Good Graft Outcome Research Articles

Characteristics of Inherited Metabolic Disorders Following Kidney Transplantation: A 13-Year Observational Study.

Background and Objectives: Inherited metabolic disorders (IMDs), primarily cystinosis, Fabry disease, and methylmalonic acidemia (MMA), are genetic conditions that typically result in multi-organ disease manifestations. Kidney function progressively deteriorates in many cases, with patients eventually reaching end-stage kidney disease (ESKD) and requiring renal replacement therapy. Kidney transplantation has been deemed the optimal renal replacement therapy option to achieve long-term survival in patients with IMD. Whilst improved long-term survival is expected, the patterns of clinical evolution for IMD after transplantation remain largely unknown. Methods: Our group conducted a retrospective observational study that included 37 adult patients with IMD (11 with cystinosis, 20 with Fabry disease, and 6 with MMA). The study evaluated the clinical status and progression of these patients following kidney transplantation between January 2010 and December 2023. Results: This generally resulted in good graft outcomes for patients with IMD. Standard immunosuppression regimes included tacrolimus, mycophenolate mofetil, and prednisolone. The mean graft survival duration was noted to be 12 years in patients with cystinosis, 11 years in patients with Fabry disease, and 7 years in patients with MMA. Suboptimal outcomes were noted with grafts of cadaveric origin and poor adherence to the prescribed post-transplant immunosuppression regime. A greater extra-renal morbidity burden was associated with a reduced duration of graft function and increased mortality in patients with IMD. Conclusions: Our findings emphasise the need for a multi-disciplinary approach in the care of IMD patients following kidney transplantation.

#601 Overweight-obese kidney transplant recipients have altered tacrolimus clearance and need lower doses for target levels with good graft outcomes

Abstract Background and Aims CYP3A4 which has been associated with altered tacrolimus (Tac) clearance. Clearances for drugs that are CYP3A4 substrates are generally reduced by 10%-35% in obese compared to normal-weight individuals. This study assessed the early and late Tac levels and weight-based total daily dose (TDD) for target Tac level in overweight-obese kidney transplant (KT) recipients and its relation to graft outcomes. Methods A retrospective study included 62 live-related KT recipients: overweight-obese KT recipients (N=32) with body mass index (BMI) >25 and normal-weight KT recipients (N=30) with BMI <25. The Tac level and weight-based TDD were examined in the 1st 3 months and 1 year after kidney transplantation with assessment of graft outcome. Results The overweight-obese patients' mean BMI was 31.29 and normal-weight patients' mean BMI was 22.20 p-value (0.0001). There was no significant difference between overweight-obese patients and normal-weight patients in mean Tac levels in 1st 3 months and after 1-year (mean 8.902, 6.99 ng/ml versus 8.906, 6.91 ng/ml respectively) p-values (0.992, 0.850) respectively. The weight-based TDD for target Tac level in 1st 3 months and after 1-year was significantly lower in overweight-obese than normal-weight patients (mean 0.108, 0.073 ng/ml versus 0.167, 0.102 ng/ml) respectively with p-value (0. 00035, 0.0076) respectively. KT recipients with BMI >30 showed lower weight-based TDD versus KT recipients with BMI 25-30 in 1st 3 months (0.094 versus 0.131 ng/ml) p-value (0.0255) while no difference after 1-year p-value (0.353). Graft outcomes did not significantly differ between overweight-obese versus normal-weight patients; the mean serum creatinine (1.22 versus 1.27 mg/dl) p-value (0.680) and graft rejection was (6 patients versus 6 patients) p-value (0.104) without graft loss. The weight-based TDD after 1-year was negatively correlated with BMI and transplant duration {r −0.369, p 0.003, r −0.278, p 0.028} respectively. Conclusion Overweight-obese patients have altered Tac clearance and they need lower doses to achieve target Tac level in the early and late periods post-transplant which is linked to good graft outcomes. According to these preliminary data the department is planning to study the effect of CYP 3A4/5 genetic polymorphisms on Tac dose requirement in most of these patients.

