Background: Heart failure is frequently associated with kidney disease, and patients with kidney disease are at increased risk of heart failure. The co-occurrence of both entities not only significantly increases morbidity and mortality but also complicates therapy. Summary: Cardiorenal syndrome often requires a broad, comprehensive, and multidisciplinary approach. As a result, a need has arisen to create specialized cardiorenal units that allow for rigorous and personalized management of this condition. Moreover, in some cases, cardiorenal syndrome is more complex, owing to an acute and critical situation that requires the concept of the cardiorenal unit to be extended toward advanced diagnostic and therapeutic positions, thus confirming the need for an advanced cardiorenal unit. The creation of these units constitutes a real challenge, necessitating a specific multilevel action plan, covering governance and management, type of patient, personnel requirements, service portfolio, care process, information systems, and other resources. Specific lines of action must be proposed for each of the relevant points in order to facilitate development of these units, together with continuous evaluation of unit activity through specific indicators, and to detect areas for improvement. Key Messages: This study addresses the conditions and organizational characteristics that enable the creation, development, and continuous improvement of advanced cardiorenal units.

Heart failure (HF) is a concerning public health problem. In Spain, it affects around 2% of adults, although this figure is expected to increase in the coming years owing to progressive aging of the population [1‒3]. Patients with HF are at significant risk of hospitalization and death. This risk is higher in patients who have recently experienced decompensation [4], thus generating high disease-associated costs [5]. In addition, patients with HF frequently have associated comorbidities, which not only increase the risk of complications but also hinder appropriate management. Chronic kidney disease (CKD) is one of the most prevalent comorbidities in HF. Recent studies in Spain show that up to 30% of patients with HF also have CKD [4].

CKD has been associated with an increased risk of progression to end-stage renal disease. Furthermore, it increases the risk of all-cause mortality, cardiovascular death, coronary artery disease, and hospitalization for HF. This risk increases as renal function worsens. Importantly, HF is one of the most prevalent clinical manifestations in patients with CKD [6‒8].

HF and CKD co-occur and share risk factors, that is, the presence of one favors the development of the other. Moreover, when both circumstances occur concomitantly, the risk of developing complications and mortality increases notably [6, 9]. Furthermore, CKD may limit the use of disease-modifying therapies in HF patients, in particular, renin angiotensin system inhibitors, thus further aggravating prognosis [10].

In this context, cardiorenal syndrome (CRS) is a relevant clinical condition that impacts both the heart and the kidneys. Acute or chronic involvement of one can lead to acute or chronic alteration of the other; this relationship is bidirectional and further worsens the clinical situation. The risk of adverse events increases, with high morbidity and mortality having been reported [11‒16]. The pathophysiology of CRS is complex, multifactorial, and dynamic and includes bidirectional hemodynamic changes associated with heart and kidney failure, neurohormonal abnormalities, and an increased oxidative and inflammatory response (Fig. 1) [11‒16]. Consequently, it is necessary to move from the old concept of renal dysfunction or kidney failure due to low cardiac output, and vice versa, to the current concept of heart-kidney interaction in the setting of HF.

Fig. 1.

Relationships between cardiac and renal physiology in cardiorenal syndrome. CKD, chronic kidney disease; GFR, glomerular filtration rate; HF, heart failure.

Fig. 1.

Relationships between cardiac and renal physiology in cardiorenal syndrome. CKD, chronic kidney disease; GFR, glomerular filtration rate; HF, heart failure.

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CRS has been classified into 5 subgroups, depending on the initial cause, thus highlighting differences in etiology, pathophysiology, duration, and pattern of cardiac and/or renal dysfunction. In fact, this classification reflects the wide spectrum of cardiorenal (CR) disease and the bidirectional relationship between both organs. CRS is common, affecting 40–50% of patients in subtypes 1–4 and up to 70% in the case of secondary CRS (Fig. 1) [17‒22].

A key problem in clinical practice is that although cardiologists and nephrologists provide adequate care to their patients, the approach to CRS is beset by specific difficulties. Therefore, a comprehensive diagnostic and therapeutic approach would provide considerable clinical and prognostic benefits. This necessitates training in heart and kidney disease and the creation of specific units to treat affected patients in a more complete and comprehensive manner. Multidisciplinary units, comprising mainly cardiologists and nephrologists, could fulfill an unmet medical need, with a considerable impact on healthcare [23‒27].

