How to approach a patient with chronic kidney disease (CKD) and potential comorbidities such as diabetes or hypertension?

Approach to a Patient with Chronic Kidney Disease

Screen immediately with both eGFR and urinary albumin-to-creatinine ratio (UACR), stage the disease using both parameters, then implement blood pressure control with ACE inhibitor or ARB for albuminuria ≥30 mg/g, add SGLT2 inhibitor if diabetic with eGFR ≥20 mL/min/1.73 m², initiate statin therapy, and refer to nephrology when eGFR <30 mL/min/1.73 m². 1, 2

Initial Assessment and Diagnosis

Confirm CKD Diagnosis

• Measure both serum creatinine (to calculate eGFR using CKD-EPI 2021 equation) and UACR on a random spot urine sample simultaneously, as either abnormality independently confirms CKD and provides complementary prognostic information 1, 2
• CKD is defined as eGFR <60 mL/min/1.73 m² OR UACR ≥30 mg/g persisting for at least 3 months 1, 3
• Review historical eGFR measurements to confirm chronicity (>3 months duration) and distinguish from acute kidney injury 2
• If duration unclear or <3 months, repeat serum creatinine and eGFR within 2-4 weeks 2

Determine Disease Severity and Prognosis

• Stage CKD using both eGFR categories (G1-G5) and albuminuria categories (A1-A3) together, as this combination determines progression risk, cardiovascular risk, and monitoring intensity 4, 1
• eGFR stages: G1 (≥90), G2 (60-89), G3a (45-59), G3b (30-44), G4 (15-29), G5 (<15 mL/min/1.73 m²) 4
• Albuminuria stages: A1 (<30 mg/g), A2 (30-300 mg/g), A3 (>300 mg/g) 4, 1

Identify Underlying Cause

• Obtain detailed history focusing on diabetes duration (type 1 ≥5 years or any type 2), hypertension duration and control, cardiovascular disease, family history of kidney disease, and nephrotoxin exposure (NSAIDs, lithium, calcineurin inhibitors, aminoglycosides) 4, 1, 2
• Diabetes accounts for 30-40% of CKD cases and is the leading cause in developed countries 2, 3
• Hypertension is present in 91% of CKD patients and can both cause and result from kidney disease 4, 2
• Perform urinalysis to look for hematuria, pyuria, or casts suggesting glomerulonephritis or other primary kidney diseases 2
• Consider kidney biopsy if atypical features suggest non-diabetic kidney disease, as up to 30% of presumed diabetic kidney disease has alternative diagnoses 2

Baseline Laboratory Evaluation

• Complete metabolic panel (sodium, potassium, chloride, bicarbonate, calcium, phosphate) to screen for metabolic acidosis, hyperkalemia, and mineral abnormalities 1, 2
• Complete blood count to assess for anemia 1
• Lipid panel for cardiovascular risk stratification 1
• Hemoglobin A1c if diabetic 1
• Intact parathyroid hormone (PTH) when eGFR <60 mL/min/1.73 m² (Stage 3 or higher), as PTH begins rising at this threshold 2
• 25-hydroxyvitamin D level when eGFR <60 mL/min/1.73 m² 1

Blood Pressure Management

Target Blood Pressure

• Target <130/80 mmHg for all CKD patients with albuminuria ≥30 mg/g 4, 1
• Target <140/90 mmHg for CKD patients with albuminuria <30 mg/g 4
• Monitor for postural hypotension regularly when treating with blood pressure medications 4

First-Line Antihypertensive Therapy

• Initiate ACE inhibitor or ARB for all patients with UACR 30-300 mg/g (A2) and hypertension 4, 1
• Initiate ACE inhibitor or ARB for all patients with UACR ≥300 mg/g (A3) regardless of blood pressure level (1B recommendation) 4, 1
• Titrate ACE inhibitor or ARB to maximum tolerated doses shown in clinical trials 4, 1
• Check serum creatinine and potassium within 2-4 weeks after initiation or dose escalation 4, 1
• Continue therapy unless creatinine rises >30% within 4 weeks in absence of volume depletion 1, 2

Additional Antihypertensive Agents

• Add long-acting dihydropyridine calcium channel blocker as second agent if blood pressure remains uncontrolled 1
• Add thiazide or thiazide-like diuretic (if eGFR ≥30 mL/min/1.73 m²) or loop diuretic (if eGFR <30 mL/min/1.73 m²) as third agent 1
• Do NOT combine ACE inhibitor with ARB, as this increases adverse events without additional benefit 4, 1, 2

Dietary Sodium Restriction

• Restrict sodium intake to <2 g/day (<5 g salt/day) to optimize antihypertensive effectiveness and reduce albuminuria 4, 1

Diabetic CKD-Specific Management

SGLT2 Inhibitor Therapy

• 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 protection and cardiovascular benefits independent of glucose lowering 1, 2
• Continue SGLT2 inhibitor until dialysis or transplantation, even as eGFR declines 1

Metformin Management

• Add metformin when eGFR ≥30 mL/min/1.73 m² for additional glycemic control 1
• Reduce metformin to maximum 1000 mg daily when eGFR 30-44 mL/min/1.73 m² 1
• Discontinue metformin when eGFR <30 mL/min/1.73 m² due to lactic acidosis risk 1