#3176 STUDY OF UNUSUAL/RARE INFECTIONS IN RENAL TRANSPLANT RECIPIENTS

Abstract Background and Aims Infections are the most common cause of mortality in solid organ transplant patients. Kidney transplant is the most common organ transplantation worldwide. Since its successful outcomes and longevity of patients, wide literature is available about the long term outcomes and infections. They are more susceptible to infections in the first six months of transplant as per Rubin's calendar when immunosuppression is high. The most common opportunistic infections like Pneumocystis jirovecii, CMV infection, reactivation of tuberculosis, other viral infections like hepatitis B and hepatitis C viruses and fungal infections like Cryptococcus were well studied. There are very few studies on atypical infections about their clinical presentation, anibiogram and outcomes of the patients. Method It is retrospective analysis of clinical presentation, methods of diagnosis, antibiogram, graft's & patient's outcomes of renal allograft recipients with atypical infections. All renal allograft recipients from 2006 to 2021 who had atypical infections were included. The clinical data obtained from hospital data and collected using epidata software and results were analyzed using PSPP software. Results A total of 1498 patients underwent renal transplant in this center during 2006 to 2021. Only 33 patients had unusual/rare infections like nocordosis (12), Rhodococcus (1), Meliodosis (2), Pheohypomycosis (3), Aspergillosis (6), Histoplasmosis (1), and Parvovirus (8). Nocorodiosis occurred after mean duration of 6.3 years after transplant. Most of the patients with nocordiosis, presented with prolonged fever and cutaneous abscesses, culture which grew nocordiosis. They responded to Imipenem and Septran, but few strains were septran resistant for which fluroquinolones were given. Overall the outcomes of graft and Patients were good. The patient with rhodococcus presented with sepsis with MODS and was expired. The patients with pheohyphomycosis presented with cutaneous abscess and responded to prolonged course of Itraconazole with good graft outcome without mortality. Out 6 patients with Aspergillus Pneumonia which developed after 4.6 years after renal transplantation, 3 patients were expired with graft loss. The patients of parvovirus infection presented with refractory post-transplant anemia and evaluation showed pure red cell aplasia on bone marrow studies. Most of them developed within one year of transplant and four of them received anti-rejection therapy. Five patients responded to standard treatment with IV immunoglobulin, but three patients required 2 doses of Inj. Rituximab 500 mg each in view of probable Parvo virus triggered auto immune hemolytic anemia. Conclusion This study focused on the atypical infections like nocordosis, Rhodococcus, Meliodosis,Pheohypomycosis, Aspergillosis, Histoplasmosis, Parvovirus and their antibiogram and outcomes of graft and mortality. The high index of suspicion should be present when patient is not responding to empirical antibiotics and culture didn't grow routine organsims. The role of invasive investigations like bronchoscopy with BAL fluid whoudl be considered whenever the infections like nocordiosis and aspergillus were considered. Transplant with cutaneous abscesses should not be treated with empirical antibiotics and always culuture should be done to rule out infections like nocordiosis, pheohypomycosis and histoplasmosis as treatment is different for each orgaims. Post-transplant refractory anemia requires bone marrow evaluation to look for Parvovirus infection which responds to IVIg. Overall, the high index of suspicion, timely diagnosis, correct drug and duration of treatment will save the graft and patient.

P8.065: COVID-19 and Pediatric Kidney Transplantation: Iberoamerican Multicentric Study

Introduction: Concern on the effect of COVID-19 in children recipients of kidney transplant (KT) lead to an initial decline in the transplantation activity. Our aim is to present graft and clinical outcomes of a multicenter cohort of pediatric KT performed during COVID-19 pandemic and compare it with an historic control group. Our secondary goal is to report the clinical evolution of children who suffered COVID-19 after transplantation. Methods: A retrospective analysis in seven pediatric KT centers of Iberoamerica, from January 2019 to December 2020 was done. In the included institutions, 168 pediatric KT were performed: 97 patients were control group (year 2019) and 71 the study group (year 2020). Baseline demographics and comorbidities were comparable. Graft outcome showed no significant differences in terms of the need of post transplant renal replacement therapy and glomerular filtration rate in the last visit. Graft hydronephrosis, urinary tract infection, and other complications were similar (Table 1). Results: Six (8,4%) out of 71 patients transplanted in 2020 developed COVID 19 after the transplant. The infection occurred at a mean 71,8 days after the transplant (range: 5-214 days). Three patients were asymptomatic, two presented with fever and one with cough. Three patients were managed on an outpatient basis, two were admitted but remain in a common room, whereas one child required hospitalization in intensive care unit but, without the need of mechanical ventilatory assistance. In 3 patients mycophenolate was suspended, and in the other 3 there were no changes in the immunosuppressive scheme. There were no mayor respiratory complications such as COVID-19 pneumonia or acute respiratory distress syndrome. Hospital stay was a mean of 13 days (range: 0-39). All six patients had good graft outcome, with no need renal replacement therapy, with a mean glomerular filtration rate of 86,36 mL/min/1.73 m2 (range:58 -126). One patient had recurrence of original renal disease. Conclusion: Despite initial concerns about the increased risk of severe complications of COVID-19 and the graft survival in children with KT, our multicentric series showed similar initial graft outcome and no mayor respiratory complications. Longer follow up is needed to assess the long-term evolution of these grafts and patients.

