How should I initiate treatment for chronic kidney disease, including staging, blood pressure control, glycemic management, renal‑protective agents, complication management, lifestyle measures, monitoring, and referral criteria?

Chronic Kidney Disease Management

Initial Assessment and Staging

Diagnose CKD when kidney abnormalities persist >3 months, defined by eGFR <60 mL/min/1.73 m² OR albuminuria ≥30 mg/g, and stage using BOTH GFR and albuminuria categories together to guide treatment intensity. 1, 2

Essential Diagnostic Tests

• Measure serum creatinine and calculate eGFR using the CKD-EPI creatinine equation (without race variable) 2, 3
• Obtain urine albumin-to-creatinine ratio (ACR) - neither eGFR nor ACR alone is sufficient 2
• If eGFR 45-59 mL/min/1.73 m² without other kidney damage markers, confirm with cystatin C-based eGFR for accuracy 2, 3
• Establish chronicity through repeat measurements within and beyond 3 months, or review of past GFR/albuminuria results 2

Risk Stratification

• Use validated risk prediction tools to estimate absolute risk of kidney failure and guide referral timing 1
• Higher GFR decline (≥4 mL/min/1.73 m²/year) indicates rapid progression requiring intensified monitoring 4

---

Blood Pressure Control

Target systolic BP <130 mmHg for all CKD patients with albuminuria ≥30 mg/g; target <140/90 mmHg if albuminuria <30 mg/g. 4, 2

First-Line Antihypertensive Therapy

• Start ACE inhibitor or ARB for all patients with albuminuria ≥30 mg/g (moderately increased), titrating to maximum tolerated doses 1, 4, 2
• For albuminuria ≥300 mg/g (severely increased), ACE inhibitor or ARB is a strong (1B) recommendation regardless of diabetes status 1, 4
• For diabetic patients with albuminuria ≥30 mg/g, ACE inhibitor or ARB is strongly recommended (1B) 1

Monitoring and Adjustments

• Check serum creatinine and potassium within 2-4 weeks after initiation or dose increase 1, 4
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation 1, 4
• Continue ACE inhibitor/ARB even when eGFR falls below 30 mL/min/1.73 m² 1
• Never combine ACE inhibitor + ARB + direct renin inhibitor - this increases adverse events without benefit 1

Additional Antihypertensive Agents

• Add long-acting dihydropyridine calcium channel blocker if BP remains uncontrolled 4
• Restrict sodium intake to <2 g/day to optimize antihypertensive effectiveness 4, 2

Managing Hyperkalemia

• Attempt dietary potassium restriction, diuretics, sodium bicarbonate, or GI cation exchangers before discontinuing ACE inhibitor/ARB 1, 4
• Reduce dose or discontinue only for symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment 1

---

Glycemic Management in Diabetic CKD

Initiate SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m² in all diabetic CKD patients, regardless of glycemic control, as this provides kidney and cardiovascular protection independent of glucose lowering. 1, 4

SGLT2 Inhibitor Therapy

• Continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² after initiation, unless not tolerated or kidney replacement therapy starts 1, 4
• Withhold temporarily during prolonged fasting, surgery, or critical illness (ketosis risk) 1
• The reversible eGFR decrease on initiation is not an indication to discontinue 1

Additional Glucose-Lowering Agents

• Add metformin when eGFR ≥30 mL/min/1.73 m² for additional glycemic control 4
• Reduce metformin to 1000 mg daily when eGFR 30-44 mL/min/1.73 m² 4
• Discontinue metformin when eGFR <30 mL/min/1.73 m² (lactic acidosis risk) 4
• Consider GLP-1 receptor agonist if glycemic targets unmet or if SGLT2 inhibitor/metformin cannot be used 4

Glycemic Targets

• Target HbA1c ≤7% for most diabetic CKD patients, individualized based on hypoglycemia risk, life expectancy, and comorbidities 1, 2
• Check HbA1c every 3 months when adjusting therapy, at least twice yearly when stable 4

Advanced Therapy for Persistent Albuminuria

• Consider nonsteroidal mineralocorticoid receptor antagonist (finerenone) for type 2 diabetic patients with eGFR >25 mL/min/1.73 m², normal potassium, and albuminuria >30 mg/g despite maximum tolerated ACE inhibitor/ARB 1, 4
• Select patients with consistently normal potassium and monitor regularly after initiation 1
• Most appropriate for high-risk patients with persistent albuminuria despite ACE inhibitor/ARB and SGLT2 inhibitor 1

---

Non-Diabetic CKD with Albuminuria

For non-diabetic CKD patients with eGFR ≥20 mL/min/1.73 m² and albuminuria ≥200 mg/g, or those with heart failure regardless of albuminuria level, initiate SGLT2 inhibitor (1A recommendation). 1

• Consider SGLT2 inhibitor for eGFR 20-45 mL/min/1.73 m² with albuminuria <200 mg/g (2B recommendation) 1

---

Cardiovascular Risk Reduction

Initiate statin therapy in all CKD patients with diabetes, targeting LDL-C <100 mg/dL (consider <70 mg/dL for very high risk). 4

