Table 3:
A comprehensive summary of the main publications pertaining to serum and urinary biomarkers of ATIN.
| Reference | Population samples | Relevant findings | Association in distinguishing between different etiologies? |
|---|---|---|---|
| Dantas et al., Kidney Blood Press Res (2007) [52] | Glomerulopathy n = 37 | The urinary MCP-1 was correlated with the extent of tubulointerstitial infiltrate by macrophages, but not with the degree of glomerular infiltrate | Until the present research, it was not sensitive, as it was found to be significantly higher in different etiologies [63, 92, 53, 59] |
| Wu et al., Clin J Am Soc Nephrol (2010) [53] | Drug-induced ATIN n = 40Healthy controls n = 20 | ATIN patients had higher levels of MCP-1, α1-MG, NGAL and NAG compared with controls; the urinary levels of MCP-1were correlated with the extent and severity of the acute lesions | It is important to classify drugs based on their pathomechanism, since different drugs can induce ATIN through different pathomechanism which may aid in identifying the culprit drug |
| Nakashima et al., Clin Nephrol (2010) [54] | IgG4 disease-related ATIN n = 4Other cause ATIN n = 16 | The expression of IL-4, IL-10 and TGF-β RNA in kidney tissue was observed to be higher in patients with IgG4 disease, as compared with other causes of ATIN | Due to the small sample size and the presence of such biomarkers in other autoimmune diseases, these are not universally applicable as a diagnostic biomarkers in IgG4-disease-related ATIN |
| Shi et al., Am J Med Sci (2013) [55] | Drug-induced ATIN n = 51 | The rate of GFR decline was faster in patients with higher urinary levels of NAG, metalloproteinase 2 (MMP2) and MMP9 | It is important to classify drugs based on their pathomechanism, since different drugs can induce ATIN through different pathomechanism which may aid in identifying the culprit drug |
| Aoyagi et al., CEN Case Rep (2014) [56] | One case of TINU | During follow-up of an episode of TINU, serum TNF-α, IL-8 and IFN-γ levels decreased | Several studies have found that these biomarkers are higher in various etiologies, making them non-sensitive and non-specific |
| Chen et al., Braz J Med Biol Res (2018) [57] | ATIN n = 30Healthy controls n = 15 | The serum levels of IL-6, IL-10 and TNF-α were significantly higher in ATIN patients than in controls | Several studies have found that these biomarkers are higher in various etiologies, making them non-sensitive and non-specific |
| Zhao et al., Am J Physiol Renal Physiol (2019) [58] | ATIN n = 44Healthy controls n = 24 | ATIN patients had higher urinary levels of KIM-1 and C5b9 compared with healthy controls; urinary C5b9 correlated with the extent of tubulointerstitial infiltrates in kidney biopsy in ATIN patients | Several studies have found that these biomarkers are higher in various etiologies, making them non-sensitive and non-specific |
| Yun et al., BMC Nephrol (2019) [59] | ATIN n = 113Healthy controls n = 40 | Serum IL-1β, IFN-α2, TNF-α, MCP-1, IL-8, IL-17A, IL-18 and IL-23 were higher in ATIN patients compared with healthy controls; urinary IFN-α2, MCP-1, IL-6, IL-8, IL-12p70 and IL-17A were higher in ATIN patients compared with healthy controls | There are various biomarkers that may be due to the combined study of various etiologies; therefore, it is necessary to study among various etiologies in order to find specific biomarkers for each etiology |
| Moledina et al., JCI Insight (2019) [60] | ATIN n = 32Other kidney diseases n = 186 | Urinary TNF-α and IL-9 were higher in ATIN patients compared with other kidney diseases; urinary IL-5 was higher among ATIN patients with prominent eosinophil infiltrates | ATIN vs other kidney diseases, cannot analyze such findings among various ATIN etiologies from this study |
| Moledina et al., Nephron (2019) [61] | ATIN n = 32ATN n = 41 | Urinary TNF-α and IL-9 were higher in ATIN patients | ATIN vs ATN, cannot analyze such findings among various ATIN etiologies from this study |
| Moledina et al., JCI (2023) [62] | AIN n = 31Healthy controls n = 57 | CXCL9 was significantly higher in AIN patients compared with healthy controls | It is therefore necessary to further study to determine the correlation between various etiologies of AIN |
NAG: N-acetyl-neuraminidase; α1-MG: α1-microglobulin; NGAL: neutrophil gelatinase-associated lipocalin; TGF-β: transforming growth factor-β; GFR: glomerular filtration rate; KIM-1: kidney injury molecule.