Association of Vascular Endothelial Growth Factor 936 C/T Gene Polymorphism with Renal Allograft Outcome: A Study from North India.

The significance of vascular endothelial growth factor (VEGF) and its polymorphisms in renal allograft rejection has recently become the subject of extensive research. Recently, some studies have shown some role of VEGF in rejection episodes and graft survival. VEGF +936 C>T polymorphism is significant in the transcription regulation of VEGF. Herein, we report the results of a prospective, single-center study seeking an association of VEGF +936 C/T gene polymorphism and allograft rejection. One hundred and forty-seven kidney transplant recipients with age-and sex-matched controls were included in this study. VEGF 936 C/T genes were studied using restriction fragment length polymorphism analysis of the blood specimen of these patients. All patients were studied for allograft rejection, response to treatment, and overall graft survival. We found that CT genotype and T allele carrier state were associated with good graft outcomes (P = 0.008 and 0.002, respectively). There was a lower number of rejection episodes with T allele, although it was not a significant finding (P = 0.880). Our findings suggest that good graft outcome in kidney transplant recipients is associated with an increased frequency of the VEGF 936 CT genotype and T allele, and that determination of the T allele might be helpful for the identification of recipients with overall good graft survival.

Living Donor Kidney Transplantation in Patients With Donor-Specific HLA Antibodies After Desensitization With Immunoadsorption.

Due to the current organ shortage, living donor kidney transplantation is increasingly performed across HLA (human leukocyte antigen) or ABO antibody barriers. There is still uncertainty about the risk of antibody-mediated rejection (AMR) episodes, which may limit long-term graft survival. From March 2007 to December 2016, 58 sensitized living donor kidney transplant candidates were identified and 38 patients eventually included in the study: 36 patients (95%) had pre-transplant and pre-desensitization Luminex-detected donor-specific HLA antibodies (DSA), and 17/36 patients (47%) in addition had a positive crossmatch result. Two patients had no detectable DSA but a positive CDC B-cell crossmatch result. Patients were treated with pre- and post-transplant apheresis and powerful immunosuppression including the anti-CD20 antibody rituximab (N = 36) in combination with thymoglobulin (N = 20) or anti-IL2 receptor antibody (N = 18). The results of the 38 successfully desensitized and transplanted patients were retrospectively compared to the results of 76 matched standard-risk recipients. Desensitized patients showed patient and graft survival rates similar to that of standard-risk recipients (P = 0.55 and P = 0.16, respectively). There was a trend toward reduced death-censored graft survival in desensitized patients (P = 0.053) which, however, disappeared when the 34 patients who were transplanted after introduction of sensitive Luminex testing were analyzed (P = 0.43). The incidence of rejection episodes without borderline changes were in desensitized patients with 21% similar to the 18% in standard-risk patients (P = 0.74). Thirty-six patients had pre-transplant HLA class I and/or II DSA that were reduced by 85 and 81%, respectively, during pre-transplant desensitization (P < 0.001 for both). On day 360 after transplantation, 20 of 36 (56%) patients had lost their DSA. The overall AMR rate was 6% in these patients, but as high as 60% in 5 (14%) patients with persistent and de novo DSA during year 1; 2 (40%) of whom lost their graft due to AMR. Eleven (31%) patients with persistent DSA but without de novo DSA had an AMR rate of 18% without graft loss while one patient lost her graft without signs of AMR. Our desensitization protocol for pre-sensitized living donor kidney transplant recipients with DSA resulted in good graft outcomes with side effects and rejection rates similar to that of standard-risk recipients. Adequate patient selection prior to transplantation and frequent immunological monitoring thereafter is critical to minimize rejection episodes and subsequent graft loss.

Satisfactory outcomes in orthotopic liver transplantation for hepatic sarcoidosis: The UK experience

• Hepatic sarcoidosis is a rare indication for liver transplantation. • Previous data suggested worse graft and patient outcomes compared to other cholestatic liver diseases. • We present NHSBT registry data that demonstrates good graft and patient outcomes over the last decade • Further work is required in order to characterize the factors that lead to disease recurrence in the graft • A UK-wide collaboration would be a welcome step to improve data collection and inform transplant listing decisions.

