Clinical Kidney Journal, 2023, vol. 16, no. 5, 780–792 https:/doi.org/10.1093/ckj/sfac258 Advance Access Publication Date: 7 December 2022 CKJ Review CKJ REVIEW Practical approaches to building up a cardiorenal clinic Rafael de la Espriella1,∗ , Marta Cobo Marcos 2,3,∗ , Claudio Ronco4,5,6 , Debasish Banerjee 7,8 , Miguel González9,10 , José Luis Górriz 9,10 , Borja Quiroga 11 , María José Soler 12 , Javier Díez 3,13,14,15 and Julio Núñez 1,3,10 1 Department of Cardiology, Hospital Clínico Universitario de Valencia, Valencia, Spain, 2 Department of Cardiology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain, 3 Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares, Madrid, Spain, 4 Department of Medicine, University of Padova, Padova, Italy, 5 International Renal Research Institute of Vicenza, Vicenza, Italy, 6 Department of Nephrology, San Bortolo Hospital, Vicenza, Italy, 7 Renal and Transplantation Unit, St George’s University Hospitals National Health Service Foundation Trust, London, UK, 8 Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, UK, 9 Department of Nephrology, Hospital Clínico Universitario de Valencia, Valencia, Spain, 10 Department of Medicine, Universitat de Valencia, Valencia, Spain, 11 Department of Nephrology, Hospital Universitario de la Princesa, Madrid, Spain, 12 Department of Nephrology, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Nephrology and Kidney Transplant Research Group, Vall d’Hebron Research Institute, Barcelona, Spain, 13 Department of Cardiology, University of Navarra Clinic, Pamplona, Spain, 14 Department of Nephrology, University of Navarra Clinic, Pamplona, Spain and 15 Program of Cardiovascular Diseases, Center of Applied Medical Research, University of Navarra, Pamplona, Spain ∗ Equal first authors. Correspondence to: Julio Núñez; E-mail: yulnunez@gmail.com or juenuvi@uv.es ABSTRACT 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. Received: 22.8.2022; Editorial decision: 7.11.2022 © The Author(s) 2022. Published by Oxford University Press on behalf of the ERA. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 780 Building up a cardiorenal clinic 781 GRAPHICAL ABSTRACT Keywords: cardiorenal clinics, cardiorenal disease, cardiorenal program, heart failure, kidney disease seems to accelerate the presentation and progression of the THE NEED FOR CARDIORENAL PROGRAMS other [8–10]. Moreover, despite the undisputed efficacy of cur- Heart failure (HF) is a major public health problem associated rent pharmacological treatment options to reduce morbidity with high use of resources and healthcare costs [1]. Although and mortality in patients with HF, treatment-induced changes the incidence has remained stable or even slightly declined in kidney function are often perceived as deleterious, result- over time, the prevalence is projected to increase due to pop- ing in ineffective drug implementation. As a result, there is a ulation longevity and an increase in cardiovascular risk factors risk–treatment paradox in managing patients with HF and ad- and associated comorbidities [2, 3]. Therefore it is a priority vanced CKD, such that patients with the highest morbimortal- to implement solid population healthcare strategies with well- ity burden are treated with lesser disease-modifying medical defined objectives throughout the care process. One of these therapies [11]. strategies has been the development of specific HF management On the other hand, the perception and understanding of kid- programs aimed at improving diagnosis, appropriate evidence- ney disease as a cardiovascular risk factor and as a global cardio- based therapy, education and suitable follow-up [4]. However, HF vascular risk multiplier has evolved significantly in recent years. often coexists with relevant comorbidities that worsen progno- However, little progress has been made in developing manage- sis and complicate management, requiring a multidisciplinary ment structures that offer individualized and coordinated team approach to provide holistic, coordinated and specialized care. Although cardiologists and nephrologists are expected to care. have advanced knowledge and skills to manage each disease Chronic kidney disease (CKD) is one of the most prevalent separately, patients are sent back and forth from cardiologists comorbidities in patients with HF, and at the same time, pa- to nephrologists (and vice versa), often leading to conflict- tients with CKD (especially those with advanced stages) ex- ing diagnostic and therapeutic approaches. The interaction hibit a high to very high risk for cardiovascular disease (CVD) between cardiologists and nephrologists in the context of an and incident HF [5–7]. Given the high burden of both conditions interdisciplinary care model should ensure goal-directed treat- and their pathophysiological interrelationship, the cardiorenal ment selection (pharmacological and non-pharmacological) nexus represents a real clinical challenge since one condition based on the individual characteristics of each patient. For 782 R. de la Espriella et al. Table 1: Specific objectives. 1. Improve communication and coordination between specialists involved in the management of patients with cardiorenal disease at the different health care levels 2. Guarantee continuity of care through collaborative teamwork according to patient needs and disease stage severity 3. Develop common protocols and structured clinical pathways 4. Ensure equity of care 5. Optimize patient flow to enable timely, efficient, and high-quality care 6. Reduce clinical variability, applying current clinical practice criteria and agreed protocols 7. Optimize pharmacological and device-based treatment according to current clinical practice recommendations and individualize therapies according to eGFR strata 8. Ensure the best pharmacological treatment selection/combination based on the individual characteristics of each patient 9. Educate patients and caregivers in self-care 10. Facilitate access to advanced treatment options; supportive and palliative care 11. Reduce the number of patient encounters with healthcare with more time at home 12. Promote telemedicine tools to improve monitoring, enhance communication through the different care levels, and optimize health resources 13. Reduce the number of emergency room visits 14. Promote multidisciplinary research and specific training instance, an example of that could be the choice of carvedilol/ DEFINITION AND OBJECTIVES bisoprolol over metoprolol in patients on haemodialysis (HD), the selection of home dialysis therapies, specifically Definition home HD (HHD) or peritoneal dialysis (PD) over conven- The cardiorenal clinical program is a specialized care model, tional HD sessions in patients with concomitant HF or ad- defined as a set of coordinated and multidisciplinary interven- vanced CVD, among many other patient-centred management tions designed to systematically address the specific manage- strategies. ment and clinical follow-up of patients with cardiorenal disease. Even though scientific statements support the need for a dedicated cardiorenal multidisciplinary team approach, specific cardiorenal care models are still scarce [12]. Although the Primary objective barriers to implementing these multidisciplinary care models The primary goal of cardiorenal clinical programs is to offer a may vary between countries and healthcare systems, fragmen- comprehensive and coordinated clinical approach, providing a tation of health services, geographic disparities, inadequate more efficient and structured model that guarantees