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1.
Transplant Proc ; 55(7): 1561-1567, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37393170

ABSTRACT

BACKGROUND: This study examines outcomes of deceased donor kidney transplantation (DDKT) in recipients of kidney allografts with marginal perfusion parameters. METHODS: Allografts with marginal perfusion parameters (resistance index [RI] >0.4 and pump flow rate [F] <70 mL/min; MP group) were compared with those with good parameters (RI <0.4 and F >70 mL/min; GP group) for DDKT recipients between January 1996 and November 2017 after hypothermic pulsatile perfusion. Demographics, creatinine, cold ischemia times (CIT), delayed graft function (DGF), and recipient glomerular filtration rate at pre- and post-transplant were noted. The primary outcome was graft survival post-transplant. RESULTS: In the MP (n = 31) versus GP (n = 1281) group, the median recipient was aged 57 years versus 51 years; the median donor was aged 47 versus 37 years; terminal creatinine was 0.9 versus 0.9 mg/dL; CIT was 10.2 versus 13 hours, and the RI and flow were 0.46 and 60 mL/min versus 0.21 and 120 mL/min. The DGF rate was 19% (MP) versus 8% (GP). The graft survival in the MP versus GP group was 81% versus 90% (1 year), 65% versus 79% (3 years), 65% versus 73% (4 years), and 45% versus 68% (5 years). CONCLUSION: Carefully selected kidney allografts after comprehensive donor and recipient evaluation may allow for the use of these routinely discarded kidneys with marginal perfusion parameters.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Creatinine , Kidney , Tissue Donors , Graft Survival , Perfusion/adverse effects , Allografts , Delayed Graft Function/etiology
2.
Clin Transplant ; 37(9): e15007, 2023 09.
Article in English | MEDLINE | ID: mdl-37170811

ABSTRACT

INTRODUCTION: Thrombotic microangiopathy (TMA) on kidney biopsy shows a variable combination of features: arterial mucoid intimal thickening, acellular closure of glomerular capillary loops, fragmented red blood cells, fibrin thrombi, and arterial fibrinoid necrosis. However, some early post-transplant kidney biopsies show only arterial mucoid intimal thickening. We aimed to elucidate the importance of this finding. METHODS: We identified 19 biopsies showing isolated arterial mucoid intimal thickening and compared them with 22 bona fide TMA biopsies identified based on the pathological findings (excluding rejection) (2011-2020). Additionally, delayed graft function (DGF) (n = 237), and no DGF (control, n = 1314) groups were included for survival analysis. RESULTS: Seven of 19 cases with isolated arterial mucoid intimal thickening showed peripheral blood schistocytes but no other systemic features of TMA. Eight patients underwent adjustments in maintenance immunosuppression (mainly calcineurin inhibitors). None of the cases progressed to full-blown TMA on consecutive biopsies. The overall and death-censored graft survival rates in this group were comparable to the DGF group, but significantly better than the TMA group (P = .005 and .04, respectively). CONCLUSIONS: Isolated arterial mucoid intimal thickening in early post-transplant biopsies may be an early/mild form of TMA, probably requiring adjustment in immunosuppressive regimen. Careful exclusion of known causes of TMA, and donor-derived arterial injury are important.


Subject(s)
Kidney Transplantation , Thrombotic Microangiopathies , Humans , Kidney Transplantation/adverse effects , Transplantation, Homologous , Thrombotic Microangiopathies/etiology , Kidney Glomerulus/pathology , Graft Survival , Allografts/pathology , Biopsy , Kidney/pathology , Graft Rejection/diagnosis , Graft Rejection/etiology , Graft Rejection/pathology
3.
Case Rep Transplant ; 2022: 5274521, 2022.
Article in English | MEDLINE | ID: mdl-35937758

ABSTRACT

Background: Core needle and wedge biopsies are the two main pathologic ways to determine the suitability of a kidney allograft and to have a baseline allograft biopsy in case of future rejection. Case Presentation. A 57-year-old patient developed a renal arteriovenous fistula causing postoperative and recurrent hematuria after allograft pretransplant renal core needle biopsy and treated with selective Interventional radiology coil embolization. Conclusion: Delayed profound hematuria can be seen after pretransplant core needle renal biopsies and can recur again even after complete resolution, due to arteriovenous fistula formation in the renal calyceal system.