Successful Multiorgan Donation From a Brain-dead Donor Following Liquid Nicotine Voluntary Intoxication: A Case Report.

Successful Multiorgan Donation From a Brain-dead Donor Following Liquid Nicotine Voluntary Intoxication: A Case Report.

Survival and transplant outcomes among young children requiring kidney replacement therapy.

Young children starting kidney replacement therapy (KRT) suffer high disease burden with unique impacts on growth and development, timing of transplantation and long-term survival. Contemporary long-term outcome data and how these relate to patient characteristics are necessary for shared decision-making with families, to identify modifiable risk factors and inform future research. We examined outcomes of all children ≤ 5 years enrolled in the Australia and New Zealand Dialysis and Transplant Registry, commencing KRT 1980-2017. Primary outcomes were patient and graft survival. Final height attained was also examined. We used generalized additive modelling to investigate the relationship between age and graft loss over time post-transplant. In total, 388 children were included, of whom 322 (83%) received a kidney transplant. Cumulative 1-, 5- and 10-year patient survival probabilities were 93%, 86% and 83%, respectively. Death censored graft survival at 1, 5 and 10 years was 93%, 87% and 77%, respectively. Most children were at least 10 kg at transplantation (n = 302; 96%). A non-linear relationship between age at transplantation and graft loss was observed, dependent on time post-transplant, with increased risk of graft loss among youngest recipients both initially following transplantation and subsequently during adolescence. Graft and patient survival have improved in recent era. Young children commencing KRT have good long-term survival and graft outcomes. Early graft loss is no reason to postpone transplantation beyond 10 kg, and among even the youngest recipients, late graft loss risk in adolescence remains one of the greatest barriers to improving long-term outcomes.

Quantitative Polymerase Chain Reaction Detection of Microchimerism in Female Transplant Renal Recipients

Introduction: Microchimerism (MC) is the presence of a small amount of foreign cells or DNA within a person’s circulation or tissues. It has been identified also in recipients of solid organ transplants where it seems to be critical for the development and maintenance of immunological tolerance. Nevertheless, natural and/or iatrogenic MC can be acquired prior to transplantation, through pregnancy and/or blood transfusion. Objective: The aim of this study was to detect the presence of MC in women after renal transplantation from male cadaveric donors and its relationship with graft outcomes. Methods: We studied by qPCR the presence of the DYS14 gene sequence of the Y chromosome in 12 females who received a kidney graft from a male donor before transplantation (T0), after 15 days (T1) and 1 year of transplantation (T2). We found the sequence in all recipients after renal transplantation. Results: All the women were negative for this sequence prior to transplantation (T0). Mean (SD) Y-related DNA quantity was 0.80 (0.69) ng/mL plasma and 0.15 (0.26) ng/mL plasma at T1 and T2, respectively. No acute rejection was observed, and mean (SD) estimated Cr clearance was 68.8 (16.9) mL/min within 1 year from transplantation. Conclusions: Presence of MC was associated with good kidney graft outcomes after 1 year of transplantation, but further studies will be needed to investigate the relationship between clinical outcomes and the development of MC in renal transplant recipient.

TRANSPLANTATION OF PEDIATRIC RENAL ALLOGRAFTS FROM DONORS AGED 1 YEAR AND UNDER: AN ANALYSIS OF THE AUSTRALIAN AND NEW ZEALAND DIALYSIS AND TRANSPLANT REGISTRY (ANZDATA) FROM 1963 TO 2018