personal- infrastructure, insufficient human resources and reluctance ized and optimized care, reducing clinical variability and offer- to change are some of the most critical and generalized ob- ing a faster response capacity, with the ultimate goal of improv- stacles. In fact, in a recent study conducted in Spain, only ing patient outcomes and quality of life and, at the same time, 10% of specialized HF clinics reported a specific cardiorenal reducing healthcare costs. clinical program and only 30% had established protocols among cardiologists and nephrologists for managing patients with cardiorenal disease [13]. Local, regional and national healthcare Specific objectives providers should support the development of these models of care, ensure the redistribution of resources and facilitate the Operational considerations necessary structural changes to ensure the long-term viability Cardiorenal clinics should be patient-centred, adapting avail- of the cardiorenal clinics. Therefore, efforts should be made to able resources (infrastructure, facilities, staff and finances) and quantify the cost-effectiveness of these models at an institu- administrative policies to the patient’s needs (Table 1). The fol- tional level, given that spreading its results may enhance the lowing characteristics and components should be considered to dissemination of cardiorenal clinic initiatives at a regional level. build a solid, accessible and functional program (Table 2). For instance, Nguyen et al. [14] showed that a novel interdis- ciplinary cardiorenal clinic improved guideline-recommended Clinical staff medication prescription and iron status in 124 patients with HF and advanced CKD. Moreover, Sankaranarayanan et al. [15] Although staffing models may vary according to local healthcare described the usefulness of a monthly cardio-nephrology meet- structure, a nephrologist, HF specialist and specialized cardiore- ing to provide expert consensus decision-making, reducing nal nurses are critical to the functioning of any cardiorenal clin- unnecessary outpatient visits. Specialized cardiorenal care has ical program. Supplementary Table 1 summarizes the proposed also been developed in other clinical scenarios with promising qualification standards that a cardiorenal nurse should have. results, such as in hospitalized patients with concomitant Ideally, all members of the cardiorenal team should be present heart and kidney disease or in high-risk kidney transplant during each clinical visit to provide holistic and coordinated candidates [16, 17]. management in order to reduce clinical variability. Furthermore, In this article we aim to define the organizational as- patients with cardiorenal disease often have multiple comor- pects and key elements that a cardiorenal program should bidities and geriatric domain impairments that adversely affect have to improve the management of patients with cardiorenal their prognosis. Accordingly, coordinating care with other pro- disease. fessionals with unique yet complementary expertise is essential Building up a cardiorenal clinic 783 Table 2: Checklist to consider when building a cardiorenal clinic. Mandatory 1. Cardiology and nephrology hospitalization wards 2. Availability of kidney replacement therapy 3. Hospital-day setting with a dedicated space for ambulatory parenteral treatment administration (i.e. diuretics, intravenous iron) and managing KRT-derived procedures and complications 4. Readily accessible laboratory monitoring 5. Clinic appointment structure 6. Ultrasound equipment and bioimpedance monitor system 7. Clinical practice protocols Optional 8. Educational materials and resources for patients and caregivers 9. Virtual visit infrastructure 10. Build or join a research network to reduce care fragmentation and improve outcomes. Members although further studies are needed to confirm the best entry of such a multidisciplinary and allied care team may include, criteria, we propose targeting the following patient profiles: but are not limited to, a primary care clinician, social worker, dietitian, pharmacist, physical therapist, vascular/dialysis ac- cess surgeon, urologist, transplantation team and palliative care 1 Inpatient clinician. a Patients with a prior history of very high-risk CKD [eGFR Another important aspect when organizing interdisciplinary <30 ml/min/1.73 m2 or eGFR 30–44 ml/min/1.73 m2 and urine care models is determining who will lead the program. From an albumin:creatinine ratio (UACR) >30 mg/g] or CKD progres- operational perspective, and until a dedicated cardionephrolo- sion discharged from the hospital with uncorrected or per- gist subspecialty becomes available, cardiorenal clinics should sistent cardiovascular conditions (i.e. stage C or D HF, non- use a model centred around both specialties, with shared leader- revascularized ischaemic heart disease, uncorrected valvular ship in ensuring the delivery of high-quality, safe and evidence- heart disease). based patient care. b Patients discharged from the hospital with uncorrected or persistent cardiovascular conditions (i.e. stage C or D HF, non- revascularized ischaemic heart disease, uncorrected valvular Assess the physical location of the cardiorenal clinic heart disease) who developed stage 2 (creatinine ≥2 times baseline or urine volume <0.5 ml/kg for ≥12 h) or stage 3 Cardiorenal clinical programs need to be attached to centres (creatinine ≥3 times baseline or increase to ≥4.0 mg/dl or with both cardiology and nephrology hospitalization wards, HF acute dialysis, or urine volume <0.3 ml/kg for ≥24 h) acute outpatient clinics and the availability of kidney replacement kidney injury (AKI) according to the current Kidney Disease: therapy (KRT). In addition, considering the relevance of conges- Improving Global Outcomes (KDIGO) definition, or stage 2–3 tion, anaemia and iron deficiency (both absolute and functional) acute kidney disease during the 7- to 90-day period after the in patients with cardiorenal disease, cardiorenal clinics should initial AKI. have a dedicated space where patients can be comprehensively c Patients who required transient aquapheresis procedures due evaluated using multiparametric tools (i.e. echocardiography or to refractory congestion during admission. ultrasound equipment, bioimpedance monitoring system), re- 2 Outpatient ceive intravenous therapy, and have readily accessible laboratory a Patients with a history of uncorrected or persistent cardio- monitoring. For patients included in the PD or HHD programs, vascular conditions (i.e. stage C or D HF, non-revascularized educational materials and resources and a dedicated space for ischaemic heart disease, uncorrected valvular heart training and monitoring should be readily available to patients disease) with concomitant very high-risk CKD (eGFR and their family members. <30 ml/min/1.73 m2 or eGFR 30–44 ml/min/1.73 m2 and UACR >30 mg/g) or CKD progression. b Patients with very high-risk CKD (eGFR <30 ml/min/1.73 m2 Referral criteria or eGFR 30–44 ml/min/1.73 m2 and UACR >30 mg/g) or rapidly Although it is unclear which patients are most likely to bene- progressive CKD who develop either acute or progressive fit from being followed in a multidisciplinary cardiorenal clinic, high-risk cardiovascular conditions. available evidence suggests that patients with stage 4–5 CKD c Patients with HF and refractory congestion in whom inten- [18, 19] and those with HF with high-risk features may bene- sive diuretic treatment is ineffective to achieve euvolemia and fit the most [20]. In addition, relatively large observational reg- who might be considered for KRT or intermittent aquaphere- istries have shown a significant association between incident sis programs. cardiovascular-related hospitalizations and an accelerated kid- d Patients with cardiorenal disease who require a transplant ney function decline, particularly in patients with lower baseline workup (heart, kidney or combined). estimated glomerular filtration rate (eGFR) [21, 22]. Moreover, pa- e Patients who require consensus decision-making regarding tients with combined HF and advanced CKD are precisely the pharmacological or device therapy in ‘gray-zone’ areas (e.g. most vulnerable to adverse clinical events and in whom disease- eGFR <30 ml/min/1.73 m2 ). modifying therapies have been classically underused because of f Hyperkalaemia due to renin–angiotensin–aldosterone system concerns of kidney-related adverse events [11]. Accordingly, and (RAAS) inhibitors. 