4.
Case Rep Transplant ; 2022: 3823066, 2022.
Article in English | MEDLINE | ID: mdl-35813933

ABSTRACT

Background: Patients with more than two prior kidney transplant procedures pose unique surgical challenges. Once both the right and left retroperitoneal spaces have been dissected, intra-abdominal implantation is usually necessary. If the external iliac arteries have been used previously, it is sometimes necessary to use the aorta and vena cava for implantation. Gaining safe exposure in these cases can be complicated by history of prior laparotomy, adhesive disease, and other surgical histories. Case Presentation. A 58-year-old female with type 1 diabetes and end-stage renal disease presented for surgical evaluation for kidney transplant. Surgical history was notable for prior simultaneous kidney-pancreas transplant followed by both a living donor kidney transplant and a pancreas after kidney transplant. She had undergone both an allograft nephrectomy and an allograft pancreatectomy and currently had a nonfunctioning kidney in the left retroperitoneal position and a nonfunctioning pancreatic allograft on the right common iliac artery. The entire distal aortoiliac system was surgically inaccessible. She was listed for transplantation, and a cadaveric graft was allocated. Intraoperatively, severe lower abdominal and pelvic adhesions prevented any use of the iliac system. A left native nephrectomy was performed, and the allograft was implanted in the left orthotopic position. The native left renal vein was used for outflow, the donor renal artery was joined end-to-side to the infrarenal aorta, and a uretero-ureterostomy was created. The operation was uneventful. The allograft functioned without delay, and almost one year later, the GFR is approximately 50 mg/dL. Conclusion: The left orthotopic position can be a good choice for kidney transplant candidates with histories of prior complex lower abdominal surgery.

5.
Case Rep Transplant ; 2022: 2058600, 2022.
Article in English | MEDLINE | ID: mdl-35637902

ABSTRACT

Complications are a part of surgery. Spinal infarctions are a dreaded complication of aortic surgery. We present a patient who developed a spinal infarct after a kidney transplant. We were unable to find a causative factor in our search for etiology. In our review of the literature, we were unable to find a similar report. We present this case report to highlight a rare complication of kidney transplantation and to reinforce that patients requiring kidney transplant are complex patients with multiple comorbidities that can cause a multitude of complications in the periop period.

6.
Am J Surg ; 223(4): 804-811, 2022 04.
Article in English | MEDLINE | ID: mdl-34253338

ABSTRACT

BACKGROUND: Hypothermic machine perfusion (HMP) parameters are influenced by donor variables which further affect recipient outcome. Interplay between these parameters can help to predict kidney performance on pump and the long term outcome. METHODS: All the kidneys transplanted at our center between May 2013 through November 2017 were included in the study. Donor and recipient data was obtained from internal database. Multiple logistic regression models with backward selection were used to determine significant donor and pump variables. RESULTS: Donor BMI, KDPI, age and donor sex had a significant association with pump flow. Donor sex, donor type, KDPI and age had significant effect on RI. Diastolic pressure and KDPI were significantly associated with DGF. Duration on pump, KDPI, flow, donor creatinine and type of donor were significantly associated with day 5 creatinine. KDPI was significantly associated with Day 365 creatinine. CONCLUSION: HMP effects early graft function while the long term function depends on donor parameters.


Subject(s)
Delayed Graft Function , Kidney Transplantation , Allografts , Creatinine , Graft Survival , Humans , Kidney , Organ Preservation , Perfusion , Tissue Donors
7.
Clin Transplant ; 35(1): e14102, 2021 01.
Article in English | MEDLINE | ID: mdl-32985025

