Five-day fever • elevated creatinine levels • kidney transplant 10 months prior • Dx?

THE CASE

A 39-year-old man who had received a living non-related donor kidney transplant 10 months earlier presented with a 5-day history of fever, chills, myalgias, dysuria, and urinary urgency. His medications included mycophenolate mofetil 1 g PO bid, tacrolimus 2 mg PO bid, prednisone 5 mg/d PO, and nifedipine extended release 60 mg/d. He also took acyclovir 400 mg PO tid for a history of herpes simplex virus seropositivity in a kidney transplant patient, and trimethoprim/sulfamethoxazole double strength (800 mg/160 mg) PO daily for prophylaxis of urinary tract infections (UTIs). He reported sexual activity with his wife only and denied any new sexual partners. He also denied any missed medication doses.

On examination, the patient appeared to be in mild distress. His vital signs included: temperature 38.5°C, blood pressure 136/94 mm Hg, pulse 89 beats/min, and respiratory rate 18 breaths/min. Cardiopulmonary, abdominal, and genitourinary examinations were unremarkable. A well-healed scar was seen in the right lower quadrant at the site of the renal allograft and was nontender to palpation.

Laboratory values showed a white blood cell (WBC) count of 4.3 × 10⁹/L and an elevated creatinine of 1.16 mg/dL. Six months prior to presentation, his creatinine was 0.98 mg/dL. Blood cultures were obtained, and ceftriaxone (1 g) was given prior to obtaining a urine specimen. A urine dipstick revealed moderate leukocyte esterase, small blood, and 30 mg/dL of protein. Urine microscopy showed >50 WBCs per high power field (hpf), 6-10 red blood cells (RBCs), 30 mg/dL of protein, and an absence of bacteria.

THE DIAGNOSIS

Fever and urinary symptoms in a renal transplant patient may be due to acute graft pyelonephritis (AGP) or acute renal allograft rejection. Initial assessment should be focused on empiric treatment for infection while also evaluating for the possibility of rejection.

Patients with AGP present with lower urinary tract symptoms suggestive of cystitis (frequency, urgency, dysuria, hematuria, suprapubic pain) along with upper urinary tract symptoms (fever, chills, pain at graft site). However, since the kidney graft is denervated, lack of tenderness over graft site does not rule out pyelonephritis.¹

This patient was hospitalized and continued on ceftriaxone. Renal ultrasound showed an 11-cm transplanted kidney without hydronephrosis and normal Doppler flow at the anastomotic sites of the renal artery and vein. On hospital Day 2, his urine and blood cultures were negative, but ceftriaxone was continued since it had been given prior to obtaining urine culture. The patient’s tacrolimus level was slightly elevated at 15.6 mcg/L (therapeutic range: 5-15 mcg/L). He also tested negative for chlamydia and gonorrhea; a urine Wright stain was negative for eosinophils.

On hospital Day 4, the patient remained febrile, urinary symptoms persisted, and creatinine increased to 1.5 mg/dL. Tacrolimus was stopped and mycophenolate mofetil dosing was decreased to 500 mg PO bid, then 250 mg PO bid, and then stopped on hospital Day 5. Tacrolimus was reinitated on hospital Day 6 at 1 mg PO bid.

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