What is the initial treatment approach for a patient with Chronic Kidney Disease (CKD), particularly those with underlying conditions such as diabetes and hypertension?

Initial Treatment Approach for CKD with Diabetes and Hypertension

For patients with CKD, diabetes, and hypertension, immediately initiate an SGLT2 inhibitor (if eGFR ≥20 mL/min/1.73 m²), an ACE inhibitor or ARB (if albuminuria is present), metformin (if eGFR ≥30), and a moderate-to-high intensity statin—this comprehensive pharmacologic strategy addresses kidney protection, cardiovascular risk reduction, and glycemic control simultaneously. 1, 2

First-Line Pharmacologic Therapy

SGLT2 Inhibitors (Highest Priority)

• Start an SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m², regardless of current glycemic control or HbA1c level. 1, 2 This is the single most important intervention because SGLT2 inhibitors provide kidney protection, reduce cardiovascular events, and decrease heart failure hospitalizations independent of their glucose-lowering effects. 2
• Continue SGLT2 inhibitors until dialysis or transplantation is initiated, even as eGFR declines below 20 mL/min/1.73 m², since kidney and cardiovascular benefits persist at lower eGFR levels. 1, 2
• Before initiating, assess hypoglycemia risk, particularly if the patient is on insulin or sulfonylureas, and consider reducing doses of these agents to prevent hypoglycemia. 2

RAS Blockade for Hypertension and Albuminuria

• Initiate an ACE inhibitor or ARB in all patients with diabetes, hypertension, AND albuminuria (≥30 mg/g), titrating to the maximum tolerated dose. 1, 2, 3 This is a Grade 1B recommendation from KDIGO 2020. 1
• For patients with albuminuria ≥300 mg/g, ACE inhibitor or ARB use is a strong recommendation. 3
• If the patient has diabetes and albuminuria but normal blood pressure, ACE inhibitor or ARB therapy may still be considered. 1
• Monitor serum creatinine and potassium within 2-4 weeks after starting or increasing the dose. 1, 2, 3
• Continue therapy unless creatinine rises >30% within 4 weeks—if this occurs, evaluate for acute kidney injury, volume depletion, renal artery stenosis, or concomitant nephrotoxins (NSAIDs, diuretics). 1, 2, 3
• Do not immediately discontinue ACE inhibitors or ARBs for hyperkalemia—first attempt dietary potassium restriction, add diuretics, sodium bicarbonate, or GI cation exchangers. 1, 2, 3
• Never combine an ACE inhibitor with an ARB, as this increases adverse events (hyperkalemia, acute kidney injury) without additional benefit. 3, 4

Metformin for Glycemic Control

• Add metformin when eGFR ≥30 mL/min/1.73 m² for additional glycemic control. 1, 2, 3
• Reduce metformin dose to 1000 mg daily when eGFR is 30-44 mL/min/1.73 m². 2, 3
• Discontinue metformin when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk. 2, 3

Statin Therapy for Cardiovascular Protection

• Initiate a moderate-to-high intensity statin in all patients with diabetes and CKD stages 1-4. 1, 2, 3 This applies to both type 1 and type 2 diabetes. 2
• Target LDL-C <100 mg/dL, or consider <70 mg/dL for very high-risk patients. 3

Blood Pressure Targets and Additional Antihypertensive Agents

Blood Pressure Goals

• Target blood pressure <130/80 mm Hg if albuminuria ≥30 mg/g is present. 3 This is based on the most recent American Heart Association guidelines. 3
• Target blood pressure <140/90 mm Hg if albuminuria <30 mg/g. 1, 3, 4 This applies to all age groups, including patients over 60 years old—CKD patients are specifically excluded from the more lenient <150/90 mm Hg target used in the general elderly population. 1, 4
• Do not lower diastolic blood pressure below 70 mm Hg, as this increases cardiovascular risk, particularly coronary events. 4

Additional Antihypertensive Agents

• If blood pressure remains uncontrolled on ACE inhibitor or ARB monotherapy, add a thiazide-type diuretic or long-acting dihydropyridine calcium channel blocker as second-line therapy. 1, 3, 4
• All three classes (ACE inhibitor/ARB, diuretic, calcium channel blocker) are often needed to achieve blood pressure targets. 1

