P1670GLOMERULAR C4D IN POST-TRANSPLANT IG-A GLOMERULONEPHRITIS IS ASSOCIATED WITH DECREASED ALLOGRAFT SURVIVAL

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Željko Kikić ◽  
Haris Omic ◽  
Georg A Böhmig ◽  
Nicolas Kozakowski ◽  
Michael Eder
Keyword(s):  
Graft Survival ◽  
Cox Regression ◽  
De Novo ◽  
Graft Loss ◽  
Allograft Survival ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
Therapeutic Decisions ◽  
C4d Staining

Abstract Background and Aims Post transplant (pTX) glomerulonephritis (GN) is an important factor contributing to early and late allograft failure. De novo or recurrent IgA GN are the most frequent pTX-GN forms, however little is known about the optimal risk and therapeutic assessment. Recently, immunopathological evidence of glomerular C4d staining has been suggested as a prognostic tool in native glomerular kidney disease, in particular IgA GN. While peritubular capillary C4d is an accepted diagnostic criterion for antibody mediated rejection (ABMR), the role of glomerular C4d in pTX-GN is unkown. The primary hypothesis was that the finding of immunohistochemical glomerular C4d may be associated renal graft survival in post TX IgA GN. Method This large retrospective cohort study included all indication biopsies performed for cause in 885 kidney allografts from 1999-2006. Cases were screened for biopsy verified de novo or recurrent pTX-GN. GN cases were re-assessed by a single nephropathologist (NK). Primary endpoint was death-sensored graft survival followed until 01.01.2017. Results The prevalence of pTX-GN was 9.6% (n=85/885). De novo or recurrent IgA-GN was the most common pTX GN form with 40%. Of the 34 cases with pTX IgA GN, 27 had adequate material for interpretation of immunohistochemical glomerular C4d in the biopsy specimen. Eighteen of the 27 cases (66%) with pTx-IgA GN showed positive immunohistochemical C4d staining along glomerular capillary walls. There was no difference in renal function at biopsy or after one year comparing glomerular C4d positive vs. C4d negative pTX IgA GN. In univariate KM analysis glomerular C4d positive pTX-IgA GN showed significantly worse renal allograft survival rates (28%) compared to glomerular C4d negative pTX IgA GN (50%) or cases without GN (66%), p<0.001, respectively. In a multivariate Cox-Regression analysis including baseline covariates as well C4d+ABMR, Borderline lesion and TCMR, C4d+pTX IgA-GN remained independently associated with death censored graft-loss (HR 2.92, 95% CI 1.51-5.64, p=0.001). Conclusion Glomerular C4d staining in post transplant IgA glomerulonephritis is an independent risk factor for worse allograft survival and may provide a valuable risk assessment tool for prognostic and therapeutic decisions in post transplant glomerulonephritis.

scholarly journals Influence of Persistent Inflammation in Follow-Up Biopsies After Antibody-Mediated Rejection in Kidney Transplantation

2021 ◽  
Vol 8 ◽  
Author(s):  
Gaston J. Piñeiro ◽  
Enrique Montagud-Marrahi ◽  
José Ríos ◽  
Pedro Ventura-Aguiar ◽  
David Cucchiari ◽  
...  
Keyword(s):  
Graft Survival ◽  
Cox Regression ◽  
Graft Loss ◽  
Graft Function ◽  
Kidney Graft ◽  
Cox Regression Analysis ◽  
Antibody Mediated Rejection ◽  
Persistent Inflammation ◽  
Increased Risk

