Systemic and rapidly progressive light-chain deposition disease initially presenting as tubulointerstitial nephritis

Takahashi, Satoko; Soma, Jun; Nakaya, Izaya; Yahata, Mayumi; Sakuma, Tsutomu; Yaegashi, Hiroshi; Sato, Akiyoshi; Wano, Masaharu; Sato, Hiroshi

doi:10.1007/s13730-012-0026-1

Cited by 4 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of the deposition of monotypical light chains, this variant could be conceptualized as an interstitial form of light chain deposition disease. 52 The main clinical presentation was acute renal failure (40% of these patients). These cases were a combination of j and k light chain-related lesions.…”

Section: Metabolism Of Light Chains In Proximal Tubules/handling Of Pmentioning

confidence: 99%

Proximal Tubulopathies Associated With Monoclonal Light Chains: The Spectrum of Clinicopathologic Manifestations and Molecular Pathogenesis

Herrera

2014

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

Context.—Lesions associated with monoclonal light and heavy chains display a variety of glomerular, tubular interstitial, and vascular manifestations. While some of the entities are well recognized, including light and heavy chain deposition diseases, AL (light chain) and AH (heavy chain) amyloidosis, and light chain (“myeloma”) cast nephropathy, other lesions centered on proximal tubules are much less accurately identified, properly diagnosed, and adequately understood in terms of pathogenesis and molecular mechanisms involved. These proximal tubule–centered lesions are typically associated with monoclonal light chains and have not been reported in patients with circulating monoclonal heavy chains. Objective.—To determine the incidence of proximal tubulopathies in a series of patients with monoclonal light chain–related renal lesions and characterize them with an emphasis on clinical correlations and elucidation of molecular mechanisms involved in their pathogenesis. Design.—A study of 5410 renal biopsies with careful evaluation of light microscopic, immunofluorescence, and electron microscopic findings was conducted to identify these monoclonal light/heavy chain–related lesions. In selected cases, ultrastructural immunolabeling was performed to better illustrate and understand molecular mechanisms involved or to resolve specific diagnostic difficulties. Results.—In all, 2.5% of the biopsies were diagnosed as demonstrating renal pathology associated with monoclonal light or heavy chains. Of these, approximately 46% were classified as proximal tubule–centered lesions, also referred to as monoclonal light chain–associated proximal tubulopathies. These proximal tubulopathies were divided into 4 groups defined by characteristic immunomorphologic manifestations associated with specific clinical settings. Conclusions.—These are important lesions whose recognition in the different clinical settings is extremely important for patients' clinical management, therapeutic purposes, and prognosis. These entities have been segregated into 4 distinct variants, conceptualized morphologically and clinically. Specific mechanisms involved in their pathogenesis are proposed.

show abstract

Section: Metabolism Of Light Chains In Proximal Tubules/handling Of Pmentioning

confidence: 99%

Proximal Tubulopathies Associated With Monoclonal Light Chains: The Spectrum of Clinicopathologic Manifestations and Molecular Pathogenesis

Herrera

2014

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

show abstract

“…The authors recognize that in rare instances a process initially considered as LC-ATIN may progress to or be later characterized as LCDD with prominent tubulointerstitial involvement as additional evidence becomes available, as demonstrated by the case report of Takahashi et al 41 This represents an additional example of the complexity and heterogeneity of renal lesions associated with nephrotoxic light chains, which essentially depend on the extremely varied physicochemical characteristics of light chains involved. 42 The conceptual understanding of the intricacies of these diseases is still evolving.…”

Section: Discussionmentioning

confidence: 99%

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

Cheng

Turbat‐Herrera

et al. 2019

Archives of Pathology &Amp; Laboratory Medicine

View full text Add to dashboard Cite

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.

show abstract

Concurrent non‐crystalline light chain proximal tubulopathy and light chain deposition disease: a case report

et al. 2020

View full text Add to dashboard Cite

Systemic and rapidly progressive light-chain deposition disease initially presenting as tubulointerstitial nephritis

Abstract: A 42-year-old woman was admitted to a hospital after first-time detection of proteinuria and hematuria during a routine medical check-up. Because her serum creatinine level had rapidly increased from 0.9 to 3.2 mg

Cited by 4 publications

References 22 publications

Proximal Tubulopathies Associated With Monoclonal Light Chains: The Spectrum of Clinicopathologic Manifestations and Molecular Pathogenesis

Proximal Tubulopathies Associated With Monoclonal Light Chains: The Spectrum of Clinicopathologic Manifestations and Molecular Pathogenesis

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

Concurrent non‐crystalline light chain proximal tubulopathy and light chain deposition disease: a case report

Contact Info

Product

Resources

About