GLP-1 Receptor Agonist

• Add GLP-1 receptor agonist if glycemic targets unmet or if SGLT2 inhibitors/metformin cannot be used 1

Finerenone (Nonsteroidal MRA)

• Consider finerenone for persistent albuminuria ≥30 mg/g despite first-line therapy (ACE inhibitor/ARB + SGLT2 inhibitor) and normal potassium 1
• Monitor potassium at 1 month after initiation, then every 4 months 2

Glycemic Targets

• Target HbA1c between 6.5-8.0%, individualized based on hypoglycemia risk, life expectancy, and comorbidities 1
• Check HbA1c every 3 months when adjusting therapy, at least twice yearly when stable 1

Dietary Protein Restriction

• Limit dietary protein to 0.8 g/kg/day for non-dialysis CKD patients 1

Cardiovascular Risk Reduction

Statin Therapy

• Initiate moderate-to-high intensity statin in all CKD patients with diabetes or LDL-C >100 mg/dL, targeting LDL-C <100 mg/dL (consider <70 mg/dL for very high risk) 1, 2
• Do NOT initiate statins in type 2 diabetics on maintenance hemodialysis without specific cardiovascular indication 1

Additional Cardiovascular Measures

• Obtain 12-lead ECG to assess for left ventricular hypertrophy and arrhythmias 1
• Consider echocardiography if ECG abnormal or cardiac symptoms present 1
• Recommend tobacco cessation for all tobacco users 1
• Advise moderate-intensity physical activity ≥150 minutes weekly, compatible with cardiovascular tolerance 1

Monitoring for CKD Complications

Monitoring Frequency Based on Risk Stratification

• Low risk (eGFR ≥60 with UACR <30 mg/g): Monitor eGFR and UACR annually 1, 2
• Moderate risk (eGFR 45-59 or UACR 30-300 mg/g): Monitor every 6 months 1, 2
• High risk (eGFR 30-44 or UACR >300 mg/g): Monitor every 3-4 months 1, 2
• Very high risk (eGFR <30 or rapid decline ≥5 mL/min/1.73 m²/year): Monitor every 1-3 months 4, 1

Define CKD Progression

• Decline in GFR category accompanied by ≥25% drop in eGFR from baseline 4
• Rapid progression defined as sustained decline in eGFR of ≥5 mL/min/1.73 m²/year 4
• Small fluctuations in GFR are common and not necessarily indicative of progression 4

Complications Monitoring (when eGFR <60 mL/min/1.73 m²)

• Anemia: Check hemoglobin when eGFR <60 mL/min/1.73 m² 1
• Mineral bone disease: Check serum calcium, phosphate, intact PTH, and 25-hydroxyvitamin D 1, 2
• Metabolic acidosis: Check serum bicarbonate; correct if <22 mEq/L 1
• Hyperkalemia: Monitor potassium, especially in patients on ACE inhibitors/ARBs; attempt dietary modification, diuretics, sodium bicarbonate, or GI cation exchangers before discontinuing RAAS blockade 1, 2

Nephrotoxin Avoidance

• Avoid NSAIDs, as they reduce renal blood flow and can precipitate acute kidney injury 1, 3, 5
• Avoid aminoglycosides, contrast agents (use lowest dose with adequate hydration when necessary), and other nephrotoxins 1, 2
• Adjust medication dosing based on eGFR for renally cleared drugs (many antibiotics, oral hypoglycemic agents) 3, 5

Nephrology Referral

Absolute Indications for Referral

• eGFR <30 mL/min/1.73 m² (Stage 4 or higher) 1, 2, 3, 5
• Albuminuria ≥300 mg/g despite optimal treatment with ACE inhibitor/ARB 1, 2
• Rapidly declining kidney function (eGFR decline ≥5 mL/min/1.73 m²/year or ≥25% drop with GFR category decline) 4, 1, 2

Relative Indications for Referral

• Uncertainty about CKD etiology or atypical features suggesting non-diabetic kidney disease 1, 2
• Difficulty managing CKD complications (anemia, mineral bone disease, metabolic acidosis, hyperkalemia) 1, 2
• Resistant hypertension despite 3-4 antihypertensive agents 1, 2
• Continuously increasing albuminuria despite optimal management 1, 2

Benefits of Early Referral

• Early referral (Stage 4) reduces cost, improves quality of care, and delays dialysis 1
• Preparation for kidney replacement therapy should begin during Stage 4, well before uremic symptoms develop 1

Common Pitfalls to Avoid

• Do NOT rely on serum creatinine alone; always calculate eGFR using validated equations (CKD-EPI 2021) 2
• Do NOT skip albuminuria testing; eGFR and UACR provide independent prognostic information for cardiovascular events, CKD progression, and mortality 1, 2
• Do NOT discontinue ACE inhibitors/ARBs for minor creatinine increases (<30%) in absence of volume depletion 1, 2
• Do NOT combine ACE inhibitors with ARBs 4, 1, 2
• Do NOT screen asymptomatic adults without risk factors (diabetes, hypertension, age >60, family history, cardiovascular disease, obesity), as universal screening lacks evidence of benefit 4, 2