Dialysate sodium and short-term blood pressure variability in patients with intradialytic hypertension: a randomized crossover study.

Increased blood pressure (BP) variability (BPV) is associated with high cardiovascular risk in hemodialysis. Patients with intradialytic hypertension (IDH) also exhibit an increased cardiovascular risk compared to hemodialysis patients without this condition. The impact of non-pharmacological BP-lowering interventions on BPV in this population remains unknown. This analysis evaluated the effect of low (137mEq/L) compared to standard (140mEq/L) dialysate sodium concentration on short-term BPV in patients with IDH. In a randomized cross-over manner, 29 IDH patients underwent 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/L) dialysate sodium or vice versa. 48 h ambulatory BP measurement was performed from the start of the 4th session on each dialysate sodium. BPV indices during the 48 h, 24 h, day-time and night-time periods were calculated. Mean 48 h BP was 5.3/2.6 mmHg lower with low compared to standard dialysate sodium concentration, (p = 0.005/p = 0.007 respectively). All 48 h systolic BPV indices examined showed non-significant differences between low and standard dialysate sodium (SBP-SD: 16.99 ± 5.39 vs. 16.98 ± 4.33 mmHg, p = 0.982; SBP-wSD: 15.93 ± 5.02 vs. 16.12 ± 4.16 mmHg, p = 0.769; SBP-ARV: 11.99 ± 3.67 vs. 11.45 ± 3.35 mmHg, p = 0.392; SBP-CV: 12.36 ± 3.65 vs. 11.92 ± 3.18%, p = 0.302, with low vs. standard dialysate sodium, respectively). Diastolic BPV indices were numerically, but not statistically, lower with low dialysate sodium. Overall, significant differences were observed in some comparisons with a trend for lower BPV during day-time 2 and higher BVP during night-time 2 with low dialysate sodium. In conclusion, low dialysate sodium concentration does not affect BPV levels in patients with IDH. Future research should explore alternative interventions to reduce BP and BPV in this high-risk population.

Clinical Properties and Non-Clinical Testing of Mineralocorticoid Receptor Antagonists in In Vitro Cell Models.

Mineralocorticoid receptor antagonists (MRAs) are one of the renin-angiotensin-aldosterone system inhibitors widely used in clinical practice. While spironolactone and eplerenone have a long-standing profile in clinical medicine, finerenone is a novel agent within the MRA class. It has a higher specificity for mineralocorticoid receptors, eliciting less pronounced adverse effects. Although approved for clinical use in patients with chronic kidney disease and heart failure, intensive non-clinical research aims to further elucidate its mechanism of action, including dose-related selectivity. Within the field, animal models remain the gold standard for non-clinical testing of drug pharmacological and toxicological properties. Their role, however, has been challenged by recent advances in in vitro models, mainly through sophisticated analytical tools and developments in data analysis. Currently, in vitro models are gaining momentum as possible platforms for advanced pharmacological and pathophysiological studies. This article focuses on past, current, and possibly future in vitro cell models research with clinically relevant MRAs.

Treatment of acute kidney injury with continuous renal replacement therapy and cytokine adsorber (CytoSorb®) in critically ill patients with COVID-19.

INTRODUCTION: This retrospective study aimed to evaluate the 30 and 60-day survival of critically ill patients with COVID-19 and AKI. METHODS: Inflammatory and biochemical biomarkers, length of intensive care unit (ICU) stay and mortality at Day 30 and Day 60 after ICU admission were analyzed. A total of 44 patients treated with continuous renal replacement therapy (CRRT) with cytokine adsorber (CA group) were compared to 58 patients treated with CRRT alone (non-CA group). RESULTS: Patients in CA group were younger, had better preserved kidney function prior to the beginning of CRRT and had higher levels of interleukin-6. There were no statistically significant differences in their comorbidities and in other measured biomarkers between the two groups. The number of patients who died 60 days after ICU admission was statistically significantly higher in non-CA group (p = 0.029). CONCLUSION: Treatment with CRRT and cytokine adsorber may have positively influenced 60-day survival in our COVID-19 ICU patients with AKI.

Low dialysate sodium and 48-h ambulatory blood pressure in patients with intradialytic hypertension: a randomized crossover study.