Background: Despite recent advances in immunosuppression treatment, antibody-mediated rejection (ABMR) remains the leading cause of kidney graft loss. Information about prognostic markers and the efficacy of treatment is scarce.Methods: Retrospective study with kidney recipients diagnosed an active ABMR from January 1, 2004 to December 31, 2019 to explore the influence of persistent inflammation in follow-up biopsies on graft survival after ABMR treatment.Results: About 116 patients were included. Active ABMR were treated with a combination of plasma exchange (PE), intravenous immunoglobulin (IVIg), rituximab, and steroids. At 6 months of treatment, 63 (54.3%) patients presented a stabilization or improvement in kidney-graft function. The effectiveness varied depending on the timepoint of the presentation between transplantation and rejection, which is lower for those with late ABMR (63 vs. 21% for early vs. late ABMR, respectively). Ninety patients (77%) underwent a control biopsy after ABMR treatment, from which 46 (51%) responded to the treatment. Microvascular inflammation (MVI) persisted in 64 (71%) biopsies, whereas tubulitis persisted in 17 (19%) biopsies. Death-censored graft survival at 1 year was significantly lower in patients with persistent MVI (86% vs. 95% without persistent MVI, P = 0.002), or with persistent tubulitis (44% vs. 66% without tubulitis, P = 0.02). In the Cox Regression analysis, the persistence of MVI [hazard ratio (HR), 4.50 (95%CI, 1.35–14.96), P = 0.01] and tubulitis [HR 2.88 95%CI (1.24–6.69), P = 0.01) in follow-up biopsies significantly increased the risk of graft failure.Conclusion: Persistent inflammation in follow-up biopsies after ABMR treatment was associated with an increased risk of graft loss, even without meeting Banff rejection criteria.Study Registration: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS): 14566/RG 24161. Study code: UTRINM-2017-01.

scholarly journals P1654INCIDENCE AND RISK FACTORS OF THROMBOTIC MICROANGIOPATHY AFTER KIDNEY TRANSPLANTATION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Kenta Futamura ◽  
Goto Norihiko ◽  
Hiroki Fukuhara ◽  
Takaaki Nawano ◽  
Akiko Kanda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Transplantation ◽  
Graft Survival ◽  
Thrombotic Microangiopathy ◽  
De Novo ◽  
Pathological Findings ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
Abo Incompatibility ◽  
Biopsy Specimens

Abstract Background and Aims Thrombotic microangiopathy (TMA) is characterized by mechanical hemolytic anemia, thrombocytopenia, and renal impairment. TMA that occurs in kidney transplant recipients has multiple etiologies and may be de novo or recurrent. Main causes of TMA among recipients are atypical hemolytic uremic syndrome (aHUS), immunosuppressive drugs, ischemia-reperfusion injury (IRI), viral infections, and antibody-mediated rejection (ABMR). Pathological findings of TMA with thrombosis in glomeruli and arterioles are not rare in graft biopsies, but the clinical signs vary widely by etiologies, and incidence and risk factors for each are uncertain. The purpose of this study is to clarify the current status of TMA after kidney transplantation. Method The subjects were 1,336 patients (5,425 biopsy specimens) who underwent kidney transplantation (851 ABO-compatible and 485 ABO-incompatible) at Japanese Red Cross Nagoya Daini Hospital and Masuko Memorial Hospital from January 1, 2000 to June 30, 2018. We investigated patient characteristics and graft survival in 69 patients with pathological findings of TMA (12 with symptomatic TMA and 57 with asymptomatic TMA) and 1,207 patients without findings of TMA. Sixty patients were excluded because of incomplete data or biopsy specimens. TMA patients with acute kidney injury (AKI) were defined as symptomatic TMA in this study. Results The incidence of post-transplant TMA was 5.2% (symptomatic TMA : 0.9%, asymptomatic TMA : 4.3%) in our cohort. Multivariate analysis revealed significant risk factors for TMA were presence of donor specific antibodies (DSA) and use of cyclosporine (odds ratio [OR] 3.52; 95% confidence interval [CI] 1.58-7.88; p=0.002 and OR 3.70; 95% CI 1.68-8.11; p=0.001, respectively). Causes of symptomatic TMA were ABMR : 66.7% (5 patients with ABO-incompatibility, 3 with preformed DSA), aHUS : 16.7%, cytomegalovirus and adenovirus infection : 8.3%, and causes of asymptomatic TMA were drug-induced: 40.4% (21 patients with calcineurin inhibitor, 2 with everolimus), ABMR: 31.6% (10 with ABO-incompatibility, 8 with de novo DSA), IRI : 14.0 %. Onset of post-transplant TMA was significantly associated with lower graft survival (Figure A), with a stronger correlation in symptomatic TMA than in asymptomatic TMA (Figure B and C). Conclusion TMA with AKI that occurred after kidney transplantation had a poor graft prognosis. Therefore, avoiding transplantation, changing donors or using tacrolimus instead of cyclosporine should be considered for patients with DSA or ABO-incompatibility.

