How is chronic kidney disease staged and what is the recommended management for adults?

Chronic Kidney Disease Staging and Treatment

CKD is staged using both eGFR categories (G1-G5) and albuminuria categories (A1-A3), with treatment centered on SGLT2 inhibitors, ACE inhibitors or ARBs, blood pressure control, and cardiovascular risk reduction to prevent progression and reduce mortality.

CKD Staging System

CKD staging requires simultaneous assessment of both kidney function (eGFR) and kidney damage (albuminuria) to properly stratify risk and guide treatment intensity. 1

eGFR Categories (G1-G5)

• G1: eGFR ≥90 ml/min/1.73 m² (normal or high kidney function with other evidence of kidney damage) 1
• G2: eGFR 60-89 ml/min/1.73 m² (mildly decreased kidney function) 1
• G3a: eGFR 45-59 ml/min/1.73 m² (mild to moderately decreased) 1
• G3b: eGFR 30-44 ml/min/1.73 m² (moderately to severely decreased) 1
• G4: eGFR 15-29 ml/min/1.73 m² (severely decreased) 1
• G5: eGFR <15 ml/min/1.73 m² (kidney failure) 1

Albuminuria Categories (A1-A3)

• A1: <30 mg/g (<3 mg/mmol) - normal to mildly increased 1
• A2: 30-300 mg/g (3-30 mg/mmol) - moderately increased 1
• A3: >300 mg/g (>30 mg/mmol) - severely increased 1

Diagnostic Approach

• Use creatinine-based eGFR (eGFRcr) for initial assessment; if cystatin C is available, use combined creatinine and cystatin C-based eGFR (eGFRcr-cys) for more accurate staging 1
• Measure urine albumin-to-creatinine ratio (UACR) in a first-void morning spot urine specimen; random spot urine is acceptable if first-void is not practical 2
• Confirm chronicity by repeating abnormal eGFR or albuminuria measurements after 3 months, or establish chronicity through review of past measurements, imaging showing reduced kidney size, or pathological findings 1

Progression Monitoring

• Define progression as both a change in eGFR category AND ≥25% decline in eGFR to avoid misinterpreting small fluctuations 1
• Monitor frequency based on combined eGFR and albuminuria risk: higher risk categories (lower eGFR, higher albuminuria) require more frequent monitoring (up to 4 times per year for G4-G5 with A3) 1

Core Treatment Strategies

SGLT2 Inhibitors (First-Line Therapy)

SGLT2 inhibitors are recommended for all adults with CKD and eGFR ≥20 ml/min/1.73 m² who have type 2 diabetes, or who have albuminuria ≥200 mg/g or heart failure regardless of diabetes status. 1

• For type 2 diabetes with CKD and eGFR ≥20 ml/min/1.73 m²: initiate SGLT2i (1A recommendation) 1
• For adults with eGFR ≥20 ml/min/1.73 m² with UACR ≥200 mg/g or heart failure: initiate SGLT2i regardless of diabetes status (1A recommendation) 1
• For adults with eGFR 20-45 ml/min/1.73 m² with UACR <200 mg/g: consider SGLT2i (2B recommendation) 1
• Continue SGLT2i even if eGFR falls below 20 ml/min/1.73 m² unless not tolerated or kidney replacement therapy is initiated 1
• Withhold SGLT2i during prolonged fasting, surgery, or critical illness due to ketosis risk 1
• The reversible eGFR decrease upon SGLT2i initiation is not an indication to discontinue therapy 1

ACE Inhibitors or ARBs (Renin-Angiotensin System Blockade)

ACE inhibitors or ARBs are mandatory for all CKD patients with albuminuria >300 mg/g (A3 category), using the highest tolerated dose. 1

• For albuminuria >300 mg/g: prescribe ACE inhibitor or ARB at maximum approved tolerated dose (1B recommendation) 1
• Continue ACE inhibitor or ARB even when eGFR falls below 30 ml/min/1.73 m² 1, 3
• Check blood pressure, serum creatinine, and potassium within 2-4 weeks of initiation or dose increase 1, 3
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation or dose increase 1, 3
• Manage hyperkalemia with potassium-lowering measures (dietary restriction, diuretics, potassium binders) rather than stopping ACE inhibitor/ARB 1, 3
• Consider dose reduction or discontinuation only for: symptomatic hypotension, uncontrolled hyperkalemia despite medical treatment, or eGFR <15 ml/min/1.73 m² with uremic symptoms 1, 3

