ట్రాన్స్‌ప్లాంటేషన్ టెక్నాలజీస్ & రీసెర్చ్

Background: It is not known if the reduced risk of graft-versus-host disease (GVHD) among patients receiving reduced intensity conditioning (RIC) as opposed to myeloablative conditioning (MAC) is due to differences in mixed donor-recipients chimerism, or to the intensity of the regimen.
Methods: We compared patients with acute myeloid leukemia (AML) selected for RIC (n=47) to 46 patients selected for MAC before allogeneic hematopoietic stem cell transplantation (HSCT).
Results: Time to neutrophils >0.5 x 109/L was median 15 days in the MAC group, which was faster than 17 days in the RIC group (p=0.001). MAC patients required more erythrocytes (p=0.001) and platelet transfusions (p=0.003). At four weeks, mixed donor-recipient T-cell chimerism was seen in 29% of the MAC patients and 46% of the RIC patients. Acute GVHD grades II-IV was 55% and 17% in the two groups, respectively (p<0.001). In multivariate analysis, acute GVHD was reduced using RIC (hazards ratio (HR) 0.23, p<0.001), for year of HSCT (HR 1.27, p=0.01), but not for mixed donor-recipient T-cell chimerism (HR 1.11, p=0.80). Transplant-related mortality (TRM) at three years was 15% versus 13%. Chronic GVHD and relapse were similar. Overall mortality was not affected by conditioning (HR 1.39, p=0.36).
Discussion: To conclude, patients treated with RIC had an increased risk of acute GVHD as opposed to recipients of MAC, which was due to less intense conditioning and not due to mixed donor T-cell chimerism.

We report a case of elevated plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)-like immunoreactive substance (IS) level after multiple doses of a recombinant human erythropoietin (rHuEPO), darbepoetin alfa, in a 50 year-old Japanese female who underwent kidney transplantation. Plasma AcSDKP-IS levels showed a gradual decline after kidney transplantation. However, plasma AcSDKP-IS level showed a rapid rise on day 70, and remained at high levels for a period of time and then declined sharply on day 119. After maintaining relatively constant levels from day 119, plasma AcSDKP level showed a rapid rise again on day 168, and declined again on day 238. The two abrupt increases and subsequent sharp decreases of plasma AcSDKP-IS levels correlated temporally with the initiation and discontinuation of the two course of darbepoetin alfa. Although further detailed studies are necessary, administration of darbepoetin alfa may cause a marked increase in plasma AcSDKP level.

The impact of donor age, especially from older donors (≥ 60 years), on recipient outcomes in living donor kidney transplantation were retrospectively evaluated in 181 consecutive primary kidney transplant recipients. Patients were categorized according to donor age: age ≤ 39 (n=15), 40‒49 (n=28), 50‒59 (n=71), and ≥ 60 years (n=67). Cox proportional hazard multivariate analysis was used to calculate the relative risk of patient and graft survival. Cox analysis showed that donor age, as a continuous variable, was not a risk factor for patient or graft survival. Deathuncensored (65.4%) and censored (73.1%) graft survival rates in the oldest donor group were lowest, although the differences did not reach statistical significance (p=0.086 and 0.127, respectively). Mean estimated glomerular filtration rates one year after transplantation in these 4 groups were 63.1 ± 13.9, 60.4 ± 18.5, 49.2 ± 15.4 and 42.6 ± 11.4 ml/ min/1.73 m2, respectively (p < 0.001). Subdivision by age of recipients of kidney donors ≥ 60 years into those aged, ≤ 39, (n=31), 40-59, (n=25) and ≥ 60 (n=11) years, showed optimal results in old for old combination transplants. The death-uncensored graft survival rates in the 3 subgroups were 64.5%, 76.0% and 90.9%, respectively (p=0.869), whereas their mean estimated glomerular filtration rates 1 year after transplantation were 40.7 ± 7.4, 41.0 ± 10.7 and 51.4 ± 14.3 ml/min/1.73 m2, respectively (p=0.025). Age-matching may be beneficial when performing living donor kidney transplantation from older donors.