BACKGROUND AND HYPOTHESIS: Intradialytic-hypertension (IDH) is associated with increased risk for cardiovascular events and mortality. Patients with IDH exhibit higher 48-h blood pressure (BP) levels than patients without this condition. Volume and sodium excess are considered a major factor contributing in the development of this phenomenon. This study evaluated the effect of low (137mEq/L) compared to standard (140mEq/L) dialysate sodium concentration on 48-h BP in patients with IDH. METHODS: In this randomized, single-blind, crossover study, 29 patients with IDH underwent 4 hemodialysis sessions with low (137mEq/L) followed by 4 sessions with standard (140mEq/L) dialysate sodium or vice-versa. Mean 48-h BP, pre-/post-dialysis and intradialytic BP, pre-dialysis weight, interdialytic weight gain (IDWG) and lung ultrasound B-lines were assessed. RESULTS: Mean 48-h SBP/DBP were significantly lower with low compared to standard dialysate sodium concentration (137.6±17.0/81.4±13.7mmHg with low vs 142.9±14.5/84.0±13.9mmHg with standard dialysate sodium, p=0.005/p=0.007 respectively); SBP/DBP levels were also significantly lower during the 44-h and different 24-h periods. Low dialysate sodium significantly reduced post-dialysis (SBP/DBP: 150.3±22.3/91.2±15.1mmHg with low vs 166.6±17.3/94.5±14.9mmHg with standard dialysate sodium, p<0.001/p=0.134 respectively) and intradialytic (141.4±18.0/85.0±13.4mmHg with low vs 147.5±13.6/88.1±12.5mmHg with standard dialysate sodium, p=0.034/p=0.013, respectively) BP compared with standard dialysate sodium. Pre-dialysis weight, IDWG and pre-dialysis B-lines were also significantly decreased with low dialysate sodium. CONCLUSIONS: Low dialysate sodium concentration significantly reduced 48-h ambulatory BP compared with standard dialysate sodium in patients with IDH. These findings support low dialysate sodium as a major non-pharmacologic approach for BP management in patients with IDH.Registered at ClinicalTrials.gov with study number NCT05430438.

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

Sex disparities in mortality and cardiovascular outcomes in chronic kidney disease.

Sex (biologically determined) and gender (socially constructed) modulate manifestations and prognosis of a vast number of diseases, including cardiovascular disease (CVD) and chronic kidney disease (CKD). CVD remains the leading cause of death in CKD patients. Population-based studies indicate that women present a higher prevalence of CKD and experience less CVD than men in all CKD stages, although this is not as clear in patients on dialysis or transplantation. When compared to the general population of the same sex, CKD has a more negative impact on women on kidney replacement therapy. European women on dialysis or recipients of kidney transplants have life expectancy up to 44.8 and 19.8 years lower, respectively, than their counterparts of similar age in the general population. For men, these figures stand at 37.1 and 16.5 years, representing a 21% to 20% difference, respectively. Hormonal, genetic, societal, and cultural influences may contribute to these sex-based disparities. To gain a more comprehensive understanding of these differences and their implications for patient care, well-designed clinical trials that involve a larger representation of women and focus on sex-related variables are urgently needed. This narrative review emphasizes the importance of acknowledging the epidemiology and prognosis of sex disparities in CVD among CKD patients. Such insights can guide research into the underlying pathophysiological mechanisms, leading to optimized treatment strategies and ultimately, improved clinical outcomes.

COVID-19 and cardiovascular disease in patients with chronic kidney disease.

Millions of people worldwide have chronic kidney disease (CKD). Affected patients are at high risk for cardiovascular (CV) disease for several reasons. Among various comorbidities, CKD is associated with the more severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is particularly true for patients receiving dialysis or for kidney recipients. From the start of the SARS-CoV-2 pandemic, several CV complications have been observed in affected subjects, spanning acute inflammatory manifestations, CV events, thrombotic episodes and arrythmias. Several pathogenetic mechanisms have been hypothesized, including direct cytopathic viral effects on the myocardium, endothelial damage and hypercoagulability. This spectrum of disease can occur during the acute phase of the infection, but also months after recovery. This review is focussed on the CV complications of coronavirus disease 2019 (COVID-19) with particular interest in their implications for the CKD population.

