Pretransplant interferon-γ secretion by CMV-specific CD8+ T cells informs the risk of CMV replication after transplantation.

In this prospective study we analyzed pretransplant interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells to assess its possible utility in determining the risk of CMV replication after solid organ transplantation. A total of 113 lung and kidney transplant patients were enrolled in the study but only 55 were evaluable. All CMV-seronegative recipients were pretransplant "nonreactive" (IFNγ <0.2 IU/mL) (11/11), whereas 30/44 (68.2%) CMV-seropositive (R+) recipients were "reactive" (IFNγ ≥0.2 IU/mL) and 14/44 (31.8%) were "nonreactive". In the R(+) "nonreactive" group, 7/14 (50%) developed posttransplant CMV replication, whereas the virus replicated only in 4/30 (13.3%) of the R(+) "reactive" patients (p = 0.021). According to the best multivariate model, pretransplant "nonreactive" recipients receiving an organ from a CMV-seropositive donor had a 10-fold increased risk of CMV replication compared to pretransplant "reactive" recipients (adjusted OR 10.49, 95% CI 1.88-58.46). This model displayed good discrimination ability (AUC 0.80) and calibration (Hosmer-Lemeshow test, p = 0.92). Negative and positive predictive values were 83.7% and 75%, respectively. The accuracy of the model was 82%. Therefore, assessment of interferon-γ secretion by cytomegalovirus (CMV)-specific CD8+ T cells prior to transplantation is useful in informing the risk of posttransplant CMV replication in solid organ transplant patients.

Human fibrinogen patches application reduces intra-abdominal infectious complications in pancreas transplant with enteric drainage.

PURPOSE: The purpose of the study was to analyze the incidence of intra-abdominal infectious complications after the application of a fibrinogen sealant to the duodenojejunal anastomosis in simultaneous pancreas-kidney transplants (SPK) with enteric drainage. METHODS: Results of 68 SPKs with enteric drainage were prospectively assessed. A fibrinogen and thrombin sheet was applied to the duodenojejunal anastomosis in 34 patients, who were compared to a control group of 34 patients. The incidence and severity of intra-abdominal infectious complications and the 1-year patient and grafts survival were analyzed. RESULTS: Eighteen patients experienced intra-abdominal infectious complications. Grade 1a complications occurred in the study group, whereas surgery was required only in patients from the control group: complications grade 3a (15%) and complications grade 3b (18%) (p = 0.003 vs. study group, respectively). The overall rate of anastomotic leakage (complications grade 2b and 3b) was 10%, all of which occurred in the control group. The length of hospital stay was higher in the control group was 34.6 ± 11.3 days vs. 22.8 ± 11.1 days (p = 0.03). There were no significant differences in 1-year patient and graft survival between groups. CONCLUSIONS: In our study, the application of fibrinogen and thrombin sheets was associated to a decrease in the number and severity of intra-abdominal infectious complications.

Cancer incidence and survival in kidney transplant patients.

Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer. This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC. We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007. Results were contrasted with a cohort of patients from the same center without malignancies. The mean follow-up of patients in our series was 10 years. The mean age at presentation of the malignancy was 61 +/- 5 years. The malignancy and NMSC incidences were 6% and 5%, respectively. Patients with malignancy had a longer posttransplant time and greater recipient and donor age. In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 3.1, P = .004); greater patient age (HR 1.09, P < .001), longer posttransplant time (HR 1.2, P = .004) and tacrolimus treatment (HR 4.4, P = .001). Risk factors associated with developing any malignancy were: patient age (HR 1.06, P < .001), number of grafts (HR 3.2, P = .019), tacrolimus treatment (HR 2.5, P = .035), and time posttransplantation (HR 1.2, P = .011). The mean times to development of an NMSC, solid organ malignancy, on PTLD were 7.5, 6.1, or 3.9 years, respectively. The mean survival time from the diagnosis of any malignancy was 9.6 months (95% confidence interval, 0.12-30) for solid organ malignancies and 1 month (95% confidence interval, 0.24-1.87) for PTLD.

