A novel bilateral grafting technique for studying patterning in Hydra.

Control of patterning and the specification of body axes are fundamental aspects of animal development involving complex interactions between chemical, physical, and genetic signals. The freshwater polyp Hydra has long been recognized as a useful model system to address these questions due to its simple anatomy, optical transparency, and strong regenerative abilities, which enabled clever grafting experiments to alter and probe patterning. Reliable methods exist for the transplantation of small tissue pieces into the body column or the combination of sections cut perpendicular to the body axis, which can be used to examine oral-aboral gradients and axis induction potential of tissue fragments. However, existing methods do not allow researchers to probe questions of axis alignment and lateral information exchange. We therefore developed a technique to produce chimeric animals split longitudinally along the body axis of the animal by anesthetizing the animals with the terpene linalool and threading the donor pieces onto pairs of fine glass needles. Our novel approach can be applied to study questions in Hydra research that have thus far been inaccessible, including patterning processes acting perpendicular to the oral-aboral axis and the extent of lateral cell migration.

Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets.

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8-15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

Osteogenic and Regenerative Potential of Free Gingival Graft.

We studied immunolocalization of CD29, CD44, osteocalcin, and TGF-ß1 in the bone tissue of the mandible of miniature pigs with extra-bone fixation of a free gingival graft. Three months after surgery, neoosteogenesis foci with high expression of the studied markers were found in the contact area of the free gingival graft with the alveolar bone. The markers were localized in the layer of external circumferential lamellae, on the surface of concentric lamellae of the growing osteons, and in the connective tissue of the Haversian canals. TGF-ß1-immunopositive cells predominated in the connective tissue of the Haversian and Volkmann canals and in the adventitia and inner lining of the vascular wall. The established morphochemical patterns of osteogenous cells indicate significant reparative capabilities of a free gingival graft and allows considering it as an effective osteoinductive factor.

Cellular Ex Vivo Lung Perfusion Beyond 1 Hour May Improve Marginal Donor Lung Assessment.

BACKGROUND: Ex vivo lung perfusion (EVLP) permits extended evaluation of donor lungs for transplant. However, the optimal EVLP duration of Lund protocol is unclear. Using human lungs rejected for clinical transplant, we sought to compare the results of 1 versus 2 h of EVLP using the Lund protocol. METHODS: Twenty-five pairs of human lungs rejected for clinical transplant were perfused with the Lund EVLP protocol. Blood gas analysis, lung compliance, bronchoscopy assessment, and perfusate cytokine analysis were performed at both 1 and 2 h. Recruitment was performed at both time points. Donor lung transplant suitability was determined at both time points. RESULTS: All cases were divided into four groups based on transplant suitability assessment at 1 h and 2 h of EVLP. In group A (n = 10), lungs were judged suitable for transplant at both 1 and 2 h of EVLP. In group B (n = 6), lungs were suitable at 1 h but nonsuitable at 2 h. In group C (n = 2), lungs were nonsuitable at 1 h but suitable at 2 h. Finally, in group D (n = 7), lungs were nonsuitable for transplant at both time points. In both groups B and C (n = 8), the transplant suitability assessment changed between 1 and 2 h of EVLP. CONCLUSIONS: In human lungs rejected for transplant, transplant suitability differed at 1 versus 2 h of EVLP in 32% of lungs studied. Evaluation of lungs with Lund protocol EVLP beyond 1 h may improve donor organ assessment.

Early graft function and intrarenal resistant index after kidney transplantation using Biolasol-A new solid organ preservation fluid.

Biolasol is a newly developed preserving solution for cold organ storage prior to transplantation. To date, only animal model experiments results are available. The aim of this single-center analysis was to summarize the clinical experience concerning the early post-transplant course of kidney grafts preserved with Biolasol in comparison with other preservation solutions. Before transplantation, 173 kidney grafts were preserved using Biolasol and 240 organs with other solutions (University of Wisconsin-UW, Institute Georges Lopez-IGL-1, or StoreProtect Plus solutions). Early graft function was defined based on serum creatinine concentration at day 3 (<3 mg/dL-immediate graft function, IGF or >3 mg/dL-slow graft function, SGF) or the need of dialysis therapy during first post-operative week (delayed graft function, DGF). The analysis included intrarenal resistive indices measured by Doppler sonography early after transplantation and before discharge from the hospital. IGF was more frequent in patients with organs preserved with IGL-1 (33.5%) and StoreProtect Plus (38.8%) than Biolasol (18.5%), whereas there was no difference in the occurrence of DGF. Both initial and discharge median resistance index values were significantly higher in the Biolasol subgroup (0.77 and 0.75) than in all three other subgroups (P values for all comparisons <.001), also after 1:1 propensity score matching for baseline characteristics. Multiple logistic regression analysis based on the propensity score-matched cohort revealed that the use of Biolasol solution [OR 0.59 (0.35-0.98); P < .05] independently decreased the occurrence of IGF. In our single-center clinical experience, kidney preservation using Biolasol solution was associated with significantly higher intrarenal resistant index in comparison with other preservation fluids, as well as worse early graft function than in the IGL-1 and the StoreProtect Plus subgroups. Long-term follow-up is needed in order to assess the kidney graft and patient survival.

