What is the management for a patient with proteinuria, ketonuria, and impaired renal function?

Management of Proteinuria, Ketonuria, and eGFR 60

This patient with Stage 3 CKD (eGFR 60 mL/min/1.73 m²) and proteinuria requires immediate quantification of proteinuria, initiation of ACE inhibitor or ARB therapy if proteinuria exceeds 1 g/day, and nephrology referral if proteinuria is >1 g/day or if there are features suggesting glomerular disease. 1

Immediate Diagnostic Steps

Quantify Proteinuria

• Obtain spot urine albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR) to determine the severity and type of proteinuria 1
• If ACR ≥60 mg/mmol or PCR ≥100 mg/mmol (approximately 1 g/day), this indicates significant proteinuria requiring nephrology referral 1
• Proteinuria of grade 1+ on dipstick (≥30 mg/dL or protein-to-creatinine ratio ≥300 mg/g) warrants quantification 1

Address Ketonuria

• Ketonuria suggests metabolic stress, starvation, uncontrolled diabetes, or inadequate carbohydrate intake
• Check blood glucose, HbA1c if diabetic, and assess nutritional status
• Rule out diabetic ketoacidosis if diabetic, or starvation ketosis if dietary intake is poor

Additional Workup

• Renal ultrasound to assess kidney size, echogenicity, and rule out obstruction 1
• Serologic testing: hepatitis B and C, complement levels, ANA, serum and urine protein electrophoresis 1
• Blood pressure measurement and cardiovascular risk assessment 1

Treatment Algorithm Based on Proteinuria Level

If Proteinuria <1 g/day (ACR <60 mg/mmol or PCR <100 mg/mmol)

• Initiate ACE inhibitor or ARB if hypertensive or if proteinuria persists despite treating underlying cause 1
• Target systolic blood pressure <120 mmHg using standardized office measurement 1
• Uptitrate ACE inhibitor or ARB to maximally tolerated dose 1
• Monitor serum creatinine and potassium within 1-2 weeks of initiation; accept up to 30% increase in creatinine if stable 1
• Primary care management is appropriate with annual monitoring 1

If Proteinuria ≥1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol)

• Refer to nephrology as kidney biopsy may be indicated and immunosuppressive therapy may be needed 1
• Start ACE inhibitor or ARB immediately while awaiting nephrology consultation 1, 2
• Target proteinuria reduction to <1 g/day as this reduces progression risk 1
• Consider low protein diet (0.6 g/kg/day) supplemented with ketoanalogs if proteinuria is heavy (>3 g/day), as this reduces proteinuria 3-fold and slows eGFR decline 3, 4

Specific Pharmacologic Management

ACE Inhibitor or ARB Therapy

• First-line therapy for proteinuria with or without hypertension 1, 2
• Losartan specifically reduces proteinuria by 34% and slows GFR decline by 13% in diabetic nephropathy 2
• Uptitrate to maximum tolerated dose (e.g., losartan 100 mg daily) 2
• Monitor labs frequently: check creatinine and potassium 1-2 weeks after initiation or dose change 1
• Do not discontinue if creatinine increases up to 30% and remains stable 1
• Stop if creatinine continues to worsen beyond 30% or if refractory hyperkalemia develops 1

Blood Pressure Management

• Target systolic BP <120 mmHg in most patients 1
• Use ACE inhibitor or ARB as first-line agent 1
• Add loop diuretics for volume management if needed 1
• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 1

Hyperkalemia Management

• Use potassium-wasting diuretics and/or potassium-binding agents to maintain normal potassium, allowing continuation of ACE inhibitor/ARB 1
• Treat metabolic acidosis if serum bicarbonate <22 mmol/L 1

Nephrology Referral Criteria

Mandatory Referral Indications

• Persistent proteinuria >1 g/day (ACR ≥60 mg/mmol or PCR ≥100 mg/mmol) as biopsy and immunosuppression may be indicated 1
• eGFR <30 mL/min/1.73 m² (though this patient has eGFR 60) 1, 5
• Abrupt sustained decrease in eGFR >20% after excluding reversible causes 1
• Uncertainty about diagnosis or suspected glomerulonephritis 1
• Inability to tolerate renal protective medications 1

Timing Considerations

• Avoid late referral (defined as <1 year before needing dialysis), which increases morbidity and mortality 1, 5
• At eGFR 60 with significant proteinuria, early referral allows for timely intervention 1

Common Pitfalls to Avoid

• Do not delay ACE inhibitor/ARB initiation while awaiting nephrology consultation if proteinuria is significant 1
• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30% if stable 1
• Counsel patients to hold ACE inhibitor/ARB during volume depletion (sick days, diarrhea, vomiting) 1
• Avoid nephrotoxic medications including NSAIDs, which can precipitate acute kidney injury 1, 6
• Do not use calcium channel blockers if patient is on protease inhibitors (drug interaction concern) 1
• Adjust medication doses for reduced GFR, particularly antibiotics and oral hypoglycemic agents 6

Monitoring Strategy

• Repeat proteinuria measurement in 3 months to assess response to therapy 1
• Monitor eGFR and electrolytes every 3-6 months if stable 6
• Check for complications: hyperkalemia, metabolic acidosis, anemia, secondary hyperparathyroidism 6
• Annual cardiovascular risk assessment as CKD patients primarily die from cardiovascular causes 1