ABSTRACT

BACKGROUND: Currently, there is limited literature evaluating rATG induction dosing and incidence of opportunistic viral infections when using steroid-free maintenance immunosuppression. METHODS: This single-center, retrospective, study compared high rATG (>4.5 mg/kg) versus low (<4.5 mg/kg) induction dosing and the overall incidence of early opportunistic viral infection at 180 days in the setting of maintenance immunosuppression consisting of tacrolimus, mycophenolate, rapid steroid withdrawal, and a tiered antiviral prevention strategy based on donor-recipient Cytomegalovirus (CMV) serostatus. RESULTS: A total of 209 patients were included; 76 patients received low-dose and 133 patients received high-dose rATG. Incidence of overall opportunistic viral infection occurred more frequently in patients who received high compared to low dose (29.8% vs 25% p = .030). Incidence of CMV infection was also significantly increased in the high-dose group (31.6% vs 18.4% p = .039). In a multivariable model, rATG dose, as a continuous variable, remained a significant independent predictor of infection along with CMV risk (OR 1.46, 95% CI 1.02-2.09) controlling for age and CMV risk. There were no differences in graft-related outcomes at 180 days. CONCLUSION: Higher cumulative rATG induction dose was associated with increased incidence of opportunistic viral infections, in the setting of a steroid-free maintenance immunosuppression in the early post-transplant period.


Subject(s)
Cytomegalovirus Infections , Graft Rejection , Antilymphocyte Serum , Cytomegalovirus Infections/epidemiology , Graft Rejection/epidemiology , Graft Rejection/etiology , Graft Rejection/prevention & control , Humans , Immunosuppression Therapy , Immunosuppressive Agents/therapeutic use , Incidence , Retrospective Studies , Steroids
8.
Clin Transplant ; 34(12): e14115, 2020 12.
Article in English | MEDLINE | ID: mdl-33048383

ABSTRACT

The use of diabetic kidneys is increasing worldwide with better outcome than being on waitlist and possible reversal of diabetic changes in transplanted kidneys. But particular caution is warranted in diabetic donor-recipient combination. Total 1223 deceased donor kidney transplants were performed at our center between 2008 and 2018. 689 from non-diabetic donor (NDD) to non-diabetic recipient, 400 from non-diabetic donor to diabetic recipient, 97 from diabetic to non-diabetic recipient, and 32 from diabetic donor (DD) to diabetic recipient. The DD was older than NDDs (median age 48 vs 39 years, P < 0.0001). DD had higher BMI (35.6 vs 26.9, P < 0.0001), higher KDPI (74% vs 37%, P < 0.0001), and higher terminal creatinine (1.10 mg/dl vs 0.95 mg/dl, p 0.0046) than the NDD. Diabetes recipients were comparatively older (57 vs 54, P < 0.001). DD recipients had higher serum creatinine at 6 months (1.70 vs 1.50 mg/dl, p 0.00304) and 2 years post-transplant (1.70 vs 1.50 mg/dl P < 0.0002). DD recipients had more favorable end CPRA than NDD recipients (77.5% at 0% vs 67.4% at 0, P = 0.0074). Ten-year patient and graft survival was best in NDD-recipient pair and worse in DD-recipient pair. Diabetic donor kidneys to diabetic recipients have lower 1-, 3-, and 5-year graft survival.


Subject(s)
Diabetes Mellitus , Kidney Transplantation , Graft Survival , Humans , Kidney , Middle Aged , Tissue Donors
9.
Am J Transplant ; 20(10): 2675-2685, 2020 10.
Article in English | MEDLINE | ID: mdl-32243663

ABSTRACT

Active antibody-mediated rejection (AMR) is a potentially devastating complication and consistently effective treatment remains elusive. We hypothesized that the reversal of acute AMR requires rapid elimination of antibody-secreting plasma cells (PC) with a proteasome inhibitor, bortezomib, followed by the sustained inhibition of PC generation with CTLA4-Ig or belatacept (B/B). We show in mice that B/B therapy selectively depleted mature PC producing donor-specific antibodies (DSA) and reduced DSA, when administered after primary and secondary DSA responses had been established. A pilot investigation was initiated to treat six consecutive patients with active AMR with B/B. Compassionate use of this regimen was initiated for the first patient who developed early, severe acute AMR that did not respond to steroids, plasmapheresis, and intravenous immunoglobulin after his third kidney transplant. B/B treatment resulted in a rapid reversal of AMR, leading us to treat five additional patients who also resolved their acute AMR episode and had sustained disappearance of circulating DSA for ≤30 months. This study provides a proof-of-principle demonstration that mouse models can identify mechanistically rational therapies for the clinic. Follow-up investigations with a more stringent clinical design are warranted to test whether B/B improves on the standard of care for the treatment of acute AMR.