Introduction: Recent times have seen a change in donor demographics internationally in order to mitigate the shortage of organs. Although there is established evidence that transplantation with pediatric kidneys yields good outcomes, there exists reluctance in many centers to utilize organs from very small paediatric1-3. We describe the collective experience of transplantation using kidneys from small pediatric donors aged 1 year and under in Australian and New Zealand. Materials and Methods: We analysed the ANZDATA registry on all deceased donor kidney transplants from paediatric donors aged 1 year and under. We compared the recipient characteristics and outcomes between 1963 to 1999 and 2000 to 2018. Results: There were 42 paediatric donors <=1 years of age (27/42;64% males); eight (19%) were transplanted into paediatric recipients and 34 (81%) into adult recipients.Thirty-five (83%) were transplanted en-bloc, five (12%) were transplanted as single kidneys, and two (5%) were not recorded. Donor and recipient characteristics are shown in Table 1.Comparing the two time intervals, there were notable differences in recipient characteristics. In the earlier period, children accounted for 44% (7/16) of total recipients compared to 4% (1/26) in the later period when the vast majority of recipients were adults (25/26;96%); p<0.01. Mean serum creatinine at one and five years were 87+/-61 µmol/L and 80 µmol/L for children and 98+/-35 µmol/L and 86+/-3 µmol/L for adults. Five (5/34,15%) adults and zero (0/8) children had delayed graft function; p=0.55. Death-censored graft survival from 1963-1999 was 50% and 43% at 1 and 5 years compared to 85% at 1 and 5 years from 2000-2018. Death-censored graft survival was superior in adults compared to children; p<0.01.From 1963-1999, patient survival was 75% and 69% at 1 and 5 years compared to 100% at 1 and 5 years from 2000 to 2018; p=0.70. Causes of graft loss are listed in Table 2.Surgical complications were responsible for graft loss in 3 (38%) pediatric recipients and 4 (12%) adult recipients. Thrombosis was the cause of graft loss in two (25%) pediatric and two (6%) adult recipients; p=0.16. Acute rejection was the cause of graft loss in two (25%) children and one (3%) adult; p=0.09. Conclusion: Kidneys from very small donors have the potential to significantly expand the donor pool. Surgical complications remain a major impediment to the widespread use of small pediatric kidneys. We advocate the judicious use of grafts from donors <= 1year old, into adult recipients. Meticulous surgical technique and careful monitoring of clinical course, especially in the early postoperative period, is the key to good long-term graft outcomes. Optimal selection of recipients, in particular with regards to recipient age, is an important factor in avoiding surgical complications such as vascular thrombosis. We encourage strategies to reduce discard of this precious resource as well as techniques to reduce early graft loss.

Deceased donor transplantation – Our experience in the last 4 years

Background: Kidney transplant is the best treatment option for end stage kidney disease. Deceased donor transplantation has helped in increasing the donor pool for waitlisted dialysis patients. We received seventy deceased donor kidneys through the Kerala Network of Organ Sharing (KNOS) over the past 4 years from August 2013 to August 2017 and transplanted sixty six with good outcome. Pre-implantation biopsy performed in marginal donors helped in decision making to take the kidney and increase the donor pool. Aims and Objectives: 1)To evaluate outcome of renal transplant recipients in deceased donor transplantation. 2)To evaluate the role of pre-implantation biopsy to improve donor selection for better long term outcome. Materials and Methods: Sixty-six deceased donor kidneys were transplanted into the recipients from our pool of 253 patients registered with the KNOS. Four cadaver kidneys were rejected based on pre-implantation biopsy. Fifty-nine transplants were done at VPS Lakeshore and seven were done at PVS Memorial Hospital, Kochi. Donors of age less than 65 years were considered. Pre-tranpslant evaluation of recipients on waiting list including lab and cardiac evaluation with PRA status was done. Cross match was done prior to transplant. Triple immunosuppression including cyclosporine, mychophenolate mofetil and prednisolone with basiliximab as induction agent was used in all cases. Low dose tacrolimus was introduced after the third month in some cases. Pre-implantation biopsy was done in marginal donors for better donor selection. Results: Of the 66 recipients, 52 (78.8%) were males and 14 (21.2%) were females. PRA status was negative in all recipients. Deceased donors 56% IFTA changes, and other had 30%–40% IFTA changes. Results at 4 years post-transplant showed graft survival in 55/66 (83.34%) and patient survival in 60/66 (90.91%) cases. Six patients died: two with pneumocystis carinii pneumonia (PCP) (at 9 months/3.3 years post-transplant), one with mucormycosis (at 16 months post-transplant), one with acute coronary syndrome (immediate post-transplant), and two patients with sepsis. The average serum creatinine was 2.4 mg/dl in 1 (1.8%) case. The surgical outcome was good in all (100%) patients with no intraoperative surgical complications. Delayed graft function was noted in 18% of patients. Prolonged cold ischemia time was noted in patients with acute tubular necrosis. Six patients had acute rejection, of which two were antibody mediated, and four had acute cellular rejection. One patient had tacrolimus toxicity on biopsy and was shifted to everolimus. Infections included one patient with surgical wound infection, 12 patients with urinary tract infections, one patient with invasive fungal infection, and two patients with PCP. At 4 years, deceased donor transplantation has good graft and patient outcomes. Conclusion: Deceased donor transplantation has good graft outcome which is comparable to live non related donors. It has minimal paper work and less costly than routine live transplant. Pre-implantation biopsy should be considered in marginal donors for appropriate donor selection and avoid organ wastage in doubtful cases. In our study we noted that transplant outcome was better in recipients receiving kidney from with in the city limits because of less cold ischemia time. Hence facilities for early transportation of organs with minimal procedural hurdles to minimize cold ischemia time should be carried out by the concerned authorities. Proactivity from the Government at state, zonal and national level is needed to improve deceased donor pool and cadaver transplantation in India.

