What is the recommended treatment approach for an adult with chronic kidney disease, including blood pressure targets, use of angiotensin‑converting enzyme inhibitors or angiotensin‑receptor blockers, SGLT2 inhibitors, glycemic control, lipid management, lifestyle modifications, and stage‑specific management?

Treatment for Chronic Kidney Disease

All adults with CKD should receive SGLT2 inhibitors as foundational first-line therapy (when eGFR ≥20 mL/min/1.73 m²) combined with RAS inhibition (ACE inhibitor or ARB at maximum tolerated dose) when hypertension or albuminuria is present, plus statin therapy, forming the core triad of kidney and cardiovascular protection. 1, 2

First-Line Pharmacological Therapy

SGLT2 Inhibitors (Universal Foundation)

• Initiate SGLT2 inhibitors immediately for most CKD patients when eGFR ≥20 mL/min/1.73 m² and continue until dialysis or transplantation. 1, 2
• Continue SGLT2 inhibitors even as eGFR declines below 20 mL/min/1.73 m² until dialysis initiation. 2
• SGLT2 inhibitors provide kidney protection, cardiovascular protection, heart failure prevention, and mortality reduction in both diabetic and non-diabetic CKD. 1, 3, 4

RAS Inhibition (ACE Inhibitors or ARBs)

• ACE inhibitors or ARBs are mandatory first-line therapy when albuminuria ≥30 mg/24 hours (or equivalent ACR ≥30 mg/g) is present, regardless of diabetes status. 1, 2
• When hypertension exists with albuminuria, RAS inhibitors must be the initial antihypertensive agent. 1, 2
• Titrate to maximum tolerated dose for optimal kidney and cardiovascular protection. 2, 5
• For albuminuria ≥300 mg/24 hours, RAS blockade is strongly recommended in both diabetic and non-diabetic adults. 1
• Continue RAS inhibitors unless serum creatinine increases by >30% within 4 weeks—modest increases up to 30% are expected and acceptable. 5

Statin Therapy (Cardiovascular Protection)

• All adults ≥50 years with eGFR <60 mL/min/1.73 m² require statin or statin/ezetimibe combination therapy. 1, 2
• Adults ≥50 years with eGFR ≥60 mL/min/1.73 m² (GFR categories G1-G2) should receive statin therapy. 1
• Adults aged 18-49 years with CKD should receive statin treatment if they have coronary disease, diabetes, prior ischemic stroke, or estimated 10-year cardiovascular risk >10%. 1
• Add ezetimibe 10 mg daily if LDL targets are not met or if high ASCVD risk exists. 2
• Consider PCSK9 inhibitors for patients with CKD who have an indication for their use. 1

Blood Pressure Management

Target Blood Pressure

• Aim for systolic BP <120 mmHg for most CKD patients to reduce progression risk and cardiovascular events. 1, 2
• For patients with albuminuria <30 mg/24 hours, target BP ≤140/90 mmHg. 1, 6, 5
• For patients with albuminuria ≥30 mg/24 hours, target BP ≤130/80 mmHg. 1, 6, 5

Antihypertensive Agent Selection

• When albuminuria is present, ACE inhibitors or ARBs must be the first-line agent. 1, 2
• Without albuminuria, dihydropyridine calcium channel blockers or diuretics can be considered as first-line alternatives. 1
• Add dihydropyridine calcium channel blockers and/or diuretics if needed to achieve BP targets beyond RAS inhibition. 1
• All three classes (RAS inhibitor, calcium channel blocker, diuretic) are often needed to attain BP targets. 1
• Monitor for postural hypotension regularly when treating with BP-lowering drugs. 1

Advanced Kidney and Heart Protection

Nonsteroidal Mineralocorticoid Receptor Antagonists (ns-MRA)

• Use ns-MRA (such as finerenone) in patients with diabetes and an indication for use, as they provide additive kidney and cardiovascular protection beyond SGLT2 inhibitors and RAS blockade. 1, 2, 6
• Steroidal MRA may be used if needed for resistant hypertension. 1

GLP-1 Receptor Agonists

• Manage hyperglycemia as per KDIGO Diabetes Guideline, including use of GLP-1 RA where indicated for additional cardiovascular and kidney protection. 1

Lifestyle Modifications

Physical Activity and Weight Management

• Recommend moderate-intensity physical activity for a cumulative duration of at least 150 minutes per week. 1, 2
• Target optimal body weight appropriate for age, gender, and comorbidities (BMI 20-25 kg/m² when feasible). 1, 5
• Weight management is particularly important as mortality risk associated with BMI differs with increasing age and stage of kidney disease. 1

Dietary Interventions

• Advise a healthy and diverse diet with higher consumption of plant-based foods compared to animal-based foods and lower consumption of ultra-processed foods. 1, 2
• Consider a plant-based "Mediterranean-style" diet to reduce cardiovascular risk. 1, 2
• Maintain protein intake of 0.8 g/kg body weight/day in adults with CKD G3-G5 (eGFR <60 mL/min/1.73 m²). 1, 2
• Avoid high protein intake (>1.3 g/kg/day) in adults with CKD at risk of progression. 1
• Restrict dietary sodium to <2,300 mg/day (<2 g/day) to control blood pressure and reduce cardiovascular risk. 2, 6, 5