Subject(s)
Kidney Transplantation , Abatacept/therapeutic use , Animals , Antibody Formation , Bortezomib/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Humans , Isoantibodies , Mice
10.
Clin Transplant ; 34(3): e13822, 2020 03.
Article in English | MEDLINE | ID: mdl-32037573

ABSTRACT

BACKGROUND: Hospital readmission (HR) after surgery is considered a quality metric. METHODS: Data on 2371 first-time adult kidney transplant (KT) recipients were collected to analyze the "early" (≤30 days) and "late" (31-365 days) HR patterns after KT at a single center over a 12-year time span (2002-2013). RESULTS: 30-day, 90-day, and 1-year HR were 31%, 41%, and 53%, respectively. Risk factors for HR included age >50, female sex, black race, BMI >30, transplant LOS >5 days, and pre-transplant time on dialysis >765 days. Indications for early (n = 749) and late (n = 508) HR were similar. Early HR (OR: 3.80, P = .007) and black race (OR: 2.38, P = .009) were associated with higher odds of 1-year graft failure while frequency (1-2, 3-4, 5+) of HR (ORs: 4.68, 8.36, 9.44, P < .001) and age > 50 (OR: 2.11, P = .007) were associated with higher odds of 1-year mortality. Transplant LOS > 5 days increased both odds of 1-year graft failure (OR: 3.51, P = .001) and mortality (OR: 2.05, P = .006). One-year graft and recipient survival were 96.7% and 94.8%, respectively. CONCLUSIONS: Hospital readmission was associated with reduced graft and patient survival; however, despite a relatively high and consistent HR rate after KT, overall 1-year graft and patient survival was high.


Subject(s)
Kidney Transplantation , Adult , Female , Graft Survival , Humans , Patient Readmission , Renal Dialysis , Risk Factors , Transplant Recipients
11.
Transplantation ; 104(11): 2424-2434, 2020 11.
Article in English | MEDLINE | ID: mdl-32032292

ABSTRACT

BACKGROUND: We recently reported that a novel CXCR5IFN-γCD8 T-cell subset significantly inhibits posttransplant alloantibody production in a murine transplant model. These findings prompted the current study to investigate the association of human CD8 T cells with the same phenotype with the development of de novo donor-specific antibody (DSA) after kidney transplantation. METHODS: In the current studies, we prospectively and serially analyzed peripheral blood CD8 and CD4 T-cell subsets and monitored for the development of de novo DSA in kidney transplant recipients during the first-year posttransplant. We report results on 95 first-time human kidney transplant recipients with 1-year follow-up. RESULTS: Twenty-three recipients (24.2%) developed de novo DSA within 1-year posttransplant. Recipients who developed DSA had significantly lower quantities of peripheral CXCR5IFN-γCD8 T cells (P = 0.01) and significantly lower ratios of CXCR5IFN-γCD8 T cell to combined CD4 Th1/Th2 cell subsets (IFN-γCD4 and IL-4CD4 cells; P = 0.0001) compared to recipients who remained DSA-negative over the first-year posttransplant. CONCLUSIONS: Our data raise the possibility that human CXCR5IFN-γCD8 T cells are a homolog to murine CXCR5IFN-γCD8 T cells (termed antibody-suppressor CD8 T cells) and that the quantity of CXCR5IFN-γCD8 T cells (or the ratio of CXCR5IFN-γCD8 T cells to Th1/Th2 CD4 T cells) may identify recipients at risk for development of DSA.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , HLA Antigens/immunology , Histocompatibility , Interferon-gamma/blood , Isoantibodies/blood , Kidney Transplantation , Receptors, CXCR5/blood , Adult , Aged , Biomarkers/blood , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Female , Humans , Kidney Transplantation/adverse effects , Male , Middle Aged , Phenotype , Prospective Studies , Time Factors , Treatment Outcome
12.
J Diabetes Res ; 2020: 9282310, 2020.
Article in English | MEDLINE | ID: mdl-33426086