There is already evidence of the benefits of multidisciplinary care in CRS, both for patients and for the healthcare system. The creation of multidisciplinary cardiology-nephrology teams would facilitate the implementation of therapies with prognostic benefit in patients with HF and even in those with advanced CKD [28, 29]. Furthermore, joint meetings between nephrology and cardiology teams would improve patient flow, avoiding unnecessary consultations [30]. However, while clinical practice guidelines recommend development of special units [14], only 10% of HF units in Spain have a specific program to care for patients with CRS and only 30% have developed protocols between both specialties for the management of this entity [31].

With the aim of promoting a comprehensive approach to patients with CRS through the development of units and protocols for combined action, the Spanish Society of Cardiology and the Spanish Society of Nephrology produced a joint document establishing the basis for the creation of CR units [26]. The document aims to define the general lines along which the approach to the CR patient should be based. However, not all healthcare centers have the same level of complexity, not all HF units are oriented in the same way, and not all CRS patients have the same severity of disease, which may exceed the capacity of some units to provide adequate care. Consequently, although the creation of multidisciplinary units for the comprehensive care of patients with CRS should be encouraged, the fact is that in centers with greater capacity and the possibility of caring for more complex patients, advanced CR units (ACRUs) should be implemented to provide an adequate response to the general population. More complex patients include those admitted to critical care units (intensive care unit [cardiogenic shock], anesthesia and resuscitation unit), patients with HF and associated medical complications, patients with a diagnosis of HF and renal dysfunction who are to undergo cardiac or noncardiac surgery and implantation of circulatory/ventricular assist devices for heart-kidney failure (short, medium, and long duration), transplant recipients (simultaneous CR transplant), and children with CRS. Thus, the ACRU provides comprehensive care for both outpatients and hospitalized patients. Even within hospitalized patients, it includes the management of patients with CR disease treated in intensive care units. This document sets out the principles for the development and implementation of the ACRU, based on the strategic plan developed at Hospital Universitari i Politècnic La Fe, Valencia, Spain. The protocol was implemented at a public reference hospital. Given that logistics can vary between health systems, centers with different characteristics or private centers may have specific needs and resources. These basic principles could be applied to reference centers for advanced HF worldwide, enabling them to improve their quality of care through an ACRU.

The main objective of an ACRU is to improve the CR health of patients with CRS without excluding any type or degree of CR dysfunction. A highly relevant prerequisite is to adequately define and classify the CRS patient. This will make it possible to calculate the real prevalence of the disease, to define the problem appropriately, and to chart and analyze a plan of action.

Development Phases and Requirements

Three main stages must be established for the start-up and implementation of an ACRU (Fig. 2). The first involves an analysis of the current situation, considering the management model, as well as the processes and resources available. It is also necessary to identify possible deficiencies and key areas for improvement. The second is to establish a strategic plan in which the lines of action are defined to generate a model of excellence for the ACRU that takes into account real clinical scenarios and their impact on the resources needed to guarantee success of the venture. The third stage consists of an action plan, which should include the evaluation of the impact generated by the ACRU through the analysis of key performance indicators (KPIs).

Fig. 2.

Stages for the initiation of an ACRU. ACRU, advanced cardiorenal unit; KPIs, key performance indicators.

Fig. 2.

Stages for the initiation of an ACRU. ACRU, advanced cardiorenal unit; KPIs, key performance indicators.

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The implementation of the ACRU requires several levels to be addressed, namely, governance (management organization chart, operating committee), the type of patients to be attended (inclusion/exclusion criteria, referral protocols), personnel requirements (sizing the staff appropriately), the service portfolio, development of the care process (action protocols that respond to the different clinical situations of the CRS patient), information systems, and other resources (Fig. 3).

Fig. 3.

General requirements for an ACRU. ACRU, advanced cardiorenal unit; CKD, chronic kidney disease; CRS, cardiorenal syndrome; HF, heart failure.

