Peritubular capillaries in chronic renal allograft rejection: A quantitative ultrastructural study

Iványi, Béla; Fahmy, Hanan; Brown, Holly; Szenohradszky, P.; Halloran, P.; Solez, Kim

doi:10.1053/hupa.2000.16677

Cited by 80 publications

(61 citation statements)

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“…Peritubular capillary profiles with several circumferential basement membrane layers occurred exclusively in chronic rejection (transplant capillaropathy; for a definition, see Table 1). We also experienced that EM of the glomeruli verified transplant glomerulopathy more precisely than did light microscopy (11). Pooled data indicate that acute rejection episodes or ongoing, subclinical rejection injuries to peritubular and glomerular capillary endothelial cells lead to the development of transplant capillaropathy and transplant glomerulopathy (11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 80%

“…The ultrastructural features of acute cellular rejection include hypertrophied endothelial cells, increased adherence and passage of lymphocytes, lymphocytes in the capillary wall, separation of endothelial cells from the basement membrane, defects in the endothelial lining and balloon-like fragmentation or apoptosis of endothelial cells in the vicinity of lymphocytes (12,23,24). In chronic rejection, the wall of the peritubular capillaries frequently contained lymphocytes, separating the endothelial cells from the laminated basement membrane (11). The observations suggest that transplant capillaropathy is the final result of ongoing or repeated episodes of endothelial cell damage or death and subsequent regeneration.…”

Section: Transplant Capillaropathymentioning

confidence: 93%

“…The site of reading of the peritubular capillary basement membrane layers was the narrow peritubular interstitium. The multilayering of the basement membrane was regarded as circumferential if it was seen in at least three of the four portions of the capillary circumference (11). The median numbers of glomeruli and peritubular capillary profiles per examined biopsy were 1.8 (range: 1-4) and 15.5 (range: 6 -32), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…A few conditions, however, should be borne in mind during the diagnosis of transplant capillaropathy. Two capillary profiles with five or six layers have been very occasionally observed in chronic tubulointerstitial nephritis and hemolytic-uremic syndrome, and marked basement membrane multiplication has been noted in a biopsy specimen of native end-stage kidney from an adult with reflux nephropathy (11). Because cases with reflux nephropathy are seldom biopsied, data on peritubular capillary changes in this condition are lacking.…”

Section: Transplant Capillaropathymentioning

confidence: 99%

“…The process is associated with a loss of fenestration, a serrated shape, and splitting and multilayering of the basement membrane. In semithin sections, the capillaropathy appears as a serrated profile with a thick, ribbon-like basement membrane layer (11), enhancing the sampling of the lesion. Transplant capillaropathy may be encountered sooner than 6 months after transplantation.…”

Section: Transplant Capillaropathymentioning

confidence: 99%

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The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

et al. 2001

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The main causes of the late dysfunction of renal allografts are chronic rejection and chronic transplant nephropathy. Both are clinicopathologic entities, with a similar clinical presentation, but different histologic appearances. Chronic rejection is characterized by the presence of alloantigeninduced lesions (transplant arteriopathy and transplant glomerulopathy), and chronic transplant nephropathy by nonspecific sclerosing changes. The incidence of transplant arteriopathy and transplant glomerulopathy is relatively low. Electron microscopy (EM) may overcome the limitations in the histologic diagnosis of chronic rejection, because it verifies alloantigen-induced chronic microvasculopathy in the peritubular capillaries (transplant capillaropathy), and identifies transplant glomerulopathy more precisely than does light microscopy. To assess the value of EM in chronic rejection diagnosis, a retrospective search for transplant capillaropathy and transplant glomerulopathy was performed in a consecutive series of 91 biopsies performed >6 months after implantation (median: 26 months, range 6 -186) and the diagnoses were reclassified on the basis of the ultrastructural findings. The definitions used were: transplant capillaropathy: a peritubular capillary profile with seven or more circumferential basement membrane layers, or at least three profiles with five or six circumferential layers; ultrastructurally verified transplant glomerulopathy: thickening of the capillary wall in at least three loops in consequence of the widening of the subendothelial space by abnormal basement membrane material, and the formation of a new layer(s) of basal lamina; and chronic rejection: the presence of transplant capillaropathy and/or transplant glomerulopathy and/or transplant arteriopathy. Histologically, chronic transplant nephropathy, chronic rejection, chronic cyclosporine nephrotoxicity, glomerulonephritis, acute rejection, "suspicious" for acute rejection, and "others" were diagnosed in 37%, 34%, 21%, 19%, 57%, 30%, and 5% of the specimens, respectively. The results of EM increased the diagnosis of chronic rejection to 69% of the cases, and decreased chronic transplant nephropathy to 15%. The individual incidence of transplant capillaropathy and transplant glomerulopathy was 79% and 57%, respectively, and their cumulative incidence was 92%. Five biopsies exhibited merely transplant arteriopathy. A late dysfunction typically had more than one cause; the most frequent combination was chronic rejection and acute rejection. In conclusion, the EM search for transplant capillaropathy and transplant glomerulopathy doubled the frequency of the diagnosis of chronic rejection. Currently, the evaluation of renal allograft biopsies from recipients with a late dysfunction relies on standard light microscopy. Because light microscopy per se proved to be insensitive in the diagnosis of chronic rejection, incorporation of EM into the evaluation of late dysfunction biopsies is strongly recommended. The long-term survival of renal allografts is ...

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mentioning

confidence: 80%

Section: Transplant Capillaropathymentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Transplant Capillaropathymentioning

confidence: 99%

Section: Transplant Capillaropathymentioning

confidence: 99%

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The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

et al. 2001

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Renal Transplantation

Bonsib¹

2013

Atlas of Medical Renal Pathology

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Humoral rejection of human organ transplants

Michaels

Fishbein

Colvin

2003

Springer Seminars in Immunopathology

139

117

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Although T-cell mediated rejection has remained the most common form of acute rejection, humoral rejection now accounts for a substantial fraction in patients with kidney or heart allografts, and probably causes the majority of acute graft losses. The frequency, variously estimated at 20-30%, is attributed to improved methods of detection, including staining for C4d in tissues, which is more sensitive and specific than histological features. Detection of circulating anti-donor reactive antibody (usually to donor HLA antigens) confirms the diagnosis. The clinico-pathological entity of acute humoral rejection is well accepted in kidney and increasingly in heart transplantation. Recent evidence points to a new category of chronic humoral rejection, which accounts for about 60% of chronic rejection of kidneys. Importantly, the hallmark of humoral rejection, C4d, can be detected in the grafts before development of histological evidence of chronic rejection. Humoral rejection is generally not responsive to the usual anti-T cell immunosuppressive agents, but small, non-controlled trials suggest humoral rejection can be reversed with plasmapheresis, intravenous immunoglobulin, anti-CD20 and other treatments, all of which deserve formal clinical evaluation. Prophylaxis for chronic rejection is expected to require donor-specific serological monitoring and protocol biopsies.

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Peritubular capillaries in chronic renal allograft rejection: A quantitative ultrastructural study

Cited by 80 publications

References 0 publications

The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

The Value of Electron Microscopy in the Diagnosis of Chronic Renal Allograft Rejection

Renal Transplantation

Humoral rejection of human organ transplants

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