Myelomeningocele Repair Combining a Double Cryopreserved Amniotic Membrane Homograft and the Keystone Flap in a 3-Year-Old Child: A Case Report.

INTRODUCTION: Early repair in patients affected by myelomeningocele (MMC) is of paramount importance in order to prevent infection, minimize neural tissue damage, and reduce mortality. Treatment must include duraplasty and possibly an adequate soft tissue coverage. Delayed surgery in MMC patients can be more tedious due to the less clear borders between the placode and the skin. Moreover, the risks of wound infection and breakdown increase significantly. CASE PRESENTATION: We present the unusual case of a large MMC in a 3-year-old patient treated by combining the recently described cryopreserved amniotic membrane (AM) as homograft for dural reconstruction and a bilateral Keystone flap for soft tissue reconstruction. DISCUSSION: Thanks to its anti-inflammatory and elastic proprieties, the AM can play an important role in preventing adhesion between the reconstructed layers, thus reducing the risk of spinal cord tethering. The Keystone flap, at the same time, allows the wound tension to be distributed widely over the flap margins and not only along the midline, which overlies the duraplasty, enhancing the scar quality and lowering the risk of cerebrospinal fluid recurrence and wound dehiscence, with no donor site morbidity.

Stiffness and shape of the ACL graft affects tunnel enlargement and graft wear.

PURPOSE: Tunnel enlargement and graft rupture are common complications associated with ACL reconstruction (ACLR). This study aims to explore how variations in graft stiffness and shape affect the strain energy density (SED) around bone tunnel entrances and stress on the graft and subsequently influencing the level of tunnel enlargement and graft wear. METHODS: Finite element ACLR models were developed using different graft stiffnesses (323 N/mm, 545 N/mm and 776 N/mm) and shapes (circular and elliptical). The models were subjected to a combined loading of 103 N anterior tibial load, 7.5 Nm internal tibial moment, and 6.9 Nm valgus tibial moment at joint flexion of 30°. SED at tunnel entrances and stresses on the graft was recorded and compared among the different models. RESULTS: Increasing the graft stiffness resulted in greater stress on the graft (17.2, 24.4 and 31.7 MPa for graft stiffnesses of 323 N/mm, 545 N/mm and 776 N/mm), but had little effect on the SED reduction around the tunnel entrances. Changing the cross section of the graft from circular to elliptical caused an additional reduction in SED (56.8 vs 2.8 kJ/m3) at the posterior zone of the femoral tunnel entrance and increased the stress on the graft (31.7 MPa vs 38.9 MPa). CONCLUSIONS: This study recommends using ACL grafts with lower stiffness and a circular cross section to reduce tunnel enlargement and graft wear following ACLR.

Graft bending angle of the reconstructed posterior cruciate ligament gradually decreases as knee flexion increases.

PURPOSE: The purpose of the study was to determine the change in the graft bending angles at the femoral and tibial tunnel aperture in single-bundle posterior cruciate ligament (PCL) reconstruction. It was hypothesized that different knee flexion and different tunnel directions may affect changes of the femoral and tibial graft bending angle. METHODS: The right knees of 12 male subjects were scanned with a high-resolution computed tomography scanner at 4 different knee flexion angles (0°, 45°, 90° and 135°). To begin with, the 3D knee models were created and manipulated with the use of several modeling programs. Single-bundle PCL reconstruction was then virtually conducted in a 90° flexion model: The femoral and tibial graft bending angle, according to the various knee flexion angles, was calculated using a special software program. RESULTS: The femoral graft bending angle significantly decreased as the knee flexion increased between 0° and 135° (all p < 0.001). The femoral graft bending angle of the AL graft showed the most obtuse angles among the three types of the graft beyond 45° of knee flexion. For the tibial graft bending angle, the anteromedial tunnel group showed significantly more acute tibial graft bending angle than the anterolateral tunnel group in all three types of the graft at all flexion angles (all p < 0.001). CONCLUSION: Changes in the femoral graft bending angle were generally affected by different knee flexion angles. The effect of tibial tunnel direction on the tibial graft bending angle was found to be significant. The clinical relevance is that a mostly obtuse femoral graft bending angle was shown by the AL graft among three types of the graft.

