KDIGO 2024 CKD Guidelines: A Framework for Cardiorenal Integration

Abstract

The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) represents a pivotal shift toward a unified, multidisciplinary approach centered on the Cardiorenal-Metabolic (CKM) syndrome framework. 

This updated guidance emphasizes early diagnosis and aggressive, evidence-based management to mitigate the dual risk of kidney failure and cardiovascular events. 

Key updates include the stratification of risk using estimated Glomerular Filtration Rate (eGFR) and Albuminuria Category (ACR), and the universal mandate for SGLT2 inhibitors in patients meeting criteria, irrespective of diabetic status. 

Furthermore, the guidelines solidify the role of non-steroidal Mineralocorticoid Receptor Antagonists (nsMRAs), such as Finerenone, for enhanced cardiorenal protection in patients with type 2 diabetes and albuminuria. 

The new guidelines prescribe a comprehensive, stepwise approach to pharmacotherapy, integrating RAAS blockade, SGLT2 inhibition, and nsMRA use, demanding close collaboration between nephrology, cardiology, and primary care to optimize patient outcomes.

Introduction: The Cardiorenal-Metabolic (CKM) Imperative

Chronic Kidney Disease (CKD) is a globally prevalent public health crisis defined by abnormalities of kidney structure or function, present for over three months, with health implications. 

It is characterized clinically by decreased Estimated Glomerular Filtration Rate (eGFR) and/or albuminuria. While historically viewed as a distinct organ disorder, CKD is now recognized as one axis of the complex Cardiorenal-Metabolic (CKM) syndrome, a paradigm shift formalized by leading medical societies. CKM syndrome reflects the intricate and bidirectional pathophysiologic relationship linking metabolic disorders (e.g., type 2 diabetes and obesity) with cardiovascular disease (CVD) and CKD.

The primary significance of CKD lies in its profound association with accelerated atherosclerotic and non-atherosclerotic CVD, which remains the leading cause of morbidity and mortality in this patient population. Patients with CKD are significantly more likely to die from a cardiovascular event than to progress to kidney failure requiring renal replacement therapy.

The 2024 KDIGO CKD Clinical Practice Guideline updates provide a comprehensive, risk-based framework for identifying and treating CKD, emphasizing integrated management of the CKM triad. These updates prioritize therapeutic interventions proven in major Randomized Controlled Trials (RCTs) to simultaneously provide kidney and cardiovascular protection, moving the focus beyond solely slowing eGFR decline to enhancing overall prognosis.

Evolution of CKD Classification and Risk (CGA)

Risk stratification in CKD is based on the CKD-G.A. Classification (CGA) system, which combines GFR categories (G1 to G5) with Albuminuria categories (A1 to A3). This system remains the foundation for prognostic assessment and treatment intensity, with progression through higher G and A stages correlating with an exponential increase in the risk of all-cause mortality, major adverse cardiovascular events (MACE), and end-stage kidney disease (ESKD).

Defining the Cardiorenal-Metabolic Syndrome (CKM)

CKM syndrome acknowledges that the presence of metabolic risk factors (such as insulin resistance, dyslipidemia, and hypertension) drives the parallel development and progression of both heart failure and kidney dysfunction. Inflammation, endothelial dysfunction, and RAAS overactivation serve as central mechanistic links. 

This holistic view necessitates an interdisciplinary approach, moving away from siloed care to a multidisciplinary model involving primary care, cardiology, endocrinology, and nephrology.

Diagnostic Precision and Risk Stratification Updates

Accurate diagnosis and prognostic stratification are paramount for guiding resource allocation and therapeutic intensity in CKD. The KDIGO 2024 guidelines reinforce the use of the eGFR and Albuminuria Category (CGA) framework while introducing refinements to enhance diagnostic precision and personalize risk assessment.

Enhanced GFR Estimation: Role of Cystatin C

The guidelines continue to advocate for the initial estimation of GFR using a serum creatinine-based equation. However, recognizing the limitations of creatinine (e.g., variation due to muscle mass, diet, and certain medications), the 2024 updates strengthen the recommendation for the routine use of Cystatin C in specific clinical scenarios.