Fig. 3.

General requirements for an ACRU. ACRU, advanced cardiorenal unit; CKD, chronic kidney disease; CRS, cardiorenal syndrome; HF, heart failure.

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Selection Criteria and Referral Protocol

The general inclusion criteria would be as follows:

  • HF and kidney failure (glomerular filtration rate [GFR] <30 mL/min/1.73 m2)

  • HF and kidney failure (GFR <45 mL/min/1.73 m2) in a patient admitted for HF in the previous 6 months

  • HF and refractory congestion (GFR ≥45 mL/min/1.73 m2)

  • heart and/or kidney transplantation or ventricular/circulatory assistance with a GFR <60 mL/min/1.73 m2

Patients who should be excluded and treated in other care settings are characterized by the following:

  • a life expectancy of less than 1 year not due to HF

  • inability to attend visits regularly

  • poor compliance and self-care and lack of social and family support

Adequate evolution of the unit should be based on criteria for referral and patient flow between care settings in order to allow rapid and appropriate management of CRS (Fig. 4). Patients may be referred from hospital admission, from cardiology or nephrology units, by interdepartmental consultation with the ACRU, or from the outpatient setting (outpatient cardiology or nephrology clinics), with delay in care adjusted to the needs of the individual patient (clinical stability). Within the ACRU, the patient will be seen in the HF or advanced CKD clinic, which are coordinated by cardiology and nephrology units, depending on the case, with the possibility of referring the patient to the outpatient hospital for intravenous treatment (e.g., levosimendan, iron, diuretics, hypertonic saline solution), specific procedures (e.g., paracentesis), to nephrology for peritoneal dialysis, or to cardiology for peripheral ultrafiltration. After a period of stabilization, critically ill patients are transferred to cardiology or nephrology units before discharge [32‒36].

Fig. 4.

Criteria for referral and patient flow to the ACRU. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HF, heart failure; IV, intravenous; PD, peritoneal dialysis.

Fig. 4.

Criteria for referral and patient flow to the ACRU. CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; HF, heart failure; IV, intravenous; PD, peritoneal dialysis.

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Portfolio of Services

The portfolio of services should be well defined in order to establish the human, technical, and material resources necessary for the appropriate functioning of the ACRU. It should cover the diagnostic and therapeutic requirements for adequate care of the CRS patient via a comprehensive and coordinated approach at the hospital, day hospital, outpatient clinic, and remote follow-up levels (Fig. 5).

Fig. 5.

ACRU services portfolio. ACKD, advanced chronic kidney disease; HF, heart failure; CRS, cardiorenal syndrome.

Fig. 5.

ACRU services portfolio. ACKD, advanced chronic kidney disease; HF, heart failure; CRS, cardiorenal syndrome.

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The advanced ACRU model should be defined based on analysis and modification of protocols and processes to optimize care procedures for patients with CRS. To this end, the referral charts should be updated and reviewed according to the evolution of the unit, and appropriate referral of patients from the different clinical departments of the hospital to the unit should be evaluated. The aim is to establish a process of continuous improvement while simultaneously adjusting the total number of patients attended in the unit. Likewise, after considering the material resources available to the ACRU, the need for a dedicated space for adequate follow-up and management of affected patients should be assessed. The hospital should be reorganized to provide specific physical spaces, both for routine consultations and for parenteral treatments and implementation of the unit’s own vascular accesses. In addition, the information systems of the ACRU will be reviewed to identify those elements necessary to ensure the development of the unit’s services in order to ensure more personalized attention. Among these actions, single-act consultations should be promoted with the aim of optimizing the care provided by both departments, thus improving the patient’s length of stay and experience. In addition, management should be modified to optimize care of the CRS patient by both departments on the same day and to improve patient identification by using the same code (standardized coding), thus facilitating data collection for the analysis of the KPIs measured in the ACRU.