Blood Pressure Control

Blood pressure targets differ based on albuminuria status, with lower targets for patients with significant proteinuria. 1

• For albuminuria <30 mg/24 hours: target BP ≤140/90 mmHg (1B recommendation) 1
• For albuminuria ≥30 mg/24 hours: target BP ≤130/80 mmHg (2D recommendation) 1

Nonsteroidal Mineralocorticoid Receptor Antagonists

For patients with type 2 diabetes, eGFR >25 ml/min/1.73 m², normal potassium, and persistent albuminuria despite maximum tolerated ACE inhibitor/ARB, add nonsteroidal MRA (finerenone). 1

• Initiate finerenone for type 2 diabetes with persistent albuminuria >30 mg/g despite maximum RAS inhibition (2A recommendation) 1
• Nonsteroidal MRA can be added to both ACE inhibitor/ARB and SGLT2i 1
• Dosing based on eGFR and potassium: 10 mg daily if eGFR 25-59 ml/min/1.73 m², 20 mg daily if eGFR ≥60 ml/min/1.73 m², only if potassium ≤4.8 mmol/L 1
• Hold if potassium >5.5 mmol/L; continue if potassium 4.9-5.5 mmol/L with close monitoring 1
• Monitor potassium at 1 month after initiation, then every 4 months 1

GLP-1 Receptor Agonists

For type 2 diabetes with CKD not achieving glycemic targets despite metformin and SGLT2i, add long-acting GLP-1 RA with proven cardiovascular benefits. 1

• Prescribe long-acting GLP-1 RA for type 2 diabetes with CKD when glycemic targets not met with metformin and SGLT2i (1B recommendation) 1
• Prioritize GLP-1 RA agents with documented cardiovascular benefits 1

Cardiovascular Risk Reduction

All CKD patients should be considered at increased cardiovascular risk and treated aggressively with statins. 1

• For age ≥50 years with eGFR <60 ml/min/1.73 m² (G3a-G5): prescribe statin or statin/ezetimibe combination (1A recommendation) 1
• For age ≥50 years with eGFR ≥60 ml/min/1.73 m² (G1-G2): prescribe statin (1B recommendation) 1
• For age 18-49 years with known coronary disease, diabetes, prior stroke, or 10-year cardiovascular risk >10%: prescribe statin (2A recommendation) 1
• Use low-dose aspirin for secondary prevention in CKD patients with established ischemic cardiovascular disease (1C recommendation) 1
• Consider PCSK-9 inhibitors for patients with indication for their use 1

Lifestyle Interventions

Lifestyle modifications are essential adjuncts to pharmacotherapy for slowing CKD progression. 1

• Reduce sodium intake to <2 g per day 1
• Achieve and maintain BMI 20-25 kg/m² 1
• Complete smoking cessation 1
• Exercise 30 minutes, 5 times per week 1
• For diabetes: target HbA1c of 7% 1
• Consider plant-based Mediterranean-style diet to reduce cardiovascular risk 1

Common Pitfalls and Caveats

ACE Inhibitor/ARB Management

• Do not discontinue ACE inhibitor/ARB based solely on eGFR falling below 30 ml/min/1.73 m²; continue unless specific contraindications develop 1, 3
• Do not stop ACE inhibitor/ARB for hyperkalemia without first attempting medical management with potassium binders, dietary modification, and diuretics 1, 3
• A creatinine rise up to 30% within 4 weeks is acceptable and expected; only discontinue if rise exceeds 30% 1, 3

SGLT2 Inhibitor Management

• The initial eGFR dip after SGLT2i initiation is hemodynamic and reversible; do not interpret this as kidney injury or reason to stop therapy 1
• Remember to withhold SGLT2i during periods of prolonged fasting, surgery, or critical illness to prevent ketoacidosis 1

Progression Assessment

• Do not diagnose progression based on small eGFR changes that cross category boundaries (e.g., 61 to 59 ml/min/1.73 m²); require both category change AND ≥25% decline 1
• Single abnormal eGFR or albuminuria measurements may reflect acute kidney injury rather than CKD; confirm chronicity with repeat testing or historical data 1

AKI Risk Awareness

• All CKD patients are at increased risk for acute kidney injury and require heightened vigilance during intercurrent illness, contrast exposure, or nephrotoxic medication use 1