Interpreting CD56+ and CD163+ Infiltrates in Early versus Late Renal Transplant Biopsies

2015 ◽  
Vol 41 (4-5) ◽  
pp. 362-369 ◽  
Author(s):  
Sung Shin ◽  
Young Hoon Kim ◽  
Yong Mee Cho ◽  
Yangsoon Park ◽  
Seungbong Han ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Failure ◽  
Interstitial Fibrosis ◽  
Human Kidney ◽  
The Other ◽  
Cell Infiltration ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Other Hand ◽  
Histologic Lesion

Background: CD56+ and CD163+ cell infiltration in human kidney transplant biopsies have not been fully evaluated. Methods: We investigated the association of CD56+ and CD163+ cell infiltration with human kidney transplant biopsies with antibody- or T-cell-mediated rejection (TCMR) and other histologic lesions. One hundred and seventy four clinically indicated transplant biopsies were included in this analysis. Immunohistochemical staining for C4d, CD56 and CD163 was performed. Results: One hundred and seventy four indication biopsies were divided into early (≤1 year posttransplant; n = 49) and late (>1 year posttransplant; n = 125) biopsies. High numbers of CD56+ cells were uncommon in early biopsies except for those with antibody-mediated rejection (AMR) only. On the other hand, high numbers of CD56+ cells were observed in late biopsies diagnosed as TCMR only, AMR only, and TCMR combined with AMR. In early biopsies, both CD56+ and CD163+ infiltrates correlated strongly with interstitial inflammation, tubulitis, and peritubular capillaritis (ptc) scores. The ci and ct scores, however, were correlated only with the number of CD56+ cells. In late biopsies, on the other hand, the number of CD56+ infiltrates was correlated only with ptc, while the number of CD163+ infiltrates was weakly correlated with any histologic lesion. Multivariable analyses showed that chronic active AMR and the number of CD56+ cells/10 HPF were independently associated with death-censored graft failure post-biopsy. The number of CD163+ cells was not correlated with any pathologic lesion and post-biopsy graft failure. CD56+ infiltrates were also associated with interstitial fibrosis and tubular atrophy. Conclusions: Intragraft CD56+ cell infiltrates were significantly associated with AMR and subsequent poor clinical outcomes.

scholarly journals CD56+CD57+ infiltrates as the most predominant subset of intragraft natural killer cells in renal transplant biopsies with antibody-mediated rejection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hey Rim Jung ◽  
Mi Joung Kim ◽  
Yu-Mee Wee ◽  
Jee Yeon Kim ◽  
Monica Young Choi ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Nk Cells ◽  
Natural Killer ◽  
Kidney Transplant ◽  
Graft Failure ◽  
Nk Cell ◽  
Cell Infiltration ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Antibody Mediated Rejection

Abstract Little is known about the characteristics and clinical implications of specific subsets of intragraft natural killer (NK) cells in kidney transplant recipients. We analyzed 39 for-cause renal transplant biopsies performed at our center from May 2015 to July 2017. According to histopathologic reports, 8 patients (20.5%) had no rejection (NR), 11 (28.2%) had T cell-mediated rejections (TCMR) only, and 20 (51.3%) had antibody-mediated rejection (ABMR). NK cells were defined as CD3–CD56+ lymphocytes that are positive for CD57, CD49b, NKG2A, or KIR. The density of NK cells was significantly higher in the ABMR group (2.57 ± 2.58/mm2) than in the NR (0.12 ± 0.22/mm2) or the TCMR (0.25 ± 0.34/mm2) group (P = 0.002). Notably, CD56+CD57+ infiltrates (2.16 ± 1.89) were the most frequently observed compared with CD56+CD49b+ (0.05 ± 0.13), CD56+NKG2A+ (0.21 ± 0.69), and CD56+KIR+ (0.15 ± 0.42) cells in the ABMR group (P < 0.001). Death-censored graft failure was significantly higher in patients with NK cell infiltration than those without (Log-rank test, P = 0.025). In conclusion, CD56+CD57+ infiltrates are a major subset of NK cells in kidney transplant recipients with ABMR and NK cell infiltration is significantly associated with graft failure post-transplant.

scholarly journals IgE-Mediated Immune Response and Antibody-Mediated Rejection

2020 ◽  
Vol 15 (10) ◽  
pp. 1474-1483 ◽  
Author(s):  
Federica Rascio ◽  
Paola Pontrelli ◽  
Giuseppe Stefano Netti ◽  
Elisabetta Manno ◽  
Barbara Infante ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cells ◽  
Kidney Transplant ◽  
Interstitial Fibrosis ◽  
Graft Function ◽  
Specific Marker ◽  
Tubular Atrophy ◽  
Antibody Mediated Rejection ◽  
Ige Mediated ◽  
Study Participants