24-Hour Proteinuria Versus Spot Protein-Creatinine Ratio for Kidney Transplant Management in Clinical Practice.

BACKGROUND: 24-hour proteinuria (24h-P) has been the most widespread test for clinical follow-up of proteinuria after kidney transplantation (KT), but urine collection is often not properly collected. Spot protein-creatinine ratio (P/Cr) has become the alternative to 24h-P for proteinuria evaluation in many KT units. However, its reliability, equivalence to 24h-P, and prognostic value regarding allograft outcome remain unknown. Therefore, the aim of this study was to evaluate the correlation and agreement between both methods for assessing proteinuria and to analyze which of them is a better predictor of graft survival. METHODS: We collected proteinuria measurements from KT patients in our center. 24h-P was adjusted for body surface area. Pearson correlation test and the Bland-Altman method were used to analyze correlation and agreement. Survival analysis was performed with the use of the Kaplan-Meier method and multivariate Cox proportional hazard model. RESULTS: A total of 8,549 urine samples were analyzed from 472 patients in whom 24h-P and P/Cr were simultaneously measured. A significant correlation was observed between 24h-P and P/Cr (r = .76; P < .001); however, the agreement between methods showed that P/Cr overestimated proteinuria compared with 24h-P, particularly when the latter was >1 g/24 h. The Cox regression multivariate model showed an increased risk of graft loss associated with proteinuria when assessed by either 24h-P (hazard ratio [HR] 6.53, 95% confidence interval [CI] 2.49-17.1) or P/Cr (HR 3.34, 95% CI 1.04-10.7). CONCLUSIONS: P/Cr is an method interchangeable with 24h-P for detecting proteinuria after KT. When proteinuria increases, the P/Cr overestimates 24h-P, even though it also has a significant and similar prognostic value for predicting graft survival.

Prevalence and Survival of Cancer After Pancreas-Kidney Transplantation.

BACKGROUND: Malignancy is an important cause of mortality in solid organ transplantation. There have been few studies of de novo solid organ malignancy (NSOM) after pancreas-kidney transplantation (PKT). The aim of this study was analyze the prevalence of NSOM and transplant outcomes. METHODS: We studied the development of NSOM after PKT in our center from May 1990 to February 2017. We analyzed demographic characteristics, prevalence of cancer, and survival after cancer diagnosis. We excluded nonmelanoma skin cancer and patients with history of malignancy before transplantation. RESULTS: We included 194 patients who received 206 PKTs (184 simultaneous PKTs and 22 pancreas after kidney transplants) with triple immunosuppressive therapy and basiliximab in more than 95%. The mean age at transplantation was 39 ± 7 years and 74% were male patients. Twelve patients developed malignancies (6.1%). Median time from transplant to NSOM was 6.6 (interquartile range [IQR] 0.2-11.7) years. The malignancies were 2 cecal appendix tumors, 2 hematologic tumors, 2 breast tumors, 1 melanoma, 1 native kidney tumor, 1 brain tumor, 1 bladder tumor, 1 prostate tumor, and 1 leiomyosarcoma. Thirty-five of the 194 patients of the whole cohort died throughout the follow-up, 4 of whom died after NSOM diagnosis (11.4%). Patient and grafts survivals were lower in recipients with tumor compared with recipients without tumor, but the difference was not statistically significant: renal graft survival was 80% vs 90% at 10 years (P = .86); and pancreatic graft survival was 45% vs 70% at 10 years (P = .15), respectively. The mean patient survival time from the diagnosis of cancer was 36.6 (IQR 18-54) months. Patient survival after NSOM diagnosis was 90% at 1 year and 50% at 5 years. CONCLUSION: The prevalence of NSOM in our PKT recipients is low, despite the scarce series of published data for comparison. Also hematologic tumors rate is very low, possibly influenced by age and type of induction.

What Is the Influence of Both Risk Donor and Risk Receiver on Simultaneous Pancreas-Kidney Transplantation?