784 R. de la Espriella et al. Figure 1: Referral sources and multidisciplinary evaluation and management of related comorbidities. Referral sources, follow-up and monitoring care providers to improve transition efficiency from one setting to the next (Fig. 2). Considering that patients fulfilling these entry criteria generally correspond to a high-risk population, referrals will probably originate predominantly from HF clinics and advanced kidney Hospital–home transition. Early follow-up after discharge is an care clinics, followed by hospitalization wards, emergency essential step in the success of the transition from the acute departments, general cardiologists/nephrologists and a small phase to long-term outpatient management [24]. An early proportion from primary care physicians (Fig. 1). follow-up visit should be scheduled, ideally within the first Once a patient has been included in the program, it is impor- 7–10 days post-discharge. This intervention should include a tant to determine appropriate follow-up intervals. For example, systematic evaluation using checklists (Table 3) to confirm that stable patients not included in KRT programs and with minimal the patient is euvolemic; reinforce patient and caregiver sup- symptoms should be seen at intervals no longer than 6 months port and education; evaluate potential clinical, haemodynamic, to ensure they are receiving the optimal doses of guideline- renal or electrolyte deterioration; detect drug-related adverse directed therapies and are adhering to their medication regimen events; reconcile medications and optimize treatment based on and to check for symptoms, laboratory monitoring and pre- current guidelines. vention and treatment of CKD-related complications such as anaemia, acidosis and metabolic disorders. Conversely, shorter follow-up intervals might be necessary for patients recently Transitions of care in patients with acute exacerbations. Cardiorenal discharged from the hospital, those with advanced or rapidly disease encompasses changes in the clinical risk of hospital- progressive CKD or worsening symptoms, patients included ization and death over time, with risk increasing from pre- to in KRT programs or those undergoing up-titration of cardio- new-onset cardiorenal syndrome, and further increasing with or nephroprotective medication. We encourage developing an each episode of decompensation, where there is often a deteri- individualized standard operating procedure to properly define oration of kidney function and cardiovascular signs/symptoms and formalize the components and coordinated processes that requiring hospitalization or outpatient interventions. Therefore the cardiorenal team needs to perform (Table 3). Although on- cardiorenal clinics should include readily accessible outpatient site visits are the preferred review modality for most patients, care (day-hospital setting) to deal with such problems in a timely different ways of communication (e-consult, telemedicine) manner, particularly in the period of close proximity to the wors- should also be offered to patients and caregivers to moni- ening event. Importantly, this phase should be based on active tor laboratory results, assess treatment adherence, evaluate communication with other levels of care to identify red flags or drug-related adverse effects and facilitate early detection of de- implement alert systems that allow cardiorenal team members compensations and management of possible adverse outcomes. to be aware of such decompensations and adopt prompt inter- In addition, considering the high prevalence of associated co- ventions. morbidities on a population level, we propose developing well- designed clinical care pathways that guarantee a dynamic flow Transitions of care after clinical/functional stabilization/remission. Al- of patients between the cardiorenal clinic program, primary care though we caution against ‘stable’ cardiorenal disease termi- and other clinical specialties within and outside of cardiorenal nology, some patients exhibit clinical improvement along with medicine to ensure adequate attention to comorbid conditions resolution/remission of previously present structural and func- and non-cardiovascular preventive care (Fig. 1). tional heart and kidney disease. In this phase, patients can be discharged from the program as long as the connectiv- ity among existing care networks and transitional care inter- Transitions between different levels of care ventions and protocols focus on optimizing disease-modifying One of the most important aspects of any multidisciplinary clin- therapies are guaranteed. Therefore the cardiorenal clinic ical model that offers integrated care is the subsequent follow- should ensure a close relationship with the various participants up and transition from different levels of care depending on the from different disciplines involved in patient care and deter- disease stage and progression [23]. Therefore it is imperative to mine the relational structures needed to achieve optimal care develop coordinated and consensed protocols between health- coordination. Building up a cardiorenal clinic 785 Structured follow-up Rapid and effective treatment of Congestion Early follow-up decompensations assessment and treatment Initiate/optimize disease-modifying Diagnostic therapies Laboratory work-up monitoring Comorbidity assessment and treatment Advanced cardiac and Patient-centered kidney therapies clinical pathway Educational support Figure 2: General follow-up approach. Transition towards advanced cardiac and kidney therapies. tion loss) or long-lasting side effects (wasting and sarcopenia) develop [26, 27]. In this scenario, an incremental PD strategy in- creasing dialysis dose in a step-wise manner may help preserve Kidney replacement therapy/kidney transplantation. By residual kidney function while still achieving individualized monitoring the patient closely through frequent laboratory clearance goals [28]. In addition, the time window between and clinical evaluations (fluid retention and patient-reported catheter placement and treatment initiation can be used to pre- symptoms) when the GFR is decreasing or in cases of persistent train the patient and caregivers for the upcoming procedures, and refractory congestion, it is possible to tailor KRT initiation reduce intra-abdominal pressure through ascites drainage in to when both the patient and cardiorenal team feel the timing is those with recurrent ascites and provide a home visit by PD staff optimal. At this point, the cardiorenal team should move away to check for hygiene problems and storage capacity for PD ma- from the traditional ‘one-size-fits-all’ approach and provide terials and solutions. However, although