the situation gained complexity with new potential thrombosis localizations. Several thrombectomy methods are available for recanalization of thrombosed AVFs ranging from invasive surgical methods to minimal invasive endovascular approaches. Early assessment, diagnosis and treatment is crucial for prolonging the life span of an AVF and preventing the need for placement of central venous catheters. To our best knowledge, we present the first case in which an obstructed antecubital communicating vein (aka perforating vein) of an endovascular created AVF was re-opened via interventional thrombectomy with the Rotarex® System (BD Interventional). The procedure was performed primarily under ultrasound guidance with fluoroscopic support. Our case report shows that this method, if done correctly and successfully, may prevent loss of the dialysis access. Additionally, we point towards the central role of ultrasound in this method.

Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials.

Background: Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown. Method: In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events. Results: During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m2 or >60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m2 vs. 73.2 ± 19.4 ml/min/1.73 m2 (P < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: -9.5% (95% confidence interval (CI) -13.0% to -5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: -31.1% (95% CI -32.1% to -30.1%)). Conclusion: Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event.

[Cardiovascular treatment in chronic kidney disease]. / Kardiovaskuläre Therapie bei chronischer Nierenerkrankung.

Patients with combined cardiac and renal diseases are particularly challenging in the routine clinical practice due to the substantial risk profile for increased morbidity and mortality. As cardiorenal patients have often been underrepresented in randomized, controlled interventional trials, guideline recommendations regarding the choice of treatment are often weaker for these individuals than for cardiovascular patients without chronic kidney disease. Furthermore, there are limitations in the approval of certain medications depending on the kidney function. This review addresses some considerations in crucial treatment areas for patients with cardiovascular diseases, whose treatment is significantly influenced by concomitant chronic kidney disease.

ELOVL2-methylation and renal and cardiovascular event in patients with chronic kidney disease.

BACKGROUND: Methylation of the Elongation Of Very Long Chain Fatty Acids-Like 2 (ELOVL2) gene promoter may predict premature ageing and cardiovascular risk. METHODS: We studied the cross-sectional associations between blood ELOVL2-methylation and cardiovascular risk factors in 350 patients with chronic kidney disease (CKD) stage G2-G4 aged between 22 and 90 years. In a follow-up study for a mean of 3.9 years, we investigated the association between baseline ELOVL2-methylation and renal or cardiovascular events including death. RESULTS: ELOVL2-methylation at seven CpG cites increased with age (the correlation coefficients between 0.67 and 0.87, p < 0.001). The ELOVL2-CpGs methylation was lower in patients with CKD stage G2 versus those in stage G3a, G3b and G4, but the differences were explained by age. ELOVL2-CpGs methylation showed no correlations with cardiovascular risk factors after adjusting for age. During the follow-up, 64 patients showed deterioration in renal function or died and 77 showed cardiovascular events or died. The hazard ratio and 95% confidence intervals for renal or cardiovascular events according to baseline ELOVL2-CpGs methylation were not significant after adjustment for covariates. CONCLUSIONS: ELOVL2-hypermethylation showed a strong association with age, but was not independently associated with cardiovascular risk factors or with future renal or cardiovascular events in patients with CKD. ELOVL2 gene methylation is not likely to be itself a cause for ageing or illnesses, but it could be rather influenced by other upstream processes that deserve investigation.

Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.

AIMS: Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT). METHODS AND RESULTS: The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence. CONCLUSION: Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.

Plasma biomarkers outperform echocardiographic measurements for cardiovascular risk prediction in kidney transplant recipients: results of the HOME ALONE study.

Background: Since kidney transplant recipients (KTRs) have a high cardiovascular disease burden, adequate risk prediction is of importance. Whether echocardiographic parameters and plasma biomarkers, natriuretic peptides [N-terminal pro-B-type natriuretic peptide (NT-proBNP)] and troponin T provide complementary or overlapping prognostic information on cardiovascular events remains uncertain. Methods: The prospective Heterogeneity of Monocytes and Echocardiography Among Allograft Recipients in Nephrology (HOME ALONE) study followed 177 KTRs for 5.4 ± 1.7 years. Predefined endpoints were hospitalization for acute decompensated heart failure or all-cause death (HF/D) and major atherosclerotic cardiovascular events or all-cause death (MACE/D). At baseline, plasma NT-proBNP, plasma troponin T and echocardiographic parameters [left atrial volume index, left ventricular (LV) mass index, LV ejection fraction, and LV filling pressure] were assessed. Results: Among all echocardiographic and plasma biomarkers measured, only NT-proBNP was consistently associated with HF/D in univariate and multivariate {third versus first tertile: hazard ratio [HR] 4.20 [95% confidence interval (CI) 1.02-17.27]} analysis, and only troponin T was consistently associated with MACE/D in univariate and multivariate [third versus first tertile: HR 8.15 (95% CI 2.75-24.18)] analysis. Conclusion: Our data suggest that plasma biomarkers are robust and independent predictors of heart failure and atherosclerotic cardiovascular events after kidney transplantation, whereas standard echocardiographic follow-up does not add to risk prediction.