INTRODUCTION: Some factors affect the pancreas of a marginal donor, and although their influence on graft survival has been determined, there is an increasing consensus to accept marginal organs in a controlled manner to increase the pool of organs. Certain factors related to the recipient have also been proposed as having negative influence on graft prognosis. The objective of this study was to analyze the influence of these factors on the results of our simultaneous pancreas-kidney (SPK) transplantation series. MATERIALS AND METHODS: Retrospective analysis of 126 SPK transplants. Donors and recipients were stratified in an optimal group (<2 expanded donor criteria) and a risk group (≥2 criteria). A pancreatic graft survival analysis was performed using a Kaplan-Meier test and log-rank test. Prognostic variables on graft survival were studied by Cox regression. Postoperative complications (graded by Clavien classification) were compared by χ2 test or Fisher test. RESULTS: Median survival of pancreas was 66 months, with no significant difference between groups (P > .05). Multivariate analysis showed risk factors to be donor age, cold ischemia time, donor body mass index, receipt body mass index, and receipt panel-reactive antibody. CONCLUSIONS: In our series, the use of pancreatic grafts from donors with expanded criteria is safe and has increased the pool of grafts. Different variables, both donor and recipient, influence the survival of the pancreatic graft and should be taken into account in organ distribution systems.

Intraoperative Heparinization During Simultaneous Pancreas-Kidney Transplantation: Is It Really Necessary?

INTRODUCTION: The use of intraoperative sodium heparin during simultaneous pancreas-kidney transplantation (SPKT) remains as a routine practice in some referral centers to minimize pancreatic graft thrombosis rate. One of its disadvantages is the theoretical increased risk of postoperative bleeding. In our center, we have abandoned its use since 2011. MATERIALS AND METHODS: We performed a retrospective analysis among 198 SPKTs performed in our center between the years 1989 and 2017. The variables of our study were vascular thrombosis of the pancreatic graft and hemoperitoneum and upper gastrointestinal bleeding in the mediate postoperative period (up to 2 months after the transplant). We compared these results between SPKT recipients who had undergone intraoperative heparinization (n = 157) and those who had not (n = 51). To avoid bias, a second comparison was performed using propensity score matching on the following characteristics: sex, recipient age, recipient body mass index, cold ischemia time, preoperative hemodialysis or peritoneal dialysis, time of diabetes, and Pancreas Donor Risk Index. Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas χ2 or Fisher exact test was used to compare categorical data. RESULTS: No statistically significant differences were found when comparing the use of intraoperative heparin, even after the homogenization of both groups. CONCLUSIONS: In our experience, intraoperative heparinization during SPKT surgery was not useful because it did not significantly decrease the graft thrombosis rate, and its withdrawal did not enhance hemoperitoneum or upper gastrointestinal bleeding postoperative rates.

Pancreas Donor Hypernatremia: Is it Really a Risk Factor for Simultaneous Pancreas-kidney Transplantation?

INTRODUCTION: Solid organ donor hypernatremia has been classically reported to be a risk factor for cell lysis and graft damage. National criteria for pancreatic donation consider severe hypernatremia (sodium level more than 160 mEq/L) to be relative exclusion criteria. The aim of our study is to review the postoperative outcomes of our simultaneous pancreas-kidney transplantation (SPKT) sample in terms of pancreatic fistula, intra-abdominal abscesses, pancreatitis, pancreas graft thrombosis, early pancreatectomy, and reoperation rates regarding different ranges of donor sodium levels. MATERIAL AND METHODS: We performed a retrospective analysis among 161 SPKTs performed in our center between the years 2001 and 2017. We compared the aforementioned postoperative variables in two situations: 1) Whether the donor pancreas sodium levels were inferior to 149 mEq/L, or equal to or greater than 150 mEq/L; and 2) If they had severe hypernatremia (considering sodium levels greater than or equal to 160 mEq/L as threshold) or not. To ensure the comparability of the groups, a second comparison was performed on new samples after using propensity score matching. A Student t test or Mann-Whitney U test was used for intergroup comparisons of quantitative variables where appropriate, whereas a χ2 test or Fisher's exact test was used to compare categorical data. RESULTS: No statistically significant differences were found between the groups that relate high donor serum sodium levels with the morbidity variables included in our study or with early pancreatic graft loss. CONCLUSIONS: In our cohort, early postoperative main morbidity and pancreas graft loss of SPKT recipients do not differ significantly regarding donor serum sodium levels.

