Strategies for prevention and treatment of SARS-COV-2 infection in patients with chronic kidney disease: Literature review.

COVID-19 has proven to be particularly aggressive in patients with chronic kidney disease (CKD). The lower immune response rate and the greater susceptibility to progress to severe forms of the disease have contributed to this phenomenon, which has persisted in the post-vaccination era of the pandemic. Paradoxically, CKD has been excluded from most clinical trials of the main therapeutic tools developed against SARS-CoV-2. However, experience in the use of these drugs has been accumulating in different stages of CKD, supporting their use with guarantees of efficacy and safety. The objective of this review is to gather all treatment indications for COVID-19 in the different phases of the disease, tailored to CKD in its various stages, including renal replacement therapy.

Treatment of Chronic Heart Failure in Advanced Chronic Kidney Disease: The HAKA Multicenter Retrospective Real-World Study.

INTRODUCTION: Chronic heart failure (HF) has high rates of mortality and hospitalization in patients with advanced chronic kidney disease (aCKD). However, randomized clinical trials have systematically excluded aCKD population. We have investigated current HF therapy in patients receiving clinical care in specialized aCKD units. METHODS: The Heart And Kidney Audit (HAKA) was a cross-sectional and retrospective real-world study including outpatients with aCKD and HF from 29 Spanish centers. The objective was to evaluate how the treatment of HF in patients with aCKD complied with the recommendations of the European Society of Cardiology Guidelines for the diagnosis and treatment of HF, especially regarding the foundational drugs: renin-angiotensin system inhibitors (RASi), angiotensin receptor blocker/neprilysin inhibitors (ARNI), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). RESULTS: Among 5,012 aCKD patients, 532 (13%) had a diagnosis of HF. Of them, 20% had reduced ejection fraction (HFrEF), 13% mildly reduced EF (HFmrEF), and 67% preserved EF (HFpEF). Only 9.3% of patients with HFrEF were receiving quadruple therapy with RASi/ARNI, BB, MRA, and SGLT2i, but the majority were not on the maximum recommended doses. None of the patients with HFrEF and CKD G5 received quadruple therapy. Among HFmrEF patients, approximately half and two-thirds were receiving RASi and/or BB, respectively, while less than 15% received ARNI, MRA, or SGLT2i. Less than 10% of patients with HFpEF were receiving SGLT2i. CONCLUSIONS: Under real-world conditions, HF in aCKD patients is sub-optimally treated. Increased awareness of current guidelines and pragmatic trials specifically enrolling these patients represent unmet medical needs.

Consensus on the approach to hydrosaline overload in acute heart failure. SEMI/SEC/S.E.N. recommendations.

Most of the signs and symptoms of heart failure can be explained by fluid overload, which is also related to disease progression. Fluid overload is a complex phenomenon that extends beyond increased intravascular pressures and poses challenges for accurate diagnosis and effective treatment. Current recommendations advise a multiparametric approach, including clinical data (symptoms/signs), imaging tests, and biomarkers. This article proposes a practical therapeutic approach to managing hydrosaline overload in heart failure in both inpatient and outpatient settings. This document is an initiative of the Spanish Society of Internal Medicine (SEMI) in collaboration with the Spanish Society of Cardiology (SEC) and the Spanish Society of Nephrology (S.E.N.).

Practical Approaches to the Management of Cardiorenal Disease beyond Congestion.

BACKGROUND: The coexistence of heart and kidney diseases, also called cardiorenal syndrome, is very common, leads to increased morbidity and mortality, and poses diagnostic and therapeutic difficulties. There is a risk-treatment paradox, such that patients with the highest risk are treated with lesser disease-modifying medical therapies. SUMMARY: In this document, different scientific societies propose a practical approach to address and optimize cardiorenal therapies and related comorbidities systematically in chronic cardiorenal disease beyond congestion. Cardiorenal programs have emerged as novel models that may assist in delivering coordinated and holistic management for these patients. KEY MESSAGES: (1) Cardiorenal disease is a ubiquitous entity in clinical practice and is associated with numerous barriers that limit medical treatment. (2) The present article focuses on the practical approaches to managing chronic cardiorenal disease beyond congestion to overcome some of these barriers and improve the treatment of this high-risk population.

Opportunities to improve the management of anemia in peritoneal dialysis patients: lessons from a national study in routine clinical practice.