Anticoagulation management in haemodialysis patients with atrial fibrillation: evidence and opinion.

In the absence of robust evidence to guide clinical decision-making, the optimal approach to prevent stroke and systemic embolism in haemodialysis (HD) patients with atrial fibrillation (AF) remains moot. In this position paper, studies on oral anticoagulation (OAC) in HD patients with AF are highlighted, followed by an evidence-based conclusion, a critical analysis to identify sources of bias and practical opinion-based suggestions on how to manage anticoagulation in this specific population. It remains unclear whether AF is a true risk factor for embolic stroke in HD. The currently employed cut-off values for the CHA2DS2-VASc score do not adequately discriminate dialysis patients deriving a net benefit from those suffering a net harm from OAC. Anticoagulation initiation should probably be more restrictive than currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) observed in the general population and in moderate chronic kidney disease can be extended to the HD population. VKA may be especially harmful in dialysis patients and should therefore be avoided, in particular in patients with a high bleeding risk and labile international normalized ratio. Dose-finding studies of DOACs suggest that rivaroxaban 10 mg daily and apixaban 2.5 mg twice daily are appropriate choices in dialysis patients. Combined treatment with oral anticoagulants and antiplatelet agents should be reserved for strong indications and limited in time. Left atrial appendage occlusion is a potential attractive solution to reduce the risk of stroke without increasing bleeding propensity, but it has not been properly studied in dialysis patients.

FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease.

INTRODUCTION: High plasma fibroblast growth factor 23 (FGF-23) predicts cardiovascular events in chronic kidney disease (CKD) patients. Experimental evidence suggests FGF receptor 4 (FGFR4) activation by FGF-23, and deficiency of the soluble form of its co-receptor Klotho promotes left-ventricular hypertrophy (LVH). To evaluate the clinical relevance of these findings, a Mendelian randomization study analyzed the association of genetic variants of FGFR4 and Klotho with echocardiographic parameters and cardiac events in CKD patients. METHODS: The prospective Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg Evaluation study recruited CKD G2-G4 patients, of whom 519 consented to SNP genotyping (FGFR4: rs351855; Klotho: rs9536314). Echocardiographic examinations at baseline and 5 years later assessed prevalence of LVH by measurement of left-ventricular mass index (LVMI). Patients were followed for 5.1 ± 2.1 years for the primary endpoints of cardiac decompensation and atherosclerotic cardiovascular disease (ASCVD). RESULTS: Carriers of the different alleles did neither differ in baseline LVMI (rs351855: p = 0.861; rs9536314: p = 0.379) nor in LVMI changes between baseline and follow-up (rs351855: p = 0.181; rs9536314: p = 0.995). Hundred and four patients suffered cardiac decompensation, and 144 patients had ASCVD. Time to cardiac decompensation (rs351855: p = 0.316; rs9536314: p = 0.765) and ASCVD (p = 0.508 and p = 0.800, respectively) did not differ between carriers of different alleles. DISCUSSION/CONCLUSION: rs351855 and rs9536314 were not associated with LVMI or cardiac events. These findings do not provide evidence for a relevant clinical role of either FGFR4 stimulation or soluble form of Klotho deficiency in LVH development.

[The impact of immunosuppression and chronic kidney disease on immunogenicity of COVID-19 vaccines]. / Der Einfluss von Immunsuppression und chronischen Nierenerkrankungen auf das Ansprechen auf COVID-19-Impfungen.

