Interstitial Nephritis Induced by Repeated Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Use for Persistent Fever: A Case Report

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively utilized for their analgesic and anti-inflammatory efficacy, yet they pose a significant risk for renal adverse events, notably drug-induced acute interstitial nephritis (DI-AIN). Prompt recognition and appropriate management are paramount to prevent irreversible kidney damage. We present the case of a 46-year-old male with NSAID-induced DI-AIN, emphasizing the diagnostic utility of a specific urinary biomarker profile and the rationale for empirical steroid therapy initiated before histopathological confirmation. Our patient developed acute kidney injury (AKI) following daily ibuprofen administration for persistent fever. Despite ibuprofen discontinuation on day eight, renal function failed to improve, necessitating hospital admission on day 14. On day 15, his serum creatinine (Cr) level was 1.86 mg/dL. Urinalysis revealed mild proteinuria [urine protein-to-creatinine ratio (UPCR): 0.24 g/gCr] but strikingly elevated urinary tubular injury markers: N-acetyl-β-D-glucosaminidase (NAG): 20.9 U/L (on day one), β2-microglobulin (β2MG): 6028 μg/L, and L-type fatty acid-binding protein (L-FABP): 27.75 ng/mL. Based on a strong clinical suspicion of DI-AIN, a kidney biopsy was performed on day 15, and oral prednisolone (PSL, 0.8 mg/kg/day) was commenced the same evening before biopsy results were available. Serum creatinine improved to 1.56 mg/dL by discharge on day 23. Post-discharge, kidney biopsy results confirmed AIN. PSL was gradually tapered and discontinued after approximately 10 months, with sustained renal function recovery (serum creatinine: ~1.1 mg/dL). This report underscores the importance of suspecting DI-AIN in patients with AKI and a history of NSAID exposure. The pronounced elevation of urinary tubular markers, despite only mild proteinuria, was pivotal in raising clinical suspicion. The negative autoimmune serology further strengthened the diagnosis of a drug-induced etiology. Empirical steroid therapy, initiated due to compelling clinical evidence before histopathological confirmation, appeared to be an effective intervention. While this single case cannot establish a therapeutic standard, it illustrates a clinical scenario where early, empirically-guided treatment may be justified. Kidney biopsy remains indispensable for definitive diagnosis. The report also highlights the pressing need for enhanced patient education on appropriate NSAID utilization. Repeated use of common NSAIDs can precipitate DI-AIN. A diagnostic profile of elevated urinary tubular markers with only mild proteinuria can be a key indicator for suspecting this condition. Empirical steroid therapy, guided by strong clinical suspicion, can be an effective early intervention, with subsequent kidney biopsy providing definitive diagnostic validation. Enhanced patient education on appropriate NSAID use is essential.

Keywords: #aki; acute interstitial nephritis (ain); drug induced aki; n-acetyl glucosaminidase(nag); nsaid abuse; steroid use.

Figure 1. Chest and abdominal CT on admission

(A) Non-contrast chest CT. The axial CT image of the chest shows clear lung fields bilaterally, with no evidence of pulmonary infiltrates, consolidation, or pleural effusion. This finding rules out significant acute pulmonary pathology, such as pneumonia, as a cause for the patient's symptoms. (B) Non-contrast abdominal CT focusing on the kidneys. The axial CT image of the abdomen demonstrates the normal size and contour of both kidneys. There is no evidence of hydronephrosis, renal calculi, or significant cortical atrophy, which argues against obstructive uropathy or pre-existing chronic structural kidney disease CT: computed tomography

Figure 2. Serum creatinine trend during hospitalization.

Following admission, the serum Cr level increased to a peak of 2.01 mg/dL. After the initiation of prednisolone therapy, the Cr level began to decrease, reaching 1.56 mg/dL by the time of discharge Cr: creatinine

Figure 3. Histopathological findings of the kidney biopsy (periodic Acid-Schiff stain)

(A) A medium-power view of the renal cortex demonstrates significant tubulointerstitial changes. There is prominent interstitial infiltration by inflammatory cells (red arrows), accompanied by tubular epithelial cell injury (tubulitis) and expansion of the interstitial space due to edema. These findings are characteristic of acute interstitial nephritis. (B) A high-power view reveals a glomerulus with preserved architecture. The glomerulus appears normocellular, with patent capillary loops (red arrow) and no evidence of mesangial expansion, endocapillary hypercellularity, or other features of glomerulonephritis

Figure 4. Long-term serum creatinine trend during outpatient follow-up

During outpatient follow-up, the serum Cr level continued to improve, gradually decreasing and stabilizing at approximately 1.1 mg/dL from the sixth month onwards during the period of prednisolone tapering Cr: creatinine