PD is an excellent KRT more individualized or personalized care offering the best KRT modality for many cardiorenal patients, clinical complications modality according to the patient profile. such as catheter malfunctions, peritonitis and ultrafiltration failure may occur, requiring conversion from PD to HD. PD. PD is an excellent mode of KRT for patients with advanced cardiorenal disease, as it provides greater preservation of residual kidney function, continuous ultrafiltration with better Chronic HD. Conventional thrice-weekly in-centre HD is usu- haemodynamic tolerability and efficient volume control while ally not the first-choice KRT modality for most cardiorenal concurrently correcting the metabolic consequences of dimin- patients because of haemodynamic stability concerns during ished kidney function [25]. Although the optimal timing for sessions (which often limits fluid removal) and the possibility of PD initiation in patients with cardiorenal disease is unclear, it interdialytic volume overload [29]. However, conventional HD is should be considered when one or more of the following are sometimes the only available KRT modality (i.e. urgent require- present: uraemic-related symptoms, inability to control volume ment for KRT, elderly and frail patients with barriers to self-care, status with diuretics or congestion-related organ damage (i.e. anatomic contraindication to PD, healthcare structure, financing congestive nephropathy/hepatopathy in the context of right- and delivery), and the cardiorenal team may provide supportive sided HF) but well before critical (medically resistant acid–base care to achieve patient-centred goals. For instance, an integra- or electrolyte abnormalities, low residual diuresis, kidney func- tive and comprehensive assessment of the cardiac function and 786 R. de la Espriella et al. Table 3: General considerations to be included in standard operating procedures. Referral criteria Inpatient Outpatient 1. Patients with CKD stages ≤G3bA2 or CKD progression prior to 1. Patients with prior history of uncorrected or persistent admission who are discharged with uncorrected or persistent cardiovascular conditions with concomitant CKD stages cardiovascular conditions ≤G3bA2 or CKD progression 2. Patients discharged with uncorrected or persistent 2. Patients with CKD stages ≤G3bA2 or CKD progression who cardiovascular conditions who developed persistent stage 2–3 develop either acute or progressive high-risk AKI according to the KDIGO definition or stage 2–3 AKD during cardiovascular conditions the 7- to 90-day period after the initial AKI 3. Patients with refractory congestion who might be considered 3. Patients who required transient aquapheresis procedures due to for KRT or intermittent aquapheresis programs refractory congestion during the index admission 4. Patients with cardiorenal disease who require transplant workup (heart, kidney, or combined) 5. Patients who require consensus decision-making regarding pharmacological or device therapy in ‘gray-zone’ areas (e.g. eGFR <30 ml/min/1.73 m2 ) Follow-up and monitoring 1. Early follow-up visit (7–30 days) Systematic checklist evaluation to be performed in each follow-up • Patients recently discharged from the hospital (ideally within clinical visit the first 7–10 days post-discharge) Multiparametric assessment of congestion • AKI/AKD Kidney function, electrolyte, and acid-base monitoring • Worsening symptoms/persistent congestion Assess drug-related adverse events • Cardio- or nephroprotective treatment initiation/up-titration Medication reconciliation Initiation or up-titration of GDMT 2. Short follow-up intervals (1–3 months) Monitoring and treatment of CKD-related complications • Patients included in KRT programs or transplant workup (i.e. anaemia, iron deficiency, mineral and bone disorder) • Rapidly progressive CKD or CKD stages G4–G5 Reinforce patient and caregiver education • More than two worsening HF events within the last year Risk stratification and care planning despite Provide non-pharmacological advice optimal medial and device therapy Identify the need for, coordinate and provide palliative care • Patients refractory/intolerant to GDMT 3. Long follow-up intervals (6 months) • Stable eGFR (if eGFR >30 ml/min/1.73 m2 ) and UACR • Improving heart/kidney function and biomarker profile • Stable symptoms/signs • Optimal GDMT Flexibility to modify the frequency of follow-up as needed based on the patient’s trajectory, needs and stage of the disease AKD: acute kidney disease; GDMT: guideline-directed medical therapy. volume status combining ultrasound techniques, bioimpedance the cardiorenal team should be aware of this negative associ- tools and biomarkers (dry weight revisited) may guide the need ation and balance the pros and cons of AVF closure in selected and the rate of fluid removal, enhancing haemodynamic tol- cases. Moreover, patients with advanced cardiorenal disease erance [30–32]. Furthermore, HHD is emerging as an attractive are often not considered eligible for an AVF because of their modality that may overcome the adverse consequences of inter- high burden of comorbid conditions that increase surgical risks, dialytic cycles of hypervolemia coupled with rapid and aggres- shortened life expectancy and/or poor vasculature. As a result, sive ultrafiltration commonly seen with conventional HD [29]. tunnelled HD catheters are the most commonly used vascular By increasing the frequency (daily) and duration of HD sessions, access in this population, increasing the risk of bacteriemia and HHD may decrease the ultrafiltration rate (better haemodynamic having the highest rate of vascular access dysfunction [34]. tolerance) while ensuring daily fluid and uraemic solute removal On the other hand, emerging evidence supports the feasi- [29]. However, both HHD and conventional HD require perma- bility and efficacy of intermittent aquapheresis programs in se- nent vascular access [i.e. tunnelled central venous catheter, lected patients for volume control [38]. arteriovenous fistula (AVF) or arteriovenous graft], which con- fers an additional source of adverse events [33, 34]. Although a Mechanical circulatory support/heart transplantation. In mature AVF is generally well tolerated and has the best profile patients with advanced HF referred for long-term mechanical in terms of access-related complications and patency rates, it circulatory support (LT-MCS) or heart transplantation, kidney may have deleterious haemodynamic effects in patients with disease is highly prevalent and is one of the most powerful concomitant heart disease, mainly driven by decreased sys- predictors of post-intervention survival [39]. In fact, advanced temic vascular resistance and increased venous return [35]. This kidney dysfunction (eGFR <30 ml/min/1.73 m2 ) deemed ‘ir- aspect is especially relevant in patients with concomitant right- reversible’ and chronic KRT are contraindications for both sided HF and pulmonary hypertension, in which an AVF may LT-MCS and heart transplantation [4]. Although distinguishing accelerate disease progression [36, 37]. In this particular setting, irreversible forms of kidney dysfunction from likely reversible Building up a cardiorenal clinic 787 forms is challenging, a comprehensive and multiparametric or up-titrate these therapies, as any deterioration in kidney evaluation of congestion/hypoperfusion, including point-of-care function is often perceived as deleterious. In fact, the presence ultrasound, invasive assessment (i.e. right heart catheteriza- of kidney disease is one of the main reasons for