scholarly journals Glomerular C4d in Post-Transplant IgA Nephropathy is associated with decreased allograft survival

2020 ◽  
Author(s):  
Michael Eder ◽  
Nicolas Kozakowski ◽  
Haris Omic ◽  
Christof Aigner ◽  
Johannes Kläger ◽  
...  
Keyword(s):  
Risk Factor ◽  
Graft Survival ◽  
Assessment Tool ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Allograft Survival ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
Risk Patients ◽  
Allograft Loss

Abstract Background Glomerulonephritis (GN), including post-transplant IgAN (post-Tx IgAN) is an important contributor to decreased long-term allograft survival. The immunopathological detection of the complement degradation product C4d in glomeruli (C4dG) has been recently described as a risk factor in native kidney IgAN, however little is known about C4dG deposition in post-Tx IgAN. We hypothesized that glomerular C4d may indicate a more aggressive disease course and worse allograft survival in patients with post-Tx IgAN. Methods In this retrospective study we assessed the presence and clinical relevance of C4dG in patients with post-transplant IgAN. We analyzed 885 renal allograft recipients, including 84 patients with post-transplant GN. All patients were transplanted between January 1999 and April 2006 and underwent at least one biopsy for differnt causes. The primary endpoint was death-censored graft survival, with a median follow-up of 9.6 (IQR 3.8–13.2) years. Results The prevalence of post-Tx GN was 9.5%. Twenty-seven patients with post-Tx IgAN were included. C4dG positive patients (N = 18, 66.7%) had significantly worse allograft survival compared to C4dG negative post-Tx IgAN patients and patients without post-Tx IgAN [C4dG positive: 27.8% vs. 55.6% and 66.0%; log-rank: p = 0.01]. C4dG remained a significant risk factor (HR 2.22, 95% CI 1.27–3.87) for allograft loss even after adjustment for T cell mediated rejection (TCMR) and antibody mediated rejection. Conclusion Glomerular C4d deposition is an independent risk factor for worse graft-survival in patients with post-Tx IgAN, even after adjusting for other risk factors such as antibody mediated rejection.  Assessment of glomerular C4d deposition may provide a valuable prognostic risk assessment tool to identify high risk patients in post-Tx IgAN. Graphic abstract

Thrombotic microangiopathy after kidney transplantation: causes, clinical specifics and outcomes

2020 ◽  
Vol 48 (3) ◽  
pp. 177-186
Author(s):  
E. I. Prokopenko ◽  
E. O. Shcherbakova ◽  
R. O. Kantaria ◽  
V. A. Stepanov
Keyword(s):  
Kidney Transplantation ◽  
Renal Transplant ◽  
Graft Survival ◽  
Thrombotic Microangiopathy ◽  
De Novo ◽  
Renal Transplant Recipients ◽  
Post Transplant ◽  
Antibody Mediated Rejection ◽  
Renal Graft ◽  
Kidney Transplantations

