Can nitrofurantoin be used to treat a urinary tract infection (UTI) in a patient with Chronic Kidney Disease (CKD) stage 3b and impaired renal function?

Nitrofurantoin Use in CKD Stage 3b for UTI

Nitrofurantoin should generally be avoided in CKD stage 3b (eGFR 30-44 mL/min/1.73m²) for treating UTIs, as current guidelines and drug labeling contraindicate its use when creatinine clearance is below 60 mL/min, though emerging evidence suggests it may retain efficacy down to CrCl 30-40 mL/min for uncomplicated lower UTIs. 1, 2

Guideline-Based Contraindication

• The FDA-approved product labeling contraindicates nitrofurantoin when creatinine clearance is below 60 mL/min, a restriction that has been in place since approximately 2003 3
• This contraindication stems primarily from concerns about subtherapeutic urinary concentrations and increased risk of adverse effects (particularly peripheral neuropathy and pulmonary toxicity) rather than robust clinical efficacy data 3
• Multiple international guidelines, including WHO recommendations, list nitrofurantoin as first-line therapy for uncomplicated lower UTIs in the general population, but these recommendations assume normal renal function 4, 1

Evidence Challenging the Strict Cutoff

• A 2017 retrospective study of hospitalized adults with renal insufficiency (CrCl <60 mL/min) found nitrofurantoin achieved uropathogen eradication in 69% of patients overall, with only 2 of 26 failures attributable to renal insufficiency specifically (both had CrCl <30 mL/min) 5
• Among patients with CrCl 30-60 mL/min in this study, nitrofurantoin was highly effective when used against susceptible organisms, suggesting the 60 mL/min cutoff may be overly conservative 5
• A 2015 population-based study of older women (median eGFR 38 mL/min) found that while nitrofurantoin had higher treatment failure rates compared to ciprofloxacin, this pattern was also observed in women with normal kidney function, suggesting factors other than renal impairment were responsible 6
• A 2013 systematic review concluded that data supporting the contraindication at CrCl <60 mL/min are essentially nonexistent, and limited available data would support considering use in patients with CrCl ≥40 mL/min 3

Clinical Decision Algorithm for CKD Stage 3b

For CKD Stage 3b (eGFR 30-44 mL/min):

• First-line alternatives to nitrofurantoin: Use trimethoprim-sulfamethoxazole (if local E. coli resistance <20%) or amoxicillin-clavulanate for uncomplicated lower UTIs 4, 1
• If considering nitrofurantoin despite contraindication: Only for uncomplicated lower UTI (cystitis) with documented susceptible organism, CrCl ≥40 mL/min, and when first-line alternatives cannot be used due to allergy, resistance, or intolerance 5, 3
• Absolute avoidance: Do not use nitrofurantoin if CrCl <30 mL/min, for pyelonephritis/upper UTI (inadequate tissue concentrations), or for complicated UTIs 1, 5, 2

Important Caveats

• Nitrofurantoin does not achieve adequate tissue concentrations for pyelonephritis or kidney cyst infections, making it inappropriate for upper UTIs regardless of renal function 1
• The drug is specifically contraindicated for treating UTIs in ADPKD patients with kidney cyst infections, where lipid-soluble antibiotics like trimethoprim-sulfamethoxazole or fluoroquinolones are required 1
• Serious adverse effects (pulmonary toxicity, peripheral neuropathy, hepatotoxicity) are primarily associated with long-term use rather than short courses, but risk may be elevated in renal insufficiency 2, 3
• Treatment duration should not exceed 5-7 days for acute cystitis 1, 5

Recommended Alternatives for CKD Stage 3b

• For uncomplicated lower UTI: Amoxicillin-clavulanate or trimethoprim-sulfamethoxazole (if local resistance permits) 4, 1
• For mild-to-moderate pyelonephritis: Ciprofloxacin (if local resistance <10%) or ceftriaxone/cefotaxime 4
• For severe pyelonephritis: Ceftriaxone, cefotaxime, or amikacin 4