Simply adding oral nutritional supplementation to haemodialysis patients may not be enough: a real-life prospective interventional study.

Introduction: Protein-energy wasting (PEW) is a common and serious co-morbidity in haemodialysis (HD) patients. Its importance as a prognostic factor has been increasingly recognised during the past decades. Much effort has been invested in the improvement of nutritional status and amelioration of consequences through different therapeutic approaches, either intradialytic parenteral nutrition or more commonly oral nutritional supplementation. In the article, we present the results of a prospective study in HD patients after 12 months of therapeutic intervention with oral nutritional supplements (ONS). Methods: A total of 92 HD adult patients were enrolled in the study after 3 months of wash-out period. Baseline nutritional status was assessed using composite scores, laboratory markers, bioelectrical impedance analysis, and hand-grip strength test. Patients recognised as undernourished or at high risk for undernutrition received renal-specific commercially available ONS on HD day in addition to their regular diet. After 12 months, the effect of ONS on surrogate markers of undernutrition, serum albumin level, phase angle, and hand-grip strength was analysed in 71 surviving patients. Results: After 12 months, data for 71 patients, 39 (54.9%) men, 62.4 ± 12.9 years, and median haemodialysis vintage 53.3 (IQR 27.5-92.8) months, were available. Patients were divided into three groups: group A patients were with normal nutritional status at baseline not necessitating ONS; group B patients received ONS; and group C patients were entitled to receive but refused to take ONS. The baseline results showed statistically significant differences between the groups in serum albumin levels and phase angle but not hand-grip strength. Differences between the groups remained statistically significant at month 12; we did not find any statistically significant positive changes within the groups, indicating no positive effect of intervention with ONS. Conclusion: In a prospectively designed interventional single-centre study, we did not find a statistically significant change in surrogate markers of PEW in our cohort of HD patients, receiving ONS for 12 months. Since PEW is an independent risk factor influencing the survival of HD patients, efforts should be directed towards a timely and comprehensive nutritional approach, including intensive, personalised dietary counselling, increase in protein and energy intake and advocating tight control of nutritional status during HD treatment, possibly providing psychological support and motivation.

The Role of Oxidative Stress in Kidney Injury.

Acute kidney injury and chronic kidney disease are among the most common non-communicable diseases in the developed world, with increasing prevalence. Patients with acute kidney injury are at an increased risk of developing chronic kidney disease. One of kidney injury's most common clinical sequelae is increased cardiovascular morbidity and mortality. In recent years, new insights into the pathophysiology of renal damage have been made. Oxidative stress is the imbalance favoring the increased generation of ROS and/or reduced body's innate antioxidant defense mechanisms and is of pivotal importance, not only in the development and progression of kidney disease but also in understanding the enhanced cardiovascular risk in these patients. This article summarizes and emphasizes the role of oxidative stress in acute kidney injury, various forms of chronic kidney disease, and also in patients on renal replacement therapy (hemodialysis, peritoneal dialysis, and after kidney transplant). Additionally, the role of oxidative stress in the development of drug-related nephrotoxicity and also in the development after exposure to various environmental and occupational pollutants is presented.

Higher Body Mass Index is associated with increased arterial stiffness prior to target organ damage: a cross-sectional cohort study.

BACKGROUND: Obesity is associated with several neurohumoral changes that play an essential role in organ damage. Increased arterial stiffness causes functional vessel wall changes and can therefore lead to accelerated target organ damage as well. Whether obesity causes an independent increase in central arterial stiffness is, however, not yet fully known. METHODS: One hundred thirty-three patients (63.2% male) were included. Body Mass Index (BMI) was defined as body weight in kilograms, divided by the square of body height in meters. Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation was used to estimate the glomerular filtration rate (eGFR). Non-invasive applanation tonometry was used for arterial stiffness measurements (Sphygmocor Atcor Medical, Sydney, Australia). All patients underwent coronarography. RESULTS: The mean age of our patients was 65.0 ± 9.2 years. Their mean BMI was 28.5 ± 4.4 kg/m2, eGFR 75.5 ± 17.2 ml/min/1.73 m2 and ankle-brachial index (ABI) 1.0 ± 0.1. Their arterial stiffness measurements showed mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.7 m/s, subendocardial viability ratio (SEVR) 164.4 ± 35.0%, and pulse pressure (PP) 47.8 ± 14.5 mmHg. Spearman's correlation test revealed a statistically significant correlation between BMI and SEVR (r = -0.193; p = 0.026), BMI and cfPWV (r = 0.417; p < 0.001) and between BMI and PP (r = 0.227; p = 0.009). Multiple regression analysis confirmed an independent connection between BMI and cfPWV (B = 0.303; p < 0.001) and between BMI and SEVR (B = -0.186; p = 0.040). There was no association between BMI and kidney function, ABI, or coronary artery disease. CONCLUSION: Increased BMI is independently associated with augmented central arterial stiffness and reduced subendocardial perfusion but not with coronary artery disease, kidney function, or ABI.