Kidney Transplantation Results in Very Highly Sensitized Patients Included in a Virtual Crossmatch Program: Analysis of Kidney Pairs.

BACKGROUND: Kidney transplantation in highly-sensitized (HS) patients can improve with organ-exchange strategies based on virtual crossmatch (V-XM). Experience in very-HS patients is limited. METHODS: In June 2012, Andalusia started a V-XM protocol for very-HS patients (calculated panel reactive antibodies ≥95%). After organ allocation a cytotoxic-XM performed immediately before transplantation had to be negative for surgery to proceed. We analyzed results up until December 2015. Whenever possible we also compared the course of the recipient (non-HS) of the other kidney from the same donor. RESULTS: Of the 57 grafts, 52 kidney transplantations were performed (the pretransplantation cytotoxic-XM was positive in 5; predictive value 91.3%). Five patients (9.6%) experienced acute rejection (4 antibody-mediated rejections [AMRs]; 7.6%). Donor-specific antibodies developed in 10 patients. No patient died. One-year graft survival was 98%. We compared the course of the non-HS recipient of the other kidney, excluding cases with no pair (n = 5), pairs who were children recipients (n = 3), pancreas-kidney recipients (n = 5), or pairs already included in the V-XM protocol (n = 4). Finally, 35 pairs were studied. More HS-patients developed donor-specific antibodies (P = .016). No significant differences were seen in acute rejection, but AMR was more common (P = .057). No deaths occurred in either group, and there were no differences in graft survival or renal function. CONCLUSIONS: Although a few patients still developed AMR, our V-XM based protocol with a final pretransplantation cytotoxic-XM achieved very satisfactory results. Although the number of patients was limited, the initial survival of these high-risk recipients was comparable to the controls.

Short-Term Outcome of Untreated Versus Treated Asymptomatic Bacteriuria in Renal Transplant Patients.

BACKGROUND: Infection of the urinary tract (UTI) is the most common form of bacterial infection in renal transplant patients, but its management is still controversial. We compared symptomatic and asymptomatic bacteriuria, treated or untreated, during two different months (summer or winter). METHODS: This longitudinal, prospective study involved routine urine cultures collected during September 2014 or March 2015. Demographic, clinical, and microbiological characteristics from the patients with positive urine cultures were described. The main outcomes were the need of hospitalization, the bacterial clearance, and the selection of the resistant pathogen. RESULTS: From the 538 urine cultures collected, only 61 were positive urine cultures. Twenty were untreated asymptomatic bacteriuria (AB), 28 were treated AB, and 13 were treated symptomatic bacteriuria. The more prevalent micro-organisms were E coli (27%), K pneumoniae (11%), and E faecalis (7%). There were no differences in the demographic, clinical, and microbiological characteristics depending on the month when the urine cultures were collected. Only 10 patients required hospitalization during follow-up, and all of them belonged to the treated group. Bacterial clearance after the treatment occurred in 20 patients of the 41 treated (48.9%) and spontaneously in 14 of the 20 patients untreated (70%). Of the treated patients, 47.6% developed a new resistance to another antibiotic. CONCLUSIONS: Only 7.6% of the routine urine cultures on renal transplant were positive. Untreated AB did not require hospitalization, and 70% had spontaneous bacterial clearance.

Non-Heart-Beating Donor Kidney Transplantation Survival Is Similar to Donation After Brain Death: Comparative Study With Controls in a Regional Program.