Background: Cardiac retransplantation (ReTx) remains an infrequent event, and bridging patients with mechanical circulatory support provides another option while patients await suitable donors.

Methods: The United Network for Organ Sharing database was retrospectively reviewed to identify patients undergoing ReTX between 1995-2012. Of the total 28,464 transplants performed during that period, 850 were retransplants and 29 (3.4%) had VAD support prior to retransplant with available data. The primary outcome investigated was overall survival and patients were stratified based on presence of VAD and time between transplant and retransplant (PRVTXDIF). Comparison was undertaken between four groups (G1: ReTX without VAD and PRVTXDIF > 30days, G2: ReTX with VAD and PRVTXDIF <=30days, G3: ReTX with VAD and PRVTXDIF >30 days, G4: ReTX without VAD and PRVTXDIF <=30 days).These were tested with univariate logistical regression and multivariate Cox regression models. Results: In multivariable analysis, the relative risk of death for patients in G3 vs G1 was not statistically significant (RR=0.37, 95% CI=(0.1, 1.5), P=0.16); and the relative risk of death was 1.7 times higher in G2 compared to that in G4, which was not statistically significant (RR=1.7, 95% CI=(0.8, 4.0), P=0.20) . Donor’s age (RR: 1.1, P=0.038) and ischemic time greater than 4 hours (RR: 1.6, P=0.001) were significant predictors of survival. Conclusion: Cardiac retransplantation may be undertaken safely when patients are maintained on mechanical support and further out from primary transplant.

Chondrocytes grown from cartilage explants and then cultured with rehydrated previously desiccated thin strands of cartilage called “cartilage fluff matrix” or “fluff” filled the gaps between the strands of fluff making new cartilage and invaded the cartilage strands. The cells stained similar to the deep layers of normal articular cartilage though at least 60 days of culture. The chondrocytes binded the cartilage strands together and filled the gaps with new cartilage creating a solid construct.

Acute kidney injury (AKI) has long-term biological effects on many organ systems and high mortality. Incomplete recovery of renal function from AKI is frequently observed, particularly when AKI is superimposed on chronic kidney disease (CKD), and this situation may further facilitate the progression of CKD. Patients with severe AKI in the intensive care unit typically have several failed extrarenal organ systems, including haemodynamic instability and respiratory failure. Consistent with these observations, AKI is associated with increased rates of graft failure and mortality after non-renal transplantation. For example, AKI is a common complication of liver transplantation and is associated with reduced patient and graft survival. AKI after lung transplantation also affects the clinical outcomes. The toxicity of calcineurin inhibitors, intraoperative hypoxemia, hypoperfusion due to diuretics overuse, and the use of antibiotics may be predisposing factors that leads to AKI after lung transplantation. While delayed graft function (DGF) caused by ischemic-reperfusion injury during the early phase of kidney transplantation affects graft function, pretransplantation AKI affecting donor kidneys may not have an adverse effect on long-term outcomes. Several biomarkers, such as gelatinase-associated lipocalin, have been evaluated for predicting DGF and long-term graft function; however, additional studies are required to establish the optimal use of these biomarkers. Recent studies also indicate that AKI during in the maintenance phase of kidney transplantation, frequently associated with sepsis and/or urinary tract infection, is a significant risk factor for graft failure. In this review, we focus on the impact of AKI on non-renal and renal transplant graft survival.