Lipid Management

• Prescribe statin for all adults ≥50 years with CKD stages 1-2, and all adults with CKD stages 3a-5 2
• Consider statin/ezetimibe combination for additional LDL reduction 2
• Do not initiate statins in type 2 diabetics on maintenance hemodialysis without specific cardiovascular indication 4

Additional Cardiovascular Measures

• Obtain 12-lead ECG to assess for left ventricular hypertrophy and arrhythmias 4
• Consider echocardiography if ECG abnormal or cardiac symptoms present 4
• Recommend tobacco cessation for all tobacco users 4
• Advise moderate-intensity physical activity ≥150 minutes weekly, compatible with cardiovascular tolerance 4, 2

---

Lifestyle Modifications

Dietary Recommendations

• Limit dietary protein to 0.8 g/kg/day for non-dialysis CKD patients (stages 3-5) - this slows GFR decline without compromising nutrition 1, 4, 2
• Avoid protein intake >1.3 g/kg/day or >20% of daily calories, as this accelerates kidney function loss 1
• Restrict sodium to <2 g/day 4, 2
• Follow plant-based "Mediterranean-style" diet 2

Physical Activity

• Engage in moderate-intensity exercise for cumulative 150 minutes per week 2

---

Monitoring for CKD Complications

Begin monitoring for anemia, bone disease, metabolic acidosis, and hyperkalemia when eGFR <60 mL/min/1.73 m² (Stage 3). 1, 4

Monitoring Frequency Based on Risk

• eGFR ≥60 mL/min/1.73 m² with normal albuminuria: Check eGFR and ACR annually 1, 4
• eGFR 45-59 mL/min/1.73 m² or moderate albuminuria: Check every 6-12 months 1, 4
• eGFR 30-44 mL/min/1.73 m² (Stage 3b): Check every 3-6 months 1, 4
• eGFR 15-29 mL/min/1.73 m² (Stage 4): Check every 3-5 months 1, 4
• eGFR <15 mL/min/1.73 m² (Stage 5): Check every 1-3 months 1, 4
• Established diabetic kidney disease: Monitor ACR and eGFR 1-4 times per year depending on stage 1

Specific Complications to Monitor

• Anemia: Check hemoglobin; if low, assess iron, iron saturation, and ferritin 1
• Metabolic bone disease: Measure serum calcium, phosphate, PTH, and 25-hydroxyvitamin D 1
• Metabolic acidosis: Monitor serum electrolytes 1
• Hyperkalemia: Assess serum potassium, especially in patients on ACE inhibitor/ARB 1, 4
• Volume overload: Assess at every clinical contact through history, physical examination, and weight 1
• Blood pressure: Monitor at every visit 1

---

Medication Safety and Nephrotoxin Avoidance

• Review all medications at each visit and adjust doses based on current eGFR 2
• Avoid NSAIDs - these are nephrotoxic and accelerate CKD progression 5, 6
• Avoid proton-pump inhibitors when possible 6
• Avoid iodinated contrast in advanced CKD (eGFR <30 mL/min/1.73 m²) 3
• Avoid oral phosphate-containing bowel preparations when eGFR <60 mL/min/1.73 m² 1
• Dose-adjust antibiotics and other renally cleared medications 5

---

Vaccination

• Vaccinate early against hepatitis B virus in individuals likely to progress to end-stage kidney disease 1
• Implement routine vaccinations per standard guidelines 1

---

Nephrology Referral Criteria

Refer to nephrologist when eGFR <30 mL/min/1.73 m² (Stage 4), or earlier if specific high-risk features are present. 1, 4, 2

Specific Indications for Referral

• eGFR <30 mL/min/1.73 m² (stages 4-5) - all patients require nephrology involvement 1, 4
• Albuminuria ≥300 mg/g despite ACE inhibitor/ARB therapy 1, 4
• Rapid progression: GFR decline ≥4 mL/min/1.73 m²/year or sustained fall in GFR 1, 4
• Acute kidney injury or abrupt sustained fall in GFR 1
• Urinary red cell casts or RBC >20 per high power field sustained and unexplained 1
• Resistant hypertension (uncontrolled on 4+ antihypertensive agents) 1, 4
• Persistent hyperkalemia or other electrolyte abnormalities 1, 4
• Recurrent or extensive nephrolithiasis 1
• Hereditary kidney disease 1
• Uncertainty about CKD etiology 4, 2
• Questions about albuminuria etiology or difficulty decreasing albuminuria despite ACE inhibitor/ARB 1
• Side effects or contraindications to ACE inhibitor/ARB therapy in patients with albuminuria >300 mg/g 1

Timing of Referral for Kidney Replacement Therapy

• Refer for kidney replacement therapy planning when validated risk prediction tools estimate 10-20% or higher risk of kidney failure within 1 year 1
• Preparation for dialysis and transplantation should begin during Stage 4, well before uremic symptoms develop 1
• Late referral (<1 year before kidney replacement therapy) is associated with increased mortality 1

Model of Care

• Primary care physicians and nephrologists should share responsibility for CKD care 1
• Most patients with stages 1-3 CKD can be managed by primary care with nephrology consultation as needed 1
• Formal nephrology comanagement is essential for Stage 4-5 CKD 1