Explant portal vein for reconstructing middle hepatic vein in right lobe living donor liver transplantation-outcome analysis

BackgroundThe aim of the study was to study the four week patency rates of the reconstructed neo middle hepatic vein specifically using the explant portal vein (PV) in right hemiliver live donor liver transplantation (LDLT). We hypothesized that short term patency of the neo-MHV should result in good graft and patient outcomes. MethodsPre, intra and post operative variables were prospectively collected for 88 consecutive patients undergoing right hemiliver LDLT from January 2014 to October 2015. ResultsExplant PV was used to reconstruct neo-MHV in 76 (86.4%, 76/88) patients. Neo MHV patency rate at 28 days with explant PV was 89.4% (59/66) and with other conduit (PTFE) was 90.9% (10/11). All occlusions were detected after 7 days. There was no impact of the patency of the neo-MHV on the incidence of early allograft dysfunction, sepsis, rejection, morbidity or mortality, despite the contribution of the anterior sector to the graft volume being more than 50% in close to two-thirds of patients. ConclusionThe reconstructed neo-MHV has excellent short term patency rates at 4 weeks. Perhaps due to the absence of early occlusions, there was no impact on graft or patient outcomes in the study population.

Changes of NK cell subsets with time post-transplant in peripheral blood of renal transplant recipients

BackgroundThere is evidence that NK cells with low cytotoxicity but strong immunoregulatory characteristics contribute to good graft outcome. We attempted to investigate which NK cell subsets increase post-transplant and might affect graft function. MethodLymphocyte and NK cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients pre-transplant and post-transplant. In total, 31 transplant recipients were studied. ResultsWhen cell numbers were compared in 9 patients pre- and 6 months post-transplant, post-transplant CD56dimCD16+ (p = 0.011) NK cells with the phenotype CD158a+ (p = 0.008), CD158e+ (p = 0.038), NKG2A+ (p = 0.008), NKG2D+ (p = 0.011), IFNyR+ (p = 0.008), perforin+ (p = 0.008), granzymeB+ (p = 0.008), perforin+granzymeB+ (p = 0.008) and perforin-granzymeB- (p = 0.021) were lower than those pre-transplant, indicating a post-transplant reduction of cytotoxic NK cells. In 28 patients NK cell subsets were analyzed with respect to time post-transplant (median 888 days post-transplant). CD56dimCD16+ NK cells co-expressing CD158a (p = 0.014), NKG2D (p = 0.047), IL4R (p = 0.038), IL10R (p = 0.008) and IFNy (p = 0.036) as well as CD56bright NK cells with the phenotype TGFß+ (p = 0.017), TGFR+ (p = 0.035), CD158a+ (p = 0.042) and perforin-granzymeB- (p = 0.048) increased with time post-transplant. ConclusionPost-transplant, cytotoxic NK cells were lower than pre-transplant and remained low, whereas NK cell subsets with potentially immunoregulatory properties increased.

Kidney transplant in patients with abnormal bladder: Experience of tertiary care center in developing country-Is the outcome same?

Background: Fifteen percent of adults and 20%–30% of pediatric patients develop renal failure, results from structural urological abnormalities. Successful renal transplantation depends partly on a bladder which has adequate capacity, good compliance, and efficient voluntary emptying. Urinary bladder rehabilitation with augmentation or diversion is necessary before transplant in these patients to achieve good graft outcome. We, hereby report our last 10 years' experience of such patients undergoing kidney transplant in abnormal bladder. Materials and Methods: A total of 14 patients underwent renal transplantation in rehabilitated bladder from 2006 to 2016. Demographic details, prereconstruction bladder and urodynamic findings, and type of pretransplant reconstruction were recorded. Posttransplant creatinine levels, graft survival at 7 days, 3 months, 1 year, and 3 years were recorded. Results: Mean (± standard deviation) serum creatinine posttransplant at 7 days, 3 months, 1 year, and 3 years was 0.9 (±0.20), 1.58 (±0.65), 1.92 (±1.02), and 2.47 (1.17) mg/dl, respectively. Four patients developed rejection within 6 months of transplant. Kidney biopsy was suggestive of acute cellular rejection in all cases, which was treated successfully. At three years follow-up, four patients who had rejection-have rising creatinine levels and diminishing renal functions. No patient needed dialysis support till last follow-up. All these four patients had rejection, urinary tract infection (UTI) episodes and pyelonephritis in the past. Conclusion: Native bladder is the best reservoir for urinary storage and drainage. The main cause of graft dysfunction in rehabilitated bladder is UTI as a result of poor hygiene, contamination during clean intermittent self-catheterization (CISC) and noncompliance for CISC leading to high residual urine. Controlling frequent attacks of UTI posttransplant is essential, otherwise long-term graft survival and function will deteriorate faster and might trigger rejection.