Following the global initiative to develop medical innovative technologies such as living cell transplantation, the Japanese promotion plan, “Five-year Clinical Trial Vitalization Plan 2012” was launched in 2012. Subsequently, “Clinical Trials Core Hospitals” or medical care institutions that performed research and development of innovative technologies were identified, which were regularly evaluated by the “Evaluation System for Investigational Medical Care.” In addition, the regulatory guidelines for pharmaceuticals and medical devices have been reexamined and the revised Pharmaceutical Affairs Law (PAL), which was renamed as the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act), and the Act on the safety of regenerative medicine were developed in 2013 and is scheduled for implementation in November 2014. Based on these changes in the national framework for innovative medical care in Japan, this article aims to explain and evaluate the possibility for this framework to be utilized as the universal case model for stem cell and living cell transplantation.

A variety of therapeutic approaches that could be considered neurorestorative are currently in clinical trials after stroke. There are essentially two varieties of restorative approaches. One is cell-based and includes stem cell transplantation with and without augmentation with growth factors and other variety is the pharmacological approach. These strategies are being explored for the ultimate aim to regain maximum restoration possible and eventual complete normalcy of function. Functional recovery post stroke may require new synaptic connections within and away from the damaged tissue. In an infracted area, the ischemic core may not respond to any pharmacological or rehabilitative intervention. For these reasons, the prospects of repairing the neuron system, using various putative restorative strategies seems promising and urgently required for further exploration, refinement and optimization. Ongoing animal and human trials have largely helped in burgeoning our hopes on this method of restorative therapy after stroke.

The purpose of this study was to compare mate deceased donor (DD) kidney transplant (KT) outcomes in patients ≥70 versus <70 years of age in a matched-pair analysis.

Methods: Single center retrospective review of adult KT cases.

Results: From 5/03 to 3/12, we identified 33 DD kidney pairs that met the above criteria. Mean donor age and BMI were 52 years and 27.4 kg/m2, respectively, including 19 (58%) expanded criteria donors. Mean recipient ages were 73.6 and 55.3 years in the 2 groups (p<0.01). No significant differences were noted in multiple recipient and transplant characteristics in the older and younger groups. With a mean follow-up of 58 months, actual patient (79% older versus 94% younger, p=0.15) and kidney graft survival ([KGS] 64% older versus 67% younger) rates were comparable. Two-year patient (97% older versus 94% younger) and KGS (91% older versus 82% younger) rates revealed few early deaths or graft losses in the older group. Death-censored KGS (81% older versus 69% younger) rates demonstrated that the older group had more deaths with functioning grafts (DWFG, 21% versus 3%, p=0.05). Mean length of initial hospital stay, renal function, and rates of delayed graft function, acute rejection, major infection, re-operations and readmissions were comparable. In 13 patients aged 75 years and older, the incidence of DWFG was 31% in patients compared to 15% in patients aged 70-74 (p=0.33 compared to those >75), and 3% in all 33 younger patients (p=0.02 compared to those >75). The timing of DWFG was at a mean of 40.5 months in patients aged 75 and older compared to 72 months for those aged 70-74 years.  

Conclusions: When controlling for donor factors in a paired kidney analysis, medium-term outcomes are largely influenced by a higher incidence of DWFGs in the elderly, particularly in patients aged 75 and older.

The HLA class II polymorphism of 254 healthy unrelated Omanis was analyzed by PCR-SSP method, and the detected frequencies were compared to those reported in 20 other populations. The most frequent HLA class II DRB1 alleles were DRB1*16, DRB1*03 and DRB1*15 with frequencies of 0.315, 0.224 and 0.106 respectively, while the most frequent DQB1 alleles were DQB1*05 and DQB1*02 with frequencies of 0.366 and 0.283 respectively. The haplotype analysis revealed that DRB1*03-DQB1*02 was the most common HLA class II haplotype with linkage disequilibrium (a frequency of 0.206). Compared with other populations, our result, deduced from the analysis of genetic distances and the construction of neighbour joining dendrogram, indicates that Omanis are related to Mediterranean and West-Asian populations. This fact might be explained by several historic and socio-geographic factors if we consider on the long history of this population.