Background: Current guidelines establish the same hemoglobin (Hb) and iron biomarkers targets for hemodialysis (HD) and peritoneal dialysis (PD) in patients receiving erythropoiesis-stimulating agents (ESAs) even though patients having PD are usually younger, more active and less comorbid. Unfortunately, specific renal anemia [anemia in chronic kidney disease (aCKD)] trials or observational studies on PD are scanty. The aims of this study were to describe current aCKD management, goals and adherence to clinical guidelines, identifying opportunities for healthcare improvement in PD patients. Methods: This was a retrospective, nationwide, multicentre study including patients from 19 PD units. The nephrologists collected baseline data, demographics, comorbidities and data related to anemia management (laboratory values, previously prescribed treatments and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for definitions, drug prescriptions and targets. Results: A total of 343 patients (mean age 62.9 years, 61.2% male) were included; 72.9% were receiving ESAs and 33.2% iron therapy [20.7% intravenously (IV)]. Eighty-two patients were receiving ESA without iron therapy, despite 53 of them having an indication according to the European Renal Best Practice guidelines. After laboratory results, iron therapy was only started in 15% of patients. Among ESA-treated patients, 51.9% had an optimal control [hemoglobin (Hb) 10-12 g/dL] and 28.3% between 12-12.9 g/dL. Seventeen patients achieved Hb >13 g/dL, and 12 of them remained on ESA after overshooting. Only three patients had Hb <10 g/dL without ESAs. Seven patients (2%) met criteria for ESA resistance (epoetin dose >300 IU/kg/week). The highest tertile of erythropoietin resistance index (>6.3 UI/kg/week/g/dL) was associated with iron deficiency and low albumin corrected by renal replacement therapy vintage and hospital admissions in the previous 3 months. Conclusion: Iron therapy continues to be underused (especially IV). Low albumin, iron deficiency and prior events explain most of the ESA hyporesponsiveness. Hb targets are titrated to/above the upper limits. Thus, several missed opportunities for adequate prescriptions and adherence to guidelines were identified.

Adverse renal effects of check-point inhibitors (ICI) in cancer patients: Recommendations of the Onco-nephrology Working Group of the Spanish Society of Nephrology.

The most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of Onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in Onconephrology consultations.

Estimation of glomerular filtration rate in cardiorenal patients: a step forward.

The progressive reduction in estimated glomerular filtration rate (eGFR) resulting in chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) (i.e., cardiorenal disease). Cardiorenal disease is associated with poor outcomes, mainly due to increased cardiovascular (CV) complications and CV death. Data from general population-based studies and studies of cohorts with CKD and/or CVD show that compared with creatinine-based eGFR, cystatin C-based eGFR and creatinine plus cystatin C-based eGFR detect higher risks of adverse CV outcomes and add predictive discrimination to current CVD risk scores. On the other hand, growing clinical evidence supports kidney and CV protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in cardiorenal patients. However, recent data suggest that some detrimental effects of SGLT2 inhibitors on skeletal muscle mass may lead to overestimation of creatinine-based eGFR and subsequent misinterpretation of associated CV risk in patients treated with these agents. Within this framework, we suggest the advisability of using cystatin C and/or creatinine plus cystatin C-based eGFR for routine clinical practice in cardiorenal patients to more accurately stratify CV risk and evaluate the kidney and CV protective effects of SGLT2 inhibitors. In this regard, we make a call to action to investigate the protective effects of these pharmacological agents using cystatin C-based eGFR.

Selective glomerular hypofiltration syndrome.

The estimated glomerular filtration rate (eGFR) provides insight into cardiovascular disease (CVD) risk stratification and proactive management. Accumulating evidence suggests that combining eGFR calculated from serum cystatin C (eGFRcys) and from serum creatinine (eGFRcrea) improves CVD risk stratification over eGFRcrea alone. The term selective glomerular hypofiltration syndrome (SGHS) or shrunken pore syndrome has been proposed to define an eGFRcys:eGFRcrea ratio <1, which is hypothesized to result from a reduced glomerular filtration of 5- to 30-kDa molecules as compared with smaller molecules. SGHS may be identified in people with normal or reduced measured GFR, but the prevalence depends on the cut-off value of the eGFRcys:eGFRcrea ratio used, which is not yet standardized. SGHS is strongly associated with increased CVD and mortality risks and it may offer an opportunity to expand our understanding of the mechanisms linking GFR disorders with CVD risk (e.g. an altered plasma proteome), which may guide treatment decisions. However, muscle wasting may also contribute to a reduced eGFRcys:eGFRcrea ratio and there are open questions regarding the pathophysiology of a reduced eGFRcys:eGFRcrea ratio, the reference cut-off values of the ratio to define the syndrome and its clinical implications. We now critically review the SGHS concept, its pathophysiological basis and links to CVD and the potential consequences for clinical practice and propose a research agenda.

The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalizing the measurement of albuminuria to identify vascular risk and prevent vascular disease.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Clinical Characteristics and Management of Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: A Feasibility Analysis of Electronic Health Records Using Natural Language Processing.