Decreased NK cell immunity in kidney transplant recipients late post-transplant and increased NK-cell immunity in patients with recurrent miscarriage.

BackgroundThere is evidence that NK-cell reactivity might affect graft outcome in transplant recipients and pregnancy in women.MethodNK-cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients before and after renal transplantation, patients with recurrent miscarriage (RM) and healthy controls (HC).ResultsPatients late post-transplant (late-Tx) with functioning renal transplants showed abnormally low CD56dimCD16+ NK-cells containing both perforin and granzyme (vs HC p = 0.021) whereas RM patients exhibited abnormally high numbers of these cells (vs HC p = 0.043). CD56dimCD16+perforin+granzyme+ NK-cell counts were strikingly different between the two patient groups (p<0.001). In addition, recipients late-Tx showed abnormally low CD8+ NK-cells (vs HC p<0.001) in contrast to RM patients who showed an abnormal increase (vs HC p = 0.008). CD8+ NK-cell counts were strongly different between the two patient groups (p<0.001). Higher perforin+granzyme+CD56dimCD16+ and CD8+ NK-cells were associated with impaired graft function (p = 0.044, p = 0.032). After in-vitro stimulation, CD56dimCD16+ and CD56brightCD16dim/- NK-cells showed strong upregulation of CD107a and IFNy, whereas the content of perforin decreased dramatically as a consequence of perforin release. Recipients late post-Tx showed less in-vitro perforin release (= less cytotoxicity) than HC (p = 0.037) and lower perforin release was associated with good graft function (r = 0.738, p = 0.037). Notably, we observed strong in-vitro perforin release in 2 of 6 investigated RM patients. When circulating IL10+CD56bright NK-cells were analyzed, female recipients late post-Tx (n = 9) showed significantly higher relative and absolute cell numbers than RM patients (p = 0.002 and p = 0.018, respectively); and high relative and absolute IL10+CD56bright NK-cell numbers in transplant recipients were associated with low serum creatinine (p = 0.004 and p = 0.012) and high glomerular filtration rate (p = 0.011 and p = 0.002, respectively). Female recipients late post-Tx exhibited similar absolute but higher relative numbers of IL10+IFNy- NK-cells than RM patients (p>0.05 and p = 0.016, respectively).ConclusionNK-cells with lower cytotoxicity and immunoregulatory function might contribute to good long-term graft outcome, whereas circulating NK-cells with normal or even increased cytotoxicity and less immunoregulatory capacity are observed in patients with RM.

Endothelial precursor cell cross-match using Tie-2-enriched spleen cells.

Non-HLA antibodies against human endothelial progenitor cells (EPC) in pre-transplant recipient serum can have a deleterious influence on the graft. EPC enriched from peripheral blood have been commonly used for EPC cross-matching. In the present study, we describe cross-matches using EPC enriched from fresh or frozen-thawed spleen cell preparations, thereby widening the sample source for deceased-donor cross-matching and retrospective studies. EPC cross-matches were performed retrospectively using spleen cells and the flow cytometric XM-ONE cross-match test kit. Healthy controls (n=28) showed no IgG antibodies against EPC. When sera of 11 random dialysis patients were studied, 2 patients (18%) exhibited IgG EPC antibodies. When pre-transplant sera of 20 kidney graft recipients with good long-term graft outcome (serum creatinine 1.0±0.2mg/dL measured 2463±324days post-transplant) were investigated using frozen-thawed and then separated Tie-2-enriched spleen cells of the original transplant donor, 3 patients (15%) had pre-transplant IgG EPC antibodies. When pre-transplant sera of 5 patients with intra-operative graft loss were studied employing the original donor spleen cells, 4 (80%) patients showed IgG EPC antibodies. Cross-matches with spleen cell-derived EPC using the XM-ONE assay are technically possible. Our very preliminary experience suggests clinical relevance.