Planning and Design of Lines of Action: Performance Indicators

Lines of action must be defined and customized for each center. We can identify at least 15 initial challenges to be addressed for the creation of an ACRU:

  • creating of a multidisciplinary operating committee

  • recording the analysis of KPIs

  • developing a protocol for the multidisciplinary approach

  • preparing a checklist for patient referral and optimizing referral for transplantation in patients with CRS

  • designing infographics and documentation

  • implementing a continuous training plan

  • promoting the use of an internal communication tool and promoting communication between nephrology and cardiology teams

  • standardizing the coded diagnosis of CRS and promoting the existence and use of combined cardiac and renal diagnosis-related groups

  • implementing a patient database

  • implementing digital tools for collecting events

  • developing integrated CRS agendas in medical consultations

  • strengthening the brand image

  • designing a communication program to enhance visibility

  • developing expert patient workshops

  • generating alliances and a network of hospitals with ACRUs

After identifying these points, each center must establish an order of priority to subsequently establish lines of action, defining those projects that would have the greatest impact on the activity of the ACRU. In order to develop the lines of action, an implementation plan should be developed and distributed. This should cover 4 categories:

  • governance and management: design of an organizational chart and formation of an operational committee

  • coordination and protocols: coordination and drafting of a protocol for processes, functions, and decisions, as well as referrals between departments and professionals

  • information systems: computerization and/or automation of processes, digitization of documentation, and systems for data collection and data transfer

  • communication: patient training and dissemination of the model implemented

Online supplementary Material 1 and Figure 6 summarize the different lines of action for the implementation of the ACRU according to these 4 areas (for all online suppl. material, see https://doi.org/10.1159/000536104). Within each group, they are further subdivided into several lines of action, within each of which it is necessary to state goals and propose activities to be carried out during project implementation. These subgroups should also take account of stakeholders who could/should collaborate in the development of the project. In addition, the activities to be carried out should be prioritized based on the time frame needed for their implementation (short, medium, or long term).

Fig. 6.

Lines of action for the implementation of the ACRU. ACRU, advanced cardiorenal unit; CRS, cardiorenal syndrome; KPIs, key performance indicators.

Fig. 6.

Lines of action for the implementation of the ACRU. ACRU, advanced cardiorenal unit; CRS, cardiorenal syndrome; KPIs, key performance indicators.

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To be able to assess the impact of an action and detect areas for improvement, it is essential to create KPIs that are measurable and comparable, both within the hospital and with ACRUs in other centers. Table 1 and Figure 7 show the different KPIs classified according to the process as follows: general, clinical outcomes, admissions, readmissions, and mortality.

Table 1.

KPIs (ACRU KPIs)

General 
 Age (median)* 
 Sex# 
 Total number of patients diagnosed with CRS* 
 No. of visits to the emergency department for CR decompensation* 
 Unscheduled visits due to worsening HF* 
 Unscheduled visits due to worsening kidney disease* 
Clinical outcomes 
 LVEF* 
 LVEF >50%/years (%) 
 TSAT value (%)* 
 Ferritin value, ng/mL* 
 Hb value, g/dL* 
 NT-proBNP, pg/mL* 
 CA125 value, U/mL* 
 GFR value, mL/min/1.73 m2* 
 K value >5 mEq/L# 
 K value <3.5 mEq/L# 
 Na value >145 mEq/L# 
 Na value <135 mEq/L# 
 Patients undergoing UF in the cardiology department* 
 Albumin value <3.5 g/dL# 
 Patients with peritonitis due to PD* 
 Patients with indication for CR transplantation* 
 Patients with signs of overhydration >15% by BCM# 
 Patients with radiological signs of congestion (≥4 B lines or pleural effusion, cava >2.1 cm or lower reduction 50%)# 
Admissions 
 Admissions to cardiology in the previous 6 months* 
 Admissions to nephrology in the previous 6 months* 
 Days of admission (median and IQR) 
 Days of admission* 
 Admissions to hospital ≥10 days# 
 Admissions to hospital ≥14 days# 
 Origin of admission (care device)# 
Readmissions 
 Patients with readmissions# 
 Readmissions* 
 Days from previous admission to current readmission* 
Mortality 
 Patients who died# 
 Patients who died* 
 Time from previous admission to death* 
General 
 Age (median)* 
 Sex# 
 Total number of patients diagnosed with CRS* 
 No. of visits to the emergency department for CR decompensation* 
 Unscheduled visits due to worsening HF* 
 Unscheduled visits due to worsening kidney disease* 
Clinical outcomes 
 LVEF* 
 LVEF >50%/years (%) 
 TSAT value (%)* 
 Ferritin value, ng/mL* 
 Hb value, g/dL* 
 NT-proBNP, pg/mL* 
 CA125 value, U/mL* 
 GFR value, mL/min/1.73 m2* 
 K value >5 mEq/L# 
 K value <3.5 mEq/L# 
 Na value >145 mEq/L# 
 Na value <135 mEq/L# 
 Patients undergoing UF in the cardiology department* 
 Albumin value <3.5 g/dL# 
 Patients with peritonitis due to PD* 
 Patients with indication for CR transplantation* 
 Patients with signs of overhydration >15% by BCM# 
 Patients with radiological signs of congestion (≥4 B lines or pleural effusion, cava >2.1 cm or lower reduction 50%)# 
Admissions 
 Admissions to cardiology in the previous 6 months* 
 Admissions to nephrology in the previous 6 months* 
 Days of admission (median and IQR) 
 Days of admission* 
 Admissions to hospital ≥10 days# 
 Admissions to hospital ≥14 days# 
 Origin of admission (care device)# 
Readmissions 
 Patients with readmissions# 
 Readmissions* 
 Days from previous admission to current readmission* 
Mortality 
 Patients who died# 
 Patients who died* 
 Time from previous admission to death* 

