# Concept and Diagnostic Challenges of Renal-Limited Hemophagocytic Syndrome/Macrophage Activation Syndrome

## TL;DR

This review discusses a rare kidney condition linked to immune system overactivation, its unique features, and challenges in diagnosis and treatment.

## Contribution

Introduces the concept of renal-limited HPS/MAS as a distinct cause of histiocytic glomerular lipidosis.

## Key findings

- Renal-limited HPS/MAS presents with AKI but lacks full systemic HPS/MAS criteria.
- Diagnosis relies on histological evidence of foamy macrophage and lymphocyte infiltration in the glomeruli.
- Treatment with immunosuppressants and anti-inflammatory drugs often leads to favorable outcomes.

## Abstract

Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy. In this review, we introduce the recently proposed concept of renal-limited HPS/MAS as a novel etiology of histiocytic glomerular lipidosis. Patients with renal-limited HPS/MAS often develop AKI but do not fulfill the diagnostic criteria for HPS/MAS because their systemic manifestations are less severe. Therefore, the diagnosis largely depends on characteristic histological findings, that is, diffuse and global glomerular accumulation of foamy macrophages and cytotoxic lymphocytes accompanied by the interaction of these cells as well as the exclusion of various differential diseases. Although there are no established therapeutic regimens, these patients receive various types of therapies, including high-dose glucocorticoids, immunosuppressants, or anti-interleukin-1 drug, and generally achieve favorable outcomes. We summarized the concept, diagnostic challenges, and recent topics of this disease entity and discussed treatment options based on our own experiences.