Immunosuppressive drugs affect induction of IFNy+ Treg in vitro

BackgroundWe reported previously that patients with poor long-term graft function are able to form IFNy+ Treg in vitro pretransplant, but late posttransplant have more frequently undetectable or lower levels of IFNy+ Treg in the peripheral blood than patients with good long-term graft outcome. In the present study, we investigated the induction of IFNy+ and Tbet+ Treg subsets in the presence of immunosuppressants in vitro. MethodsPBL of 10 healthy individuals were stimulated with PMA/Ionomycin in the presence of different immunosuppressive drugs at 2 different concentrations that were chosen to approximately mirror the blood levels in renal transplant recipients. IFNy+, Tbet+, CD119+, and Helios+ CD4+CD25+CD127−Foxp3+ Treg subsets were analyzed using 8-color-fluorescence-flow-cytometry. ResultsCyclosporine (p<0.01) and 6α-methylprednisolone (p<0.05) at both concentrations as well as high doses of azathioprine (p<0.05) and mycophenolate mofetil (p<0.05) inhibited the induction of IFNy+ and Tbet+ Treg, whereas lower concentrations of azathioprine and mycophenolate mofetil tended to increase IFNy+, Tbet+ and CD119+ Treg (p⩽0.05). ConclusionsDrug-induced inhibition of Treg induction might result in low IFNy+ Treg levels with the consequence of T effector activation and impaired graft function. Further studies will show whether monitoring of IFNy+ Treg might help to prevent clinical complications provoked by an inappropriate immunosuppressive protocol.

Complement C5a receptor gene 450 C/T polymorphism in renal transplant recipients: association of the CT genotype with graft outcome.

Complement-mediated humoral rejection has become the main focus of research in organ transplantation. The aim of this study was to investigate the possible association of the complement C5aR gene 450 C/T polymorphism in antibody-mediated renal allograft rejection. This polymorphism was investigated in 290 first deceased donor kidney graft recipients with well functioning grafts and no rejection treatment during the first transplant year (WFG), 265 recipients with graft failure within the first transplant year (F), and 187 healthy controls. Frequency of the 450 CT genotype was lower in the total population of 555 kidney recipients (4.7%) than in 187 healthy controls (8.6%), but the difference was not statistically significant (P = 0.065). A significantly higher frequency of CT genotype was found in F patients (CT: 6.8%) when compared to WFG patients (CT: 2.8%, P = 0.027). The CT genotype was also significantly lower in WFG patients than in healthy controls (P = 0.009). Low frequency of the C5aR 450 CT genotype, which apparently is a feature of certain kidney diseases, appears to be associated with good graft outcome in kidney transplantation and might be helpful for identifying recipients who are at low risk for graft rejection.

Can only histological evaluation determine the allocation of ECD kidneys?

IntroductionThere is a recent debate on the "transplantability" of ECD (Expanded Criteria Donors) kidneys and the selection criteria used to allocate them to single or double transplantation. Remuzzi et al. have defined a protocol incorporating pre-transplant donor biopsy to guide the use of older donor organs. They allocated organs as single or double transplants on the basis of histological findings. We aim to show the pros and cons of the only histological evaluation in the allocation of ECD kidneys, to compare the different experiences in United States and Europe and thus to discuss whether this tool should be used alone or included in a comprehensive clinical and histopathological evaluation.DiscussionIn the United States many Authors stated that the biopsy actually increases the percentage of kidney discarded and they raised questions about the importance of the biopsy in evaluating ECD kidneys for transplantation. On the other hand, the experiences of the majority of european transplant centers showed that allocating kidneys as single or dual transplant based on biopsy findings may achieve good graft and patient outcomes.Moreover, the experience of some centers as ours showed that kidneys allocated as DKT (Dual Kidney Transplant) on the basis of Remuzzi’s score could have been suitable for single transplantation suggesting the need of an adjustment of the Remuzzi Score System. Many Authors, who are in favor of histological evaluation, actually believe that a comprehensive clinical and histopathological assessment before transplantation remains necessary.SummaryWe lack precise national- or international-based selection criteria to guide clinicians. An adjustment of the Remuzzi Score System could be taken into consideration such as narrowing the indication for DKT from those ECD kidneys with higher scores and including the histological evaluation in a multifactor score.