Xenotransplantation using pig cells, tissues or organs is considered to be a solution to the shortage of human allotransplants. Pigs have been selected as optimal donor for several reasons, among them physiological and economical. Before xenotransplantation will be applied broadly in the clinic three hurdles need to be overcome: (i) rejection due to immune reactions and coagulation dysfunction, (ii) physiological incompatibility and (iii) microbiological risk. Although some clinical trials have been performed in the past and some are ongoing, most experience is gained from pig-to-non human primate experiments. To overcome immune rejection, numerous multitransgenic and knock-down animals were produced or are in preparation. The physiological compatibility is still badly studied, mainly due to the short survival time of the recipient animals. Last not least, xenotransplantation may be associated with the risk of transmission of porcine microorganisms. Most of them can be eliminated by designated pathogen free breeding of the animals; however, porcine endogenous retroviruses (PERVs) represent a special risk. PERVs are integrated as proviruses in the genome of all pigs, they can be released as viral particles and infect human cells. An extensive screening program and selection of donor animals with a low expression of PERV accompanied by the development of different strategies to prevent PERV transmission is therefore requested. Finally, a broad discussion within the scientific community and the society concerning ethical aspects of xenotransplantation had been taken place.

There are many people who lost their valuable lives due to organ loss or improper functioning of particular organ, which leads to the death of that particular person. Transplantation can be defined as the transfer of any essential organ, cell, or tissue from one location to another with in a same individual or from one person to another for the purpose of replacing the patient’s damaged organs. There are different types of transplantations depending up on the type of transplant, which includes, Heart, kidney, liver, lung, pancreas, intestine, and thymus, bones, cornea, skin, heart valves, nerves and veins. Although there are several drawbacks involved, transplantation has become an unbelievable evolution by developing day by day and becoming available to the common people to save their valuable lives, thus it can be regarded as an amazing gift to the human population.

Polyomavirus infection has emerged as an important cause of polyomavirus-associated nephropathy (PVAN) leading to allograft dysfunction and loss. The aim of this study is to investigate pathological features and clinical characteristics of PVAN. We prospectively investigated 351 renal allografts performed in Jinling Hospital. PVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. 31 patients were diagnosed with PVAN (8.8%). The patients with PVAN typically presented as allograft dysfunction with an asymptomatic rise in serum creatinine about 3 to 39 months posttransplant. Urinary decoy cells were positive in 4 patients (12.9%). The histologic changes of PVAN are not pathognomonic and can be mistaken for allograft rejection, i.e. tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis, tubular atrophy and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining is positive in allograft. CD3, CD4, CD8, CD68 positive cells are increased in PVAN group than the non-PVAN group, but none of HLA-DR and IL-2R expression is positive in PVAN patients. MPA AUC 0-12 and TAC trough levels are increased in PVAN group than non-PVAN group at biopsy. We have treated 31 patients with biopsy-proven PVAN with leflunomide. Increased intensity of immunosuppression appears to increase the likelihood of PVAN. The definitive diagnosis of PVAN requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of PVAN.

Completely duplicated ureters are not commonly used in renal transplantation due to increased risk of postoperative complications, such as urinary tract infections, stricture, reflux and urinary leakage. Although recent results have indicated that the occurrence of these complications is similar to that of a single ureter, few reports exist of renal transplantations of kidneys with ureteral duplication. Here, we report successful renal transplantation of a cadaveric kidney with completely duplicated ureters to a 52-year-old final stage renal disease patient who had been on dialysis for 19 years. A modified extravesical ureteroneocystostomy technique was employed, in which distal ureteric ends were spatulated and their medial edges were approximated. Double-j stent catheters were inserted during the ureteroneocystostomy and removed after 21 days when progressive serum creatine levels had decreased. During 6 months following the operation so far, no urinary tract infections, hydronephrosis, pyelonephritis, stricture, or reflux was reported. We conclude that modified extravesical ureteroneocystostomy, a newly described technique is suitable for the transplantation of a cadaveric kidney with complete ureteral duplication.