Measurement of GFR using a creatinine- and cystatin C-based equation (e.g., the CKD-EPI 2021 equation) is recommended when the diagnosis of CKD, risk stratification, or clinical decision-making is dependent on a precise GFR estimate. This is particularly relevant when:

• eGFR based on creatinine is ≥ 45 to 59 mL/min/1.73 m² (G3a).
  
  
• Non-glomerular determinants of creatinine (such as extreme body habitus, amputation, malnutrition, or high meat intake) are present.
  
  

The incorporation of Cystatin C offers a potentially more accurate and unbiased estimate of GFR, leading to more appropriate clinical categorization, particularly for patients near key therapeutic thresholds.

Risk Prediction and Personalized Prognosis

The core principle of risk stratification remains anchored in the CGA heat map, which cross-tabulates five GFR categories (G1–G5) and three Albuminuria categories (A1: Normal/Mild, A2: Moderately Increased, A3: Severely Increased) to determine prognostic risk (Low, Moderately Increased, High, and Very High).

Albuminuria (ACR) remains the most powerful independent prognostic marker for CKD progression and cardiovascular events. A sustained increase in Urine Albumin-to-Creatinine Ratio (ACR) above 30 mg/g (A2) significantly elevates the risk across all GFR categories.

Evaluation of CKD Etiology

The guidelines stress the importance of determining the underlying cause of CKD, as etiology dictates specific management pathways (e.g., immunosuppression for glomerulonephritis). Identifying the cause helps clinicians forecast the likely trajectory of the disease and implement non-specific CKD interventions (e.g., blood pressure control) within the context of the primary condition. 

All patients presenting with CKD of unknown etiology or rapid progression require a prompt and systematic diagnostic workup.

Core Pharmacologic Strategies for Cardiorenal Protection

The KDIGO 2024 guidelines mandate a dramatic shift in pharmacologic management, moving from a stepped approach to simultaneous, early introduction of Guideline-Directed Medical Therapy (GDMT) with proven cardiorenal benefits. The goal is to maximize kidney and cardiovascular risk reduction through combinatorial therapy.

SGLT2 Inhibitors: The Foundational Cardiorenal Pillar

Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors have become the cornerstone of therapy for many patients with CKD, regardless of the presence of diabetes. Their cardiorenal protective effects are attributed to a multifactorial mechanism, including improved renal hemodynamics (restoration of tubuloglomerular feedback), reduced inflammation and fibrosis, and proven effects in heart failure and major adverse cardiovascular events (MACE).

The guidelines strongly recommend an SGLT2 inhibitor (e.g., Dapagliflozin or Empagliflozin) for adults with CKD who have:

• eGFR ≥ 20 mL/min/1.73 m² and ACR ≥ 30 mg/g (A2 or A3), or
  
  
• Type 2 Diabetes (T2D) with eGFR ≥ 20 mL/min/1.73 m².
  
  

This recommendation is based on compelling data from major RCTs. The DAPA-CKD trial demonstrated that Dapagliflozin significantly reduced the composite endpoint of worsening kidney function, ESKD, and death from renal or cardiovascular causes in patients with and without T2D (Hazard Ratio [HR] 0.61; 95% Confidence Interval [CI] 0.51–0.72). 

Similarly, the EMPA-KIDNEY trial further solidified these benefits, showing that Empagliflozin significantly slowed the progression of kidney disease or cardiovascular death (HR 0.72; 95% CI 0.64–0.82) across a broad spectrum of CKD severity.

RAAS Blockade Optimization (ACEi/ARB)

Angiotensin-Converting Enzyme Inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) remain Class I recommendations for patients with hypertension and albuminuria (ACR ≥ 30 mg/g). They reduce intraglomerular pressure and decrease albuminuria, thereby slowing CKD progression.

The updated guidelines address the synergy between RAAS inhibitors and SGLT2 inhibitors. It is advised to maintain RAAS inhibitor therapy when initiating an SGLT2 inhibitor.

Although there is a risk of initial transient eGFR drop when combining agents, this should not typically lead to discontinuation, as the long-term clinical benefits are clear. Dose adjustments should prioritize achieving the target blood pressure while monitoring for hyperkalemia and acute kidney injury (AKI).

Non-Steroidal Mineralocorticoid Receptor Antagonists (nsMRAs)

The addition of an nsMRA, specifically Finerenone, represents a critical therapeutic advance for patients with T2D and CKD. Finerenone selectively blocks the mineralocorticoid receptor (MR), mitigating the pro-inflammatory and pro-fibrotic effects driven by MR overactivation, which persists even with maximum RAAS blockade.

