Checkpoint inhibitors (pembrolizumab · nivolumab · ipilimumab)
Immune checkpoint inhibitor
Acute interstitial nephritis with long latency.
AIN
ModerateOpen →
Nonsteroidal antiandrogen
Bicalutamide
Casodex · Bical
Nonsteroidal antiandrogen for prostate cancer; largely kidney-neutral with no renal dose adjustment and only rare interstitial nephritis reports.
Mildestablished · approved 1995
Advanced prostate cancer (50 mg with an LHRH analogue or surgical castration)Early (localized or locally advanced) nonmetastatic prostate cancer (150 mg monotherapy, regional)
Signature kidney injury
Acute Interstitial Nephritis
Bicalutamide is largely kidney-neutral. Pharmacokinetics are unaffected by renal impairment and no renal dose adjustment is required. Acute interstitial nephritis is, at most, a rare idiosyncratic case-report-level event; no meaningful incidence rate is established.
Source: Cockshott et al., Clin Pharmacokinet 2004 (no renal dose adjustment; AIN rare/idiosyncratic)
Mechanism of kidney injury
Bicalutamide is cleared almost exclusively by hepatic metabolism (CYP-mediated oxidation of the (R)-enantiomer and glucuronidation), with little or no unchanged drug in urine, so it does not accumulate in renal impairment and lacks an intrinsic nephrotoxic pathway. Any acute interstitial nephritis would represent a rare, hypersensitivity-type idiosyncratic immune reaction rather than dose-dependent toxicity.
Clinical presentation
Renally asymptomatic in the vast majority. A rare AIN would present with subacute creatinine rise, possibly with pyuria, low-grade proteinuria, or hypersensitivity features. Antiandrogen pharmacologic effects (gynecomastia, breast tenderness, hot flushes) are common but non-renal.
Onset
If AIN occurs, typically subacute over weeks of exposure (idiosyncratic).
Reversibility
Reversible
Anticancer mechanism
Bicalutamide is a nonsteroidal pure antiandrogen; its activity resides almost exclusively in the (R)-enantiomer, which competitively binds the androgen receptor and blocks androgen-driven transcription, inhibiting growth of androgen-dependent prostate cancer. It is used as monotherapy or combined with LHRH analogues/castration.
Management
For suspected drug-induced AIN, discontinue bicalutamide and provide supportive care; corticosteroids may be considered per nephrology assessment in confirmed/biopsy-proven AIN. Otherwise no renal-specific management is required.
Risk factors
- Idiosyncratic hypersensitivity predisposition (for rare AIN)
- Concurrent nephrotoxins or other AIN-associated drugs
- Severe hepatic impairment (slower elimination — a hepatic, not renal, consideration)
Prevention
- Routine renal monitoring is generally sufficient; no renal dose adjustment needed
- Review concomitant medications for additive AIN/nephrotoxicity risk
- Maintain the usual prostate-cancer monitoring (LFTs, PSA)
Note · Renal angle is reassuring: PK reviews explicitly show no effect of renal impairment on bicalutamide pharmacokinetics and no renal dose adjustment. AIN is rare/idiosyncratic and not quantified.
Clinical depth
Renal dose adjustment
No dose adjustment for renal impairment. Dose with caution in severe hepatic impairment (slower (R)-enantiomer elimination).
Dialyzability & ESKD dosing
Not meaningfully dialyzable expected given high protein binding and hepatic clearance; not clinically relevant to dosing.
Differential diagnosis
Distinguish rare AIN from other causes of AKI in prostate-cancer patients: obstructive uropathy (bladder outlet/ureteral obstruction), prerenal azotemia, and concurrent nephrotoxic medications.
Monitoring
- Serum creatinine/eGFR (routine)
- Liver function tests (hepatic metabolism/rare hepatotoxicity)
- PSA for treatment response
- Urinalysis if AIN suspected
Key trials & series
- Casodex dose-ranging and pharmacokinetic studies (PMID 9471040, PMID 8560674) show efficacy with no effect on renal function and no renal-impairment effect on PK; PMID 15509184 is the definitive clinical pharmacokinetics/metabolism review.
Clinical pearls
- Bicalutamide is hepatically cleared with negligible unchanged drug in urine — no renal dose adjustment needed.
- Renal impairment does not alter its pharmacokinetics; severe hepatic impairment is the real PK caveat.
- Think drug-induced AIN only as a rare, idiosyncratic event — and rule out obstruction first in a prostate-cancer patient with rising creatinine.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Injury signatures
Acute Interstitial NephritisElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of nonsteroidal antiandrogens.
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- QT, hypertension, fluid retention
Musculoskeletal
Myalgia, myositis, rhabdomyolysis, ONJ
- Bone loss, fatigue, hot flashes
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis (abiraterone)
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkBicalutamide: clinical pharmacokinetics and metabolism.Cockshott ID et al. · Clin Pharmacokinet 2004 · PMID 15509184Definitive PK review: bicalutamide is cleared almost exclusively by hepatic metabolism with little unchanged drug in urine and no relationship between steady-state concentrations and renal impairment, supporting a kidney-neutral profile.PMIDCasodex 10-200 mg daily, used as monotherapy for the treatment of patients with advanced prostate cancer. An overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group.Tyrrell CJ et al. · Eur Urol 1998 · PMID 9471040Phase II dose-ranging data showing no effect on renal function and no effect of renal impairment on pharmacokinetics, reinforcing absence of renal dose adjustment.PMIDPharmacodynamics and pharmacokinetics of bicalutamide: defining an active dosing regimen.Denis L et al. · Urology 1996 · PMID 8560674Pharmacodynamic/PK overview confirming pharmacokinetics are not affected by renal impairment, supporting kidney-neutral dosing.