Interstitial eosinophilic infiltration in diabetic nephropathy is indicative of poor prognosis, with no therapy benefit from steroid

Abstract

Background: Studies suggested that eosinophils in diabetes might be associated with severity of diabetic nephropathy (DN). In a retrospective study of 102 Chinese patients with biopsy-proven DN, we aimed to evaluate relationships of both blood and renal eosinophils (Eos) to the severity of DN and check whether Eos can serve as an indicator of prognosis as well as the therapeutic effect of steroids. Methods: One hundred and two patients diagnosed with DN were enrolled. Demographical and clinical data and histopathological scores were associated. Interstitial eosinophilic aggregates (IEA) were defined as the presence of ≥10 Eos in at least one high-power field. End-stage renal disease was defined as the end point. Results: We observed that log 2 (blood eosinophil counts) correlated with neutrophil counts, proteinuria, and tubulointerstitial inflammatory cell infiltration. IEA was observed in 33.3% of the DN patients and was associated with decreased estimated glomerular filtration rate, higher proteinuria, hematuria, higher HbA1c, increased blood eosinophil counts, tubular injury, tubulointerstitial chronicity, and interstitial inflammation. IEA was associated with worse renal prognosis (hazard ratio [HR] 2.424, P = 0.008). Consistently, urine eosinophil cationic protein (ECP) (ng/mgCr) was associated with renal injury and poor renal prognosis (HR 1.173, P = 0.020). Patients with IEA were more likely to be treated with steroid/immunosuppressants (47.1% vs 14.7%, P = 0.001) but did not show renal benefit.

Pathogenesis and Clinical Significance of In-Stent Restenosis in Patients with Diabetes

“…The meta-analysis performed by Gong et al confirmed that allergy to stent material worsens the prognosis of patients after coronary stent implantation [112]. Interstitial eosinophil infiltration has been proven to have prognostic value in patients with diabetic nephropathy [113]. In patients with T1DM, eosinophils have been shown to be characterised by increased activity assessed by features such as a high level of myeloid alpha-defensins and myeloperoxidase [114].…”

The Pathogenesis of End-Stage Renal Disease from the Standpoint of the Theory of General Pathological Processes of Inflammation

“…Interstitial fibrosis and tubular atrophy in the renal medulla, hyalinosis of arterioles and arteriosclerosis, expansion of the subendothelial space, and neovascularization can also be revealed [ 94 ]. These changes have individual signs characteristic of the focus of classical inflammation (for example, interstitial fibrinous edema) and, in some cases, are accompanied by the involvement of migrating leukocytes, including T and B lymphocytes, in the process [ 92 , 94 , 95 , 96 ]. As a result, the pathogenesis of DKD is characterized not only by metabolic abnormalities but also by multiple immunological and inflammatory mechanisms [ 96 , 97 ], making it a challenge to distinguish between ChLGI and traditional inflammation processes in this pathology.…”

“…As a result, some kinds of proliferative glomerulonephritis may be characterized by proinflammatory Th17 function, whereas others are characterized by Th1 function [ 137 , 140 ]. At the same time, the mechanisms of the i2 immune response are also involved in the development of renal inflammation, including the possibility of interstitial eosinophilic infiltration in DKD [ 95 ] and activation of mast cells [ 97 ]. The involvement of i2 cytokines (IL-4 and eotaxin) [ 141 ], other profibrogenic cytokines, and growth factors of T and mast cells [ 104 ] in the development of interstitial inflammation have also been noted.…”

Clinical Acute Kidney Injury and Histologic Acute Tubular-Interstitial Injury and Their Prognosis in Diabetic Nephropathy

“…Our study revealed that a high percentage of hATI among patients without cAKI was diagnosed by renal biopsy, emphasizing the significant status of renal biopsy for ascertaining acute kidney injury. Prior studies have reported that interstitial inflammation [14, 27] was related to adverse renal outcomes in patients with DN. Our findings showed significantly increase in the degrees of interstitial infiltration among patients with hATI relative to those without hATI.…”