Tubular Injury and Dendritic Cell Activation Are Integral Components of Light Chain–Associated Acute Tubulointerstitial Nephritis

Abstract

Context.— Light chain–associated acute tubulointerstitial nephritis (LC-ATIN) is a variant of light chain proximal tubulopathy (LCPT). It is characterized by interstitial inflammation with tubulitis and deposition of monoclonal light chains in the tubulointerstitium. LC-ATIN is a rather poorly recognized pattern of LCPT and not much is known about this entity. Objective.— To determine the clinicopathologic features of patients with LC-ATIN and investigate the proximal tubular injury and mechanism of interstitial inflammation in LC-ATIN. Design.— A total of 38 cases of LC-ATIN were identified from the archives of 5043 renal biopsy specimens. In all cases, routine light microscopic examination, immunofluorescence, and electron microscopic examination were performed. In selected cases, immunofluorescent staining of dendritic cells and immunohistochemical staining for 4 tubular injury markers—KIM-1, p53, bcl-2, and Ki-67—were performed. Results.— A characteristic finding in LC-ATIN cases was immunofluorescence staining of monoclonal light chains along tubular basement membranes in linear fashion and inside proximal tubular cells with a granular pattern. No monoclonal light chains were present in glomerular or vascular compartments confirmed with immunofluorescence, electron microscopy, and ultrastructural gold labeling. Ten of 15 LC-ATIN cases (67%) were concurrently positive for the 4 tubular injury markers. Dendritic cells were identified within the tubulointerstitium in the renal biopsy specimens, interacting with surrounding tubules with light-chain deposits and inflammatory cells. Conclusions.— Significant proximal tubular injury occurs associated with LC-ATIN, and the monoclonal light chains accumulated in proximal tubular cells contribute to the injury. Dendritic cells are involved in the pathogenesis of interstitial inflammation in LC-ATIN.

Light Chain Restriction in Proximal Tubules—Implications for Light Chain Proximal Tubulopathy

“…We found one case with single crystals associated with lambda-LC, which is also very rarely reported in literature ( 11 ). None of the cases included in our cohort, after thorough search, met the criteria of the acute tubulointerstitial nephritis variant of LCPT, as defined previously ( 9 , 34 ). This goes in line with a cohort of LCPT published by Stokes et al ( 12 ).…”

Identification and verification of vascular cell adhesion protein 1 as an immune-related hub gene associated with the tubulointerstitial injury in diabetic kidney disease

“…We observed increased infiltration of DCs, especially activated DCs and conventional DCs, indicating a role for these cells in the tubulointerstitial pathogenesis of DKD. Previous studies have reported that DCs were identified morphologically within the tubulointerstitium and might be involved in the pathogenesis of interstitial inflammation in drug-induced acute interstitial nephritis [ 34 ] and light chain-associated tubulointerstitial nephritis [ 35 ] . The specific mechanism requires additional experimental evidence.…”

Morphometric Analysis of Lysosomes in the Renal Tubule in Monoclonal Gammopathy Using Transmission Electron Microscopy: “Mottled Appearance” and Beyond

“…LCPT is an excessive accumulation of free light chains in proximal tubule epithelial cells that causes reabsorption dysfunction, tubular injury, and inflammatory reactions (Herrera, 2014; Bridoux et al, 2015; Stokes et al, 2016; Cheng et al, 2019). As reasonably conjectured, lysosomal precipitation of the monoclonal light chain is considered pathognomonic or sometimes the only pathological finding in LCPT (Larsen et al, 2011; Herrera, 2014; Stokes et al, 2016; Sethi et al, 2018; Leung et al, 2019).…”