Interstitial Eosinophilic Aggregates and Kidney Outcome in Patients with CKD

Abstract

Background Interstitial eosinophilic aggregates are observed in various kidney diseases, but their clinical implications remain unknown. We assessed the association between interstitial eosinophilic aggregates and kidney outcomes and further analyzed the association between blood eosinophil count, as a surrogate for interstitial eosinophilic aggregates, and the risk of kidney failure in patients with advanced CKD. Methods We analyzed datasets from two retrospective cohort studies: (1) the kidney biopsy cohort including 563 patients who underwent native kidney biopsy at Osaka University Hospital between 2009 and 2021 and (2) the retrospective CKD cohort including 2877 patients with an eGFR of 10–60 ml/min per 1.73 m2 referred to the nephrology outpatient center at Osaka University Hospital between 2005 and 2018. Interstitial eosinophilic aggregates were defined as ≥5 interstitial eosinophils in the high-power field on hematoxylin and eosin staining. This study outcome was initiation of KRT or ≥40% decline in eGFR. Results In the kidney biopsy cohort, interstitial eosinophilic aggregates were found in 17% of patients, most frequently in those with diabetic nephropathy (50%). Interstitial eosinophilic aggregates were associated with a higher rate of the composite kidney outcome after adjustment for clinical and histological variables (hazard ratio, 3.61; 95% confidence interval, 2.47 to 5.29; P < 0.001). LASSO revealed that blood eosinophil count was the strongest predictor of interstitial eosinophilic aggregates. In the retrospective CKD cohort, higher baseline and time-updated blood eosinophil counts were significantly associated with a higher rate of KRT initiation in Cox proportional hazards models and marginal structural models. Conclusions Interstitial eosinophilic aggregates were associated with a higher risk of a composite of KRT initiation or ≥40% decline in eGFR.

The association between peripheral eosinophil count and chronic kidney disease: evidence from NHANES 1999–2018

“…Coincidentally, a recent study confirmed the causal relationship between eosinophils and an increased risk of diabetic nephropathy using Mendelian randomization analysis [ 31 ]. These findings suggested that eosinophils in the blood may have a causal relationship with interstitial eosinophilic aggregates in renal tissue, potentially influencing the development and progression of CKD and even leading to ESKD, as indicated by two recent cohorts [ 6 ]. Furthermore, eosinophil fractions were found to be positively associated with glomerular basement membrane width and negatively associated with glomerular filtration surface density, which may contribute to albuminuria [ 32 ].…”

“…Several studies have suggested a correlation between peripheral eosinophil counts (PEC) and CKD, encompassing disease incidence, progression, and prognosis [ 6–18 ] ( Table 1 ). It has been reported that patients with CKD exhibit higher PEC compared to non-CKD individuals [ 16 ].…”

“…However, there is limited contradictory evidence available to clarify the association between PEC and the severity of renal impairment, such as albuminuria and glomerular filtration rate. While some studies suggested that patients with high PEC levels are more likely to have a lower estimated glomerular filtration rate (eGFR) and higher proteinuria [ 6 ], others, like Yen CH et al. have reported that PEC was not significantly higher in CKD patients compared to the non-CKD population and was not significantly correlated with eGFR [ 9 ].…”