What is the approach to working up and managing adult patients with chronic kidney disease (CKD) stages 3-5, particularly those with a history of hypertension or diabetes?

Working Up Chronic Kidney Disease Stages 3-5

For patients with CKD stages 3-5, particularly those with hypertension or diabetes, begin with a three-dimensional classification (cause, GFR category, albuminuria category), comprehensive laboratory evaluation, and immediate initiation of ACE inhibitor or ARB therapy if albuminuria is present, while simultaneously assessing for complications and determining nephrology referral timing based on eGFR thresholds. 1

Initial Diagnostic Confirmation and Classification

Establish Chronicity

• Confirm CKD by repeating abnormal eGFR or albuminuria tests after 3 months to distinguish from acute kidney injury 1
• Chronicity can also be established through review of past measurements, imaging showing reduced kidney size or cortical thinning, kidney biopsy findings of fibrosis, or medical history of conditions causing CKD 1

Three-Dimensional Classification System

• Classify all CKD patients using three dimensions simultaneously: cause, GFR category, and albuminuria category 1
• Establish etiology through clinical context, personal and family history (especially first-degree relatives with diabetes, hypertension, or kidney disease), social and environmental factors, medications, physical examination, laboratory measures, imaging, and when indicated, genetic testing or kidney biopsy 2, 1
• GFR categories: G3a (45-59 mL/min/1.73 m²), G3b (30-44 mL/min/1.73 m²), G4 (15-29 mL/min/1.73 m²), G5 (<15 mL/min/1.73 m²) 1
• Albuminuria categories: A1 (ACR <30 mg/g), A2 (ACR 30-300 mg/g), A3 (ACR >300 mg/g) 1

Comprehensive Laboratory Workup

Essential Initial Testing

• Serum creatinine for eGFR calculation and spot urine albumin-to-creatinine ratio (ACR) 1
• Complete metabolic panel (electrolytes, calcium, phosphorus, bicarbonate, albumin) 1
• Complete blood count (assess for anemia) 1
• Lipid panel 1
• Hemoglobin A1c (for diabetic patients or screening) 1
• Parathyroid hormone (PTH) and 25-hydroxyvitamin D (for bone-mineral disorder assessment) 1
• Iron studies (serum iron, ferritin, transferrin saturation) before treating anemia 1

Additional Considerations

• Blood pressure measurement at each visit 2
• Plasma glucose testing 2
• Urine testing for pyuria if infection suspected 2

Imaging and Structural Assessment

• Obtain renal ultrasound to assess kidney size, cortical thickness, and rule out obstruction or structural abnormalities 1
• Consider kidney biopsy when diagnosis is uncertain, when specific treatment would change management, or when rapid progression occurs without clear cause 1

Risk Stratification and Prognosis

• Use externally validated risk equations to estimate absolute risk of kidney failure in patients with CKD G3-G5 1
• 5-year kidney failure risk of 3-5% triggers nephrology referral consideration; 2-year risk >10% indicates need for multidisciplinary care; 2-year risk >40% mandates preparation for kidney replacement therapy 1
• For cardiovascular risk prediction, use externally validated models developed within CKD populations or that incorporate both eGFR and albuminuria 1

Immediate Pharmacologic Interventions

Blood Pressure and Proteinuria Management

• For hypertensive patients with diabetes and CKD stages 1-4, initiate ACE inhibitor or ARB, usually in combination with a diuretic 2
• Target blood pressure <130/80 mmHg for patients with albuminuria ≥30 mg/24 hours 3
• Target blood pressure ≤140/90 mmHg for patients with albuminuria <30 mg/24 hours 3
• For nephrosclerosis with albuminuria ≥300 mg/24 hours, ACE inhibitors or ARBs are first-line agents 3
• Losartan specifically reduces the rate of progression in type 2 diabetic nephropathy as measured by doubling of serum creatinine or end-stage renal disease 4