ineffective drug tion, invasive blood volume analysers), bioimpedance tools and implementation in HF patients [44, 45]. Therefore cardiorenal biomarkers, may provide relevant information regarding which clinics should offer a structured and personalized follow-up patients are likely to benefit from those therapies [32]. In this that favours the implementation of these life-saving therapies scenario, cardiorenal clinics may offer a window for patient and provide rapid and efficient solutions to drug-related adverse optimization before patient eligibility. effects. Transition toward end-of-life care. Patients with advanced car- Anticoagulation in atrial fibrillation (AF) diorenal disease, particularly those with stage D HF and kidney failure, often have a high symptom burden that substantially CKD is associated with a higher prevalence of AF, thromboem- affects their health-related quality of life. Furthermore, many bolic events and bleeding complications [46]. Anticoagulation of these patients will not be candidates for advanced solutions has been shown to reduce the risk of stroke and mortality in such as KRT, kidney/cardiac transplantation or mechanical cir- patients with AF and mild and moderate CKD [47]. However, pa- culatory support. Therefore, at this level of care, the objective tients with advanced CKD or those on KRT have been excluded is to enhance symptoms and quality of life through a multidis- from randomized controlled trials. Observational studies have ciplinary strategy that includes collaborative decision-making, shown conflicting results, even suggesting that treatment with palliative care planning and psychological and social support. vitamin K antagonists (VKAs) may be harmful in this end-stage If patients require hospitalization at the end of life because of CKD [47]. Other specific problems related to the use of VKAs that poor symptom control and/or suboptimal family support, direct should be considered are the increased risk of developing vas- admission to a palliative care unit is desirable. In addition, for cular calcification [48] and anticoagulant-associated nephropa- those included in KRT programs, treatment decisions such as thy [49]. The available data suggest that direct oral anticoagu- reducing dialysis dose and frequency to a minimum (palliative lants have a better safety and efficacy profile in patients with dialysis) or withdrawing completely from KRT should be individ- CKD, but data in patients with advanced CKD are scarce [50]. On ualized according to the patient’s free choice. This whole process the other hand, left atrial appendage occlusion has been shown should be well defined in the cardiorenal care pathway. to reduce the incidence of thromboembolic events in patients with AF, with a low incidence of adverse events, so this strat- egy should be considered for patients with an increased risk of Specific approaches when managing patients with bleeding [51]. cardiorenal disease The suggested specific approach for managing patients with car- Prevention of contrast-induced AKI diorenal disease is summarized in Table 4. Diagnostic and therapeutic procedures that require contrast Congestion agents are frequently needed in patients with CVDs. Although pre-existing CKD is the strongest patient-related risk factor for Fluid overload plays a major role in the pathogenesis, presen- developing contrast-induced AKI [52], the use of high contrast tation and prognosis of most patients with combined heart and volumes (>350 ml or >4 ml/kg) or repeated exposure to con- kidney disease and represents a core target for treatment. How- trast agents (within 72 h) has also been shown to increase the ever, the optimal method to assess fluid status and to determine risk [53]. Accordingly, the cardiorenal team should increase the euvolemia (‘dry weight’) in decompensated HF or kidney disease awareness among clinicians to limit large amounts of contrast remains an unresolved issue, resulting in diagnostic uncertainty media, using either iso-osmolar or low-osmolar iodinated con- and hampering therapeutic decision-making. Therefore, one of trast media rather than high-osmolar iodinated contrast media, the most important qualification standards for cardiorenal spe- and ensure prophylactic hydration in patients at risk for AKI at cialists is a deep understanding of cardiorenal physiology (with a least 6 h before and after contrast-enhanced imaging studies or particular focus on intrarenal haemodynamics and the complex interventions [54]. and dynamic interplay between the interstitial and intravascular fluid compartments) as well as diuretic pharmacokinetics and pharmacodynamics. Accordingly, one standard operating proce- PROPOSED CARDIORENAL CARE QUALITY dure in each clinical visit should be a comprehensive and mul- INDICATORS tiparametric evaluation of volume status to detect subclinical congestion, better phenotype congestion profiles [32] and offer One of the most important aspects of specific clinical manage- personalized management [40–43] strategies. ment programs lies in the continuous monitoring of measures designed to evaluate the performance of the process. These indi- Guideline-directed medical therapy implementation in cators should be directed at specific clinical outcomes (i.e. mor- patients with HF tality and readmissions) and process outcomes (Table 5). Several pharmacological treatment options, such as RAAS inhibitors, angiotensin receptor–neprilysin inhibitors, miner- THE NEED FOR SPECIFIC alocorticoid receptor antagonists and sodium–glucose cotrans- CARDIO-NEPHROLOGY EDUCATIONAL porter 2 inhibitors, have been shown to reduce morbidity and PROGRAMS mortality in patients with HF and reduced ejection fraction and are recommended as a class I indication in clinical prac- Interest in cardiorenal pathology has evolved considerably in re- tice guidelines [4]. However, as these drugs may induce an cent years. Clinical investigations and research concerning car- initial eGFR decrease [11], clinicians often struggle to initiate diorenal disease have increased significantly, to the point where 788 R. de la Espriella et al. Table 4: Specific approach for managing patients with cardiorenal disease. Therapy Recommendation/comment Congestion Congestion assessment: multiparametric approach • Identify the predominant phenotype: compartmental distribution (intravascular/tissue)—regional distribution (pulmonary/systemic) • Integrate clinical signs/symptoms, biomarkers (CA125, NT-proBNP), lung ultrasound, VExUS, bioimpedance Acute heart failure with volume overload (inpatient) • Loop diuretics as the first choice: 2–2.5 times oral dose or 60–80 mg as IV bolus in diuretic naïve; subsequent dose according to urinary sodium • Consider 500 mg IV bolus of acetazolamide during the first 3 days of admission to improve decongestion • Consider hypertonic saline solutions • Consider adding an SGLT2I to enhance decongestion and improve outcomes Ambulatory worsening symptoms with volume overload • IV or subcutaneous infusions Oral diuretic therapy optimization: • Loop diuretics as the first choice • Sequential nephron blockade • Consider adding an SGLT2I to enhance decongestion and improve outcomes Changes in creatinine/eGFR should always be seen in the clinical context/status. An increase in creatinine should not stop further decongestive therapy, especially if congestion persists. Caution if doubling serum creatinine. Consider PD or intermittent aquapheresis sessions for selected patients with refractory congestion. Pharmacological After initiating RAAS inhibitors, ARNIs or SGLT2Is, a transient decrease in