Background: Thrombotic microangiopathy (TMA) is a clinical and morphological phenomenon characterized by specific microvascular injury, microangiopathic hemolytic anemia, and damage of various target organs. TMA after kidney transplantation (post-renal transplant TMA) is a serious complication affecting the recipient and graft survival.Aim: To analyze the timing, causes, specifics of the clinical course and outcomes of TMA in renal transplant recipients.Materials and methods: This one-center study was based on a comprehensive examination and follow-up of 697 patients who had undergone 728 kidney transplantations (KT) from deceased donors in 2003–2019. Post-transplant TMA of the renal graft was confirmed morphologically in all cases.Results: We identified 32 episodes of post-transplant TMA in 32 patients; thus, the incidence of TMA was 4.4%. All cases developed after KT de novo; no recurrent TMA was observed. TMA was systemic in 37.5% and locally renal in 62.5% of the patients. The median time to the development of post-transplant TMA was 0.55 (range, 0.1 to 51.6) months. The patients with TMA did not differ from those without by gender, age, body mass index, underlying disorders, type and duration of dialysis before KT, protocols of immunosuppressive therapy, incidence of surgical, urological, infectious, cardiovascular and oncological complications. The patients with TMA were significantly more likely to have graft rejection (25.0% vs 11.2%, p = 0.035) and a never-functioning transplant (28.1% vs 4.9%, p < 0.001). The presence of TMA negatively affected the transplantation outcomes. The cumulative 1-year graft survival in the patients without and with TMA was 91% and 44%, respectively, whereas their 5-year survival rates were 68% and 25% (p < 0.001). The leading causes of TMA were: donor pathology (31.2%), antibody-mediated rejection (28.1%), and cyclosporine/tacrolimus nephrotoxicity (21.9%); the proportion of other causes was 18.8%. A combination of TMA etiological factors was identified in 68.7% of the recipients. The recipients with of calcineurin inhibitors nephrotoxicity had a more favorable prognosis compared to those with other causes of TMA.Conclusion: Post-renal transplant TMA is an infrequent but serious complication that worsens the graft survival and often is life-threatening for recipients. In most cases, TMA develops in the early post-operative period; however, it can occur any time thereafter. To improve the outcome of TMA, early diagnosis is necessary based on clinical suspicion and a prompt biopsy of the renal graft with suspected TMA. Treatment should be started quickly with consideration of the cause of the complication.

scholarly journals Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2844
Author(s):  
Christopher J. D. Wallis ◽  
Bobby Shayegan ◽  
Scott C. Morgan ◽  
Robert J. Hamilton ◽  
Ilias Cagiannos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Clinical Decision Making ◽  
Cox Regression ◽  
De Novo ◽  
Population Based ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Laboratory Markers

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan–Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71–83). The median survival was 18 months (IQR: 10–31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

scholarly journals Outcomes of Therapy Related Acute Lymphoblastic Leukemia in Adults after Allogeneic Stem Cell Transplantation - Twenty-Year Experience from a Tertiary Care Center

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5717-5717
Author(s):  
RAM V Nampoothiri ◽  
Arjun Law ◽  
Wilson Lam ◽  
Zeyad Al-Shaibani ◽  
David Loach ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cox Regression ◽  
De Novo ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Cox Regression Analysis ◽  
Gvhd Prophylaxis ◽  
One Year ◽  
Prior Malignancy ◽  
Related Mortality