Introduction: This study aimed to assess the feasibility of applying natural language processing (NLP) to analyze real-world data (RWD) and resolve clinical problems in patients with secondary hyperparathyroidism and chronic kidney disease undergoing hemodialysis (SHPT/CKD-HD). The primary objective was to evaluate how well the guideline-recommended analytical goals are achieved in a Spanish cohort of SHPT/CKD-HD patients based on RWD. Methods: Unstructured data in the electronic health records (EHRs) from 8 hospitals were retrospectively analyzed using the EHRead® technology, based on NLP and machine learning. Variables extracted from EHRs included demographics, CKD-related clinical characteristics, comorbidities and complications, mineral and bone disorder parameter levels, and treatments at baseline, 6-month, and 12-month follow-up. Results: A total of 623 prevalent SHPT/CKD-HD patients were identified; of those, 282 fulfilled the inclusion criteria. They were predominantly elderly males with cardiovascular comorbidities, and the first cause of CKD was diabetic nephropathy. Diagnosis of SHPT was associated with an improvement in median values for PTH, calcium, and phosphate. However, the percentage of patients with normal PTH ranges remained stable during the study period (52.8-60.4%), while the percentage of patients with within-target range serum calcium or phosphate values showed an increasing trend (43.2-60% and 38.8-50%). At baseline, 74.1% of patients were using SHPT-related medication, including at least one vitamin D or analog (63.1%), phosphate binders (46.8%), and/or calcimimetics (9.6%). Conclusions: This study represents the first attempt to use clinical NLP to analyze SHPT/CKD-HD patients based on unstructured clinical data. This methodology is useful to address clinical problems based on RWD and identified a high rate of out-of-range mineral-bone analytical values in patients with HPT/CKD-HD and an increasing trend of out-of-range values for serum calcium and phosphate.

Diastolic dysfunction is an independent predictor for cardiovascular events after an acute kidney injury.

BACKGROUND AND AIM: Acute kidney injury (AKI) conditions several short- and long-term complications. The aim of the present study was to analyse the impact of cardiac function and structure in the cardiovascular prognosis after an in-hospital AKI episode. MATERIAL AND METHODS: This is an observational retrospective cohorts study including all in-hospital AKI episodes in 2013 and 2014 in our centre. At baseline, epidemiological values, comorbidities and echocardiography parameters were collected. During a follow-up of 49 ±â€¯28 months, cardiovascular events (CVE) were collected, and associated factors were analysed. RESULTS: 1255 patients were included (55% male, age 75 ±â€¯13 years). Of the 676 (54%) that had a previous echocardiogram, 46% had left ventricular hypertrophy, 38% pulmonary hypertension, 38% diastolic dysfunction and 22% systolic dysfunction. During the follow-up, 484 (39%) developed a CVE. Associated factors to VCE were male sex, age, diabetes mellitus, hypertension, dyslipidemia, coronary heart disease, heart failure, atrial fibrillation, neoplasia and chronic kidney disease (also, glomerular filtration rate at baseline and after the AKI episode). Survival curves demonstrated that all the echocardiographic parameters were associated to CVE. An adjusted Cox regression model showed that age (HR 1.017), diabetes (HR 1.576) and diastolic dysfunction (HR 1.358) were independent predictors for CVE. CONCLUSION: Diastolic dysfunction is an independent predictor for long-term cardiovascular events after an in-hospital acute kidney injury episode.

Practical approaches to building up a cardiorenal clinic.

The population with concomitant heart and kidney disease (often termed 'cardiorenal' disease) is expected to grow, significantly impacting public health and healthcare utilization. Moreover, the cardiorenal nexus encompasses a bidirectional relationship that worsens prognosis and may complicate pharmacological management in often elderly and frail patients. Therefore, a more cohesive multidisciplinary team approach aiming to provide holistic, coordinated and specialized care would be a positive shift towards improving patient outcomes and optimizing healthcare resources. This article aims to define the organizational aspects and key elements for setting up a multidisciplinary cardiorenal clinical program as a potential healthcare model adapted to the particular characteristics of patients with cardiorenal disease.

Lessons from SENCOVAC: A prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has negatively impacted on patients of the whole CKD spectrum, causing high rates of morbi-mortality. SARS-CoV-2 vaccines opened a new era, but patients with CKD (including kidney transplant, hemodialysis and peritoneal dialysis) were systematically excluded from pivotal clinical trials. The Spanish Society of Nephrology promoted the multicentric national SENCOVAC study aimed at assessing immunological responses after vaccination in patients with CKD. During the first year after vaccination, patients with non-dialysis CKD and those on hemodialysis and peritoneal dialysis presented good anti-Spike antibody responses to vaccination, especially after receiving the third and fourth doses. However, kidney transplant recipients presented suboptimal responses after any vaccination schedule (initial, third and fourth dose). Especially worrisome is the situation of a patients with a persistently negative humoral response that do not seroconvert after boosters. In this regard, monoclonal antibodies targeting SARS-CoV-2 have been approved for high-risk patients, although they may become obsolete as the viral genome evolves. The present report reviews the current status of SARS-CoV-2 vaccination in the CKD spectrum with emphasis on lessons learned from the SENCOVAC study. Predictors of humoral response, including vaccination schedules and types of vaccines, as well as the integration of vaccines, monoclonal antibodies and antiviral agents are discussed.