eGFR is expected and should not prompt treatment—HF their interruption • An increase in serum creatinine of <50% above baseline, as long as it is <266 μmol/l (3 mg/dl), or a decrease in eGFR of <10% from baseline, as long as eGFR is >25 ml/min/1.73 m2 , can be considered as acceptable Specific therapies • ARNI as the first choice in HFrEF, and consider its use in HFmEF • Carvedilol/bisoprolol over metoprolol in patients on KRT • SGLT2I in HF, CKD (eGFR ≥25 ml/min/1.73 m2 ) and type 2 diabetes mellitus • Espironolactone/eplerenone in HFrEF. Consider its use in HFmEF. Caution in patients with eGFR <30 ml/min/1.73 m2 or serum potassium >5.0 mmol/l • Vericiguat in patients who had a worsening HF event despite optimal medical therapy. Do not initiate in patients with eGFR <15 ml/min/1.73 m2 Comorbidities and Atrial fibrillation related conditions • Direct oral anticoagulants may be used after appropriate dose adjustment in patients with advanced CKD (eGFR 15–30 ml/min/1.73 m2 ); dabigatran contraindicated if eGFR <30 ml/min/1.73 m2 Type 2 diabetes mellitus • GLP1a and SGLT2I as the first choice in patients with type 2 diabetes mellitus • Finerenone in patients with type 2 diabetes mellitus and CKD (eGFR ≥25 ml/min/1.73 m2 ) Hyperkalaemia • Consider new potassium binders (patiromer/sodium zirconium cyclosilicate) CKD-MBD • Monitoring serum calcium and phosphate every 3–6 months (in CKD G3b–G4) and PTH every 6–12 months. Consider shorter intervals in CKD G5 • Avoid hypercalcemia and hyperphosphatemia in CKD G3a–G5 • It is reasonable to reserve the use of calcitriol and vitamin D analogues for patients with CKD G4–G5 with severe and progressive hyperparathyroidism Dyslipidaemia • LDL-C <1.8 mmol/l (70 mg/dl) in high-risk patients and <1.4 mmol/l (55 mg/dl) in very high-risk patients • Avoid rosuvastatin and fibrates in advanced CKD Anaemia • Monitoring the iron status and evaluating the need for IV iron replacement therapy and erythropoiesis-stimulating agents [55] Contrast-induced AKI • Limit large amounts of contrast media • Use either iso-osmolar or low-osmolar iodinated contrast media • Prophylactic hydration (isotonic crystalloids, 1.0–1.5 ml/kg/h) in patients at risk for AKI at least 6 h before and after contrast-enhanced imaging studies or interventions Advanced cardiac Heart transplantation and kidney • Assess the potential impact of immunosuppressive therapy on CKD progression therapies Kidney transplantation • The severity of cardiovascular-related conditions is a significant contributor to worse patient and allograft outcomes Mechanical circulatory support Building up a cardiorenal clinic 789 Table 4: Continued. Therapy Recommendation/comment • Consider the risk:benefit ratio in patients with advanced CKD Implantable cardioverter defibrillator Cardiac resynchronization therapy • Reverse remodelling following CRT is observed across all stages of CKD, yet the response is less pronounced in advanced CKD • HD • Assess the impact on the cardiovascular system/haemodynamics • Consider cardioprotective HD (blood volume control, long sessions) PD • Preferred KRT modality in patients with heart failure and advanced structural heart disease • Consider its use in patients with refractory congestion regardless of eGFR Palliative care Primary palliative care • Control pain, dyspnoea and other symptoms • Assess and reduce emotional distress to patient and caregiver • Manage ‘trigger events’ • Predict and communicate prognosis • Choose therapy Specialist palliative care • Consider hospice utilization for advanced patients and end-of-life transition • Consider reducing dialysis dose and frequency (palliative dialysis) or withdrawing completely for KRT ARNI: angiotensin receptor–neprilysin inhibitor; CA125: antigen carbohydrate 125; CRT: cardiac resynchronization therapy; GLP1a: glucagon-like peptide-1 agonists; HFrEF: heart failure with reduced ejection fraction; HFmEF: heart failure with mildly reduced ejection fraction; LDL-C: low-density lipoprotein cholesterol; NT-proBNP: N-terminal pro-hormone B-type natriuretic peptide; PTH: parathyroid hormone; SGLT2I: sodium–glucose cotransporter-2 inhibitor; VExUS: venous excess ultrasound. Table 5: Outcome and process indicators. Outcome indicators Process indicators • 0-day, 90-day and 1-year mortality rates (all-cause, cardiovascular, • Time from external referral to cardiorenal visit kidney-related) • Proportion of patients receiving guideline-based therapies • 30-day, 90-day and 1-year hospital readmission rates (all-cause, • Proportion of CKD grade 4–5 patients with haemoglobin cardiovascular, HF-related, kidney-related) of 10–12 g/dl [28] • Emergency department visits due to hyperkalaemia, worsening • Proportion of patients with adequate iron status [4, 28] kidney function, HF-related or cardiovascular-related events • Proportion of patients with hyperphosphatemia • Unscheduled visits due to hyperkalaemia, worsening kidney • Rate of HD-related complications function, HF-related or cardiovascular-related events • Proportion of patients with accurate control of mineral and • Major renal adverse events defined as [56]: bone disorder [57] – Worsening of kidney disease (sustained >40% reduction in eGFR) • Proportion of patients with hyperkalaemia at 1 year [26] • Number of patients initiating KRT – Progression to end-stage kidney disease (eGFR <15 ml/min/1.73 m2 • Rate of PD-related complications or sustained initiation of renal replacement therapy) • Patient satisfaction – Renal death (death due to end-stage CKD when renal replacement • Staff satisfaction therapy was not initiated or was discontinued) at 30 days, 90 days and 1 year • Heart or kidney transplantation rates • Percentage of patients who required advanced circulatory support the constant advance in cardiovascular and renal diseases has Along this line, leaders in the field have proposed spe- positioned cardiorenal medicine as a new discipline [58]. cific road maps to achieve these goals. Structured training pro- However, current nephrology and cardiology training seems grams should be included during the time of specialization insufficient to encompass the complexity of cardiorenal disease in nephrology. However, postgraduate programs and fellow- and the rapid advances in the field of cardiovascular medicine. ships should also be developed to make the physician fully Therefore a change in the approach is required. There is a clear capable of providing more effective clinical care to this grow- need for specific training programs that improve nephrologists’ ing and increasingly complex population [59–61]. Moreover, a and cardiologists’ knowledge and skills in all the aspects related consensed and comprehensive core curriculum must define to managing patients with cardiorenal disease. Education is also the knowledge, skills and competencies to be achieved and required to promote the culture of shared care and avoid the cover the specific topics related to cardiorenal disease that prejudice of ‘us and them’ that often leads to antagonistic and should be included in educational resources and assessment harmful interventions. tools [59]. 