ABSTRACT

Chronic pancreatitis (CP) is a progressive disease that leads to eventual loss of endocrine and exocrine function. Total pancreatectomy and islet autotransplantation (TPIAT) is a treatment option for patients with CP; however, predicting postoperative metabolic outcomes remains elusive. In this single-center retrospective study, we report pre-TPIAT characteristics, beta cell function indices, islet yield, and post-TPIAT glucose management data to further understand their relationship. Islet yield, glucose level, and insulin requirement for 72 hours postoperatively were collected for a total of 13 TPIAT recipients between 9-2013 and 9-2018. In addition, their glucose control and basal insulin requirements at 3, 6, and 12 months post-TPIAT were analyzed. All 13 subjects had normal baseline fasting glucose levels. Median islet yield was 4882 IEq/kg (interquartile range 3412 to 8987). Median postoperative total insulin requirement on day 3 was 0.43 units/kg. Pre-TPIAT baseline glucose, insulin, or c-peptide level did not have a significant correlation with the islet yield. Similarly, there was no correlation between islet yield and insulin requirement at 72-hour postoperatively. However, there was an inverse correlation between the absolute islet yield (IEq) and insulin requirement at 6 months and 12 months following post-TPIAT. Further analysis of the relationship between 72-hour post-op insulin requirement and insulin requirement at discharge, 3, 6, and 12 months showed a positive correlation. Despite the finding of inverse correlation of islet yield with long-term basal insulin requirement, this study was not able to detect a correlation between the preoperative parameters to postoperative short-term or long-term outcome as noted in other studies. The 72-hour postoperative insulin requirement is a helpful postoperative predictor of patients needing long-term insulin management following TPIAT. This observation may identify a high-risk group of patients in need of more intensive diabetes education and insulin treatment prior to hospital discharge.


Subject(s)
Blood Glucose/drug effects , Hypoglycemic Agents/therapeutic use , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/transplantation , Insulin/therapeutic use , Islets of Langerhans Transplantation , Pancreatectomy , Pancreatitis, Chronic/surgery , Adult , Biomarkers/blood , Blood Glucose/metabolism , Female , Humans , Insulin-Secreting Cells/metabolism , Islets of Langerhans Transplantation/adverse effects , Male , Middle Aged , Ohio , Pancreatectomy/adverse effects , Pancreatitis, Chronic/diagnosis , Retrospective Studies , Time Factors , Transplantation, Autologous , Treatment Outcome , Young Adult
13.
Exp Clin Transplant ; 17(2): 274-277, 2019 04.
Article in English | MEDLINE | ID: mdl-28540837

ABSTRACT

Since the inception of pancreas transplant as a treatment for type 1 diabetes mellitus, there has been considerable debate about the best way to manage exocrine secretions and monitor patients for graft rejection. For patients who undergo bladder exocrine drainage of a pancreatic allograft, a bladder-to-enteric drainage conversion can serve as a rescue procedure in case of anastomotic leaks or other complications. However, this procedure is associated with its own complications, including a rarely described enterovesical fistula. Here we report on a 45-year-old man who underwent a simultaneous kidney and pancreas transplant with bladder drainage to the latter. He developed a pancreatic allograft duodenal leak (duodenal-vesical anastomosis) requiring a bladder-to-enteric drainage conversion. The patient returned 2 weeks after discharge with an enterovesical fistula. He was treated nonsurgically with intravenous antibiotics, bowel rest, and parenteral nutrition, and the fistula successfully closed in approximately 2 weeks. Overall, enterovesical fistula formation is a rare but treatable complication that can occur after a bladder-to-enteric drainage conversion of a pancreatic transplant allograft. It can be managed nonsurgically, which is preferable in these immunocompromised patients.