Introduction Therapy related acute leukemias are late complications of treatment with mutagenic agents for both malignant and non-malignant disorders. The prevalence of therapy induced Acute lymphoblastic leukemia(t-ALL) is thought to be much less than that of t-AML/MDS, with our institute reporting a 6.9% prevalence of t-ALL among all patients of adult ALL. There is limited data on role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in t-ALL. Recent reports suggested comparable outcomes with de-novo ALL after allo-HSCT. We aim to report our 20-year experience of allo-HSCT in t-ALL. Patients and Methods We retrospectively reviewed all cases of t-ALL who underwent allo-HSCT at our centre from October 1998 to July 2019. Patients were analysed and compared for demographic features, prior malignancy and its treatment, latent period before ALL, clinical, cytogenetic and molecular characteristics of ALL, induction and consolidation treatment received, transplant details including donor details, conditioning regimens, GVHD prophylaxis as well as post-transplant complications (including transplant related mortality, occurrence and severity of acute and chronic GVHD, CMV and EBV reactivations), relapse rate, relapse free survival (RFS) and overall survival (OS). Predictors of survival were calculated by Cox-Regression Analysis. Results A total of 18 patients underwent allo-HSCT for t-ALL. M:F ratio was 1:1. Median age at allo-HSCT was 44 years (range 20-70 years). Baseline characteristics, prior malignancy and treatment received are summarized in Table 1. Median latent period from prior malignancy to diagnosis of ALL was 44.8 months (range 6-157 months). Complex cytogenetics was present in 16.7% patients (n=3) while 11q23 rearrangement (KMT2A-MLL) and t(9;22) rearrangement was seen in 33.3% (n=6) and 22.2% (n=4) patients respectively. Median time to allo-HSCT from diagnosis of t-ALL was 5 months. Stem cell donors were matched related, matched unrelated and haplo-identical in 27.8% (n=5), 55.6% (n=10), and 16.7% (n=3) patients, respectively. Conditioning regimen was myeloablative in 44.4% (n=8) patients and reduced intensity in 55.6% (n=10) patients. GVHD Prophylaxis used was ATG-CSA-PTCy in 50% (n=9) patients, CSA/MMF in 22.2% (n=4) patients, and other regimens in 27.8% (n=5) patients. Post HSCT CMV and EBV virus reactivation occurred in- 33.3% (n=6) and 47.1% (n=8) patients, respectively. Acute GVHD (any grade) occurred in 70.6% (n = 12) while chronic GVHD (any grade) occurred in 31.3% (n=5) patients. Transplant related mortality (Death before day 100) occurred in 27.8% (n=5) patients. Four (22.2%) patients relapsed. Median RFS was 4 months (Range 0.5-194 months) while median OS was 5.88 months (Range 0.5-194 months) (Figure 1a&b). One patient (5.5%) had relapse of their primary malignancy (CA Breast) 12 years after allo-HSCT. One year RFS and OS for all patients (excluding patients who have not completed one year of followup after HSCT but have not relapsed or died) was 43.8% and 46.7% respectively. None of the basic disease characteristics, treatment characteristics, or transplant or post-transplant parameters including donor type, conditioning received, GVHD prophylaxis used, occurrence of Acute or chronic GVHD etc. were significantly predictive of OS and RFS on Cox-Regression analysis, though the analysis is limited by the small sample size. Conclusions Therapy related ALL is an uncommon but increasingly recognized disease entity. Our outcomes of Allogeneic HSCT in t-ALL were comparable to that in de novo ALL as per previously reported literature. Multicenter studies on t-ALL with more patients and longer follow up duration may provide us with predictive factors of relapse and survival post allogeneic HSCT. Disclosures Michelis: CSL Behring: Other: Financial Support. Mattsson:Celgene: Honoraria; Therakos: Honoraria; Gilead: Honoraria.

scholarly journals Long-Term Results of Kidney Transplantation in the Elderly: Comparison between Different Donor Settings

2021 ◽  
Vol 10 (22) ◽  
pp. 5308
Author(s):  
Renana Yemini ◽  
Ruth Rahamimov ◽  
Ronen Ghinea ◽  
Eytan Mor
Keyword(s):  
Graft Survival ◽  
Cox Regression ◽  
Survival Rates ◽  
The Elderly ◽  
Long Term Results ◽  
Live Donor ◽  
Allocation Policy ◽  
Cox Regression Analysis ◽  
Factors Associated

With scarce organ supply, a selection of suitable elderly candidates for transplant is needed, as well as auditing the long-term outcomes after transplant. We conducted an observational cohort study among our patient cohort >60 years old with a long follow up. (1). Patients and Methods: We used our database to study the results after transplant for 593 patients >60 years old who underwent a transplant between 2000–2017. The outcome was compared between live donor (LD; n = 257) recipients, an old-to-old (OTO, n = 215) group using an extended criteria donor (ECD) kidney, and a young-to-old (YTO, n = 123) group using a standard-criteria donor. The Kaplan−Meir method was used to calculate the patient and graft survival and Cox regression analysis in order to find risk factors associated with death. (2). Results: The 5- and 10-year patient survival was significantly better in the LD group (92.7% and 66.9%) compared with the OTO group (73.3% and 42.8%) and YTO group (70.9% and 40.6%) (p < 0.0001). The 5- and 10-year graft survival rates were 90.3% and 68.5% (LD), 61.7% and 30.9% (OTO), and 64.1% and 39.9%, respectively (YTO group; p < 0.0001 between the LD and the two DD groups). There was no difference in outcome between patients in their 60’s and their 70’s. Factors associated with mortality included: age (HR-1.060), DM (HR-1.773), IHD (HR-1.510), and LD/DD (HR-2.865). (3). Conclusions: Our 17-years of experience seems to justify the rational of an old-to-old allocation policy in the elderly population. Live-donor transplant should be encouraged whenever possible. Each individual decision of elderly candidates for transplant should be based on the patient’s comorbidity and predicted life expectancy.

