Chronic Kidney Disease: Diagnosis, Staging, and Management
Diagnosis and Confirmation
Diagnose chronic kidney disease by testing both estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) in all at-risk adults, then confirm abnormalities with repeat testing after 3 months to establish chronicity. 1
Initial Detection
- Screen all patients with diabetes, hypertension, cardiovascular disease, family history of kidney failure, age >60 years, or racial/ethnic minority status using serum creatinine for eGFR calculation and spot urine ACR 1, 2
- Use creatinine-based eGFR (eGFRcr) as the initial assessment; if cystatin C is available, combine both markers (eGFRcr-cys) for more accurate GFR estimation 1
- Following incidental detection of elevated ACR, hematuria, or low eGFR, repeat tests to confirm presence of CKD 1
Establishing Chronicity
- Proof of chronicity requires a minimum duration of 3 months, established by: 1
- Review of past measurements/estimations of GFR
- Review of past measurements of albuminuria or proteinuria
- Imaging findings (reduced kidney size, cortical thinning)
- Kidney pathological findings (fibrosis, atrophy)
- Medical history of conditions known to cause CKD
- Repeat measurements within and beyond the 3-month point
- Do not assume chronicity based on a single abnormal eGFR or ACR, as this could represent acute kidney injury or acute kidney disease 1
- Consider initiating CKD treatments at first presentation if CKD is deemed likely due to other clinical indicators 1
Staging Classification
Stage CKD using the three-dimensional KDIGO classification system: cause (etiology), GFR category (G1-G5), and albuminuria category (A1-A3). 1, 2
GFR Categories
| Stage | eGFR (mL/min/1.73 m²) | Description |
|---|---|---|
| G1 | ≥90 | Normal or high (with kidney damage markers) |
| G2 | 60-89 | Mildly decreased |
| G3a | 45-59 | Mildly to moderately decreased |
| G3b | 30-44 | Moderately to severely decreased |
| G4 | 15-29 | Severely decreased |
| G5 | <15 | Kidney failure |
Albuminuria Categories
| Category | ACR (mg/g) | Description |
|---|---|---|
| A1 | <30 | Normal to mildly increased |
| A2 | 30-300 | Moderately increased |
| A3 | >300 | Severely increased |
Establishing Cause
- Determine etiology using clinical context, personal and family history, social and environmental factors, medications, physical examination, laboratory measures, imaging, and when appropriate, genetic testing or kidney biopsy 1, 2
- Diabetic kidney disease is the largest single cause of kidney failure; the earliest manifestation is microalbuminuria with normal or elevated GFR (stage G1) 1
- Perform kidney biopsy when diagnosis is uncertain, specific treatment would change management, or rapid progression occurs without clear cause 1, 2
Comprehensive Laboratory Evaluation
Beyond eGFR and ACR, assess: 2
- Complete metabolic panel (electrolytes, calcium, phosphate)
- Complete blood count
- Lipid panel
- Hemoglobin A1c
- Parathyroid hormone (PTH) and 25-hydroxyvitamin D
- Iron studies
Management Strategy
Step 1: Initiate SGLT2 Inhibitors (First-Line Foundation)
Start an SGLT2 inhibitor (canagliflozin 100 mg daily or dapagliflozin 10 mg daily) as mandatory first-line therapy for all CKD patients with eGFR ≥20 mL/min/1.73 m², regardless of diabetes status. 3
- Continue SGLT2 inhibitors even as eGFR declines below 20 mL/min/1.73 m² until dialysis initiation or transplantation 3
- These agents provide kidney and cardiovascular protection independent of glycemic effects 3, 4
Step 2: Add RAS Inhibition
Initiate an ACE inhibitor or ARB for all patients with albuminuria ≥30 mg/24 hours, targeting blood pressure ≤130/80 mmHg. 3
- Titrate to maximum tolerated dose for optimal kidney and cardiovascular protection 3
- Begin during stages 1 and 2 to slow progression and reduce cardiovascular risk 1
- Monitor serum creatinine and potassium 1-2 weeks after initiation 5
