What is the best therapy to reverse or slow Chronic Kidney Disease (CKD) progression?

Best Therapies to Slow or Reverse Chronic Kidney Disease Progression

The most effective therapies to slow CKD progression are RAAS inhibitors (ACE inhibitors or ARBs) and SGLT2 inhibitors, which should be used as foundational therapy for patients with CKD, particularly those with proteinuria or diabetes. 1, 2

First-Line Therapies

RAAS Inhibition

• ACE inhibitors or ARBs are recommended as first-line therapy for both diabetic and non-diabetic adults with CKD and urine albumin excretion >300 mg/24 hours 1
• These medications have consistently shown effectiveness in slowing progression of both diabetic and non-diabetic nephropathy by reducing proteinuria 1
• For patients with type 2 diabetes and nephropathy, losartan is specifically indicated to reduce the rate of progression as measured by doubling of serum creatinine or development of end-stage renal disease 3

SGLT2 Inhibitors

• Recent guidelines recommend SGLT2 inhibitors alongside RAAS inhibitors as foundational therapy for CKD patients with and without type 2 diabetes 2
• SGLT2 inhibitors prevent CKD progression and reduce fatal and non-fatal kidney events, hospitalization for heart failure, and all-cause mortality 2
• Empagliflozin specifically has been shown to provide both cardiovascular and renal protection 4

Blood Pressure Management

Target Blood Pressure

• For CKD patients with urine albumin excretion <30 mg/24 hours: maintain BP ≤140/90 mmHg 1
• For CKD patients with urine albumin excretion ≥30 mg/24 hours: maintain BP ≤130/80 mmHg 1
• Blood pressure control is critical in preventing CKD progression, breaking the vicious cycle between hypertension and CKD 1

Additional Disease-Modifying Therapies

For Diabetic CKD

• Glycemic control with target HbA1c of approximately 7.0% has been established to slow CKD progression 4
• Combination therapy with RAAS inhibitors and SGLT2 inhibitors provides additive benefits for diabetic nephropathy 2

Emerging Therapies

• Mineralocorticoid receptor antagonists (such as finerenone) show promise for managing CKD, particularly in reducing proteinuria 5, 4
• Endothelin receptor antagonists (such as atrasentan) have shown potential to decrease risk of renal events in diabetic CKD patients 5
• Pentoxifylline has shown benefits in managing CKD through its anti-inflammatory properties 5

Lifestyle and Nutritional Interventions

• Regular physical activity, particularly walking, helps slow CKD progression 5
• Weight loss for overweight or obese patients can improve kidney function 5
• Low-protein diet (LPD) may slow progression in advanced CKD 5
• Mediterranean-style diet is recommended to reduce cardiovascular risk in CKD patients 1
• Smoking cessation and limiting alcohol consumption are essential to prevent CKD progression 5
• Reduced sodium intake to <2 g per day helps control blood pressure and slows progression 1

Metabolic Management

• Correction of metabolic acidosis may provide protection against CKD progression 4
• Management of hyperphosphatemia and vitamin D deficiency may be beneficial, though evidence is still limited 6
• Lipid management with statin therapy is recommended for adults ≥50 years with CKD 1

Preventive Strategies

• Avoid nephrotoxic medications (NSAIDs, aminoglycosides, etc.) to prevent acute kidney injury episodes 4
• All CKD patients should be considered at increased risk of acute kidney injury, which can accelerate CKD progression 1
• Regular monitoring of kidney function and albuminuria is essential to track disease progression and treatment response 1

Important Caveats

• Despite evidence for individual therapies, a comprehensive approach combining multiple interventions yields the best outcomes 1
• The degree of proteinuria reduction correlates directly with kidney protection and reduced cardiovascular risk 1
• While these therapies can significantly slow progression, complete reversal of CKD is rarely achievable with current treatments 6
• Early identification and intervention provide the best opportunity to preserve kidney function 2
• Treatment must be individualized based on CKD stage, albuminuria level, comorbidities, and underlying cause 1