Subject(s)
Anastomotic Leak/surgery , Drainage/adverse effects , Duodenal Diseases/etiology , Intestinal Fistula/etiology , Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Urinary Bladder Fistula/etiology , Anastomotic Leak/diagnostic imaging , Anastomotic Leak/etiology , Duodenal Diseases/diagnostic imaging , Duodenal Diseases/surgery , Humans , Intestinal Fistula/diagnostic imaging , Intestinal Fistula/surgery , Male , Middle Aged , Reoperation , Tomography, X-Ray Computed , Treatment Outcome , Urinary Bladder Fistula/diagnostic imaging , Urinary Bladder Fistula/surgery
14.
Cell Transplant ; 27(10): 1569-1573, 2018 10.
Article in English | MEDLINE | ID: mdl-30203686

ABSTRACT

Hepatic parenchymal disease, including chronic viral hepatitis, has traditionally been considered a relative contraindication to islet transplantation as the islets are infused into the recipient's liver. We present a case study of a patient with treated chronic hepatitis C infection (HCV) who safely received an autologous islet transplant following total pancreatectomy with excellent clinical outcomes. The patient was a 60-year-old woman diagnosed with debilitating abdominal pain secondary to chronic pancreatitis and with preserved islet function. She had previously been treated >10 years prior to surgical evaluation with interferon monotherapy for 1 year that led to sustained virologic response, including at the time of surgical evaluation for total pancreatectomy and islet autotransplantation (TPIAT). She underwent comprehensive preoperative evaluation of the liver, including liver biopsy, which showed no significant portal inflammation or fibrosis. Following a multidisciplinary meeting and discussion of the potential risks for the patient, the decision was made to proceed with TPIAT. The patient underwent a standard total pancreatectomy, and an autologous islet dose of 6638 islet equivalents/kg body weight was infused into the liver via the portal vein. Portal vein pressure was monitored throughout the infusion with a transient peak pressure of 27 cm H2O (basal pressure of 14 cm H2O) and final pressure of 23 cm H20 at 10 min post-infusion. Aside from a transient transaminitis, liver enzymes were normal at the time of hospital discharge. At greater than 1 year of follow-up, the patient has improved quality of life, with reduction in narcotic analgesia, remains insulin independent (with normal islet function), and has normal liver function. This case illustrates that islet autotransplant into the liver can be safely performed and suggests that carefully selected patients with liver disease may be eligible for TPIAT.


Subject(s)
Hepatitis C/complications , Islets of Langerhans Transplantation/methods , Pancreatectomy/methods , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/therapy , Antiviral Agents/therapeutic use , Blood Glucose/analysis , Female , Hepacivirus/drug effects , Hepatitis C/blood , Hepatitis C/drug therapy , Humans , Insulin/blood , Interferons/therapeutic use , Middle Aged , Pancreatitis, Chronic/blood , Transplantation, Autologous/methods
15.
Transpl Int ; 31(4): 424-435, 2018 04.
Article in English | MEDLINE | ID: mdl-29265514

ABSTRACT

Development of donor-specific antibodies (DSA) after renal transplantation is known to be associated with worse graft survival, yet determining which specificities in which recipients are the most deleterious remains under investigation. This study evaluated the relationship of the complement binding capacity of post-transplant de novo anti-human leukocyte antigen (HLA) antibodies with subsequent clinical outcome. Stored sera from 265 recipients previously identified as having de novo DSA were retested for DSA and their C3d binding capacity using Luminex-based solid-phase assays. Most recipients had anti-HLA class II-reactive DSA (class I = 12.5%, class II = 68.7%, class I and class II = 18.9%). The recipients that had C3d binding DSA (67.5%) had a significantly higher incidence of antibody-mediated rejection and any rejection. They also had significantly lower kidney survival, with the lowest survival in those that had both anti-HLA class I and class II C3d binding DSA. Concurrent biopsy comparison revealed a 96.2% positive predictive value and 47.4% negative predictive value for C4d peritubular capillary (Ptc) deposition. Anti-HLA class I and class II C3d binding DSA carried a twofold and 1.5-fold increased risk of kidney loss, respectively, in multivariate analysis.