Atherosclerosis and Epigenetic Modifications in Chronic Kidney Disease.

Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with prevalence currently projected at 10% and rising. Cardiovascular disease is the leading cause of morbidity and mortality in CKD patients and is integrally linked with atherogenesis and vascular stiffness. Estimated glomerular filtration rate and the level of proteinuria are not only markers of kidney function but of cardiovascular risk, as well. Despite the efforts, CKD patients still experience excessive cardiovascular burden. MicroRNAs (miRNAs) are small (18-24 nucleotides), single-stranded non-coding RNAs that regulate gene expression by blocking messenger RNA (mRNA) translation and initiating degradation of mRNA. Studies have confirmed the imperative role of miRNA dysregulation in the pathophysiology of several diseases, including atherosclerosis and CKD. This article summarizes what is currently known about the role of miRNAs in CKD patients.

Chronic Kidney Disease and Obesity.

There is a pandemic of obesity worldwide and in Europe up to 30% of the adult population is already obese. Obesity is strongly related to the risk of CKD, progression of CKD, and end-stage renal disease (ESRD), also after adjustment for age, sex, race, smoking status, comorbidities, and laboratory tests. In the general population, obesity increases the risk of death. In nondialysis-dependent CKD patients, the association between body mass index and weight with mortality is controversial. In ESRD patients, obesity is paradoxically associated with better survival. There are only a few studies investigating changes in weight in these patients and in most weight loss was associated with higher mortality. However, it is not clear if weight change was intentional or unintentional and this is an important limitation of these studies. Management of obesity includes life-style interventions, bariatric surgery, and pharmacotherapy. In the last 2 years, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist and GLP-1 and glucose-dependent insulinotropic polypeptide receptor agonist were shown to be effective in managing weight loss in non-CKD patients, but we are awaiting results of more definitive studies in CKD patients.

SGLT2i for evidence-based cardiorenal protection in diabetic and non-diabetic chronic kidney disease: a comprehensive review by EURECA-m and ERBP working groups of ERA.

Chronic kidney disease (CKD) is a major public health issue affecting an estimated 850 million people globally. The leading causes of CKD is diabetes and hypertension, which together account for >50% of patients with end-stage kidney disease. Progressive CKD leads to the requirement for kidney replacement therapy with transplantation or dialysis. In addition, CKD, is a risk factor for premature cardiovascular disease, particularly from structural heart disease and heart failure (HF). Until 2015, the mainstay of treatment to slow progression of both diabetic and many non-diabetic kidney diseases was blood pressure control and renin-angiotensin system inhibition; however, neither angiotensin-converting enzyme inhibitors (ACEIs) nor angiotensin receptor blockers (ARBs) reduced cardiovascular events and mortality in major trials in CKD. The emergence of cardiovascular and renal benefits observed with sodium-glucose cotransporter-2 inhibitors (SGLT2i) from clinical trials of their use as anti-hyperglycaemic agents has led to a revolution in cardiorenal protection for patients with diabetes. Subsequent clinical trials, notably DAPA-HF, EMPEROR, CREDENCE, DAPA-CKD and EMPA-KIDNEY have demonstrated their benefits in reducing risk of HF and progression to kidney failure in patients with HF and/or CKD. The cardiorenal benefits-on a relative scale-appear similar in patients with or without diabetes. Specialty societies' guidelines are continually adapting as trial data emerges to support increasingly wide use of SGLT2i. This consensus paper from EURECA-m and ERBP highlights the latest evidence and summarizes the guidelines for use of SGLT2i for cardiorenal protection focusing on benefits observed relevant to people with CKD.

Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease.

Diabetic kidney disease (DKD) develops in ∼40% of patients with diabetes and is the most common cause of chronic kidney disease (CKD) worldwide. Patients with CKD, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular (CV) death. The use of renin-angiotensin system (RAS) blockers to reduce the incidence of kidney failure in patients with DKD dates back to studies that are now ≥20 years old. During the last few years, sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with RAS blockers and SGLT2is, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of CV death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists (MRAs) reduce albuminuria and surrogate markers of CV disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In the FInerenone in reducing kiDnEy faiLure and dIsease prOgression in DKD (FIDELIO-DKD) study comparing the actions of the non-steroidal MRA finerenone with placebo, finerenone reduced the progression of DKD and the incidence of CV events, with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of MRAs, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic CKD.

Serum zinc values, ankle brachial index and mortality in hemodialysis patients.

INTRODUCTION: The atherosclerotic state of haemodialysis (HD) patients may be influenced by heavy metals. The purpose of our study was to assess the relationship between serum zinc (Zn) ankle brachial index (ABI) as a non-invasive diagnostic tool for atherosclerosis, and mortality in chronic haemodialysis (HD) patients. METHODS: Sixty one HD patients were included (mean age 61.2 ± 13.8 years). The ABI was measured with an automated measuring device (ABPI MD, MESI®, Slovenia). Two groups of patients were formed based on the median value of Zn (14.1 mcmol/l). The average observation time was 2.8 years. Comorbidities (arterial hypertension (AH), diabetes mellitus (DM), dyslipidaemia), smoking and oral nutritional supplements (ONS) consumption were noted. Survival rates were analysed by Kaplan-Meier and Cox regression was used to determine the influence of Zn, ABI, AH, DM, dyslipidaemia, smoking and ONS. RESULTS: Zn values were between 9.2 and 23.5 mcmol/l (14.4 ± 2.34), ABI values ranged from 0.8 to 1.4 (1.14 ± 0.12). Patients with lower Zn values had lower ABI (p = 0.036). Mean survival time of patients with higher Zn values was 985 days ± 277 days and with lower Zn values 1055 ± 143 days. Six (19.4%) patients with lower Zn and five (16.7%) patients with higher Zn died. We found statistically insignificant lower survival in patients with higher Zn. We failed to find any predictor of all-cause mortality, except for ONS consumption (95% CI 1.6-33.3; p = 0.012). CONCLUSIONS: Lower Zn is associated with lower ABI in HD patients, but we found no impact of Zn on patient survival.

Immune response to SARS-CoV-2 mRNA vaccine in patients with psoriasis treated with biologics.

The effect of psoriasis treatment with biologics on the efficacy of COVID-19 vaccines is largely unknown. Our study aimed to evaluate antibody response against SARS-CoV-2 following two doses of BNT162b2 (Pfizer/BioNTech vaccine) in patients with psoriasis receiving biologic monotherapy, and compare it with that of healthy controls.

Polypharmacy and Mental Health Issues in the Senior Hemodialysis Patient.

Hemodialysis (HD) is the most common method of chronic kidney failure (CKF) treatment, with 65% of European patients with CKF receiving HD in 2018. Regular two to three HD sessions weekly severely lower their quality of life, resulting in a higher incidence of depression and anxiety, which is present in one third to one half of these patients. Additionally, the age of patients receiving HD is increasing with better treatment and care, resulting in more cognitive impairment being uncovered. Lastly, patients with other mental health issues can also develop CKF during their life with need for kidney replacement therapy (KRT). All these conditions need to receive adequate care, which often means prescribing psychotropic medications. Importantly, many of these drugs are eliminated through the kidneys, which results in altered pharmacokinetics when patients receive KRT. This narrative review will focus on common issues and medications of CKF patients, their comorbidities, mental health issues, use of psychotropic medications and their altered pharmacokinetics when used in HD, polypharmacy, and drug interactions, as well as deprescribing algorithms developed for these patients.

Recovery of dialysis patients with COVID-19: health outcomes 3 months after diagnosis in ERACODA.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. METHODS: We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. RESULTS: In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. CONCLUSIONS: Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.