HOW EFFECTIVE ARE THE APPROVED VACCINES IN KIDNEY DISEASES AND THOSE RECEIVING IMMUNOSUPPRESSION?: Several observational studies indicated that immunosuppression is associated with a weakened or absent humoral response. Patients with chronic kidney diseases or undergoing maintenance dialysis without immunosuppression have a reduced humoral response to COVID-19 vaccines. I HAD COVID-19. SHOULD I GET VACCINATED?: It is recommended to receive a booster after SARS-CoV-2 infection with a mRNA vaccine. IS A COVID-19 VACCINATION DESPITE ONGOING IMMUNOSUPPRESSION POSSIBLE?: Patients receiving immunosuppression have a reduced humoral response, and this is especially observed when anti-CD20 therapy is used. IS THERE A POSSIBILITY THAT THE VACCINE PROVOKES REJECTION OF MY TRANSPLANTED KIDNEY OR RELAPSE OF MY GLOMERULAR DISEASE?: Several reports were published in the last months highlighting new-onset diseases, recurrences and relapses of different glomerular diseases, which occurred after the receipt of the first or second vaccine dose. As a clear association of vaccines and induction of autoimmunity still needs to be established, most of these diseases are treatable, and COVID-19 in patients under immunosuppression is often fatal, there is a clear net benefit of vaccination. DO I HAVE A PERMANENT PROTECTION AFTER VACCINATION?: The antibody titers and likely the cellular immune response is significantly reduced in patients with kidney diseases, and titers are reducing at a fast pace under ongoing immunosuppression. A booster dose should be considered, especially taking into consideration the evolvement of virus variants and their impact on vaccine efficacy. AFTER THE FIRST SERIES OF VACCINATION, NO OR ONLY A MARGINAL AMOUNT OF ANTIBODIES WERE DETECTABLE. ARE THERE STRATEGIES TO IMPROVE VACCINE RESPONSE?: Many countries recommend the application of a third dose for vulnerable patient cohorts, especially because of a weakened response and their risk to develop a severe disease course of COVID-19. Prospective clinical trials are ongoing to test the ideal strategy to improve vaccine response in these cohorts.

[Update on treatment resistant hypertension and secondary hypertension]. / Therapieresistente und sekundäre Hypertonie.

Resistant hypertension (RH) is defined in patients who do not meet their blood pressure targets despite the daily intake of three antihypertensive drugs in maximally tolerated dosages. This triple treatment should comprise (1) an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB), (2) a calcium channel blocker and (3) a diuretic. RH should also be diagnosed in patients on four or more antihypertensive drug classes. Of note, the diagnosis of RH requires the exclusion of non-adherence, "white coat effect", and incorrect BP-measurement.After diagnosing RH, it is important to recommend lifestyle interventions (e. g. low dietary salt intake, regular physical activity), to pause BP-elevating substances, and to consider the presence of secondary hypertension.Such secondary forms of hypertension primarily include endocrine disorders and renal disease (both acute kidney injury and chronic kidney disease). The leading endocrine cause is primary hyperaldosteronism, the management of which was highlighted in a recent guideline. Other endocrine causes - such as phaeochromocytoma or hypercortisolism - are much less frequent. In contrast, sleep apnoea disorders are now mostly considered as a comorbidity rather than as a cause of secondary hypertension.Treatment options for RH include lifestyle optimisation and escalation of antihypertensive medication. In most patients on triple treatment (ACE-I or ARB plus calcium channel blocker plus diuretic), mineralocorticoid receptor antagonists (MRA) should be the next treatment choice. As MRA may be associated with hyperkalemia (particularly in patients with chronic kidney disease), the concurrent use of potassium-lowering agents such as patiromer may allow a safe long-term treatment. In contrast, novel interventional treatment options in RH such as renal denervation are still controversially discussed.

Markers of cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD: An observational study.

In dialysis patients, cholesterol-lowering therapy with statins is less effective than in other high-risk patients. This may be explained by a shift from cholesterol synthesis toward cholesterol absorption. In line, markers of cholesterol absorption-such as campesterol-better predict atherosclerotic cardiovascular events than markers of cholesterol synthesis-such as lathosterol-in dialysis patients. To test the association between markers of cholesterol absorption such as campesterol-and markers of cholesterol synthesis-such as lathosterol-against cardiovascular events in non-dialysis CKD patients. Altogether 251 patients those not on lipid-lowering agents were followed annually for the composite endpoint atherosclerotic cardiovascular disease (ASCVD) and all-cause death. During follow-up of 5.2 ± 2.1 years, 61 participants reached the primary endpoint atherosclerotic cardiovascular disease/all-cause death [ASCVD/D], 47 participants suffered from ASCVD, and 46 participants died. In univariate Cox regression analysis, campesterol/lathosterol ratio did not significantly predict ASCVD/D (HR 0.643; 0.358-1.155; 3rd vs. 1st tertile), all-cause death (HR 1.309; 0.604-2.838; 3rd vs. 1st tertile) nor ASCVD (HR 0.589; 0.311-1.118; 3rd vs. 1st tertile). We did not observe a shift from cholesterol synthesis to cholesterol absorption across the spectrum of non-dialysis CKD. Campesterol/lathosterol ratio did not predict future ASCVD or all-cause death in non-dialysis CKD.

[Volume Management in Chronic kidney disease]. / Volumenmanagement bei chronischen Nierenerkrankungen.

