Can dapagliflozin (Farxiga) be initiated in a patient with a recent rise in serum creatinine from 0.9 to 1.48 mg/dL?

Can Dapagliflozin Be Initiated in a Patient with Recent Creatinine Rise from 0.9 to 1.48 mg/dL?

Yes, dapagliflozin can be initiated in this patient, provided the estimated glomerular filtration rate (eGFR) remains ≥25 mL/min/1.73 m² and the acute creatinine rise is not due to acute kidney injury requiring immediate intervention. The creatinine rise from 0.9 to 1.48 mg/dL represents a 64% increase, which meets criteria for acute kidney injury (AKI) if it occurred within 7 days 1. However, if this patient has chronic kidney disease (CKD) with stable renal function at the new baseline, dapagliflozin offers substantial cardiovascular and renal protection.

Critical Pre-Initiation Assessment

Before starting dapagliflozin, you must:

• Calculate the current eGFR to confirm it is ≥25 mL/min/1.73 m² for cardiovascular/renal protection, or ≥45 mL/min/1.73 m² if the primary goal is glycemic control 2, 3
• Exclude acute kidney injury by reviewing the timeline of creatinine rise and ruling out prerenal causes (volume depletion, hypotension), intrinsic causes (nephrotoxins, contrast, NSAIDs), or postrenal obstruction 1
• Assess volume status and correct any depletion before initiation; consider reducing concurrent diuretic doses 2, 4
• Review medication list for nephrotoxic agents (NSAIDs, contrast dye) and ensure none were recently used 1
• Check for proteinuria/albuminuria: if UACR ≥200 mg/g, the evidence for dapagliflozin's renal benefit is strongest 2, 3, 5

Understanding the Expected Initial eGFR Dip

A critical concept that prevents inappropriate discontinuation:

• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² typically occurs within the first 2–4 weeks of dapagliflozin initiation, reflecting hemodynamic changes (reduced intraglomerular pressure) rather than tubular injury 2, 6, 7
• This initial dip should NOT trigger discontinuation; it is followed by stabilization and a slower long-term eGFR decline compared to placebo 2, 6, 7
• Patients experiencing an acute eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes with slower eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) compared to those without an initial dip 2
• Re-measure eGFR 1–2 weeks after initiation to document the expected dip, then monitor every 3–6 months 2, 4

When to Proceed with Dapagliflozin Despite Elevated Creatinine

You can initiate dapagliflozin if:

• The creatinine rise represents chronic kidney disease progression rather than acute injury, and eGFR is ≥25 mL/min/1.73 m² 2, 3
• The patient has type 2 diabetes with albuminuria (UACR ≥200 mg/g) and CKD, where dapagliflozin reduces the composite renal outcome by 44% (HR 0.56,95% CI 0.45–0.68) 2, 3, 5
• The patient has heart failure (with or without diabetes), where dapagliflozin reduces cardiovascular death or heart failure hospitalization by 26–29% 2, 8
• Volume status is adequate and there are no signs of ongoing AKI 2, 4

When to Delay or Avoid Dapagliflozin

Do NOT initiate dapagliflozin if:

• eGFR <25 mL/min/1.73 m² at baseline (though it may be continued if already on treatment) 2, 3
• Active acute kidney injury with ongoing creatinine rise, oliguria, or signs of tubular necrosis 1
• Volume depletion or hypotension is present and uncorrected 2, 9
• The creatinine rise occurred within 48 hours of nephrotoxin exposure (contrast, NSAIDs) and represents AKI 1
• Pregnancy or breastfeeding 4

Dosing and Monitoring Strategy

• Start dapagliflozin 10 mg once daily—this is the fixed dose for all cardiovascular and renal indications; no titration is required 2, 4, 3
• For glycemic control alone, dapagliflozin should not be initiated if eGFR <45 mL/min/1.73 m² because glucose-lowering efficacy is significantly reduced 2, 4
• Monitor eGFR within 1–2 weeks after initiation to document the expected hemodynamic dip 2, 4
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment 2
• Continue dapagliflozin even if eGFR subsequently falls below 25 mL/min/1.73 m² until dialysis is required, as cardiovascular and renal benefits persist 2, 8

Interpreting the Creatinine Rise: AKI vs. CKD Progression

The distinction is critical:

• AKI criteria: increase in serum creatinine by ≥0.3 mg/dL within 48 hours, OR increase to ≥1.5 times baseline within 7 days 1
• A rise from 0.9 to 1.48 mg/dL (0.58 mg/dL increase, 64% rise) meets AKI criteria if it occurred within 7 days 1
• If the rise occurred over weeks to months, this represents CKD progression rather than AKI, and dapagliflozin is appropriate 2, 3
• RAS inhibitors may be continued unless creatinine increases >30% during drug initiation or dose titration 1

Evidence-Based Renal and Cardiovascular Benefits

Even in patients with elevated creatinine and reduced eGFR:

• DAPA-CKD trial enrolled patients with eGFR 25–75 mL/min/1.73 m² and UACR 200–5000 mg/g; dapagliflozin reduced the primary composite outcome (≥50% sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51–0.72) 2, 3, 5
• Renal-specific benefits: 44% reduction in kidney-specific composite outcome (HR 0.56,95% CI 0.45–0.68) 2, 3, 5
• Cardiovascular benefits: 29% reduction in cardiovascular death or heart failure hospitalization (HR 0.71,95% CI 0.55–0.92) 2, 3, 5
• All-cause mortality: 31% reduction (HR 0.69,95% CI 0.53–0.88) 2, 5
• Benefits were consistent regardless of diabetes status; 67.5% had type 2 diabetes and 32.5% did not 2, 5

Safety Precautions and Patient Education

• Genital mycotic infections occur in approximately 6% of dapagliflozin users versus 1% with placebo; advise daily hygiene 2, 4, 9
• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose; instruct patients to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain 2, 4, 9
• Sick-day rules: hold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and stop at least 3 days before major surgery or procedures requiring prolonged fasting 2, 4
• Volume depletion risk is higher in elderly patients or those on concurrent diuretics; assess volume status before initiation 2, 9

Common Pitfalls to Avoid

• Do NOT discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy 2, 4
• Do NOT stop dapagliflozin in response to the expected early eGFR dip in the first 2–4 weeks; the change is hemodynamic and reversible 2, 6, 7
• Do NOT reduce the dapagliflozin dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used the fixed 10 mg dose 2, 4
• Do NOT withhold ACE inhibitors or ARBs when starting dapagliflozin; >99% of DAPA-CKD participants were on RAS blockade, and the combination provided additive renal protection 2, 4

Integration with Other CKD Therapies

• Continue ACE inhibitors or ARBs unchanged when initiating dapagliflozin as part of first-line CKD management 2, 4
• Metformin can be continued if eGFR ≥30 mL/min/1.73 m², but should be dose-reduced if eGFR 30–44 mL/min/1.73 m² 2, 4
• GLP-1 receptor agonists can be added for additional cardiovascular protection and glycemic control if eGFR >30 mL/min/1.73 m² 2, 4
• SGLT2 inhibition is positioned as foundational therapy for slowing CKD progression and preventing cardiovascular events, irrespective of glycemic status 2, 4