790 R. de la Espriella et al. In conclusion, large institutions and national/international fees from Bayer, AstraZeneca and Boehringer Ingelheim; societies must focus on developing educational resources payment or honoraria for lectures, presentations, speakers’ and promoting shared and structured programs resulting in bureaus, manuscript writing or educational events from Bayer, board certification in cardiology and nephrology. Furthermore, AstraZeneca, Novo Nordisk and Boehringer Ingelheim and sup- implementing this discipline should be encouraged, favouring port for attending meetings and/or travel from Vifor Pharma. optimal care for patients with cardiorenal disease, a closer B.Q. reports consulting fees, participation on data safety and more effective collaboration between specialists and the monitoring boards or advisory boards, support for attending stimulation of specific research that expands knowledge of meetings and/or travel and payment or honoraria for lectures, cardiorenal disease. presentations, speakers’ bureaus, manuscript writing or educa- tional events from Novartis, AstraZeneca, Sandoz, Laboratorios Bial, Esteve, Sanofi-Genzyme and Otsuka and is the secretary of CONCLUSION the Spanish Society of Nephrology. J.D. reports consulting fees In summary, given the complexity and the increasing prevalence and payment or honoraria for lectures, presentations, speak- of cardiorenal disease, there is a need to develop specialized ers’ bureaus, manuscript writing or educational events from models of care for patients with combined heart and kidney dis- AstraZeneca, Bayer and Vifor Pharma and consulting fees from ease. A multidisciplinary, coordinated and structured approach GlaxoSmithKline. M.J.S. reports grants or contracts from Insti- across the different levels of care may improve patient outcomes tuto Carlos III, Marató TV3 and Boehringer Ingelheim; honoraria and the utilization of healthcare infrastructures and resources. for lectures from Novo Nordisk, Jansen, Boehringer Ingelheim, This article provides some organizational aspects and the key Mundipharma, AstraZeneca, Ingelheim Lilly, Vifor Pharma, elements for setting up a multidisciplinary cardiorenal clinical ICU Medical, Fresenius and Travere Therapeutics; support for program as a potential healthcare model adapted to the partic- attending meetings and/or travel from Travere and participa- ular characteristics of patients with cardiorenal disease. tion on advisory boards for Novo Nordisk, Jansen, Boehringer Ingelheim, Mundipharma, AstraZeneca, Ingelheim Lilly, Vifor SUPPLEMENTARY DATA Pharma, ICU Medical, Fresenius, Travere Therapeutics and GE Healthcare. M.J.S. and J.N. are members of the CKJ editorial Supplementary data are available at ckj online. board. All other authors declare no competing interests. ACKNOWLEDGEMENTS REFERENCES We gratefully acknowledge the dedication, commitment and contribution of the nursing staff and the rest of the multidis- 1. Bhatnagar R, Fonarow GC, Heidenreich PA et al. Expenditure ciplinary team directly involved in the management of patients on heart failure in the United States: the Medical Expendi- with cardiorenal disease. ture Panel Survey 2009–2018. JACC Heart Failure 2022;10:571– 80. 2. Savarese G, Becher PM, Lund LH et al. Global burden of heart FUNDING failure: a comprehensive and updated review of epidemiol- None declared. ogy. Cardiovasc Res 2022;doi: 10.1093/cvr/cvac013. 3. Mohebi R, Chen C, Ibrahim NE et al. Cardiovascular disease projections in the United States based on the 2020 census AUTHORS’ CONTRIBUTIONS estimates. J Am Coll Cardiol 2022;80:565–78. All authors meet each of the following characteristics defined by 4. McDonagh TA, Metra M, Adamo M et al. 2021 ESC guidelines the International Committee of Medical Journal Editors in the for the diagnosis and treatment of acute and chronic heart criteria for authorship of scientific articles: substantial contri- failure: developed by the Task Force for the diagnosis and butions to the conception or design of the manuscript, drafting treatment of acute and chronic heart failure of the European the work or revising it critically for important intellectual con- Society of Cardiology (ESC) with the special contribution of tent, final approval of the version to be published and agreement the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail to be accountable for all aspects of the work in ensuring that 2022;24:4–131. questions related to the accuracy or integrity of any part of the 5. McCullough PA, Amin A, Pantalone KM et al. Cardiorenal manuscript are appropriately investigated and resolved. nexus: a review with focus on combined chronic heart and kidney failure, and insights from recent clinical trials. J Am Heart Assoc 2022;11:e024139. DATA AVAILABILITY STATEMENT 6. Ortiz A, Navarro-González JF, Núñez J et al. The unmet All data are incorporated into the article and its online supple- need of evidence-based therapy for patients with advanced mentary material. chronic kidney disease and heart failure: position paper from the Cardiorenal Working Groups of the Spanish Soci- ety of Nephrology and the Spanish Society of Cardiology. Clin CONFLICT OF INTEREST STATEMENT Kidney J 2022;15:865–72. C.R. reports payment or honoraria for lectures, presentations, 7. Núñez J, Miñana G, Santas E et al. Cardiorenal syndrome in speakers’ bureaus, manuscript writing or educational events acute heart failure: revisiting paradigms. Rev Esp Cardiol (Engl from Asahi, Baxter, Biomerieux, Jafron, Medica and GE and Ed) 2015;68:426–35. participation on data safety monitoring boards/advisory boards 8. McAlister FA, Ezekowitz J, Tarantini L et al. Renal dysfunc- for Baxter, Jafron and Biomerieux. D.B. reports research grants tion in patients with heart failure with preserved versus from Kidney Research UK and AstraZeneca ESR, payment for reduced ejection fraction: impact of the new Chronic Kid- lecture fees from AstraZeneca and Vifor Pharma and partici- ney Disease-Epidemiology Collaboration group formula. Circ pation on an advisory board for Bayer. J.L.G. reports consulting Heart Fail 2012;5:309–14. Building up a cardiorenal clinic 791 9. Tedeschi A, Agostoni P, Pezzuto B et al. Role of comorbidi- 26. Teitelbaum I. Peritoneal dialysis. N Engl J Med 2021;385:1786– ties in heart failure prognosis part 2: chronic kidney dis- 95. ease, elevated serum uric acid. Eur J Prev Cardiol 2020;27: 27. Evans M, Lopau K. The transition clinic in chronic kidney 35–45. disease care. Nephrol Dial Transplant 2020;35:ii4–10. 10. Mentz RJ, Kelly JP, von Lueder TG et al. Noncardiac comor- 28. Blake PG, Dong J, Davies SJ. Incremental peritoneal dialysis. bidities in heart failure with reduced versus preserved ejec- Perit Dial Int 2020;40:320–6. tion fraction. J Am Coll Cardiol 2014;64:2281–93. 29. Sarnak MJ, Auguste BL, Brown E et al. Cardiovascular effects 11. Mullens W, Martens P, Testani JM et al. Renal effects of of home dialysis therapies: a scientific statement from the guideline-directed medical therapies in heart failure: a con- American Heart Association. Circulation 2022;146:e146–64. sensus document from the Heart Failure Association of the 30. Romero-González G, Manrique J, Slon-Roblero MF et al. European Society of Cardiology. Eur J Heart Fail 2022;24:603– PoCUS in nephrology: a new tool to improve our diagnostic 19. skills. Clin Kidney J 2022;doi: 10.1093/ckj/sfac203. 12. Rangaswami J, Bhalla V, Blair JEA et al. Cardiorenal syn- 31. Núñez J, de la Espriella R, Rossignol P et al. Congestion in drome: classification, pathophysiology, diagnosis, and treat- heart failure: a circulating biomarker-based perspective. A ment strategies: a scientific statement from the American review from the Biomarkers Working Group of the Heart Heart Association. Circulation 2019;139:e840–78. Failure Association, European Society of Cardiology. Eur J 13. Cobo Marcos M, de la Espriella R, González Rico M et al. Heart Fail 2022;24:1751–66. Situación actual de las unidades cardiorrenales en España. 