What is the best management approach for a patient with stage 1 to stage 3 chronic kidney disease (CKD), hypertension, and/or diabetes?

Management of Stage 1-3 Chronic Kidney Disease with Hypertension and/or Diabetes

For patients with stage 1-3 CKD and diabetes/hypertension, initiate ACE inhibitors or ARBs as first-line therapy, target blood pressure ≤130/80 mmHg if albuminuria is present (≤140/90 mmHg without albuminuria), add SGLT2 inhibitors for diabetic patients with eGFR ≥20 mL/min/1.73 m² and albuminuria ≥200 mg/g, and start statin therapy for all patients ≥50 years. 1, 2

Blood Pressure Management

Target Blood Pressure Goals

• Maintain BP ≤130/80 mmHg for patients with albuminuria (any level of proteinuria) 2
• Maintain BP ≤140/90 mmHg for patients without albuminuria 2
• These targets reduce both cardiovascular events and CKD progression 3

First-Line Antihypertensive Therapy

• ACE inhibitors or ARBs are mandatory first-line agents for all hypertensive CKD stage 1-3 patients 2, 3
• ACE inhibitors or ARBs are strongly recommended (mandatory) for patients with albuminuria ≥300 mg/g creatinine and/or eGFR <60 mL/min/1.73 m² 1
• For modest albuminuria (30-299 mg/g creatinine), ACE inhibitors or ARBs are recommended 1
• ARBs have high-quality evidence supporting their use, while ACE inhibitors have moderate-quality evidence 2
• Use ARBs if ACE inhibitors are not tolerated 4, 3

Additional Antihypertensive Agents

• Non-dihydropyridine calcium channel blockers (CCBs) consistently reduce albuminuria and slow kidney function decline 3
• Dihydropyridine CCBs should never be used as monotherapy in proteinuric CKD patients—always combine with a RAAS blocker 3
• Diuretics represent the cornerstone of management and are commonly needed for volume control 3

Critical Monitoring During RAAS Blockade

• Monitor serum creatinine and potassium periodically when using ACE inhibitors, ARBs, or diuretics 1, 4
• Do not discontinue RAAS blockade for minor increases in serum creatinine (≤30%) in the absence of volume depletion 1
• Consider withholding or discontinuing therapy only if clinically significant renal function decline occurs 4
• Patients with renal artery stenosis, severe heart failure, or volume depletion are at particular risk for acute renal failure 4

Diabetes Management in CKD

SGLT2 Inhibitors (Priority Therapy)

• For type 2 diabetes with diabetic kidney disease and eGFR ≥20 mL/min/1.73 m², use SGLT2 inhibitors to reduce CKD progression and cardiovascular events 1
• SGLT2 inhibitors are specifically recommended when urinary albumin ≥200 mg/g creatinine 1
• This represents a Grade A recommendation with strong evidence for both renal and cardiovascular protection 1

Alternative Therapy: Mineralocorticoid Receptor Antagonists

• For patients at increased risk for cardiovascular events or CKD progression who cannot use SGLT2 inhibitors, use finerenone (nonsteroidal MRA) to reduce CKD progression and cardiovascular events 1
• This applies to patients with eGFR <60 mL/min/1.73 m² and albuminuria ranging from normal to 200 mg/g creatinine 1

Albuminuria Reduction Goals

• Target a 30% or greater reduction in urinary albumin (mg/g) for patients with ≥300 mg/g albuminuria to slow CKD progression 1

Glycemic Control

• Maintain hemoglobin A1c ≤7% to prevent CKD progression 5

Lipid Management

Statin Therapy (Universal Recommendation)

• Initiate statin or statin/ezetimibe combination therapy for all patients ≥50 years with CKD stage 3 2
• This is a high-quality evidence (1A) recommendation 2
• Higher doses of statins are required as GFR declines 6

Younger Patients (18-49 Years)

• Initiate statin therapy in patients 18-49 years with known coronary disease, prior ischemic stroke, or estimated 10-year cardiovascular risk >10% 2

