Effect of steroids and relevant cytokine analysis in acute tubulointerstitial nephritis

Abstract

BackgroundAcute tubulointerstitial nephritis (ATIN) is an important cause of acute kidney injury and often a potentially reversible disease. However, the role of steroids in ATIN remains controversial and the underlying mechanisms remain unresolved.MethodsA total of 113 adult patients with biopsy-proven ATIN were recruited from three tertiary referral centers. Of 102 patients with idiopathic or drug-induced ATIN, outcomes such as renal recovery, end-stage renal disease, and all-cause mortality were compared between the steroid-treated and non-treated groups. Plasma and urine inflammatory cytokine levels at the time of biopsy were analyzed in patients (n = 33) using a bead-based multiplex assay and compared with those of healthy individuals (n = 40).ResultsSteroids were used in 92 (81.4%) of the total patients and in 82 (80.3%) patients with idiopathic or drug-induced ATIN. The rate of renal recovery and the risks of end-stage renal disease and mortality were not different between the steroid-treated and non-treated groups. Despite using a propensity score matching method (n = 20 in each group), none of the outcomes were different between the two groups. Several cytokines, such as monocyte chemotactic protein-1, interferon-α, and interleukin-6 and interleukin-8 levels, were markedly elevated in plasma and urine of patients compared with those in healthy individuals. However, cytokines related to Th2 response, such as IL-10, IL-33, were not different between the two groups.ConclusionsSteroid use does not affect the overall outcome of ATIN. Based on the fact that targeting therapy should be investigated to improve outcomes, the present cytokine results will be helpful for developing a novel therapy for ATIN.Electronic supplementary materialThe online version of this article (10.1186/s12882-019-1277-2) contains supplementary material, which is available to authorized users.

Urinary Cytokines Reflect Renal Inflammation in Acute Tubulointerstitial Nephritis: A Multiplex Bead-Based Assay Assessment

“…As in the case of IL-6, TECs can produce MCP-1 but also the endothelial cells of the peritubular capillaries and macrophages can do so themselves. Higher urinary levels of MCP-1 and IL-6 in ATIN patients found in our study are consistent with the findings reported by other authors [13,14]. In addition to higher urinary levels of MCP-1, Chen et al [13] also found higher levels of serum TNFα and IL6 in ATIN patients compared to healthy controls, thus suggesting a role of the cytokines in this disease, but they did not evaluate their urinary concentration.…”

Ibrutinib-induced acute kidney injury via interstitial nephritis

“…In our case, we did not examine cytokine levels. Recently serum and urine levels of several cytokines were found to be higher in AIN patients compared to healthy ones, but cytokine levels characteristic of Th2 response did not differ [ 19 ]. Because AIN is mostly restricted to the kidneys, testing urine cytokine levels is more relevant.…”

“…With glucocorticoid treatment, proteinuria, hematuria resolved within 2 weeks, and renal function improved significantly. Glucocorticoid treatment efficacy is contentious in AIN [ 19 ], and many consider it only if no improvement in renal function is observed within 3–5 days despite omitting the responsible drug. This wait would certainly have resulted in lower GFR later.…”

New Biomarkers in Acute Tubulointerstitial Nephritis: A Novel Approach to a Classic Condition

“…Urinary MCP-1 correlated and predicted the severity of the acute lesions in kidney biopsies from these patients [ 19 ]. In the same line, Yun et al described higher MCP-1 serum and urine concentration among 113 ATIN patients from different causes in their bead-based multiplex assay [ 20 ]. Interestingly, Dantas et al found that urinary MCP-1 concentration finely correlated with the amount of tubulointerstitial infiltrate but not with the glomerular infiltrate in a cohort of patients with glomerular autoimmune diseases [ 21 ].…”

“…This is a cytokine with a local proinflammatory effect in the early stages of inflammation that also induces acute-phase production of proteins such as CRP [ 26 ]. Numerous authors reported elevated IL-6 concentration in urine and plasma from patients with ATIN compared to healthy controls [ 20 , 27 , 28 ].…”