What are the 4 pillars of renal health management in patients with chronic kidney disease (CKD)?

The 4 Pillars of Renal Medication Management in CKD

The four pillars of renal medication management are: (1) SGLT2 inhibitors, (2) ACE inhibitors or ARBs, (3) mineralocorticoid receptor antagonists (MRAs), and (4) blood pressure optimization—these form the foundation for reducing cardiovascular events, slowing CKD progression, and improving mortality in patients with chronic kidney disease. 1, 2

Pillar 1: SGLT2 Inhibitors

SGLT2 inhibitors are recommended for all patients with type 2 diabetes and CKD with eGFR ≥20 mL/min/1.73 m² and urinary albumin ≥200 mg/g creatinine to reduce CKD progression and cardiovascular events. 1

• These agents provide cardioprotective and renoprotective benefits independent of glucose-lowering effects 1
• The evidence supports their use even in non-diabetic CKD patients with significant albuminuria or heart failure 2
• A critical caveat: SGLT2 inhibitors should be temporarily discontinued 48-72 hours before elective surgery to prevent complications, but failure to restart them post-operatively leads to unintentional harm 1

Pillar 2: ACE Inhibitors or ARBs (RAS Inhibition)

ACE inhibitors or ARBs are strongly recommended for patients with urinary albumin-to-creatinine ratio ≥300 mg/g creatinine and/or eGFR <60 mL/min/1.73 m², and should be considered for those with modestly elevated albuminuria (30-299 mg/g). 1

• Start these agents in all patients with albuminuria ≥30 mg/g (A2-A3 categories), regardless of blood pressure, and titrate to maximum tolerated dose 2
• Do not discontinue RAS blockade for minor increases in serum creatinine (≤30%) in the absence of volume depletion 1
• Monitor serum creatinine and potassium levels two weeks after initiation and periodically thereafter 1
• The goal is to achieve a 30% or greater reduction in urinary albumin to slow CKD progression 1
• Blood pressure targets should be <130/80 mmHg, with more aggressive control (<120 mmHg systolic) providing cardioprotective benefits based on SPRINT trial data 1

Pillar 3: Mineralocorticoid Receptor Antagonists (Finerenone)

In patients with CKD who are at increased risk for cardiovascular events or CKD progression, or who cannot use SGLT2 inhibitors, nonsteroidal MRAs (finerenone) are recommended to reduce CKD progression and cardiovascular events. 1

• This is particularly important for patients with eGFR ≥25 mL/min/1.73 m² and urine albumin ranging from normal to 200 mg/g creatinine 1
• Finerenone provides additional benefit beyond ACE inhibitors/ARBs in reducing albuminuria and cardiovascular risk 1
• Routine use of aldosterone antagonists in advanced CKD requires careful monitoring for hyperkalemia, especially with eGFR <30 mL/min/1.73 m² 2

Pillar 4: Blood Pressure Optimization

Optimization of blood pressure control and reduction in blood pressure variability are essential to reduce risk or slow CKD progression. 1

• Target systolic BP <120 mmHg using standardized office measurement techniques provides cardioprotective and survival benefits 1
• This lower target is based on SPRINT trial evidence showing cardiovascular and mortality benefits 1
• Monitor blood pressure at every clinical encounter using standardized technique 2
• Achieving target BP usually requires multiple antihypertensive agents, including diuretics and calcium channel blockers in addition to RAS inhibitors 1

Critical Implementation Principles

Medication Safety and Monitoring

• People with CKD are more susceptible to nephrotoxic effects of medications—always weigh benefits versus potential harms 1
• Monitor eGFR, electrolytes, and therapeutic medication levels for drugs with narrow therapeutic windows 1
• Consider GFR when dosing all medications cleared by the kidneys 1
• For most clinical settings, validated eGFR equations using serum creatinine are appropriate for drug dosing 1

Drug Stewardship

• Perform thorough medication review periodically and at all transitions of care to assess adherence, continued indication, and potential drug interactions 1
• Review and limit over-the-counter medicines and herbal remedies that may be harmful 1
• Establish collaborative relationships with pharmacists to ensure proper drug stewardship 1

Adjunctive Therapies

• Prescribe statin therapy for all patients ≥50 years with CKD, or younger patients with diabetes, prior cardiovascular events, or 10-year cardiovascular risk >10% 2
• Advise sodium restriction to <2 g/day 2
• Recommend protein intake of 0.8 g/kg/day in CKD G3-G5, avoiding high protein intake >1.3 g/kg/day 1, 2

Common Pitfalls to Avoid

• Never discontinue all four pillars simultaneously during acute illness without a clear plan for restarting them—this leads to unintentional harm 1
• Do not avoid ACE inhibitors/ARBs due to fear of hyperkalemia or modest creatinine elevation—the benefits far outweigh risks when properly monitored 1
• Avoid NSAIDs and other nephrotoxins that undermine the protective effects of these four pillars 1
• Do not delay SGLT2 inhibitor initiation in eligible patients—early intervention provides maximum benefit 1, 2