Additional Risk-Based Therapies

GLP-1 Receptor Agonists

• Add a GLP-1 receptor agonist if glycemic targets (HbA1c 6.5-8.0%) are not met with metformin and SGLT2 inhibitors, or if these agents cannot be used. 1, 2, 3

Nonsteroidal Mineralocorticoid Receptor Antagonists

• Consider adding finerenone (the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits) for patients with type 2 diabetes who have persistent albuminuria ≥30 mg/g despite first-line therapy and normal potassium levels. 1, 2, 3

Glycemic Monitoring and Targets

• Target HbA1c between 6.5% and 8.0%, individualized based on hypoglycemia risk, life expectancy, comorbidities, and patient preferences. 1, 2, 3
• Check HbA1c every 3 months when therapy changes or targets are not met, and at least twice yearly in stable patients. 1, 2, 3

Lifestyle Interventions (Non-Negotiable Components)

Dietary Modifications

• Restrict sodium intake to <2 grams per day (<90 mmol/day or <5 grams sodium chloride/day) to control blood pressure, reduce proteinuria, and enhance the effectiveness of RAS inhibitors. 1, 2, 3, 4 RAS inhibitors lose efficacy in patients on high-salt diets. 4
• Limit protein intake to 0.8 g/kg/day for patients with CKD not on dialysis. 2, 3
• Recommend a diet high in vegetables, fruits, and whole grains but low in refined carbohydrates and sugar-sweetened beverages. 1

Physical Activity and Smoking Cessation

• Advise moderate-intensity physical activity for at least 150 minutes per week, or to a level compatible with cardiovascular and physical tolerance. 2, 3
• Strongly recommend tobacco cessation for all patients who use tobacco products. 2, 3

Monitoring Strategy

Regular Reassessment (Every 3-6 Months)

• Reassess glycemia, albuminuria, blood pressure, cardiovascular disease risk, and lipids every 3-6 months. 1
• Monitor serum creatinine, eGFR, and urine albumin-to-creatinine ratio at least annually for moderate-to-severe CKD. 3
• For eGFR <60 mL/min/1.73 m² or GFR decline ≥4 mL/min/1.73 m²/year, increase monitoring frequency to every 1-6 months. 3

Monitoring for CKD Complications

• Begin monitoring for anemia, bone disease, metabolic acidosis, and hyperkalemia when eGFR <60 mL/min/1.73 m² (Stage 3). 3
• Assess for hyperkalemia, particularly in patients on ACE inhibitors/ARBs, but attempt management strategies before discontinuing therapy. 2, 3

Nephrology Referral Criteria

• Refer to a nephrologist when eGFR <30 mL/min/1.73 m² (Stage 4), or earlier if there is uncertainty about etiology, difficult management issues, or rapid progression. 3
• Specific indications include: eGFR <30 mL/min/1.73 m², albuminuria ≥300 mg/g despite treatment, rapidly declining kidney function, resistant hypertension, or electrolyte disturbances. 3
• Early referral (Stage 4) reduces cost, improves quality of care, and delays dialysis. 3

Critical Pitfalls to Avoid

• Never discontinue ACE inhibitors or ARBs immediately for hyperkalemia or modest creatinine elevation (<30% increase)—these are manageable side effects that should not prevent use of these kidney-protective agents. 1, 2, 3
• Avoid nephrotoxins, particularly NSAIDs, which can precipitate acute kidney injury and worsen CKD. 3, 5
• Do not delay SGLT2 inhibitor initiation while waiting for "better" glycemic control—the benefits are independent of glucose lowering. 2
• Advise contraception in women receiving ACE inhibitor or ARB therapy and discontinue these agents in women considering pregnancy or who become pregnant. 1

Multidisciplinary Team Approach

• Engage diabetes care and education specialists, dietitians, pharmacists, and other health professionals in the care of the patient. 1 This team-based integrated approach represents a key strategy to overcome barriers to effective management. 1