This early detection and treatment of the fungal infection in the face of TNF-blockade with significant improvement in renal function on follow-up was consistent with other adult case studies and is supported by a recent FDA report that over half of the patients who experienced a delay in diagnosis ultimately died [4, 11]. In summary, the differential for acute renal failure in the immunosuppressed fungemic pediatric patient should include fungal tubulointerstitial nephritis, particularly when other fungal risk factors exist, such as with concurrent anti-TNF- therapy. species where renal biopsy led to the diagnosis of fungal tubulointerstitial nephritis in light of negative urine cultures and concurrent nephrotoxic therapy. Case report A 17-year-old female with ulcerative colitis presented with colonic inflammation on biopsy despite corticosteroid treatment. Blood and urine cultures were negative, and renal function was normal (serum creatinine 0.5?mg/dL). Infliximab was initiated at a starting infusion dose of 5?mg/kg, and the patient developed a fever. Laboratory test results were significant for an elevated white blood cell count (29.3??103/L) with band count (82%) in the face of decreased renal function (serum creatinine 1.3?mg/dL). Urinalysis revealed a specific gravity of 1 1.010, trace blood, and no protein, leukocytes, nitrites, casts, or other sediment. A blood culture was positive for that were visualized within the tubules (Fig.?1). The interstitium and tubules were infiltrated with numerous neutrophils but not eosinophils. Ruxolitinib sulfate The tubular basement membranes were disrupted, indicating likely evolution to focal renal scarring. The glomeruli were essentially normal. Neither vasculitis nor granulomas were detected. Immunofluorescence microscopy was negative for immunoglobulins, complement, and fibrin. Open in a separate window Fig.?1 Massons trichrome staining of the kidney reveals severe tubulointerstitial disease and a relatively normal glomerulus. Magnification 100. Insert Fungal organisms (several days later. Within 1 year of discharge, the patients serum creatinine had stabilized to a new baseline of 0.9?mg/dL. Discussion Before the renal biopsy, the differential diagnosis for acute MLNR renal failure in this patient included medication-mediated nephrotoxicity, an autoimmune-mediated lupus-like syndrome or cortical necrosis that has been reported with infliximab, fungal nephritis (obstructive versus interstitial), and endocarditis-associated nephritis [5, 6]. The absence of clinical signs of lupus together with a negative anti-double stranded DNA antibody made the classic diagnosis of infliximab drug-induced lupus unlikely . The absence of vegetations on the echocardiogram as well as the absence of immune-complex-mediated staining on immunohistopathology ruled out endocarditis-associated nephritis. Doppler and magnetic resonance imaging highlighted the absence of an obstructing fungal bezoar of the urinary tract, which is the more typical presentation of fungal-associated acute renal failure [2, 3, 8]. As illustrated in this case, the overlapping use of anti-tumor necrosis factor (TNF) immunosuppressive therapy and nephrotoxic agents can complicate the diagnosis of acute renal failure. Ruxolitinib sulfate The use of infliximab, similar to the use of other anti-TNF- antibody agents, presents a particularly strong risk for severe fungal infection via its binding to TNF, which is released by Ruxolitinib sulfate the immune system, constraining the patients ability to respond to infectious stimuli [9, 10]. The U.S. Food and Drug Administration (FDA) recently warned of an increase in reported invasive fungal infections with the use of TNF blockers, based on primarily adult case reports of pulmonary involvement in histoplasmosis-endemic regions . Percutaneous renal biopsy was key to the early establishment of fungal interstitial nephritis as a contributor to our patients persistent renal failure, as standard urine cultures for fungi may take up to 4 weeks to become positive . The diffuse visible yeast forms and pseudohyphae visualized within the tubules and interstitium on biopsy were striking given the prior absence of positive urinary cultures. Confirmation of a fungal cause for the renal failure allowed for targeted augmentation of antifungal therapy as well as further reductions in immunosuppressive therapy. This early detection and treatment of the fungal infection in the face of TNF-blockade with significant improvement in renal function on follow-up was consistent with other adult case studies and is supported by a recent FDA report that over half of the patients who experienced a delay in diagnosis ultimately died [4, 11]. In summary, the differential for acute renal failure in the immunosuppressed fungemic pediatric patient should include fungal tubulointerstitial nephritis,.