Finerenone is recommended for patients with T2D and CKD (eGFR ≥ 25 mL/min/1.73 m², normokalemia, and ACR ≥ 30 mg/g despite optimized standard care, including an ACEi or ARB). 

The FIDELIO-DKD and FIGARO-DKD trials (collectively, the FIDELITY program) demonstrated that Finerenone significantly reduced the risk of CKD progression and cardiovascular events compared to placebo when added to optimized background therapy. For instance, in FIDELIO-DKD, Finerenone reduced the composite kidney outcome by 18% (HR 0.82; 95% CI 0.73–0.93) and the composite cardiovascular outcome by 14% (HR 0.86; 95% CI 0.75–0.99).

Practice Highlight: Foundational Triple Therapy

For patients with CKD and T2D (eGFR ≥ 25 mL/min/1.73 m² and ACR ≥ 30 mg/g), the optimal pharmacologic regimen now consists of RAAS Blockade + SGLT2 Inhibitor + Finerenone, representing the maximal evidence-based therapy for simultaneous kidney and cardiovascular protection. 

Close monitoring for hyperkalemia is required when introducing the MRA.

Management of Key Comorbidities and Complications

The integrated management framework of the KDIGO 2024 guidelines extends beyond core cardiorenal pharmacotherapy to encompass the meticulous control of associated comorbidities, which significantly accelerate CKD progression and compound cardiovascular risk.

Blood Pressure Targets and Antihypertensive Selection

Aggressive blood pressure (BP) control remains a Class I recommendation for CKD management. The guidelines maintain that a systolic BP target of <120 mmHg (when measured accurately using a standardized office BP measurement or home/ambulatory monitoring) is appropriate for most non-dialysis CKD patients.

The selection of antihypertensive agents should be guided by the presence of albuminuria. For patients with CKD and Albuminuria Category A2 or A3 (ACR ≥ 30 mg/g), an ACE inhibitor or ARB is the preferred first-line agent, serving the dual purpose of blood pressure reduction and kidney protection (reduction in intraglomerular pressure). For those who do not tolerate RAAS inhibition or require additional BP lowering, the inclusion of calcium channel blockers (non-dihydropyridine) or diuretics should be considered based on volume status and specific clinical indications.

Glycemic Control in Diabetic Kidney Disease (DKD)

For patients with Diabetic Kidney Disease (DKD), the guidelines reinforce the need for personalized glycemic targets. While a general HbA1c goal of <7.0% is often appropriate to prevent microvascular complications, this must be balanced against the risk of hypoglycemia in elderly, frail, or high-comorbidity patients.

The pharmacological strategy prioritizes agents with demonstrated cardiorenal benefits:

• SGLT2 Inhibitors: As detailed previously, these are foundational.
  
  
• GLP-1 Receptor Agonists (GLP-1 RAs): Recommended as an additive therapy for T2D and CKD, particularly if the HbA1c target is not met with metformin and an SGLT2 inhibitor, or if an SGLT2 inhibitor is contraindicated. Major RCTs (e.g., SUSTAIN-6, LEADER, REWIND) have shown these agents reduce MACE and slow the progression of albuminuria.
  
  

Metformin remains the standard first-line agent for T2D, provided the eGFR is ≥ 30 mL/min/1.73 m², but requires dose reduction as GFR declines.

Anemia and Mineral Bone Disorder Screening

The comprehensive guideline updates also reinforce protocols for managing common CKD complications:

• Anemia of CKD: Routine screening for anemia should commence when GFR is ≤ 60 mL/min/1.73 m². Management involves identifying and treating underlying causes (e.g., iron deficiency) and, if necessary, initiating Erythropoiesis-Stimulating Agents (ESAs) once Hb levels fall below 10 g/dL, with a target of 10-11.5 g/dL.
  
  
• CKD-Mineral and Bone Disorder (CKD-MBD): Guidelines recommend regular monitoring of serum calcium, phosphate, and parathyroid hormone (PTH) starting at GFR G3. Intervention thresholds for hyperphosphatemia and secondary hyperparathyroidism are provided to prevent vascular calcification and bone disease.
  