APOL1 Genotype and Renal Function of Black Living Donors.

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

Mechanical Evaluation of Tracheal Grafts on Different Scales.

Tissue engineered (or bioengineered) tracheas are alternative options under investigation when the resection with end-to-end anastomosis cannot be performed. One approach to develop bioengineered tracheas is a complex process that involves the use of decellularized tissue scaffolds, followed by recellularization in custom-made tracheal bioreactors. Tracheas withstand pressure variations and their biomechanics are of great importance so that they do not collapse during respiration, although there has been no preferred method of mechanical assay of tracheas among several laboratories over the years. These methods have been performed in segments or whole tracheas and in different species of mammals. This article aims to present some methods used by different research laboratories to evaluate the mechanics of tracheal grafts and presents the importance of the tracheal biomechanics in both macro and micro scales. If bioengineered tracheas become a reality in hospitals in the next few years, the standardization of biomechanical parameters will be necessary for greater consistency of results before transplantations.

Successful reuse of a transplanted kidney 9 years after initial transplantation: 4-year follow-up.

BACKGROUND: Kidney transplantation is the preferred renal replacement therapy for patients with end-stage renal disease, but the waiting list for kidneys continues to grow because of a shortage of donor organs. The reuse of transplanted kidneys would seem to be a good approach to expand the pool of available organs. Here, we describe the reuse of a kidney 9 years after the initial transplantation. At 4-year follow-up, the second recipient is showing good renal function. CASE PRESENTATION: In 2005, a kidney was transplanted from a 40-year-old man, who suffered brain death due to an intracranial hemorrhage, into a 45-year-old man. Nine years later, the recipient suffered a ruptured cerebral aneurysm, resulting in brain death. The kidney was re-transplanted into a 40-year-old man with diabetic nephropathy who had received hemodialysis for 5 years. During 4 years of follow-up, the graft has functioned well. CONCLUSIONS: This case demonstrates the successful regrafting of a transplanted kidney. We believe this is the longest period for reuse of kidney after initial transplantation. The outcome suggests that a well-functioning transplanted kidney can be reused years after transplantation.

Co-Transplantation of Nanofat Enhances Neovascularization and Fat Graft Survival in Nude Mice.

BACKGROUND: Autologous fat grafting is commonly used for soft-tissue augmentation and reconstruction. However, this technique is limited by a high rate of graft absorption. Thus, approaches to improve fat graft survival that promote neovascularization are of great interest. Nanofat has several beneficial features that may render it more suitable for clinical applications than other stem-cell based approaches. OBJECTIVES: We aimed to determine whether nanofat could enhance new vessel formation and improve the long-term retention of fat grafts. METHODS: Nanofat was processed via mechanical emulsification and filtration. Fat grafts were transplanted subcutaneously under the scalps of nude mice with different nanofat volumes or without nanofat. The grafted fat was dissected 12 weeks after transplantation. Graft weight and volume were measured, and histological evaluations, including capillary density measurement, were performed. RESULTS: The co-transplantation of fat with nanofat showed higher graft weight and volume retention, better histological structure, and higher capillary density compared to that in controls. However, there were no significant differences between the two nanofat volumes utilized. CONCLUSIONS: Nanofat can enhance neovascularization and improve fat graft survival, providing a potential clinically viable approach to fat graft supplementation in plastic and reconstructive surgery.

Influence of tibial hybrid fixation on graft tension and stability in ACL double-bundle reconstruction.