Tobacco Cessation

• Mandate avoidance of all tobacco products to minimize CVD, respiratory disease, and cancer risks. 1, 2
• Referral to smoking cessation programs should be offered where available. 1

Management of CKD Complications

Anemia Management

• Monitor hemoglobin regularly; treatment is indicated when hemoglobin falls below target levels. 2
• Consider iron supplementation before or in conjunction with erythropoiesis-stimulating agents. 2

Metabolic Acidosis

• Monitor serum bicarbonate levels regularly. 2
• Treat metabolic acidosis with oral alkali supplementation to maintain serum bicarbonate within normal range. 2

Electrolyte Management

• Monitor serum potassium, especially in patients on RAS inhibitors, diuretics, or MRAs. 2
• If hyperkalemia develops, use potassium-wasting diuretics or potassium binders to allow continuation of ACE inhibitor/ARB therapy rather than discontinuing nephroprotective treatment. 5
• Individualize dietary potassium restrictions based on serum levels. 2

CKD-Mineral and Bone Disorder

• Manage CKD-MBD, including monitoring and treating secondary hyperparathyroidism where indicated. 1

Cardiovascular Disease Management

Antiplatelet Therapy

• Prescribe oral low-dose aspirin (81 mg daily) for secondary prevention in CKD patients with established ischemic cardiovascular disease. 1, 2
• Consider aspirin for primary prevention in high ASCVD risk patients. 2
• Consider other antiplatelet therapy (e.g., P2Y12 inhibitors) when there is aspirin intolerance. 1

Management of Atrial Fibrillation and ASCVD

• Use the same principles to diagnose and manage ASCVD and atrial fibrillation as in people without CKD. 1
• CKD patients are at high risk for stroke even with low CHADS-VASc scores. 1

Stage-Specific Management Considerations

Early CKD (G1-G3a)

• Focus on aggressive risk factor modification and initiation of foundational therapies (SGLT2i, RAS inhibition if indicated, statin). 1, 2
• Regular monitoring every 3-6 months including eGFR, electrolytes, urine albumin-to-creatinine ratio, hemoglobin, and blood pressure. 2

Advanced CKD (G3b-G5, eGFR <45 mL/min/1.73 m²)

• Continue SGLT2 inhibitors until dialysis or transplantation. 1, 2
• Intensify monitoring of complications (anemia, metabolic acidosis, CKD-MBD, hyperkalemia). 1, 2
• For CKD stage 4 (eGFR 15-29 mL/min/1.73 m²), monitor eGFR and proteinuria every 3 months. 5
• For CKD stage 5 (eGFR <15 mL/min/1.73 m²), monitor monthly or as clinically indicated. 5

Nephrology Referral

• Immediate nephrology referral is mandatory when eGFR <30 mL/min/1.73 m² (advanced CKD stages 4-5). 6, 5
• Refer when there is uncertainty about kidney disease etiology, resistant hypertension, or significant albuminuria increases despite good BP control. 6
• Timely planning for kidney replacement therapy is essential for optimal outcomes. 2

Monitoring Strategy

Regular Reassessment Schedule

• Conduct regular risk factor reassessment every 3-6 months including eGFR, electrolytes, urine albumin-to-creatinine ratio, hemoglobin, and blood pressure. 1, 2
• Monitor serum creatinine, potassium, and bicarbonate 2-4 weeks after initiating or titrating RAAS blockade. 5
• Use spot urine albumin-to-creatinine ratio (ACR) rather than dipstick testing for more sensitive and quantitative assessment. 5

Definition of CKD Progression

• Progression is defined as both a change in GFR category and ≥25% decrease in eGFR to avoid misinterpreting small fluctuations. 1, 6
• Rapid progression is defined as a sustained decline in eGFR of ≥5 mL/min/1.73 m²/year. 1

Integrated Care Approach

Multidisciplinary Team

• Implement a team approach with nephrologists, primary care providers, dietitians, pharmacists, and other specialists. 2
• Referral to renal dietitians or accredited nutrition providers, pharmacists, psychologists, and smoking cessation programs should be offered where indicated and available. 1, 2

Patient-Centered Care

• Prioritize patient concerns, values, and preferences in treatment decisions. 2
• Provide comprehensive medication management, including dose adjustments for kidney function, medication reconciliation, and deprescribing when appropriate. 2

Critical Medications to Avoid

Nephrotoxic Agents

• NSAIDs (ibuprofen, naproxen, ketorolac) are absolute contraindications in CKD, as they cause acute kidney injury and accelerate progression. 2
• For treatment of acute gout in CKD, low-dose colchicine or intra-articular/oral glucocorticoids are preferable to NSAIDs. 1
• Avoid ongoing exposure to other nephrotoxic agents including aminoglycosides and minimize contrast agent exposure. 1, 5

Common Pitfalls to Avoid

• Do not discontinue RAS blockade prematurely due to modest creatinine increases (<30%)—this represents hemodynamic changes rather than true kidney injury. 5
• Do not delay nephrology referral for advanced CKD (eGFR <30 mL/min/1.73 m²). 2, 5
• Do not overlook the importance of lifestyle modifications alongside pharmacotherapy. 2
• Do not fail to prepare patients for renal replacement therapy in a timely manner. 2
• Do not neglect screening for and managing CKD complications until they become severe. 2
• Do not use age-adjusted definitions of proteinuria—albuminuria carries prognostic significance at all ages. 5