Additional Therapies for Diabetic Patients

• Add SGLT2 inhibitors to RAS inhibition for diabetic nephrosclerosis with eGFR ≥20 mL/min/1.73 m² 3, 5
• Consider GLP-1 receptor agonist if glycemic targets are not met with SGLT2 inhibitors or if SGLT2 inhibitors cannot be used 5
• Target HbA1c between <6.5% and <8.0%, individualized based on hypoglycemia risk, life expectancy, and comorbidities 5

Cardiovascular Risk Reduction

• Initiate high-intensity statin therapy for all patients ≥50 years with CKD, regardless of GFR, and for ages 18-49 with high cardiovascular risk 3, 5
• Consider aspirin for secondary prevention in those with established cardiovascular disease 5

Assessment and Management of CKD Complications

Stage-Specific Complications

• Begin evaluation and treatment of complications when GFR declines to <60 mL/min/1.73 m² (stage 3), including anemia, malnutrition, bone disease, neuropathy, and quality of life issues 2
• Monitor for hypertension (both cause and complication of CKD) at all stages 2
• Assess for cardiovascular disease risk factors and manifestations 2

Specific Complication Screening

• Screen regularly for diabetic retinopathy, neuropathy, and foot complications 5
• Perform comprehensive foot examination including visual inspection, Semmes-Weinstein monofilament testing, 128-Hz tuning fork for vibratory sensation, and pedal pulse evaluation annually 2, 5
• Evaluate iron status before treating anemia 1

Monitoring Schedule

• Monitor eGFR and ACR every 6 months for CKD G3a, every 3 months for CKD G3b-G4, and monthly or as clinically indicated for CKD G5 1
• Determine HbA1c at least twice per year in stable diabetic patients achieving glycemic goals, and approximately every 3 months in patients whose therapy has changed or who are not reaching goals 2

Nephrology Referral Criteria

Mandatory Immediate Referral

• eGFR <30 mL/min/1.73 m² (stage 4-5) 1, 3
• ACR ≥300 mg/g 1
• Rapid decline in eGFR 1
• Uncertainty about kidney disease etiology 3
• Resistant hypertension 3
• Significant albuminuria increases despite good blood pressure control 3

Timing Considerations

• Nephrologist should participate in care of patients with GFR <30 mL/min/1.73 m² 2
• Preparation for kidney replacement therapy should begin during stage 4, well before kidney failure 2
• Late referral is associated with increased mortality after initiation of dialysis 2

Lifestyle and Dietary Modifications

• Restrict sodium intake to <2 g per day (<90 mmol/day or <5 g sodium chloride/day) 3, 5
• Limit protein intake to 0.8 g/kg body weight/day for stage 3 or higher CKD not on dialysis 3, 5
• Recommend Mediterranean-style diet to reduce cardiovascular risk 3
• Encourage smoking cessation, exercise, and limited sodium intake as part of comprehensive cardiovascular risk management 4

Medication Safety and Adjustments

• Avoid nephrotoxins including NSAIDs, aminoglycosides, contrast agents, and proton pump inhibitors when possible 1
• Adjust medication dosing based on eGFR for renally cleared drugs 1
• Review all medications for potential nephrotoxicity or need for dose adjustment 2

Preparation for Renal Replacement Therapy (Stage 5)

• Provide structured, monitored, individualized patient education regarding dialysis options and transplantation 5
• Initiation of dialysis and transplantation is triggered by onset of uremic symptoms 2
• Preparations for kidney replacement therapy should begin when GFR declines to <15 mL/min/1.73 m² (stage 5) 2, 5

Critical Pitfalls to Avoid

• Do not assume a single abnormal eGFR or ACR represents CKD—acute kidney injury or transient proteinuria can cause temporary abnormalities 1
• Do not delay treatment initiation while waiting to confirm chronicity if CKD is highly likely based on clinical context 1
• Do not use age-adjusted definitions of CKD—reduced eGFR and albuminuria carry prognostic significance at all ages 1
• Do not overlook family history screening—individuals with first-degree relatives with kidney failure have increased risk 2
• Recognize that progression is defined as both a change in GFR category AND ≥25% decrease in eGFR to avoid misinterpreting small fluctuations 3