Background and objectivesActive antibody-mediated rejection is the main cause of kidney transplant loss, sharing with SLE the alloimmune response and the systemic activation of the IFN-α pathway. IgE-mediated immune response plays a key role in the development of SLE nephritis and is associated with IFN-α secretion. The aim of our study was to investigate IgE-mediated immune response in antibody-mediated rejection.Design, setting, participants, & measurementsThis was a cross-sectional study of 56 biopsy-proven antibody-mediated rejection study participants, 80 recipients with normal graft function/histology (control), 16 study participants with interstitial fibrosis/tubular atrophy, and six participants with SLE. We evaluated graft IgE deposition, tryptase (a mast cell marker), and CD203 (a specific marker of activated basophils) by immunofluorescence/confocal microscopy. In addition, we measured serum concentration of human myxovirus resistance protein 1, an IFN-α–induced protein, and anti-HLA IgE.ResultsWe observed a significantly higher IgE deposition in tubules and glomeruli in antibody-mediated rejection (1766±79 pixels) and SLE (1495±43 pixels) compared with interstitial fibrosis/tubular atrophy (582±122 pixels) and control (253±50 pixels). Patients with antibody-mediated rejection, but not control patients and patients with interstitial fibrosis/tubular atrophy, presented circulating anti-HLA IgE antibodies, although with a low mean fluorescence intensity. In addition, immunofluorescence revealed the presence of both mast cells and activated basophils in antibody-mediated rejection but not in control and interstitial fibrosis/tubular atrophy. The concentration of circulating basophils was significantly higher in antibody-mediated rejection compared with control and interstitial fibrosis/tubular atrophy. MxA serum levels were significantly higher in antibody-mediated rejection compared with control and correlated with the extent of IgE deposition.ConclusionsOur data suggest that IgE deposition and the subsequent recruitment of basophils and mast cells within the kidney transplant might play a role in antibody-mediated rejection.

scholarly journals The determinants, biomarkers, and consequences of microvascular injury in kidney transplant recipients

2019 ◽  
Vol 316 (1) ◽  
pp. F9-F19 ◽  
Author(s):  
Alice Doreille ◽  
Mélanie Dieudé ◽  
Heloise Cardinal
Keyword(s):  
Kidney Disease ◽  
Kidney Transplant ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Hla Antibodies ◽  
Microvascular Injury ◽  
Antibody Mediated Rejection ◽  
Peritubular Capillaries

Independent of the initial cause of kidney disease, microvascular injury to the peritubular capillary network appears to play a central role in the development of interstitial fibrosis in both native and transplanted kidney disease. This association is explained by mechanisms such as the upregulation of profibrotic genes and epigenetic changes induced by hypoxia, capillary leakage, endothelial and pericyte transition to interstitial fibroblasts, as well as modifications in the secretome of endothelial cells. Alloimmune injury due to antibody-mediated rejection and ischemia-reperfusion injury are the two main etiologies of microvascular damage in kidney transplant recipients. The presence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies, histological findings, such as diffuse C4d staining in peritubular capillaries, and the extent and severity of peritubular capillaritis, are commonly used clinically to provide both diagnostic and prognostic information. Complement-dependent assays, circulating non-HLA antibodies, or evaluation of the microvasculature with novel imaging techniques are the subject of ongoing studies.

scholarly journals Kidney Structural Features from Living Donors Predict Graft Failure in the Recipient

2020 ◽  
Vol 31 (2) ◽  
pp. 415-423 ◽  
Author(s):  
Naim Issa ◽  
Camden L. Lopez ◽  
Aleksandar Denic ◽  
Sandra J. Taler ◽  
Joseph J. Larson ◽  
...  
Keyword(s):  
Graft Failure ◽  
Clinical Characteristics ◽  
Interstitial Fibrosis ◽  
Kidney Transplant Recipient ◽  
Structural Features ◽  
Living Donors ◽  
Nephron Number ◽  
Tubular Atrophy ◽  
Cross Sectional ◽  
Arteriolar Hyalinosis