Subject(s)
Complement C3d/metabolism , HLA Antigens/metabolism , Kidney Transplantation , Transplantation Immunology , Adult , Antibody Specificity , Complement C4b/metabolism , Female , Graft Survival , HLA Antigens/analysis , Humans , Immunoglobulin G/metabolism , Male , Middle Aged , Nephritis/immunology , Peptide Fragments/metabolism , Retrospective Studies
16.
Clin Transplant ; 30(8): 940-5, 2016 08.
Article in English | MEDLINE | ID: mdl-27218658

ABSTRACT

BACKGROUND: Deceased donor (DD) kidney quality is determined by calculating the Kidney Donor Profile Index (KDPI). Optimizing high KDPI (≥85%) DD transplant outcome is challenging. This retrospective study was performed to review our high KDPI DD transplant results to identify clinical practices that can improve future outcomes. METHODS: We retrospectively calculated the KDPI for 895 DD kidney recipients transplanted between 1/2002 and 11/2013. Age, race, body mass index (BMI), retransplantation, gender, diabetes (DM), dialysis time, and preexisting coronary artery disease (CAD) (previous myocardial infarction (MI), coronary artery bypass (CABG), or stenting) were determined for all recipients. RESULTS: About 29.7% (266/895) of transplants were from donors with a KDPI ≥85%. By Cox regression older age, diabetes, female gender, and dialysis time >4 years correlated with shorter patient survival time. Diabetics with CAD who received a high KDPI donor kidney had a significantly increased risk of death (HR 4.33 (CI 1.82-10.30), P=.001) compared to low KDPI kidney recipients. The Kaplan-Meier survival curve for diabetic recipients of high KDPI kidneys was significantly worse if they had preexisting CAD (P<.001 by log-rank test). CONCLUSION: Patient survival using high KDPI donor kidneys may be improved by avoiding diabetic candidates with preexisting CAD.


Subject(s)
Diabetes Mellitus/mortality , Kidney Failure, Chronic/surgery , Kidney Transplantation/mortality , Registries , Tissue Donors , Tissue and Organ Procurement/methods , Transplant Recipients , Adolescent , Adult , Aged , Aged, 80 and over , Donor Selection , Female , Humans , Kidney Failure, Chronic/mortality , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology , Young Adult
17.
Clin Transplant ; 29(12): 1119-27, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26382932

ABSTRACT

BACKGROUND: De novo donor-specific antibodies (dnDSA) post-transplant correlate with a higher risk of immunologic graft injury and loss following kidney and pancreas transplantation. Post-transplant dnDSA can occur within the first post-transplant year. METHODS: In this study, 817 of 1290 kidney and simultaneous kidney/pancreas recipients were tested for dnDSA post-transplant. Recipient immunosuppressive treatment at one, three, six, and 12 months post-transplant was correlated with dnDSA incidence by univariate and multivariate analyses. RESULTS: The overall incidence of dnDSA was 21.3% detected a median of 3.5 yr post-transplant. By univariate analysis, the immunosuppressive treatment at all time points correlated with dnDSA (p < 0.01). Month 6 treatment correlated best in multivariable analysis (p = 0.004). At six months, recipients receiving rapamune/mycophenolic acid (Rapa/MPA) had the highest dnDSA incidence at five yr (25.3%) and last follow-up (30.7%), those treated with cyclosporine/rapamune (CNI/Rapa) had the lowest incidence at five yr (10.8%) and last follow-up (18.6%), and cyclosporine/mycophenolic acid (CNI/MPA) treatment had an intermediate incidence at five yr (16.7%) and last follow-up (20.4%) (p < 0.01). Six-month CNI/MPA and Rapa/MPA treatment significantly correlated with dnDSA (hazard ratios of 2.36 and 1.80, respectively) by Cox proportional hazards regression modeling. CONCLUSION: The risk of post-transplant dnDSA development correlates with early immunosuppressive management.


Subject(s)
Graft Rejection/immunology , Graft Survival/immunology , Immunosuppressive Agents/therapeutic use , Isoantibodies/immunology , Kidney Transplantation/adverse effects , Pancreas Transplantation/adverse effects , Adolescent , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Graft Rejection/blood , Graft Rejection/diagnosis , Humans , Isoantibodies/blood , Male , Middle Aged , Postoperative Complications , Prognosis , Risk Factors , Tissue Donors , Young Adult
18.
J Endocrinol ; 224(3): 235-43, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25525188