scholarly journals Post-Transplant Natural Antibodies Associate with Kidney Allograft Injury and Reduced Long-Term Survival

2018 ◽  
Vol 29 (6) ◽  
pp. 1761-1770 ◽  
Author(s):  
Sarah B. See ◽  
Olivier Aubert ◽  
Alexandre Loupy ◽  
Yokarla Veras ◽  
Xavier Lebreton ◽  
...  
Keyword(s):  
Risk Factor ◽  
Confidence Interval ◽  
Graft Loss ◽  
Hazard Ratio ◽  
Natural Antibodies ◽  
Kidney Graft ◽  
Pathogenic Potential ◽  
Term Survival ◽  
Cox Regression Analysis ◽  
Post Transplant

Background The development of antibodies specific to HLA expressed on donor tissue (donor-specific antibodies [DSAs]) is a prominent risk factor for kidney graft loss. Non-HLA antibodies with pathogenic potential have also been described, including natural antibodies (Nabs). These IgG Nabs bind to immunogenic self-determinants, including oxidation-related antigens.Methods To examine the relationship of Nabs with graft outcomes, we assessed Nabs in blinded serum specimens collected from a retrospective cohort of 635 patients who received a transplant between 2005 and 2010 at Necker Hospital in Paris, France. Serum samples were obtained immediately before transplant and at the time of biopsy-proven rejection within the first year or 1 year after transplant. Nabs were detected by ELISA through reactivity to the generic oxidized epitope malondialdehyde.Results Univariate Cox regression analysis identified the development of post-transplant Nabs (defined as 50% increase in reactivity to malondialdehyde) as a significant risk factor for graft loss (hazard ratio, 2.68; 95% confidence interval, 1.49 to 4.82; P=0.001). Post-transplant Nabs also correlated with increased mean Banff scores for histologic signs of graft injury in post-transplant biopsy specimens. Multivariable Cox analyses confirmed Nabs development as a risk factor independent from anti-HLA DSAs (hazard ratio, 2.07; 95% confidence interval, 1.03 to 4.17; P=0.04). Moreover, patients with Nabs and DSAs had a further increased risk of kidney graft loss.Conclusions These findings reveal an association between Nabs, kidney graft injury, and eventual graft failure, suggesting the involvement of Nabs in immune mechanisms of rejection.

Two-Year Outcomes of Orbital Atherectomy Combined With Drug-Coated Balloon Angioplasty for Treatment of Heavily Calcified Femoropopliteal Lesions

2020 ◽  
Vol 27 (3) ◽  
pp. 492-501 ◽  
Author(s):  
Damianos G. Kokkinidis ◽  
Omar Jawaid ◽  
David Cantu ◽  
Brad J. Martinsen ◽  
Zsuzsanna Igyarto ◽  
...  
Keyword(s):  
Cox Regression ◽  
De Novo ◽  
Combined Therapy ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Effective Combination ◽  
Orbital Atherectomy ◽  
Procedural Complications

