Discussion
Establishing a clinical diagnosis of drug-induced AIN is exceedingly difficult given the numerous types of medications associated with AIN. Although AIN often occurs less than 2 weeks after drug exposure, it has been shown to vary from days to months depending on the drug [2]. However, a diagnosis of AIN may be established through knowledge of the patient’s medical history and specific laboratory tests, such as DLST [2-5]. In fact, DLST has been regarded as a useful diagnostic test for various types of drug hypersensitivity, including drug-induced AIN, by measuring drug-induced T cell proliferation in vitro [6,7]. In the current case, considering that the patient showed a specific high score for Lexaburo in DLST, the patient’s renal abnormality was initially considered to have been attributed to drug-induced AIN. We believe that the subsequent development of TINU syndrome in our patient may have been caused by the additive, synergistic, or cumulative effects of the drugs, including Lexaburo. Although DLST results are not absolute, T cell-mediated mechanisms have been proposed to play a major pathogenic role in TINU syndrome, which necessitates drug induction [2,7]. Case information on prior drug use as an estimated risk for TINU syndrome continues to accumulate [7-10]. However, similar inducers have been identified in both isolated AIN and TINU syndromes [2,7,8]. Unfortunately, determining the exact contribution of each is quite difficult. Whether AIN without TINU syndrome and uveitis is a different phenotype of the same pathology is particularly important and crucial issue that needs to be extensively investigated [11]. As such, we note that recent studies on the pathogenic role of modified CRP (mCRP) can irreversibly dissociate from native CRP in TINU syndrome [12,13]. This is because it can be one of the common target autoantigens in kidney and eye tissue [10,13,14]. Interestingly, serum levels of anti-mCRP autoantibodies may play a role in distinguishing patients with TINU syndrome from those with AIN [13,14]. Unfortunately, such a procedure is inapplicable to the current patient. Moreover, HLA-type analysis is progressing in TINU syndrome, with reports showing that HLA-DQA1, HLA-DQB1, and HLA-DRB1 are associated with the onset [11,15]. The HLA type in the current case was unknown, with the patient not consenting to genetic testing. Identifying the patient’s mCRP and HLA types may have helped establish a diagnosis, and we believe that similar cases will benefit from such tests in the future. The main treatment for AIN is to discontinue or reduce the dose of the problematic drug [2,4]. Corticosteroid therapy has shown no clear benefits after discontinuation of the problematic drug. One study showed that 72% of patients with TINU syndrome who did not use systemic steroids were expected to spontaneously recover from renal dysfunction [16]. In contrast, another report revealed that two out of four patients who did not receive steroids progressed to chronic renal failure, with one patient developing end-stage renal failure [8]. Several reports have suggested corticosteroid administration may shorten the course of renal failure [4,5,17]. Considering that no improvement in the renal function of the current patient was observed following drug discontinuation, PSL was started at 60 mg/day (1.3 mg/kg/day). The interval between drug discontinuation and start of steroid treatment was approximately 3 weeks. Immediately after starting PSL treatment, the patient’s renal function improved. This finding is consistent with that reported in previous studies, which showed that patients often respond to PSL doses of 1–2 mg/kg/day. Many authors agree with corticosteroid treatment for patients with TINU syndrome who have advanced renal failure similar to AIN. Simultaneous use of topical ocular steroids and immunosuppressants may be essential due to the prolonged and/or recurrent uveitis associated with this syndrome [18-20].