Non-heart-beating donors (NHBD) are an increasing source of organs for kidney transplantation (KT) compared with donation after brain death (DBD), but the results in each regional transplantation program require local analysis. We compared 164 KT from NHBD (83 Maastrich type II A-B [T2] and 81 type III [T3]) with 328 DBD controls. NHBD kidneys were implanted with less cold ischemia, mean time on renal replacement therapy for NHBD recipients before transplantation was less too, and a higher proportion of thymoglobulin was also used. Besides NHBD-T2 more frequently showing the A group and patients being younger (48.9 ± 11 vs DBD 55.2 ± 15 years old; P < .001), there was a lower proportion of retransplant recipients and HLA sensitization; HLA-DR compatibility was slightly worse. Proportion of nonfunctioning allograft and necessity of dialysis after transplantation for NHBD were 4.9 and 68.3% versus DBD 4.3 and 26.9% (P < .001); renal function after a year was significantly less in NHBD (serum creatinine 1.79 ± 0.9 mg/dL vs 1.46 ± 0.5 in DBD; P < .001). NHBD recipient survival rates were 96% and 96% for the 1st and 3rd years, respectively, versus 96% and 94% for DBD, respectively (not significant [NS]). Graft survival rates censored by death were 91% and 89% (1st and 3rd years, respectively) versus 95% and 94% for DBD, respectively (NS). We did not find significant differences about survival between NHBD-T2 and T3. In the multivariable survival study (Cox, covariables with statistical significance demonstrated previously in our region), NHBD is not a prognosis factor for recipient or graft survival. Regarding current criteria for choosing donors and the graft allocation applied in Andalusia, short-term survival for NHBD transplantation is similar to DBD. Renal function in the short term is slightly worse, which is why it is important to monitor results over a long term, especially those from NHBD-T2.

Donor-Specific Antibodies After Starting Hemodialysis in Nonrenal Solid Organ Transplant Recipients: Role of TH17.

BACKGROUND: Nonrenal transplantation could cause a progressive deterioration in renal function until need dialysis. It is important to know if these patients increased their risk to develop de novo donor-specific anti-HLA antibody (DSA) after starting hemodialysis (HD) and if so, try to find the mechanism. MATERIAL AND METHODS: In this double-phase study, we first analyzed the incidence of development DSA in nonrenal transplant recipients after starting HD by a retrospective study. Secondly, a prospective study was designed to analyze the pharmacokinetics of immunosuppressive drugs and the cytokine profile of these patients. RESULTS: Of 179 pancreas transplant recipients, 16 needed to start HD, and 62.5% of these patients developed de novo DSA after starting HD, with 80% of them class I DSA. In the second phase of the study, the plasma levels of the immunosuppressive drugs as measured by a limited sampling strategy of 3 sample time points (C0, C2, and C4) were stable. The cytokine profile showed that there was an increase in Th1 cytokine (interferon gamma of 0.045 ng/mL) and also in Th17 cytokines (transforming growth factor ß >10 ng/mL). CONCLUSION: Our data suggest that the development of DSA after starting HD in nonrenal transplant recipients could be mediated by Th17 immune response mechanisms.

Incidence and Long-Term Prognosis of Cancer After Kidney Transplantation.

BACKGROUND: Malignancy is an important cause of mortality in renal transplants recipients. The incidence of cancer is increased by immunosuppressive treatment and longer kidney graft survival. The aim of this study was to evaluate the incidence, prognosis and survival of posttransplant malignancies: solid organ cancer (SOC), posttransplant lymphoproliferative disorder (PTLD), and nonmelanoma skin cancer (NMSC). METHODS: We retrospectively studied the development of cancers among kidney transplants patients in our hospital from January 1979 to January 2015. We analyzed demographic and clinical characteristics, risk factors, and patient survival after tumor diagnosis. RESULTS: We included 1450 kidney transplants recipients with a mean follow-up was 10 years; among them, 194 developed malignancies. The mean age at presentation was 59 ± 10 years. The SOC, PTLD, and NMSC incidences were 6.2%, 1.2%, and 6%, respectively. The most common tumors were kidney (16.6%), colon (11%), bladder (10%), breast (10%), prostate (10%), and lung (8.8%). The median times to development of a SOC, PTLD, and NMSC were 6.86 (range, 3.7-12), 4.43 (range, 1.8-5.7), and 8.19 (range, 3.8-12.2) years, respectively. Risk factors associated with developing SOC and PTLD were patient age (odds ratio [OR], 1.03; P < .001) and time posttransplant (OR, 1.05; P = .02), whereas for NMSC were to be male (OR, 3.61; P < .001), to take calcineurin inhibitors (OR, 2.17; P = .034), patient age (OR, 1.05; P < .001) and time posttransplant (OR, 1.15; P < .01). The mean survival time from the diagnosis of SOC, PTLD, and NMSC were 2.09 (range, 0.1-5.3), 0.22 (range, 0.05-1.9), and 7.68 (range, 3.9-10.5) years, respectively (P < .001). CONCLUSIONS: SOC occurs more frequently than other malignancies among renal transplant patients. NMSC has better survival and prognosis. Older patients and prolonged graft function have a greater risk of developing malignancies.

Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program.

BACKGROUND: Donors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010-2014). METHODS: We compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. RESULTS: DCD were more frequently men from the A blood group who were younger (48.9 ± 11 vs 55.2 ± 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 ± 11 vs 53.5 ± 13 years old for DBD, P = .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA-DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1(st) and 3(rd) years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n = 445), 86% vs 92% (P = .02) in the third year, but were similar to DBD from age 50 to 59 (n = 407) and higher than DBD over age 60 (n = 636), 80% at the 3(rd) year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3(rd) year, P = .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. CONCLUSIONS: With the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present.

Passenger Lymphocyte Syndrome After Simultaneous Pancreas-Kidney Transplantation: A Case Report of an Unusual Cause of Alloimmune Hemolytic Anemia.

BACKGROUND: Passenger lymphocyte syndrome (PLS) is a disease in which the donor's lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. CASE REPORT: We report the case of a 39-year-old woman with stage V chronic kidney disease on hemodialysis secondary to poorly controlled diabetes mellitus type 1. She received a simultaneous pancreas-kidney transplant from a cadaver donor. The donor was A- and the recipient was A+ without initial complications with normal renal and pancreatic function, and her hemoglobin (Hb) level was 10.2 g/dL at discharge. Four weeks later she was admitted with acute pyelonephritis of the renal graft, with a Hb level of 7.5 g/dL, creatinine level of 0.7 mg/dL, and glucose level of 80 mg/dL. The study of anemia showed direct polyspecific direct Coombs weakly positive (w/+), presenting 2 alloantibodies against the Rh system: anti-D, anti-E. We increased Prednisone dose to 1 mg/kg/d and then decreased it in a pattern. Eight days after discharge, without transfusion, her Hb level was 9.9 g/dL and then it normalized. CONCLUSIONS: PLS is a very rare condition and should be suspected in the first few weeks after transplantation. In our case anemia was probably due to a residual population of Rh-negative donor cells in the transplanted pancreas-kidney received. It is usually a sudden onset of hemolytic anemia in patients with a solid organ transplant and different Rh or ABO lower incompatibility.

Tyrosine-phosphatase and glutamate-decarboxylase antibodies after simultaneous pancreas kidney transplantation: do they have an impact on pancreas graft survival?

INTRODUCTION: The pathogenesis of type 1 diabetes mellitus (T1DM) is associated with auto-antibodies. These auto-antibodies contribute to pancreatic ß-cell destruction. Tyrosine-phosphatases (IA-2) and glutamic acid decarboxylase (GAD65) are the most frequently used by clinicians. When T1DM patients develops advanced chronic kidney disease, simultaneous pancreas-kidney (SPK) transplantation becomes the best option. However, pancreatic graft survival is limited. The role of the auto-antibodies on pancreas graft survival remains controversial. OBJECTIVE: The aim of this study was to assess pancreas graft survival according to the presence of GAD65 and IA-2 auto-antibodies after SPK transplantation. METHODS: We analyzed all SPK transplantations performed in our hospital since January 1990 to December 2013 with at least 30 days of pancreas graft survival. We collected demographic and clinical variables from donors and recipients. Graft failure was defined as complete insulin independence after transplantation. Pancreatic graft survival was analyzed using the Kaplan-Meier method. RESULTS: Overall, 152 SPK transplantations were performed during the period. One hundred sixteen were accessed for de novo post-transplantation auto-antibodies. Also, 17.8% (n = 27) were positive for anti-GAD65, 13.8% (n = 20) for IA-2, 3.9% (n = 6) were positive for both, and the rest were negative for any auto-antibody (n = 63). Kaplan-Meier survival curves estimated a worst pancreas graft survival for patients with positive IA-2 antibodies versus those patients with negative auto-antibodies and GAD65+auto-antibodies (P = .003 and .022, respectively, by log-rank). Mean pancreas graft survival rates at first and fifth year were 72% and 64%, respectively, for those patients with positive IA-2. CONCLUSIONS: IA-2 antibodies after SPK transplantation are associated with long-term graft lost compared with the rest of the groups. Monitoring of these auto-antibodies after SPK may help to identify patients with a higher risk of graft failure.

