Non-Myeloablative Conditioning with Low-Dose Total Body Irradiation in Place of Cyclophosphamide Induces Mixed Chimerism and Long-Term Immunosuppression Free Allograft Survival without Acute Kidney Injury in HLA Mismatched Kidney Transplantation

2018 ◽  
Vol 102 ◽  
pp. S395
Author(s):  
Tatsuo Kawai ◽  
Thomas Spitzer ◽  
Nina Tolkoff-Rubin ◽  
Megan Sykes ◽  
Robert B Colvin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Kidney Injury ◽  
Mixed Chimerism ◽  
Allograft Survival ◽  
Myeloablative Conditioning ◽  
Total Body

scholarly journals Safety and effectiveness of kidney transplantation using a donation after brain death donor with acute kidney injury: a retrospective cohort study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyeong Deok Kim ◽  
Kyo Won Lee ◽  
Sang Jin Kim ◽  
Okjoo Lee ◽  
Manuel Lim ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Brain Death ◽  
Graft Survival ◽  
Low Dose ◽  
Kidney Injury ◽  
Induction Agent ◽  
Donor Pool ◽  
Donation After Brain Death

AbstractThe use of kidneys from donation after brain death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

scholarly journals Safety and Effectiveness of Kidney Transplantation Using a Donation-After-Brain-Death Donor With Acute Kidney Injury: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Kyeong Deok Kim ◽  
Kyo Won Lee ◽  
Sang Jin Kim ◽  
Okjoo Lee ◽  
Manuel Lim ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Brain Death ◽  
Graft Survival ◽  
Low Dose ◽  
Kidney Injury ◽  
Induction Agent ◽  
Donor Pool ◽  
Donation After Brain Death

Abstract The use of kidneys from donation-after-brain-death (DBD) donors with acute kidney injury (AKI) is a strategy to expand the donor pool. The aim of this study was to evaluate how kidney transplantation (KT) from a donor with AKI affects long-term graft survival in various situations. All patients who underwent KT from DBD donors between June 2003 and April 2016 were retrospectively reviewed. The KDIGO (Kidney Disease: Improving Global Outcomes) criteria were used to classify donor AKI. The cohort included 376 donors (no AKI group, n = 117 [31.1%]; AKI group n = 259 [68.9%]). Death-censored graft survival was similar according to the presence of AKI, AKI severity, and the AKI trend (p = 0.929, p = 0.077, and p = 0.658, respectively). Patients whose donors had AKI who received using low dose (1.5 mg/kg for three days) rabbit anti-thymocyte globulin (r-ATG) as the induction agent had significantly superior death-censored graft survival compared with patients in that group who received basiliximab (p = 0.039). AKI in DBD donors did not affect long-term death-censored graft survival. Low-dose r-ATG may be considered as an induction immunosuppression in recipients receiving kidneys with AKI because it showed better graft survival than basiliximab.

The patient with sarcoidosis

2015 ◽  
Author(s):  
Ravindra Rajakariar ◽  
Muhammad M. Yaqoob
Keyword(s):  
Acute Kidney Injury ◽  
Renal Impairment ◽  
Renal Disease ◽  
Low Dose ◽  
Clinical Presentation ◽  
Tubulointerstitial Nephritis ◽  
Renal Involvement ◽  
Kidney Injury ◽  
Chronic Renal Impairment

Renal involvement in sarcoidosis is common and often under-recognized. The most frequent manifestation is acute kidney injury secondary to hypercalcaemia and granulomatous tubulointerstitial nephritis. The latter can lead to both acute kidney injury and to slowly progressive chronic renal impairment with concomitant chronic damage seen on histology. This chapter describes the types of renal disease that may occur in sarcoidosis and the pathogenesis, clinical presentation, diagnosis, and treatment of the patient with sarcoidosis. Corticosteroid therapy is the cornerstone of therapy. In patients with granulomatous tubulointerstitial nephritis, the authors recommend long-term, low-dose maintenance steroids.

EXCELLENT LONG-TERM OUTCOMES OF KIDNEY TRANSPLANTATION USING KIDNEYS FROM DECEASED DONORS WITH ACUTE KIDNEY INJURY

2010 ◽  
Vol 90 ◽  
pp. 195
Author(s):  
N. Techawathanawanna ◽  
R. Kunprakan ◽  
P. Lertsithichai ◽  
K. Pipatpannawong ◽  
N. Naitook ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Kidney Injury ◽  
Long Term Outcomes ◽  
Deceased Donors

Durable engraftment of major histocompatibility complex–incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide

Blood ◽  
2001 ◽  
Vol 98 (12) ◽  
pp. 3456-3464 ◽  
Author(s):  
Leo Luznik ◽  
Sanju Jalla ◽  
Laura W. Engstrom ◽  
Robert Iannone ◽  
Ephraim J. Fuchs
Keyword(s):  
Stem Cells ◽  
Major Histocompatibility Complex ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Cytotoxic T Cell ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Total Body ◽  
Marrow Cells