LDL-C Goals

• For stage 3 CKD, target LDL-C ≤70 mg/dL (1.8 mmol/L) with at least 50% reduction from baseline 6
• For stage 4 CKD, target LDL-C ≤55 mg/dL (1.4 mmol/L) with at least 50% reduction from baseline 6
• Maximize absolute LDL cholesterol reduction to achieve largest treatment benefits 2
• Consider PCSK9 inhibitors for patients with indications for their use, particularly when combined with maximally tolerated statin doses 2, 6

Lifestyle Modifications

Dietary Interventions

• Restrict sodium intake to <2 g per day 2
• Adopt a plant-dominant, Mediterranean-style diet to reduce cardiovascular risk and preserve renal function 2
• Limit dietary protein intake to maximum 0.8 g/kg body weight per day (the recommended daily allowance) for non-dialysis-dependent stage 3 or higher CKD 1

Weight and Exercise

• Achieve and maintain a healthy BMI of 20-25 kg/m² 2
• Exercise 30 minutes, 5 times per week 2
• Complete smoking cessation 2

Cardiovascular Protection

Aspirin Therapy

• Use low-dose aspirin for secondary prevention in patients with established ischemic cardiovascular disease 2

Hyperuricemia Management

• Treat symptomatic hyperuricemia with uric acid-lowering therapy 2
• Do not treat asymptomatic hyperuricemia to delay CKD progression (no proven benefit) 2

Volume Management

Fluid Balance Principles

• Maintain optimal intravascular volume with isotonic crystalloids when expansion is needed 2, 7
• Avoid excessive diuresis with loop and thiazide diuretics 2
• Correct volume or salt depletion prior to initiating losartan or other RAAS blockers 4

High-Risk Situations Requiring Close Monitoring

• During initiation or dose adjustment of diuretics, ACE inhibitors, or ARBs 7
• During acute illness with fever, vomiting, or diarrhea 7
• In the presence of heart failure or hemodynamic instability 7
• The greatest diuretic effect occurs within the first 1-3 days of therapy, creating highest risk for AKI 7

Monitoring Strategy

Frequency of Monitoring

• Monitor more frequently based on higher GFR category and albuminuria level 2
• Monitor renal function periodically in patients at risk for acute renal failure 4, 5

Definition of Progression

• Define CKD progression as a change in GFR category AND ≥25% decline in eGFR 2
• This avoids misinterpreting small fluctuations 2

Laboratory Assessment

• Assess eGFR and albuminuria for all persons with diabetes and/or hypertension 5
• Monitor serum potassium periodically and treat hyperkalemia appropriately 4

Nephrology Referral

Referral Thresholds

• Refer to nephrology when eGFR <30 mL/min/1.73 m² 1, 5
• Refer for severe albuminuria 5
• Refer for acute kidney injury 5
• Late referral is associated with increased mortality after dialysis initiation 1

Medication Safety

Nephrotoxin Avoidance

• Avoid nonsteroidal anti-inflammatory drugs (NSAIDs) 5
• Consider eGFR level when prescribing all medications 5
• Dosage reduction or discontinuation may be required for hyperkalemia 4

Critical Pitfalls to Avoid

• Never use dihydropyridine CCBs as monotherapy in proteinuric patients 3
• Do not stop RAAS blockers for creatinine increases ≤30% without volume depletion 1
• Avoid excessive diuresis that can precipitate AKI 2, 7
• Do not delay CKD diagnosis—delayed diagnosis by 1-year increments increases risk of progression to stage 4/5 by 40% and kidney failure by 63% 8
• Recognize that volume-depleted patients are at particular risk for symptomatic hypotension when starting RAAS blockers 4

Stage-Specific Action Plan

Stages 1-2 (eGFR ≥60 mL/min/1.73 m²)

• Begin treatment of comorbid conditions, interventions to slow progression, and measures to reduce cardiovascular risk 1
• Control hypertension carefully in all patients 1

Stage 3 (eGFR 30-59 mL/min/1.73 m²)

• Evaluate and treat complications of decreased GFR including anemia, malnutrition, bone disease, neuropathy, and decreased quality of life 1
• These complications begin to rise when GFR declines below 60 mL/min/1.73 m² 1