Short-term evolution of renal transplant with grafts from donation after cardiac death: Type III Maastricht category.

BACKGROUND: Kidney transplantation from donors after cardiac death (Type III Maastricht category) is a therapeutic option for patients with terminal renal failure. MATERIALS AND METHODS: We present a cohort of 8 patients who received a kidney transplant from donors after cardiac death (DCD). We analyzed the analytical results for the first 6 months after transplantation. RESULTS: We included 8 cases of kidney transplants with organs from DCD (Type III Maastricht category). The mean age of donors was 58.40 ± 4.39 years and 3 (60%) were male. The mean creatinine (Cr) level prior to death was 1.10 ± 0.36 mg/dL. The mean age of recipients was 59.88 ± 10.58 years and 7 (87.5%) were male. Seven patients (87.5%) were on hemodialysis, whereas only 1 (12.5%) was on peritoneal dialysis. The median time on renal replacement therapy was 18 months (range, 2-76). Mean total warm ischemia time (WIT) was 24.88 ± 6.72 minutes, whereas the mean real WIT was 20.13 ± 4.51 minutes. The mean cold ischemia time (CIT) was 6 hours and 12 minutes ± 2 hours. Preimplantation biopsy showed acute tubular necrosis (extensive 40%). Tubular atrophy was mild in 100% of cases. After transplantation, 6 patients (75%) had delayed graft function requiring dialysis sessions whereas 2 patients (25%) did not require renal replacement therapy. Mean Cr level at 1, 3, and 6 months after transplantation was 2.37, 1.75, and 1.17 mg/dL, respectively. CONCLUSION: Kidney transplantation with grafts from donors after cardiac arrest Maastricht Type III evolves favorably in the short term. According to preliminary results, controlled asystole donation could be an effective alternative to transplantation.

Index high insulin resistance in pancreas-kidney transplantation contributes to poor long-term survival of the pancreas graft.

BACKGROUND: Pancreas-kidney transplantation (PKT) is the best therapeutic option for diabetic patients with end-stage renal failure. Peripheral insulin resistance and the percentage of remaining ß-cells in the PKT have been little studied in medical literature. METHODS: We analyzed PKT performed in our hospital from January 1992 to January 2014, with follow-up for 5 years. Metabolic values related to glycemic were studied, namely, proteinuria, peptide C, glucose, insulin, and glycosylated hemoglobin. We analyzed insulin resistance (homeostatic model assessment [HOMA]-IR), the percentage of remaining ß-cells (HOMA-ß), and the influence of these variables on the glycemic profile and graft survival. RESULTS: In the study period, 156 simultaneous PKT were performed in our center. At 2 years posttransplantation, the median value of HOMA-IR kidney-pancreas was 4. We compared transplantation with lower HOMA-IR (<4) and higher HOMA-IR (>4). HOMA-ß (36 [26-67] vs 29 [14-42]; P = .04), glucose (86 [80-90] vs 81 [74-89]; P = .018), and body mass index (BMI; 24 [21-27] vs 21 [19-24]; P = .013) were greater in the group HOMA-IR>4 versus HOMA-IR<4 group, respectively, after 3 months. These differences in glycemic profile were maintained until the first year after transplantation. At 2 and 5 years of follow-up, the HOMA-IR>4 group showed higher glucose levels and greater BMI, but not differences in HOMA-ß. At 1 and 5 years posttransplantation, pancreatic graft survival in the HOMA-IR>4 group (82.9% vs 92.5%) was lower compared with the HOMA-IR<4 group (67% vs 87.5%; P = .016). CONCLUSIONS: PKT exhibit an altered glycemic profile in the posttransplantation follow-up associated with the percentage of remaining ß-cells and peripheral insulin resistance. PKT patients with peripheral insulin resistance showed decreased pancreatic graft survival.

