Does Granix Cause Acute Kidney Injury?
Granix (filgrastim) can cause acute kidney injury, specifically through glomerulonephritis, though this is an uncommon adverse effect. The FDA label explicitly warns that glomerulonephritis has occurred in patients receiving filgrastim products, manifesting as azotemia, hematuria (microscopic and macroscopic), proteinuria, and confirmed by renal biopsy 1.
Mechanism of Filgrastim-Associated AKI
Glomerulonephritis is the primary mechanism by which filgrastim causes kidney injury, characterized by glomerular inflammation rather than direct tubular toxicity 1.
The injury typically presents with azotemia, hematuria (both microscopic and macroscopic), and proteinuria, distinguishing it from hemodynamic causes of creatinine elevation 1.
Mesangioproliferative glomerulonephritis with tubular necrosis has been documented on kidney biopsy in patients receiving pegfilgrastim (a long-acting form of filgrastim), with severe AKI requiring dialysis in reported cases 2.
Clinical Presentation and Severity
Severe AKI can occur, with documented cases showing serum creatinine rising from baseline 0.7 mg/dL to 6.9 mg/dL, requiring temporary dialysis 2.
The injury can be relapsing: re-exposure to pegfilgrastim after initial recovery led to recurrent severe AKI (creatinine 6.7 mg/dL) in documented cases 2.
Timing is typically 2 weeks post-administration, as observed in case reports where AKI developed approximately 14 days after pegfilgrastim injection 2.
Monitoring Recommendations
Routine monitoring of renal function and urinalysis is essential during filgrastim therapy, as milder cases may be missed without systematic surveillance 2.
If glomerulonephritis is suspected, evaluate for causality and consider dose-reduction or interruption of filgrastim 1.
Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of filgrastim products, indicating reversibility when recognized early 1.
Risk Context and Clinical Decision-Making
While glomerulonephritis is a recognized adverse effect, it remains relatively uncommon compared to other filgrastim-related complications 1.
Do not withhold filgrastim in life-threatening neutropenic conditions solely due to AKI concern, as the mortality benefit of treating severe neutropenia typically outweighs the risk of kidney injury 3.
Kidney function must be monitored in patients exposed to filgrastim to limit the risk and progression of AKI, particularly in those with pre-existing risk factors 3.
Differential Diagnosis Considerations
When AKI occurs in cancer patients receiving filgrastim, consider alternative nephrotoxic exposures including chemotherapy agents (cyclophosphamide, docetaxel), antibiotics (vancomycin, daptomycin), and sepsis 2, 4.
Vancomycin is the most common nephrotoxin in hospitalized patients and may co-occur with filgrastim use, requiring careful attribution 4.
Drug-induced AKI generally shows lower mortality than septic or ischemic AKI (25.2% vs. higher rates), though the need for acute kidney support therapy remains substantial at 31.8% 4.
Management Algorithm
Suspect filgrastim-induced glomerulonephritis when AKI develops 1-2 weeks post-administration with hematuria and proteinuria 1, 2.
Obtain urinalysis immediately: look for dysmorphic red blood cells, red cell casts, and quantify proteinuria (can exceed 3.5 g/day) 2.
Discontinue or reduce filgrastim dose if glomerulonephritis is likely, as this typically leads to resolution 1.
Consider kidney biopsy if the diagnosis is uncertain or if AKI is severe and persistent, to confirm mesangioproliferative changes and exclude other causes 2.
Avoid re-challenge with filgrastim if severe AKI occurred, as relapsing injury has been documented 2.
Common Pitfalls to Avoid
Do not attribute all AKI in cancer patients to filgrastim alone—these patients often have multiple concurrent nephrotoxic exposures including chemotherapy, antibiotics, and sepsis 2, 4.
Do not miss mild cases: routine urinalysis is critical because subclinical glomerulonephritis may progress if filgrastim is continued without recognition 2.
Do not permanently discontinue filgrastim without considering alternatives: if neutropenia is life-threatening and AKI is mild, dose reduction rather than complete cessation may be appropriate 1.