What are the latest pharmacological interventions for managing chronic kidney disease (CKD)?

Latest Drugs in CKD

The most important recent advances in CKD pharmacotherapy are SGLT2 inhibitors (initiated at eGFR ≥20 ml/min/1.73 m²) and finerenone (a non-steroidal mineralocorticoid receptor antagonist), both of which reduce kidney failure, cardiovascular events, and mortality in patients with CKD. 1

First-Line Drug Therapy for CKD

The KDIGO 2022 guidelines establish a clear hierarchy of first-line medications that should be initiated in all appropriate patients with CKD: 1

SGLT2 Inhibitors (Most Important Recent Advance)

• Initiate when eGFR ≥20 ml/min/1.73 m² and continue until dialysis or transplantation 1
• This represents a major update from the 2020 guideline which recommended initiation at eGFR ≥30 ml/min/1.73 m² 1
• SGLT2 inhibitors provide kidney protection, cardiovascular protection, and mortality reduction independent of their glucose-lowering effects 1
• Continue SGLT2 inhibitors even if eGFR falls below 20 ml/min/1.73 m² as long as tolerated, until kidney replacement therapy is initiated 1
• These benefits apply to patients with or without diabetes, though evidence is strongest in type 2 diabetes 1

RAS Inhibitors

• ACE inhibitors or ARBs should be titrated to maximum tolerated dose in patients with hypertension and albuminuria 1
• Monitor serum potassium and creatinine within 2-4 weeks of initiation or dose changes 1
• Critical pitfall: Never combine ACE inhibitors with ARBs—this combination is harmful and increases adverse events including hyperkalemia and acute kidney injury 1

Metformin

• Use when eGFR ≥30 ml/min/1.73 m² 1

Statins

• Moderate- or high-intensity statin therapy for all patients with CKD 1

Finerenone: The Newest Addition to CKD Treatment

Finerenone is the only non-steroidal mineralocorticoid receptor antagonist with proven kidney and cardiovascular benefits and represents the most significant new drug class for CKD in recent years. 1

Indications for Finerenone

• Type 2 diabetes with eGFR ≥25 ml/min/1.73 m² 1
• Albuminuria (ACR ≥30 mg/g) despite maximum tolerated RAS inhibitor therapy 1
• Normal serum potassium (<4.8 mEq/L at screening or ≤5.0 mEq/L per FDA label) 1

Evidence Base

• FIDELIO-DKD trial showed finerenone reduced composite kidney outcomes (kidney failure, sustained ≥40% decrease in eGFR, or kidney death) with HR 0.82 (95% CI 0.73-0.93) 1
• FIGARO-DKD trial demonstrated reduction in cardiovascular outcomes with HR 0.87 (95% CI 0.76-0.98) 1
• Combined FIDELITY analysis confirmed benefits across both kidney (HR 0.77) and cardiovascular (HR 0.86) outcomes 2, 3
• Albuminuria reduction with finerenone mediated 84% of the kidney protection effect and 37% of cardiovascular protection 2

Dosing Algorithm for Finerenone

• Start 20 mg daily if eGFR >60 ml/min/1.73 m² 1
• Start 10 mg daily if eGFR 25-60 ml/min/1.73 m² 1
• Check potassium 4 weeks after initiation or dose change 1
• Uptitrate to 20 mg daily if potassium <4.8 mmol/L 1
• Continue if potassium ≤5.5 mmol/L 1
• Withhold if potassium >5.5 mmol/L; restart at 10 mg when potassium ≤5.0 mmol/L 1
• Can continue with eGFR <25 ml/min/1.73 m² if potassium acceptable and drug tolerated 1

Finerenone Safety Profile

• Hyperkalemia is the primary adverse effect but occurs less frequently than with steroidal MRAs like spironolactone 3
• Hyperkalemia risk is lower when used with SGLT2 inhibitors (8.1% vs 18.7% without SGLT2i) 4
• Benefits on kidney and cardiovascular outcomes are consistent regardless of SGLT2 inhibitor use 4

GLP-1 Receptor Agonists (Additional Risk-Based Therapy)

• Use if additional glucose lowering is needed after SGLT2 inhibitor and metformin 1
• GLP-1 RAs provide cardiovascular protection and possible kidney benefits beyond glucose control 1
• Preferred over other glucose-lowering agents (DPP-4 inhibitors, sulfonylureas, thiazolidinediones) for patients with type 2 diabetes and CKD who need additional glycemic control 1

Critical Implementation Points

Layered Treatment Approach

The modern approach to CKD management involves layering therapies: 1

1. Foundation: SGLT2 inhibitor (eGFR ≥20), metformin (eGFR ≥30), RAS inhibitor (if hypertension/albuminuria), statin
2. Additional risk-based therapy: Finerenone (if ACR ≥30 mg/g and normal potassium), GLP-1 RA (if additional glucose control needed)
3. Other agents as needed: Additional antihypertensives, antiplatelet agents, lipid-lowering therapies

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation—start at eGFR ≥20 ml/min/1.73 m² and continue until dialysis 1
• Do not combine ACE inhibitors with ARBs—this increases harm without benefit 1
• Do not use steroidal MRAs (spironolactone, eplerenone) in place of finerenone for CKD protection—only finerenone has proven kidney and cardiovascular benefits in this population 1
• Monitor potassium closely with finerenone—check 4 weeks after any dose change and regularly during treatment 1
• Do not stop SGLT2 inhibitors when eGFR falls below 20—continue as tolerated until dialysis initiation 1

Monitoring Requirements

• Reassess glycemia, albuminuria, blood pressure, cardiovascular risk, and lipids every 3-6 months 1
• Monitor serum potassium and creatinine 2-4 weeks after initiating or changing RAS inhibitor dose 1
• Check potassium 4 weeks after finerenone initiation or dose adjustment 1