  

Interdisciplinary Care and Implementation in Practice

The complexity of the Cardiorenal-Metabolic (CKM) syndrome and the simultaneous introduction of multiple potent pharmacotherapies necessitate a collaborative, team-based approach for effective implementation of the KDIGO 2024 guidelines. The integration of care across specialties is no longer optional but a fundamental determinant of patient outcome.

Patient-Centered Care and Shared Decision Making

Successful management hinges on patient adherence, which is facilitated by clear communication and shared decision-making (SDM). Discussions regarding the initiation of agents like SGLT2 inhibitors and non-steroidal MRAs must clearly articulate the absolute risk reduction in both cardiovascular and renal events, balancing these benefits against potential adverse effects (e.g., mycotic infections with SGLT2i; hyperkalemia with nsMRAs).

Educating the patient on the chronic nature of CKD and the rationale for the foundational triple therapy is crucial for maintaining long-term adherence.

Referral Criteria and Multidisciplinary Team (MDT) Approach

The guidelines provide refined criteria for timely referral to a nephrologist to optimize advanced management, address complications, and coordinate potential kidney replacement therapy. Referral is strongly recommended for patients presenting with:

• Acute Kidney Injury (AKI) of unknown cause.
  
  
• Rapid progression of CKD (eGFR decline >5 mL/min/1.73 m² within 1 year).
  
  
• eGFR < 30 mL/min/1.73 m² (G4 or G5).
  
  
• Severe Albuminuria (ACR > 300 mg/g) that is non-responsive to RAAS blockade.
  
  
• Complications such as refractory hypertension, CKD-MBD requiring advanced treatment, or difficult-to-manage anemia.
  
  

The Multidisciplinary Team (MDT), involving primary care, nephrology, cardiology, endocrinology, pharmacy, and dietetics, is essential for optimizing care. 

The pharmacist is critical for complex medication reconciliation, dose adjustment, and hyperkalemia monitoring, particularly when combining RAAS inhibitors, SGLT2 inhibitors, and nsMRAs. 

The endocrinologist and cardiologist contribute expertise to glycemic and heart failure management, respectively, ensuring that the full spectrum of the CKM syndrome is addressed.

Clinical Practice Summary and Key Takeaways

The KDIGO 2024 CKD Guidelines solidify a proactive, evidence-based paradigm for managing chronic kidney disease, fundamentally integrating it within the broader context of Cardiorenal-Metabolic (CKM) syndrome. 

The ultimate objective is to simultaneously reduce the risk of kidney failure and major adverse cardiovascular events (MACE).

Key Takeaways for Clinical Practice

1. Enhanced Risk Assessment: Diagnosis and prognosis must leverage the CGA classification (eGFR and Albuminuria Category). The guidelines advocate for utilizing Cystatin C in specific cases (eGFR ≥ 45 to 59 mL/min/1.73 m²) to ensure accurate staging and risk stratification, optimizing treatment thresholds.
   
   
2. Foundational Pharmacologic Therapy: The approach pivots to early, simultaneous initiation of synergistic therapies, prioritizing agents with dual cardiorenal protection:
   
   
   • SGLT2 Inhibitors: Now a core component for most patients with CKD, with or without Type 2 Diabetes, provided eGFR ≥ 20 mL/min/1.73 m² and ACR ≥ 30 mg/g.
     
     
   • RAAS Blockade: Remains essential for all patients with hypertension and albuminuria (ACR ≥ 30 mg/g).
     
     
   • Non-Steroidal MRAs (nsMRAs): Recommended (e.g., Finerenone) for patients with T2D, CKD, and albuminuria who are optimized on RAAS blockade, offering additional anti-fibrotic and cardiorenal benefits demonstrated in the FIDELITY program.
     
     
3. Blood Pressure Control: The target is refined to <120 mmHg systolic, using standardized measurements, reinforcing the principle that aggressive BP control is a critical modifier of CKD progression and cardiovascular risk.
   
   
4. Interdisciplinary Mandate: Effective implementation requires a shift from isolated specialty care to a structured Multidisciplinary Team (MDT) approach, particularly for managing polypharmacy and complex comorbidities. Timely nephrology referral for eGFR < 30 mL/min/1.73 m² or rapid progression is crucial.
   
   

Guideline Snapshot: Therapeutic Intensification