- Do not discontinue for modest creatinine rises <30% in the absence of volume depletion 5
Step 3: Add Statin Therapy
Prescribe moderate-to-high intensity statin therapy (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily) for all CKD patients ≥50 years. 3
Step 4: Consider Advanced Kidney Protection
- For patients with diabetes and persistent albuminuria despite SGLT2 inhibitor and RAS blockade, consider adding finerenone (non-steroidal mineralocorticoid receptor antagonist) 3, 6
- GLP-1 receptor agonists provide additional cardiorenal protection in diabetic CKD 4, 6
Step 5: Lifestyle Modifications
Implement: 3
- Sodium restriction to <2 g per day
- Protein intake of 0.8 g/kg body weight per day
- Target BMI of 20-25 kg/m² through weight management
- Regular aerobic exercise
- Smoking cessation
Step 6: Manage CKD-Specific Complications
Evaluation and treatment of complications should begin during stage 3 (eGFR <60 mL/min/1.73 m²), as prevalence rises at this threshold. 1
- Anemia: Monitor hemoglobin regularly; treat with iron supplementation before or with erythropoiesis-stimulating agents 3
- Bone disease: Monitor PTH, calcium, phosphate, and vitamin D; treat secondary hyperparathyroidism 2
- Metabolic acidosis: Correct with sodium bicarbonate when serum bicarbonate <22 mEq/L
- Hyperkalemia: Manage with dietary restriction, diuretics, or potassium binders to allow continuation of RAS inhibition 6
Step 7: Cardiovascular Disease Prevention
- Aspirin 81 mg daily for secondary prevention in patients with established cardiovascular disease 3
- Aggressive blood pressure control to ≤130/80 mmHg 3
- Patients with CKD should be considered in the highest risk group for cardiovascular events 1
Monitoring Schedule
| CKD Stage | eGFR Range | Monitoring Frequency |
|---|---|---|
| G1-G2 | ≥60 | Annually |
| G3a | 45-59 | Every 6 months |
| G3b | 30-44 | Every 3 months |
| G4 | 15-29 | Every 3 months |
| G5 | <15 | Monthly or as indicated |
- eGFR and serum creatinine
- Electrolytes (sodium, potassium, bicarbonate)
- Urine albumin-to-creatinine ratio
- Hemoglobin
- Blood pressure
- Lipid panel (annually)
Nephrology Referral Criteria
Refer immediately to nephrology when: 1, 3, 2
- eGFR <30 mL/min/1.73 m² (all stage 4-5 patients)
- ACR ≥300 mg/g (nephrotic-range proteinuria)
- Rapid decline in eGFR (>20% sustained decrease)
- Persistent electrolyte abnormalities (hyperkalemia, metabolic acidosis)
- Uncontrolled hypertension despite multiple agents
- Uncertainty about etiology of kidney disease
- Active urinary sediment with dysmorphic RBCs or RBC casts
- Hematuria with proteinuria
Preparation for kidney replacement therapy should begin during stage 4 (eGFR <30 mL/min/1.73 m²), well before kidney failure. 1
Critical Medications to AVOID
- NSAIDs: Increase risk of acute kidney injury 3, 2
- Metformin when eGFR <30 mL/min/1.73 m²: Risk of lactic acidosis 3
- Sulfonylureas: Increased hypoglycemia risk 3
- Aminoglycosides: Nephrotoxic 2
- Contrast agents: Use with caution; ensure adequate hydration 2
- Proton pump inhibitors: Associated with interstitial nephritis and CKD progression 2
Common Pitfalls to Avoid
- Do not delay treatment while waiting to confirm chronicity if CKD is highly likely based on clinical context 1, 2
- Do not use age-adjusted definitions of CKD—reduced eGFR and albuminuria carry prognostic significance at all ages 1
- Do not combine ACE inhibitor with ARB—insufficient evidence and increased risk of hyperkalemia and acute kidney injury 5
- Do not withhold ACE inhibitor/ARB in normotensive patients with albuminuria—these agents confer renal protection independent of blood pressure effects 5
- Late referral to nephrology (shortly before dialysis) is associated with increased mortality after dialysis initiation 1
- Do not assume a single abnormal test represents CKD—acute kidney injury or transient proteinuria can cause temporary abnormalities 1, 2