From cardiorenal syndromes to cardionephrology: a reflection by nephrologists on renocardiac syndromes.

Cardiorenal syndromes (CRS) are broadly defined as disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. CRS are currently classified into five categories, mostly based on disease-initiating events and their acuity or chronicity. CRS types 3 and 4 (also called renocardiac syndromes) refer to acute and chronic kidney dysfunction resulting in acute and chronic heart dysfunction, respectively. The notion of renocardiac syndromes has broadened interest in kidney-heart interactions but uncertainty remains in the nephrological community's understanding of the clinical diversity, pathophysiological mechanisms and optimal management approaches of these syndromes. This triple challenge that renocardiac syndromes (and likely other cardiorenal syndromes) pose to the nephrologist can only be faced through a specific and demanding training plan to enhance his/her cardiological scientific knowledge and through an appropriate clinical environment to develop his/her cardiological clinical skills. The first must be the objective of the subspecialty of cardionephrology (or nephrocardiology) and the second must be the result of collaboration with cardiologists (and other specialists) in cardiorenal care units. This review will first consider various aspects of the challenges that renocardiac syndromes pose to nephrologists and, then, will discuss those aspects of cardionephrology and cardiorenal units that can facilitate an effective response to the challenges.

Humoral response after the fourth dose of the SARS-CoV-2 vaccine in the CKD spectrum: a prespecified analysis of the SENCOVAC study.

BACKGROUND: There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. METHODS: This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity. RESULTS: Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients. CONCLUSIONS: A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.

Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.

Inhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions. Although Slc7a5 gene inactivation in the erythrocyte lineage does not compromise the total number of circulating red blood cells (RBCs), their size and hemoglobin content are significantly reduced accompanied by a diminished erythroblast mTORC1 activity. Furthermore circulating Slc7a5-deficient reticulocytes are characterized by lower transferrin receptor (CD71) expression as well as mitochondrial activity, suggesting a premature transition to mature RBCs. These data reveal that SLC7A5/SLC3A2 ensures adequate maturation of reticulocytes as well as the proper size and hemoglobin content of circulating RBCs.

Consensus document on palliative care in cardiorenal patients.

There is an unmet need to create consensus documents on the management of cardiorenal patients since, due to the aging of the population and the rise of both pathologies, these patients are becoming more prevalent in daily clinical practice. Chronic kidney disease coexists in up to 40%-50% of patients with chronic heart failure cases. There have yet to be consensus documents on how to approach palliative care in cardiorenal patients. There are guidelines for patients with heart failure and chronic kidney disease separately, but they do not specifically address patients with concomitant heart failure and kidney disease. For this reason, our document includes experts from different specialties, who will not only address the justification of palliative care in cardiorenal patients but also how to identify this patient profile, the shared planning of their care, as well as knowledge of their trajectory and the palliative patient management both in the drugs that will help us control symptoms and in advanced measures. Dialysis and its different types will also be addressed, as palliative measures and when the decision to continue or not perform them could be considered. Finally, the psychosocial approach and adapted pharmacotherapy will be discussed.

Oral Anticoagulation in Patients with Chronic Kidney Disease and Non-Valvular Atrial Fibrillation: The FAERC Study.

Atrial fibrillation (AF) is the most common arrhythmia in patients with chronic kidney disease (CKD), and its presence is associated with a higher risk of stroke and mortality. MATERIAL AND METHODS: The FAERC study performed a retrospective multicentre analysis of historical cohorts in which data were collected from arrhythmia diagnosis onwards. RESULTS: We analysed a Spanish cohort of 4749 patients with CKD (mean eGFR 33.9 mL/min) followed up in the nephrology clinic, observing a 12.2% prevalence of non-valvular AF. In total, 98.6% of these patients were receiving anticoagulant treatment, mainly with coumarins (79.7%). Using direct-acting oral anticoagulants (DOACs) was associated with fewer cerebrovascular events than using acenocoumarol, but in contrast with other studies, we could not corroborate the association of risk of bleeding, coronary events, or death with a type of anticoagulant prescribed. CONCLUSIONS: Atrial fibrillation is highly prevalent in renal patients. Direct-acting anticoagulants seem to be associated with fewer ischemic-embolic complications, with no differences in bleeding, coronary events, or mortality rates.