BackgroundNephrosclerosis, nephron size, and nephron number vary among kidneys transplanted from living donors. However, whether these structural features predict kidney transplant recipient outcomes is unclear.MethodsOur study used computed tomography (CT) and implantation biopsy to investigate donated kidney features as predictors of death-censored graft failure at three transplant centers participating in the Aging Kidney Anatomy study. We used global glomerulosclerosis, interstitial fibrosis/tubular atrophy, artery luminal stenosis, and arteriolar hyalinosis to measure nephrosclerosis; mean glomerular volume, cortex volume per glomerulus, and mean cross-sectional tubular area to measure nephron size; and calculations from CT cortical volume and glomerular density on biopsy to assess nephron number. We also determined the death-censored risk of graft failure with each structural feature after adjusting for the predictive clinical characteristics of donor and recipient.ResultsThe analysis involved 2293 donor-recipient pairs. Mean recipient follow-up was 6.3 years, during which 287 death-censored graft failures and 424 deaths occurred. Factors that predicted death-censored graft failure independent of both donor and recipient clinical characteristics included interstitial fibrosis/tubular atrophy, larger cortical nephron size (but not nephron number), and smaller medullary volume. In a subset with 12 biopsy section slides, arteriolar hyalinosis also predicted death-censored graft failure.ConclusionsSubclinical nephrosclerosis, larger cortical nephron size, and smaller medullary volume in healthy donors modestly predict death-censored graft failure in the recipient, independent of donor or recipient clinical characteristics. These findings provide insights into a graft’s “intrinsic quality” at the time of donation, and further support the use of intraoperative biopsies to identify kidney grafts that are at higher risk for failure.

scholarly journals The causes and frequency of kidney allograft failure in a low-resource setting: Data from Iraqi Kurdistan

2021 ◽  
Author(s):  
Alaa Abbas Ali ◽  
Safaa E Almukhtar ◽  
Kais H Abd ◽  
Zana Sidiq M Saleem ◽  
Dana A Sharif ◽  
...  
Keyword(s):  
Graft Failure ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
The United States ◽  
Failure Rates ◽  
Antibody Mediated Rejection ◽  
Iraqi Kurdistan ◽  
Resource Setting ◽  
Long Term Treatment ◽  
One Year

Abstract Background In the developing world, transplantation is the most common long-term treatment for patients with end-stage renal disease, but rates and causes of graft failure are uncertain. Methods In 2019, in Iraqi Kurdistan, 301 of 871 renal transplant patients had indicated graft biopsies. Outcomes were followed over the subsequent year of 2020. Results The post-transplantation time ranged from one day to 18 years. All donors were living. Approximately 15% of transplants were preemptive. Pretransplant hemodialysis (HD) was twice weekly and less than one year. The median recipient age was 39 (IQR 28 to 48) years. 5.5% of recipients had previous transplants; 3.7% had pretransplant donor-specific antibodies (DSA). The Kaplan-Meier estimated graft failure rates for all-cause, return to HD, and death with functional graft (DWFG) were 9.1%, 6.3%, and 2.9% at one year and 23.8%, 6.3%, and 7.4% at five years. The median death-censored graft survival was 15 years. The most frequent biopsy diagnoses associated with graft failure were interstitial fibrosis and tubular atrophy (IF/TA) (23.1%), transplant glomerulopathy (13.7%), and acquired active antibody-mediated rejection (11.1%). The significant predictors of graft loss were C4d + biopsies (P < 0.01) and advanced IF/TA (P < 0.001). Conclusions These Iraqi patients had estimated graft failure rates similar to the United States (US) Renal Data System living-donor outcomes reported for the year 2000. The inability to approach recent US graft survivals may owe to inadequate pretransplant dialysis. Nevertheless, prolonged survival made chronic disorders and acquired DSA the leading causes of graft failure and is creating a need for second transplants.

scholarly journals Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function

2021 ◽  
Vol 8 ◽  
Author(s):  
Varvara Kirchner ◽  
Kristen Gillingham ◽  
Oscar Serrano ◽  
Srinath Chinnakotla ◽  
Ty Dunn ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Solid Organ ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Tubular Atrophy

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years.  For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%.  Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%.   DD recipients had lower PS(P<0.01), DCGS(P<0.01).   After 20 years, two major causes of graft loss(GL) were death with function(DwF)(58%, LD; 58%, DD) and interstitial fibrosis and tubular atrophy(IFTA)(22%, LD; 23%, DD).  Two major causes of DwF were cancer(31%, LD; 31%, DD) and cardiovascular disease(CVD)(19%, LD;17%, DD).  Per multivariate analysis(MVA), risk factors for GL after 20 years in pre–calcineurin inhibitor(CNI) era were human leukocyte antigen(HLA) mismatches >3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender.  New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant.  Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%.  To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

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