Understanding the (patho-)physiology of volume regulation and osmoregulation is fundamental to guide patient advice and therapy in chronic kidney disease (CKD). Volume regulation primarily impacts the amount of sodium in the body, and it mainly affects the extracellular space, while osmoregulation primarily impacts the amount of free water, and it affects both the intra- and extracellular space. The kidneys control water and sodium homeostasis both through their sensor (e. g. tubuloglomerular feedback) and regulator systems (e. g. sodium reabsorption). Many CKD patients are advised by non-nephrologists to a high fluid intake, although they often do not require a daily intake of more than 1.5 litres. Many CKD patients are hypervolemic, and sodium restriction is of key importance in patients' effort to utilize lifestyle changes as therapeutic means. Pharmacologically, (particularly loop) diuretics are the basis of therapy, increasing sodium excretion. Recent developments shift the focus towards classes of drugs ameliorating prognosis in CKD: sodium-glucose linked transporter 2 (SGLT2) inhibitors have proven beneficial in heart and renal failure - by sodium and fluid excretion, among others; additionally, a novel mineralocorticoid receptor antagonist (MRA), finerenone, was recently shown to improve prognosis in CKD.

[SARS-CoV-2 vaccines - what the nephrologist should know]. / SARS-CoV-2-Impfungen ­ Was muss der Nephrologe wissen?

Only fifteen months after the beginning of the COVID-19 pandemic, several vaccines are already available for clinical use. While the spike protein of SARS-CoV-2 constitutes the main target of all predominant SARS-CoV-2 vaccines, they work by different mechanisms (mRNA-based vaccines vs. vector-based vaccines vs. protein-based vaccines).Though there are slight differences regarding the level of protection against mild COVID-19, all five vaccines that have been through phase 3 trials were nearly 100 % effective in preventing severe or fatal cases of COVID-19. The side effects were of short duration.Patients with chronic kidney disease (or other significant comorbidities) were largely excluded from Phase 3 trials, which makes definite recommendations concerning their vaccination difficult. The vaccine's effectiveness may be reduced in that population due to a uremic immune defect and/or immunosuppressive medication. However, these patients have an increased risk for severe or fatal COVID-19, so that they may particularly benefit from the vaccine.

[Anemia and iron deficiency - treatment options in chronic kidney disease and in chronic heart failure]. / Anämie und Eisenmangel ­ Behandlungsoptionen bei chronischer Nierenerkrankung und chronischer Herzinsuffizienz.

Anemia and iron deficiency are highly prevalent in chronic kidney disease (CKD) and in chronic heart failure. Both may epidemiologically predict future renal and/or cardiovascular events. However, anemia treatment with either erythropoietin or erythropoiesis-stimulating agents failed to induce a prognostic benefit in either CKD or chronic heart failure. Instead, in the subgroup of chronic dialysis patients, liberal intravenous iron supplementation was beneficial, and ongoing clinical trials are testing the prognostic implication of intravenous iron supplementation in chronic heart failure. Finally, HIF stabilizers are a new treatment option for anemia in chronic kidney disease, and safety studies are currently ongoing in CKD patients. Whether patients suffering from chronic heart failure might also benefit from this treatment is currently unknown.

Current Understanding of the Relationship of HDL Composition, Structure and Function to Their Cardioprotective Properties in Chronic Kidney Disease.

In the general population, the ability of high-density lipoproteins (HDLs) to promote cholesterol efflux is a predictor of cardiovascular events, independently of HDL cholesterol levels. Although patients with chronic kidney disease (CKD) have a high burden of cardiovascular morbidity and mortality, neither serum levels of HDL cholesterol, nor cholesterol efflux capacity associate with cardiovascular events. Important for the following discussion on the role of HDL in CKD is the notion that traditional atherosclerotic cardiovascular risk factors only partially account for this increased incidence of cardiovascular disease in CKD. As a potential explanation, across the spectrum of cardiovascular disease, the relative contribution of atherosclerotic cardiovascular disease becomes less important with advanced CKD. Impaired renal function directly affects the metabolism, composition and functionality of HDL particles. HDLs themselves are a heterogeneous population of particles with distinct sizes and protein composition, all of them affecting the functionality of HDL. Therefore, a more specific approach investigating the functional and compositional features of HDL subclasses might be a valuable strategy to decipher the potential link between HDL, cardiovascular disease and CKD. This review summarizes the current understanding of the relationship of HDL composition, metabolism and function to their cardio-protective properties in CKD, with a focus on CKD-induced changes in the HDL proteome and reverse cholesterol transport capacity. We also will highlight the gaps in the current knowledge regarding important aspects of HDL biology.