Purpose: To examine whether the combination of orbital atherectomy (OA) and drug-coated balloons (DCB) can lead to superior procedural and 2-year outcomes compared with DCB only in heavily calcified femoropopliteal (FP) lesions. Materials and Methods: A retrospective chart review was conducted to identify patients treated with DCB only or OA+DCB for de novo FP lesions at a single center over a 4-year period (2014–2017). In the observation period, 113 patients met the inclusion criteria: 63 treated with DCB only (mean age 69.0±8.6 years; 62 men) vs 50 treated with OA+DCB (mean age 70.3±7.1 years; 48 men). The OA+DCB group had higher calcification rates (78% with severe calcification vs 37% in the DCB only group). Propensity score matching (PSM) was used to adjust for baseline differences between the 2 groups. Cox regression analysis was used to compare the follow-up outcomes between lesions treated with OA+DCB vs DCB only. Results: No difference in procedural complications or success was found. After PSM adjustment, the OA+DCB group was associated with lower bailout stenting rates (39.4% vs 66.7% in the DCB only group; p=0.026). The 2 groups had similar long-term outcomes, although the OA+DCB arm had a trend toward reduced TLR rates that did not reach statistical significance. The Kaplan-Meier estimates for 2-year freedom from TLR were 76.1% for the OA+DCB group vs 55.5% for the DCB only group (p=0.109). Conclusion: OA+DCB is a safe and effective combination for the treatment of calcified FP lesions. The combined therapy decreased the bailout stenting rates in the adjusted analysis. Larger cohorts and randomized trials are needed to examine OA efficacy in FP lesions.

scholarly journals P1639DEVELOPMENT OF SELF-LIMITED LOW-LEVEL BK VIREMIA/VIRURIA SUGGESTS IDEAL IMMUNOSUPPRESSION TO SUPPRESS T-CELL AND ANTIBODY-MEDIATED REJECTION AND PRESERVE KIDNEY ALLOGRAFT FUNCTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Bettina Näf ◽  
Thomas Müller ◽  
Rudolf Peter Wuthrich ◽  
Thomas Schachtner
Keyword(s):  
Lower Incidence ◽  
De Novo ◽  
Allograft Survival ◽  
Kidney Allograft ◽  
Low Level ◽  
Antibody Mediated Rejection ◽  
Maintenance Immunosuppression ◽  
Allograft Function ◽  
High Level ◽  
Egfr Slope

Abstract Background and Aims Polyomavirus BK (BKV) viremia has been suggested as a surrogate marker of overimmunosuppression. Due to recent advances in monitoring strategies and pre-emptive therapy, progression to BKV-associated nephropathy (BKVN) has been reduced. Reduction of maintenance immunosuppression during BKVN, however, has been associated with both T-cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), and inferior kidney allograft outcomes. Although the administration of intravenous immunoglobulins (IVIG) failed to treat BKVN, IVIG may have properties to reduce allosensitization. Method We studied 860 kidney transplant recipients (KTRs) predominantly under tacrolimus-based triple-drug maintenance immunosuppression from 2009 to 2018. We identified 130 KTRs (15.1%) with high-level BK viremia &gt;10,000 copies/mL (presumptive BKVN), 180 KTRs (20.9%) with low-level BK viremia &lt;10,000 copies/mL, 85 KTRs (9.9%) with isolated BK viruria, and 465 KTRs (54.1%) with no BK viruria/viremia. Kidney allograft outcomes with respect to TCMR, ABMR, development of de novo donor-specific antibodies (DSA), kidney allograft survival, and estimated glomerular filtration rate (eGFR) slope were analysed. Due to the increased incidence of TCMR and ABMR among KTRs with presumptive BKVN, 48 of 130 KTRs (36.9%) with high-level BK viremia starting from 2015 received IVIG (0.5 g/kg of body weight) on a biweekly basis during BKV replication. Results Very interestingly, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of TCMR compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p&lt;0.05). In addition, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of ABMR compared to KTRs with high-level BK viremia (p&lt;0.05). No differences were observed with respect to the development of de novo DSA (MFI&gt;5000) between KTRs with low-level BK viremia/viruria, KTRs with no BK viremia/viruria, and KTRs with high-level BK viremia (p&gt;0.05). KTRs with low-level BK viremia/viruria showed superior kidney allograft survival and lower eGFR slope compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p&lt;0.05). The administration of IVIG during high-level BK viremia didn’t impact the development of TCMR, ABMR, development of de novo DSA, eGFR slope, and kidney allograft survival (p&lt;0.05). Conclusion Our results show that low-level BK viremia/viruria is associated with suppression of TCMR and ABMR in the early period posttransplantation, and preservation of kidney allograft function in the long-term. The administration of IVIG didn’t prove beneficial to reduce allosensitization among KTRs with high-level BK viremia.

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