PURPOSE: Initial graft tension in anterior cruciate ligament (ACL) reconstruction affects stability and tension loss at follow-up. This study investigated the influence of hybrid tibial fixation in 3-tunnel double-bundle ACL reconstruction on initial graft tension and tension change and stability under anterior and combined rotatory loads. METHODS: Eleven fresh-frozen cadaveric knees were reconstructed with an ACL double bundle using a 3-tunnel technique. Grafts were tightened to 80 N in 60° (AM bundle) and 15° (PL bundle) of flexion. Anterior tibial translation under 134 N of anterior shear load and translation under combined rotatory and valgus loads (10 Nm valgus stress, 4 Nm internal tibial torque) were determined at 0°, 30°, 60°, and 90° flexion. In addition, graft tension under continuous passive motion was determined. Intact, ACL-resected and ACL-reconstructed joints with either tibial extracortical graft fixation or extracortical plus supplemental aperture graft fixation (hybrid fixation) were tested. RESULTS: Hybrid fixation did not increase graft tension in either bundle during fixation or in motion without additional load. AM-bundle tension increased (p < 0.05) at 0° under combined rotatory and valgus loads and at 30° and 60° under both loading conditions without decreasing the anterior tibial translation. PL-bundle tension increased (p < 0.05) only at 90° under combined rotatory and valgus loads. CONCLUSIONS: Tibial hybrid fixation in 3-tunnel double-bundle ACL reconstruction increases time-zero AM- and PL-bundle tensions under loading conditions, generating greater construct stiffness. This could lead to a longer preservation of ACL-graft stability in clinical follow-up before bony incorporation.

A prospective, multicentre, open-label, single-arm clinical trial for treatment of chronic complex diabetic foot wounds with exposed tendon and/or bone: positive clinical outcomes of viable cryopreserved human placental membrane.

Complex diabetic foot ulcers (DFUs) with exposed tendon or bone remain a challenge. They are more susceptible to complications such as infection and amputation and require treatments that promote rapid development of granulation tissue and, ultimately, reepithelialisation. The clinical effectiveness of viable cryopreserved human placental membrane (vCHPM) for DFUs has been established in a level 1 trial. However, complex wounds with exposed deeper structures are typically excluded from randomised controlled clinical trials despite being common in clinical practice. We report the results of a prospective, multicentre, open-label, single-arm clinical trial to establish clinical outcomes when vCHPM is applied weekly to complex DFUs with exposed deep structures. Patients with type 1 or type 2 diabetes and a complex DFU extending through the dermis with evidence of exposed muscle, tendon, fascia, bone and/or joint capsule were eligible for inclusion. Of the 31 patients enrolled, 27 completed the study. The mean wound area was 14·6 cm2 , and mean duration was 7·5 months. For patients completing the protocol, the primary endpoint, 100% wound granulation by week 16, was met by 96·3% of patients in a mean of 6·8 weeks. Complete wound closure occurred in 59·3% (mean 9·1 weeks). The 4-week percent area reduction was 54·3%. There were no product-related adverse events. Four patients (13%) withdrew, two (6·5%) for non-compliance and two (6·5%) for surgical intervention.

Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts.

We developed a novel technique of subnormothermic ex vivo liver perfusion (SNEVLP) for the storage of liver grafts before transplantation. To test the safety of SNEVLP for the nonextended criteria grafts (standard grafts), we compared it to a control group with minimal cold static storage (CS) time. Heart-beating pig liver retrieval was performed. Grafts were either stored in cold unmodified University of Wisconsin solution (CS-1), in cold University of Wisconsin solution with ex vivo perfusion additives (CS-2), or preserved with a sequence of 3 hours CS and 3 hours SNEVLP (33°C), followed by orthotopic liver transplantation. Liver function tests and histology were investigated. Aspartate aminotransferase (AST) levels during SNEVLP remained stable (54.3 ± 12.6 U/L at 1 hour to 47.0 ± 31.9 U/L at 3 hours). Posttransplantation, SNEVLP versus CS-1 livers had decreased AST levels (peak at day 1, 1081.9 ± 788.5 versus 1546.7 ± 509.3 U/L; P = 0.14; at day 2, 316.7 ± 188.1 versus 948.2 ± 740.9 U/L; P = 0.04) and alkaline phosphatase levels (peak at day 1, 150.4 ± 19.3 versus 203.7 ± 33.6 U/L; P = 0.003). Bilirubin levels were constantly within the physiological range in the SNEVLP group, whereas the CS-1 group presented a large standard deviation, including pathologically increased values. Hyaluronic acid as a marker of endothelial cell (EC) function was markedly improved by SNEVLP during the early posttransplant phase (5 hours posttransplant, 1172.75 ± 598.5 versus 5540.5 ± 2755.4 ng/mL). Peak international normalized ratio was similar between SNEVLP and CS-1 groups after transplantation. Immunohistochemistry for cleaved caspase 3 demonstrated more apoptotic sinusoidal cells in the CS-1 group when compared to SNEVLP grafts 2 hours after reperfusion (19.4 ± 19.5 versus 133.2 ± 48.8 cells/high-power field; P = 0.002). Adding normothermic CS-2 had no impact on liver injury or function after transplantation when compared to CS-1. In conclusion, SNEVLP is safe to use for standard donor grafts and is associated with improved EC and bile duct injury even in grafts with minimal CS time.

