Should I prescribe Farxiga (canagliflozin) to a patient on benazepril with leukocytosis and proteinuria?

Managing Proteinuria and Leukocytosis in a Patient on Benazepril: Should Farxiga be Added?

Yes, adding Farxiga (dapagliflozin) to benazepril therapy is recommended for this patient with proteinuria and leukocytosis to reduce chronic kidney disease progression and cardiovascular risk. 1

Rationale for Adding SGLT2 Inhibitor

• SGLT2 inhibitors like Farxiga provide renal protection independent of glycemic control in patients with proteinuria, with benefits extending to patients with eGFR as low as 20 mL/min/1.73m² 1
• The presence of proteinuria (1+) in this patient indicates kidney damage that would benefit from SGLT2 inhibitor therapy, which has been shown to reduce albuminuria by up to 31% 2
• The combination of an ACE inhibitor (benazepril) with an SGLT2 inhibitor provides complementary mechanisms for kidney protection - ACE inhibitors reduce intraglomerular pressure while SGLT2 inhibitors provide additional renoprotective effects 1
• The 2+ WBC esterase suggests leukocytosis which, along with proteinuria, indicates potential kidney inflammation that could benefit from the anti-inflammatory effects of SGLT2 inhibitors 1

Evidence Supporting SGLT2 Inhibitors in Proteinuric Kidney Disease

• The CREDENCE trial demonstrated that canagliflozin significantly reduced the risk of kidney failure, doubling of serum creatinine, or renal death by 43% compared to placebo in patients with diabetic kidney disease 1
• SGLT2 inhibitors have shown greater absolute benefits in patients with severely increased albuminuria, but provide protection across all levels of albuminuria 3
• Early reduction in albuminuria with SGLT2 inhibitors is independently associated with improved long-term kidney and cardiovascular outcomes 2
• KDIGO guidelines support using SGLT2 inhibitors to reduce CKD progression in patients with proteinuria, even when proteinuria persists despite ACE inhibitor therapy 1

Monitoring and Safety Considerations

• Monitor renal function within the first few weeks of initiating Farxiga, as there may be an initial, hemodynamically-mediated decrease in eGFR that is typically transient 1
• Be aware of potential diuretic effects when combining Farxiga with benazepril, which may require patient education about volume depletion symptoms 1
• Advise the patient to temporarily hold both medications during periods of acute illness, vomiting, or dehydration to prevent acute kidney injury 1
• The cloudy urine appearance and WBC esterase positivity suggest possible urinary tract infection, which should be addressed before starting Farxiga 1

Dosing and Administration

• Start with the lowest dose of Farxiga (5 mg daily) and monitor renal function before considering dose escalation 1
• Administer Farxiga once daily, independent of meals 1
• Continue benazepril at the current dose as it provides complementary renoprotection through different mechanisms 1, 4
• If the patient's eGFR is <45 mL/min/1.73m², closer monitoring is warranted, though Farxiga has demonstrated benefits down to an eGFR of 20 mL/min/1.73m² 1

Additional Management Considerations

• Optimize blood pressure control to target <120 mmHg systolic using standardized office BP measurement 1
• Recommend dietary sodium restriction to <2.0 g/day to enhance antiproteinuric effects of both medications 1
• Consider the presence of ketones (trace) in the urinalysis, which may reflect metabolic changes but requires monitoring after initiating SGLT2 inhibitor therapy 1
• Educate the patient about the importance of medication adherence, as interruption of ACE inhibitor therapy can lead to rapid worsening of kidney function 4