ACRU, advanced cardiorenal unit; BCM, body composition monitor; CA125, carcinoembryonic antigen 125; CR, cardiorenal; CRS, cardiorenal syndrome; GFR, glomerular filtration rate; Hb, hemoglobin; HF, heart failure; IQR, interquartile range; K, potassium; KPI, key performance indicator; LVEF, left-ventricular ejection fraction; Na, sodium; no., number; NT-proBNP, N-terminal pro-brain natriuretic peptide; PD, peritoneal dialysis; TSAT, transferrin saturation; UF, ultrafiltration.

*Number per year.

#Percentage per year.

Fig. 7.

Performance indicators. KPIs, key performance indicators.

Fig. 7.

Performance indicators. KPIs, key performance indicators.

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Development of the ACRU

An ACRU must evolve and grow continuously in various areas of interest: care (developing the lines of action, opening new lines, and specifying others), teaching (in-hospital [with conferences and sessions], out-of-hospital [with specific meetings and in the wider community], through a national training plan), research (developing various research projects such as the analysis of CR clinical profiles, methods for early diagnosis of refractory systemic venous congestion, peripheral ultrafiltration in the medical techniques unit of the emergency department, ultrafiltration in the cardiology department, KPIs 2022 vs. 2023, etc.), and management (involving new areas of the hospital, planning referral, and the departments involved). All departments directly involved in the ACRU (nephrology, intensive care, anesthesia and resuscitation, and cardiology) should be present at regular meetings where stakeholders will discuss not only complex clinical cases requiring relevant decisions but also the strategic development of the unit, leading to continuous quality improvement of all processes and protocol-based procedures for optimal patient healthcare.

CRS is a common entity in clinical practice and is associated with high morbidity and mortality. Management of affected patients is complex and requires coordinated action between cardiology and nephrology through the development of specific units. However, specific high-complexity patients should be treated in an ACRU. Consequently, the creation of an ACRU is necessary to provide adequate care to this subgroup. The development of an ACRU requires a specific action plan that takes into account aspects such as governance and management, type of patient, staffing requirements, service portfolio, care process, information systems, and other resources. Specific lines of action should be proposed for each of the relevant aspects to enable development of the ACRU. The activity of the unit should be continuously evaluated using specific indicators in order to identify areas for improvement.

Dr. Carlos Escobar is thanked for his support in the preparation of this manuscript.

The authors have no conflicts of interest to declare.

This study was funded by a non-conditional grant from AstraZeneca.

All the authors made the following contributions to the manuscript: substantial contributions to the conception or design and to the acquisition, analysis, and interpretation of study data; drafting the manuscript and revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Infographics were created with BioRender.com by Víctor Donoso Trenado.

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