Can Lipofuscin Deposition on Renal Allograft Tubular Epithelium Be a Surrogate Marker for Kidney Allograft Aging?

Kawaguchi, Yuki; Oguchi, Hideyo; Mikami, Taisei; Yamaguchi, Yutaka; Ohashi, Yasushi; Kawamura, Takeshi; Muramatsu, Masaki; Itabashi, Yoshihiro; Shinoda, Kazunobu; Hyodo, Yoji; Takahashi, Yusuke; Onishi, Hiroka; Arai, Taichi; Hamasaki, Yuko; Shibuya, Kazutoshi; Shishido, Seiichiro; Sakai, Ken

doi:10.1016/j.transproceed.2019.03.017

Cited by 2 publications

(4 citation statements)

References 10 publications

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“…These molecules have a major impact on the renal autofluorescence as kidney tissue is highly vascularized, shows a high metabolic rate, and is rich in lipofuscin. The deposition of lipofuscin is a general characteristic of ageing tissue and its accumulation is significantly increased in aged kidney biopsies [50]. With respect to applying super-resolution microscopy for diagnostic purposes, tissue samples are more likely to originate from elderly patients and thus autofluorescence might become a major issue.…”

Section: Effect Of Background Signalmentioning

confidence: 99%

Superresolving the kidney—a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier

Wunderlich

Ströhl

et al. 2020

Anal Bioanal Chem

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Immunofluorescence microscopy is routinely used in the diagnosis of and research on renal impairments. However, this highly specific technique is restricted in its maximum resolution to about 250 nm in the lateral and 700 nm in the axial directions and thus not sufficient to investigate the fine subcellular structure of the kidney’s glomerular filtration barrier. In contrast, electron microscopy offers high resolution, but this comes at the cost of poor preservation of immunogenic epitopes and antibody penetration alongside a low throughput. Many of these drawbacks were overcome with the advent of super-resolution microscopy methods. So far, four different super-resolution approaches have been used to study the kidney: single-molecule localization microscopy (SMLM), stimulated emission depletion (STED) microscopy, structured illumination microscopy (SIM), and expansion microscopy (ExM), however, using different preservation methods and widely varying labelling strategies. In this work, all four methods were applied and critically compared on kidney slices obtained from samples treated with the most commonly used preservation technique: fixation by formalin and embedding in paraffin (FFPE). Strengths and weaknesses, as well as the practicalities of each method, are discussed to enable users of super-resolution microscopy in renal research make an informed decision on the best choice of technique. The methods discussed enable the efficient investigation of biopsies stored in kidney banks around the world.

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Section: Effect Of Background Signalmentioning

confidence: 99%

Superresolving the kidney—a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier

Wunderlich

Ströhl

et al. 2020

Anal Bioanal Chem

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show abstract

“…Higher serum levels of lipofuscin were tested in KT recipients [13]. In a case series of 201 living donor kidney transplant, Kawaguchi and colleagues reviewed 260 allograft biopsies and reported prevalence of LD was 58.8% [8]. However, it is not clear from the text how the authors ensured that the granules they saw were in fact lipofuscin.…”

Section: Discussionmentioning

confidence: 99%

“…Kawaguchi and colleagues concluded that LD in the renal allograft tubular epithelium is not a surrogate marker for kidney allograft aging [8]. Although, older age of the recipients but not the donor was speculated to be involved in lipofuscin deposition.…”

Section: Discussionmentioning

confidence: 99%

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A case report on lipofuscin deposition in a graft biopsy two years after kidney transplantation: an insignificant bystander or a pathogenic benefactor?

et al. 2019

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Background Lipofuscin deposition is a characteristic manifestation of aging. There is very limited literature in humans and in animals describing these deposits in native kidneys. Overall, it is thought to be non-pathogenic and successful transplants from a donor with lipofuscin deposits have been reported. We present the case of a patient who underwent a kidney transplant and a for-cause biopsy post-transplantation incidentally revealed lipofuscin deposition. Case presentation A 48-year old gentleman with a past medical history of diabetes, hypertension, coronary artery disease, and ischemic and then hemorrhagic cardiovascular accident underwent a successful kidney transplant. His donor was an expanded criteria donor with no major past medical history. Post-transplant course was complicated by delayed graft function requiring one dialysis treatment for hyperkalemia. After that he had an uneventful course and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. On a routine 19-month follow-up he was noted to have proteinuria and an antibody against the major-histocompatibility-complex class I-related chain A. A graft biopsy revealed acute antibody-mediated rejection and impressive lipofuscin deposition. He was subsequently treated with an antibody-mediated rejection protocol that included high dose steroids, Rituximab, plasmapheresis, and intravenous immunoglobulin, but responded poorly to this regimen. A 6-month follow up biopsy continued to show lipofuscin deposition, with similar microvascular injury scores and 12-months later his creatinine remained stable but his proteinuria worsened. Patient was struggling with recurrent infectious episodes requiring hospitalizations and thus no further diagnostic or therapeutic treatments were pursued. Conclusions Lipofuscin deposition has been reported in solid organ transplants but the significance and cause are not well understood. Several physiologic and some pathologic causes to these deposits have been reported including age, diabetes, medications and a genetic syndrome. We propose that immunologic causes such as rejection in the presence of other risk factors could potentiate the oxidative stress leading to excessive lipofuscin deposition in kidney transplants. In the case of our patient, we conclude that these deposits were likely recipient-derived, and postulate that the cumulative burden of inflammation from rejection, and underlying medical conditions led to increased lipofuscin deposition. We speculate them to be an innocent bystander.

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Can Lipofuscin Deposition on Renal Allograft Tubular Epithelium Be a Surrogate Marker for Kidney Allograft Aging?

Cited by 2 publications

References 10 publications

Superresolving the kidney—a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier

Superresolving the kidney—a practical comparison of fluorescence nanoscopy of the glomerular filtration barrier

A case report on lipofuscin deposition in a graft biopsy two years after kidney transplantation: an insignificant bystander or a pathogenic benefactor?

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