ABSTRACT

There is compelling evidence that autoreactive CD8(+)T cells play a central role in precipitating the development of autoimmune diabetes in non-obese diabetic (NOD) mice, but the underlying mechanisms remain unclear. Given that ITGAE (CD103) recognizes an islet-restricted ligand (E-cadherin), we postulated that its expression is required for initiation of disease. We herein use a mouse model of autoimmune diabetes (NOD/ShiLt mice) to test this hypothesis. We demonstrate that ITGAE is expressed by a discrete subset of CD8(+)T cells that infiltrate pancreatic islets before the development of diabetes. Moreover, we demonstrate that development of diabetes in Itgae-deficient NOD mice is significantly delayed at early but not late time points, indicating that ITGAE is preferentially involved in early diabetes development. To rule out a potential contribution by closely linked loci to this delay, we treated WT NOD mice beginning at 2 weeks of age through 5 weeks of age with a depleting anti-ITGAE mAb and found a decreased incidence of diabetes following anti-ITGAE mAb treatment compared with mice that received isotype control mAbs or non-depleting mAbs to ITGAE. Moreover, a histological examination of the pancreas of treated mice revealed that NOD mice treated with a depleting mAb were resistant to immune destruction. These results indicate that ITGAE(+) cells play a key role in the development of autoimmune diabetes and are consistent with the hypothesis that ITGAE(+)CD8(+)T effectors initiate the disease process.


Subject(s)
Antigens, CD/physiology , Diabetes Mellitus, Type 1/genetics , Integrin alpha Chains/physiology , Animals , Animals, Newborn , Antibodies, Monoclonal/therapeutic use , CD8-Positive T-Lymphocytes/metabolism , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/therapy , Disease Progression , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Mice, Knockout , Pancreas/immunology , Pancreas/metabolism
19.
Clin Transplant ; 29(3): 204-10, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25529029

ABSTRACT

Hand-assisted laparoscopic donor (HALD) nephrectomy has been performed at our institution since December 1999. Through May 2014, a total of 1500 HALD procedures have been performed. We have evaluated the outcomes of HALD. The HALD procedure consists of a hand-port incision as well as two 12-mm ports. Mean donor age was 40.8 ± 10.8 yr, BMI was 27.9 ± 5.0, there were 541 males, 1271 Caucasians, and the left kidney was removed in 1236 patients. All procedures were successfully completed. Four donors (0.27%) were converted to an open technique due to bleeding. Four donors required blood transfusions. 53 donors (3.5%) were readmitted in the first month post-donation; almost half were due to gastrointestinal complaints. Six donors required reoperation; three for SBO and three for wound dehiscence. 27 patients (1.8%) developed incisional hernias. Seven donors (0.47%) developed bowel obstruction. All donors recovered well with a mean hospital stay after donation of 2.1 ± 0.3 d. All except one kidney were successfully implanted. Twenty-one recipients (1.4%) experienced DGF. Ureter complications occurred in 17 (1.1%) recipients. Early graft loss occurred in 13 patients (0.9%). In conclusion, HALD is a safe procedure for the donor with good recipient outcomes.


Subject(s)
Kidney Transplantation , Laparoscopy/methods , Living Donors , Nephrectomy/methods , Tissue and Organ Harvesting/methods , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Ohio , Outcome Assessment, Health Care , Postoperative Complications , Retrospective Studies , Young Adult
20.
Vet Surg ; 43(6): 631-41, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24909456

ABSTRACT

Pancreatic islet transplantation is a cell-based therapy that provides a potential cure for type 1 diabetes mellitus. After the introduction of an automated method for islet isolation and steroid-free immunosuppressive protocols, reversal of diabetes by islet transplantation is now performed at major human medical centers around the world. Despite extensive use of animal models in islet transplantation research, practical concerns have slowed the introduction of the technique into clinical veterinary practice and only a small number of studies have reported results of transplantation in dogs with spontaneously occurring diabetes mellitus; however, recent advances in islet isolation and encapsulation may make it possible to perform islet transplantation without immunosuppression in companion animals. This review summarizes experimental and clinical studies of pancreatic islet transplantation in dogs, including future directions for cell therapy in animals with naturally occurring disease.


Subject(s)
Diabetes Mellitus, Type 1/veterinary , Dog Diseases/therapy , Islets of Langerhans Transplantation/veterinary , Animals , Diabetes Mellitus, Type 1/therapy , Disease Models, Animal , Dogs , Humans , Immunosuppression Therapy/veterinary
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