32. de la Espriella R, Cobo M, Santas E et al. Assessment of fill- REC CardioClin 2022;57:299–302. ing pressures and fluid overload in heart failure: an updated 14. Nguyen M, Rumjaun S, Lowe-Jones R et al. Management and perspective. Rev Esp Cardiol (Engl Ed) 2023;76:47–57. outcomes of heart failure patients with CKD: experience 33. Lok CE, Foley R. Vascular access morbidity and mortality: from an inter-disciplinary clinic. ESC Heart Fail 2020;7:3225– trends of the last decade. Clin J Am Soc Nephrol 2013;8:1213–9. 30. 34. Masud A, Costanzo EJ, Zuckerman R et al. The complications 15. Sankaranarayanan R, Douglas H, Wong C. Cardio- of vascular access in hemodialysis. Semin Thromb Hemost nephrology MDT meetings play an important role in 2018;44:57–9. the management of cardiorenal syndrome. Br J Cardiol 35. Reddy YNV, Melenovsky V, Redfield MM et al. High- 2020;27:26. output heart failure: a 15-year experience. J Am Coll Cardiol 16. Bansal N, Arora N, Mariuma D et al. Mission and 1-year out- 2016;68:473–82. comes of a cardiorenal subspecialty consultation service. 36. Alkhouli M, Sandhu P, Boobes K et al. Cardiac complications Kidney360 2022;3:749–51. of arteriovenous fistulas in patients with end-stage renal 17. Junarta J, Fernandez M, Chung I et al. Role of a cardio-renal disease. Nefrologia 2015;35:234–45. multidisciplinary team meeting in managing cardiovascu- 37. Abassi Z, Nakhoul F, Khankin E et al. Pulmonary hyperten- lar risk in patients on kidney transplant waitlists. Clin Trans- sion in chronic dialysis patients with arteriovenous fistula: plant 2020;34:e14061. pathogenesis and therapeutic prospective. Curr Opin Nephrol 18. Shi Y, Xiong J, Chen Y et al. The effectiveness of multidis- Hypertens 2006;15:353–60. ciplinary care models for patients with chronic kidney dis- 38. López-Vilella R, Sánchez-Lázaro I, Guerrero Cervera B ease: a systematic review and meta-analysis. Int Urol Nephrol et al. Peripheral access ultrafiltration as a treatment 2018;50:301–12. for cardiorenal syndrome with inadequate diuretic re- 19. Hirano K, Kobayashi D, Kohtani N et al. Optimal follow- sponse. Initial experience. Rev Esp Cardiol (Engl Ed) 2023;76: up intervals for different stages of chronic kidney dis- 60–2. ease: a prospective observational study. Clin Exp Nephrol 39. Crespo-Leiro MG, Metra M, Lund LH et al. Advanced heart 2019;23:613–20. failure: a position statement of the Heart Failure Associa- 20. Greene SJ, Adusumalli S, Albert NM et al. Building a heart tion of the European Society of Cardiology. Eur J Heart Fail failure clinic: a practical guide from the Heart Failure Society 2018;20:1505–35. of America. J Card Fail 2021;27:2–19. 40. Mullens W, Damman K, Harjola VP et al. The use of diuret- 21. Ishigami J, Trevisan M, Lund LH et al. Acceleration of kidney ics in heart failure with congestion — a position statement function decline after incident hospitalization with cardio- from the Heart Failure Association of the European Society vascular disease: the Stockholm CREAtinine Measurements of Cardiology. Eur J Heart Fail 2019;21:137–55. (SCREAM) project. Eur J Heart Fail 2020;22:1790–9. 41. de la Espriella R, Santas E, Zegri Reiriz I et al. Quantification 22. Ostermann M, Bellomo R, Burdmann EA et al. Controversies and treatment of congestion in heart failure: a clinical and in acute kidney injury: conclusions from a Kidney Disease: pathophysiological overview. Nefrologia (Engl Ed) 2021;doi: Improving Global Outcomes (KDIGO) conference. Kidney Int 10.1016/j.nefro.2021.04.006. 2020;98:294–309. 42. Voors AA, Angermann CE, Teerlink JR et al. The SGLT2 23. Comín-Colet J, Enjuanes C, Lupón J et al. Transitions of care inhibitor empagliflozin in patients hospitalized for acute between acute and chronic heart failure: critical steps in the heart failure: a multinational randomized trial. Nat Med design of a multidisciplinary care model for the prevention 2022;28:568–74. of rehospitalization. Rev Esp Cardiol (Engl Ed) 2016;69:951–61. 43. Mullens W, Dauw J, Martens P et al. Acetazolamide in acute 24. Albert NM, Barnason S, Deswal A et al. Transitions of care decompensated heart failure with volume overload. N Engl J in heart failure: a scientific statement from the American Med 2022;387:1185–95. Heart Association. Circ Heart Fail 2015;8:384–409. 44. Janse RJ, Fu EL, Dahlström U et al. Use of guideline- 25. Núñez J, González M, Miñana G et al. Continuous ambula- recommended medical therapy in patients with heart fail- tory peritoneal dialysis as a therapeutic alternative in pa- ure and chronic kidney disease: from physician’s prescrip- tients with advanced congestive heart failure. Eur J Heart Fail tions to patient’s dispensations, medication adherence and 2012;14:540–8. persistence. Eur J Heart Fail 2022;24:2185–95. 792 R. de la Espriella et al. 45. Patel RB, Fonarow GC, Greene SJ et al. Kidney function and tients undergoing percutaneous coronary interventions: in- outcomes in patients hospitalized with heart failure. J Am sights from the NCDR Cath-PCI registry. JACC Cardiovasc In- Coll Cardiol 2021;78:330–43. terv 2014;7:1–9. 46. Olesen JB, Lip GY, Kamper AL et al. Stroke and bleeding in 54. Khwaja A. KDIGO clinical practice guidelines for acute kid- atrial fibrillation with chronic kidney disease. N Engl J Med ney injury. Nephron Clin Pract 2012;120:c179–84. 2012;367:625–35. 55. Mikhail A, Brown C, Williams JA et al. Renal association clini- 47. Dahal K, Kunwar S, Rijal J et al. Stroke, major bleeding, and cal practice guideline on anaemia of chronic kidney disease. mortality outcomes in warfarin users with atrial fibrilla- BMC Nephrol 2017;18:345. tion and chronic kidney disease: a meta-analysis of obser- 56. Prischl FC, Rossing P, Bakris G et al. Major adverse renal vational studies. Chest 2016;149:951–9. events (MARE): a proposal to unify renal endpoints. Nephrol 48. Eggebrecht L, Prochaska JH, Schulz A et al. Intake of vita- Dial Transplant 2021;36:491–7. min K antagonists and worsening of cardiac and vascular 57. Ketteler M, Block GA, Evenepoel P et al. Executive sum- disease: results from the population-based Gutenberg mary of the 2017 KDIGO Chronic Kidney Disease–Mineral Health Study. J Am Heart Assoc 2018;7:e008650. and Bone Disorder (CKD-MBD) Guideline Update: what’s 49. Narasimha Krishna V, Warnock DG, Saxena N et al. Oral anti- changed and why it matters. Kidney Int 2017;92:26–36. coagulants and risk of nephropathy. Drug Saf 2015;38:527–33. 58. Lv J, Li Y, Shi S et al. Frontier and hotspot evolu- 50. Malhotra K, Ishfaq MF, Goyal N et al. Oral anticoagulation in tion in cardiorenal syndrome: a bibliometric anal- patients with chronic kidney disease: a systematic review ysis from 2003 to 2022. Curr Probl Cardiol 2022;doi: and meta-analysis. Neurology 2019;92:e2421–31. 10.1016/j.cpcardiol.2022.101238. 51. Zhang HF, Zhang QX, Zhang YY et al. Efficacy and safety of 59. Ronco C, Ronco F, McCullough PA. A call to action to de- left atrial appendage occlusion in atrial fibrillation patients velop integrated curricula in cardiorenal medicine. Blood Pu- with chronic kidney disease: a systematic review and meta- rif 2017;44:251–9. analysis. Rev Cardiovasc Med 2020;21:443–51. 60. Kazory A, McCullough PA, Rangaswami J et al. Car- 52. McCullough PA, Adam A, Becker CR et al. Risk prediction dionephrology: proposal for a futuristic educational ap- of contrast-induced nephropathy. Am J Cardiol 2006;98:27K– proach to a contemporary need. Cardiorenal Med 2018;8:296– 36K. 301. 53. Tsai TT, Patel UD, Chang TI et al. Contemporary incidence, 61. Díez J, Ortiz A. The need for a cardionephrology subspecialty. predictors, and outcomes of acute kidney injury in pa- Clin Kidney J 2021;14:1491–4.