Acute renal failure following intravesical bacille Calmette-Guérin chemotherapy for superficial carcinoma of the bladder

Abstract

Sir, Intravesical chemotherapy with bacille Calmette–Guérin (BCG) is an effective treatment for superficial transitional cell carcinoma of the bladder, but is not without side effects. This case highlights two rare complications that may present to the nephrologist—interstitial nephritis and glomerulonephritis. A 72-year-old man was diagnosed with bladder carcinoma in situ in June 2003 and underwent trans-urethral resection of the tumour followed by a 6 week course of intravesical BCG chemotherapy (TICE strain). Further courses of three doses were administered in January and July 2004. The last catheterization was traumatic and, following chemotherapy, the patient became non-specifically unwell and confused. He was treated with cephalexin and then ciprofloxacin for presumed urinary tract infection, with no improvement. Two weeks later, he was re-admitted with acute renal impairment—blood urea 18.6 mmol/l and serum creatinine 258 µmol/l (92 µmol/l previously). Liver function tests were mildly abnormal, urine culture negative and renal ultrasonography normal. He continued to deteriorate and was transferred to our centre with a serum creatinine of 558 µmol/l. Renal biopsy revealed acute tubulointerstitial nephritis (no granuloma). Thirty percent of glomeruli were abnormal, with focal segmental mesangial proliferation but no necrosis. Stains for acid-fast bacilli and immunofluorescence were negative and electron microscopy was unremarkable. Prednisolone, isoniazid and rifampicin were commenced and his renal function improved, liver function tests normalized and other symptoms resolved. By 3 months after commencing treatment, his creatinine had fallen to 174 µmol/l. Urinalysis demonstrates persistent trace proteinuria and 2+ haematuria. Intravesical BCG has been used in the treatment of bladder cancer for 20 years. Common side effects are transient phenomena—cystitis and dysuria (in 80% of patients), haematuria (40%) and low-grade pyrexia (30%) [1]. Significant adverse effects occur in 1%, ranging from local pathology such as granulomatous prostatitis to disseminated BCG infection with hepatitis, pneumonitis, mycotic aneurysms and retroperitoneal abscesses. BCG ‘itis’ is a severe systemic illness occurring immediately following treatment and resembling Gram-negative sepsis [2,3]. Specific renal lesions, tubulointerstitial nephritis (often with epithelioid granuloma formation) and mesangial glomerulonephritis, have been reported [4,5]. Spread of the bacterium (or mycobacterial proteins) is thought to be haematogenous, hence traumatic instrumentation of the urinary tract, allowing access to the circulation, is a risk factor for the serious manifestations. A dose-dependent effect is apparent, with an increasing risk of renal side effects as the number of administered doses increases. Our patient's liver function was deranged, possibly due to granulomatous hepatitis, which has been described in this setting [2]. Treatment with prednisolone and anti-tuberculous chemotherapy was based on advice found in the literature [2,4,5]. Prednisolone at a starting dose of 40 mg daily, tapering over 3 months as response occurs, plus isoniazid and rifampicin for 6 months, represents current optimal therapy. Prognosis appears good, though some renal impairment may persist. We have described a patient with acute renal failure due to tubulointerstitial nephritis and glomerulonephritis following intravesical BCG treatment who recovered with steroids and antituberculous chemotherapy. The diagnosis should be considered in at-risk patients, and established with early renal biopsy, as the outcome appears to be better when treatment is initiated promptly before the interstitial lesion can progress to scarring and fibrosis. Conflict of interest statement. None declared. 1Department of Renal Medicine Lister Hospital Stevenage2 Department of Urology Luton and Dunstable Hospital Luton3 Department of Pathology University of Cambridge Addenbrooke's Hospital Cambridge UK Email: andyfry@doctors.org.uk