Development of Donor-Specific Anti-HLA Antibodies After Restarting Hemodialysis Due to Graft Failure.

BACKGROUND: Incidents of renal replacement therapy (RRT) from renal transplants are on the rise. Some authors have associated the development of donor-specific anti-HLA antibodies (DSA) with the end of immunosuppression treatment (IS) and/or the performing of a transplantectomy. The objective of this study was to analyze the characteristics of transplant patients having high immunological risk who restarted RRT and the subsequent development of DSA. METHODS: We selected incidents on RRT carried out between 1980 and 2012 in our center: 146 cases; they presented non-DSA cytotoxic antibodies prior to returning to RRT. Survival time for the graft was 77.2 months; the average follow-up period for DSA development was 131.9 months. DSA in 76 cases (52.1%). Of 146 grafts, 72 underwent transplantectomy and 41 presented DSA after returning to RRT. In 17 of these cases (41.5%), the development of DSA occurred prior to the transplantectomy. Fifty-one cases of DSA were registered at the date of completion of the IS treatment, and 40 appeared after discontinuation (median 36 weeks) and 11 with previous appearance. IS was completed, with a median of 13 weeks after the return to RRT. RESULTS: No association was found between DSA development and order of graft, transplantectomy, or premature loss of the graft (≤15 months) after the return to RRT. There were significant differences between the number of HLA incompatibilities of the donor and the development of DSA. CONCLUSIONS: The development of DSA in high-immunological risk patients after restarting RRT is not related to transplantectomy.

Cardiovascular response to hemodialysis: the effects of uremia and dialysate buffer.

Cardiovascular instability continues to be one of the primary clinical problems in hemodialysis. Acetate buffer in dialysate is one of the factors that may induce hypotension. Since uremia may have a direct effect on the regulation of the cardiovascular system, the present study was designed to investigate the separate effects of uremia and acetate hemodialysis on blood pressure in anesthesized dogs, as well as the hemodynamic parameters determined by invasive cardiovascular monitoring. Animals were separated into four groups: (1) group I, hemodialysis with acetate in controls; (2) group II, hemodialysis with acetate in uremic dogs; (3) group III, hemodialysis with bicarbonate in controls; and (4) group IV, hemodialysis with bicarbonate in uremic dogs. Acute uremia was induced by bilateral ureteral ligation and a 90-minute hemodialysis (acetate or bicarbonate) procedure was performed 72 hours later. The results obtained in this study show that, compared with dogs with normal renal function, acute uremia resulted in an elevation in mean arterial pressure (MAP; 178 +/- 13 vs. 115 +/- 23 mm Hg, P < 0.01), which was associated with an increase in cardiac index (CI) and left ventricular stroke work index (LVSWI). In these dogs, the pulmonary capillary wedge pressure (PCWP; preload) and the systemic vascular resistance index (SVRI; afterload) were not different than controls. In uremic dogs, hemodialysis with acetate, but not with bicarbonate, decreased the MAP to values similar to controls. The decrease in MAP induced by acetate hemodialysis in uremic dogs was associated with a decrease in SVRI and PCWP. These results suggest that in dogs with acute uremia, acetate hemodialysis (HD) decreases myocardial contractility that was previously increased by a direct effect of uremia. In controls, acetate produced a moderate decrease in MAP that was the result of a mild decrease in CI and SVR. Since PCWP was not significantly decreased after acetate HD, the decrease in CI can be attributed to a mild decrease in myocardial performance. In conclusion, this study in dogs suggests that uremia enhances myocardial contractility directly. Acetate hemodialysis reduces this elevated myocardial contractility to normal values.