Abstract Treatment of leukemia by myeloablative conditioning and transplantation of major histocompatibility complex (MHC)–mismatched stem cells is generally avoided because of the high risk of graft rejection or lethal graft-versus-host disease (GVHD). This study shows that MHC-incompatible cells can engraft stably after nonmyeloablative conditioning with immunosuppressive chemotherapy and low-dose total body irradiation (TBI). Long-term mixed hematopoietic chimerism, clonal deletion of donor-reactive T cells, and bidirectional cytotoxic T-cell tolerance were achieved by transplanting MHC-mismatched marrow cells into recipients conditioned with pretransplantation fludarabine or cyclophosphamide (Cy), 50 to 200 cGy TBI on day −1, and Cy 200 mg/kg intraperitoneally on day 3. In this model, long-term donor chimerism was proportional to the dose of TBI or donor marrow cells. Pretransplantation fludarabine and posttransplantation Cy were both required for alloengraftment, but the drugs had additional effects. For example, fludarabine sensitized host stem cells to the toxicity of TBI, because animals conditioned with both agents had higher chimerism than animals conditioned with TBI alone (P < .05). Also, posttransplantation Cy attenuated lethal and nonlethal GVH reactions, because F1 recipients of host-reactive, parental spleen cells survived longer (P < .05) and had lower donor cell chimerism (P < .01) if they received posttransplantation Cy than if they did not. Finally, delayed infusions of donor lymphocytes into mixed chimeras prolonged survival after leukemia challenge (P < .0001) without causing lethal GVHD. These results indicate that stable engraftment of MHC-incompatible cells can be induced after fludarabine-based, nonmyeloablative conditioning and that it serves as a platform for adoptive immunotherapy with donor lymphocyte infusions.

Low-dose total body irradiation causes clonal fluctuation of primate hematopoietic stem and progenitor cells

Blood ◽  
2005 ◽  
Vol 105 (3) ◽  
pp. 1010-1015 ◽  
Author(s):  
Mikko O. Laukkanen ◽  
Ken Kuramoto ◽  
Boris Calmels ◽  
Masaaki Takatoku ◽  
Christof von Kalle ◽  
...  
Keyword(s):  
Rhesus Macaque ◽  
Progenitor Cells ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Cytotoxic Agents ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Dose Irradiation ◽  
Total Body

Abstract Due to high frequency of side effects caused by high-dose total body irradiation (TBI) the nonmyeloablative regimen together with cytotoxic agents is currently used especially for elderly patients. However, immediate and long-term effects of low-dose irradiation used in allogeneic transplantation on stem cells is less well known. We have studied the effect of low-dose 3 Gy TBI on the number of hematopoietic stem cell (HSC) clones contributing simultaneously to granulocyte production in rhesus macaque. The number of clones after 3 Gy TBI decreased markedly by 2 to 3 weeks after 3 Gy TBI, followed by a period of clonal instability, and recovery to almost pre–3 Gy TBI clonal diversity. The clones accounting for this recovery contributed before 3 Gy TBI, suggesting the profound initial impact of TBI was on a pool of progenitor cells, whereas most of the more primitive HSCs remained unaffected and were able to again contribute to hematopoiesis after recovery. Clonal fluctuation may indirectly suggest the presence of short-term/long-term HSC populations in rhesus macaque bone marrow as reported in a mouse model. The results indicate that even low-dose irradiation affects hematopoietic clonal dynamics and have implications for design of conditioning regimens for transplantation purposes.

scholarly journals Histopathology and Long-Term Outcome of Kidneys Transplanted From Donors With Severe Acute Kidney Injury

2018 ◽  
Vol 29 (1) ◽  
pp. 36-42 ◽  
Author(s):  
Luca Cima ◽  
Francesco Nacchia ◽  
Claudio Ghimenton ◽  
Giovanni Valotto ◽  
Luigino Boschiero ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Transplantation ◽  
Acute Tubular Necrosis ◽  
Statistical Significance ◽  
Graft Function ◽  
Kidney Injury ◽  
Long Term Outcome ◽  
Tubular Necrosis ◽  
Level 3

Background: Acute kidney injury is a treatable entity although difficult to recognize without diagnostic biopsy. We investigated the potential association between clinically defined deceased donors and acute kidney injury with preimplantation histological findings and recipient outcomes. Methods: Kidney biopsies from donors were classified using the Acute Kidney Injury Network criteria and assessed for percentage glomerulosclerosis, tubular atrophy, interstitial fibrosis, and vascular narrowing with the Remuzzi score and for acute tubular necrosis. Differences in incidence rates of delayed graft function (DGF) and cumulative rejection episodes were compared between recipients transplanted with normal and 3 levels of acute kidney injury using the analysis of variance with Bonferroni correction ( P = .0012). Results: Sixteen out of 335 donors showed a severe acute kidney injury level 3 with a median serum creatinine of 458 µmol/L. Fourteen (88%) had 0-3 Remuzzi score and were used for single kidney transplantation and 2 (12%) were used for dual kidney transplantation (score: 4-6). Recipients who received a kidney from a donor with level 3 acute kidney injury had a higher percentage of DGF (47%) without statistical significance ( P = .008). The rate of cumulative rejection (45%) at 2 years was not significantly increased ( P = .09). Conclusions: Recipients receiving level 3 acute kidney injury kidneys, selected with Remuzzi histopathological score and acute tubular necrosis assessment, had a greater incidence of DGF but a similar long-term cumulative rejection compared to no injury and level 1 and level 2 acute kidney injury donors. The application of the histopathological examination allowed expansion of the kidney donor pool.

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