High-load preconditioning of soft tissue grafts: an in vitro biomechanical bovine tendon model.

PURPOSE: No consensus exists regarding the optimal preconditioning protocol that will minimize postoperative elongation while creating a graft that is biomechanically equivalent to the native anterior cruciate ligament (ACL). It was hypothesized that a preconditioning protocol of specific mode and magnitude would create a graft with equivalent stiffness to the native ACL. METHODS: Thirty-six bovine extensor tendon grafts were randomly allocated among six preconditioning groups (n = 6 per group) including three cyclic (10 cycles at 0.5 Hz between 10-80, 100-300, and 300-600 N) and three static loading protocols (20 s at 80, 300, and 600 N). Grafts were then cyclically loaded between 50 and 250 N at 0.5 Hz for 500 cycles to simulate an early rehabilitation protocol. RESULTS: Cyclic 300-600 N and static 600 N loading protocols both demonstrated significantly less elongation during simulated rehabilitation when compared to lower, current clinical standard preconditioning levels of 10-80 N (-62% Δ) and 80 N (-69% Δ). The same high-load preconditioning protocols demonstrated statistical equivalence in stiffness when compared to the previously reported stiffness of the native ACL. CONCLUSIONS: In this experimental model, increased force applied to soft tissue grafts during preconditioning significantly decreased the subsequent elongation experienced during simulated early rehabilitation. A static load of 600 N removed the most graft elongation during preconditioning, had the least amount of cyclic displacement during simulated early rehabilitation, and was statistically equivalent to the native ACL stiffness. Implementation of high-load preconditioning of soft tissue grafts may help improve outcomes following ACL reconstruction by reducing residual knee laxity resulting from postoperative graft elongation and the intrinsic viscoelastic properties of the graft tissue while imparting biomechanical characteristics (e.g. stiffness) equivalent to the native ACL.

Effect of fixation angle and graft tension in double-bundle anterior cruciate ligament reconstruction on knee biomechanics.

PURPOSE: To compare the effect of graft fixation angle and tension in double-bundle anterior cruciate ligament (ACL) reconstruction on knee biomechanics. METHODS: Fourteen cadaver knees were tested using a robotic system under two loadings: (1) an 89-N anterior tibial load (ATL) at full extension (FE), 15°, 30°, 45°, 60°, and 90°, and (2) combined 7 N m valgus and 5 N m internal tibial torques (simulated pivot-shift test) at FE, 15° and 30°. Four graft fixation angles and tensions were used for the anteromedial (AM) and posterolateral (PL) bundles, respectively: (Recon 1) 30°/20N and FE/20N, (Recon 2) 30°/30N and FE/10N, (Recon 3) 45°/20N and 15°/20N, and (Recon 4) 45°/30N and 15°/10N. RESULTS: All fixation protocols closely restored the intact knee kinematics under ATL and simulated pivot-shift loading. For the AM bundle under ATL, the in situ force (ISF) with Recon 3 at the FE was significantly lower than that of the intact knee. For the PL bundle under ATL, the ISF with Recon 3 at the FE, 15° and 30° was significantly higher than that of the intact knee. In PL bundle under simulated pivot-shift loading, the ISF with Recon 1 and Recon 2 at FE was lower and the ISF of the PL bundle with Recon 3 at the 15° was higher than that of the intact knee. CONCLUSION: The AM-45°/30N and PL-15°/10N fixation most closely matched intact knee kinematics; however, stabilizing the knee during anterior tibial translation may risk an imbalance of the AM and the PL bundle loading. The results indicate that ACL bundle forces may not be restored even if the clinical assessment shows good results with the Lachman test and pivot-shift test. This may alter the loading on other structures of the knee.

[The impact of donor-to-recipient gender match and mismatch on the renal function of living donor renal graft recipients]. / Compatibilidad de género entre donador y receptor puede ser un factor pronóstico en la funcióndel injerto de trasplante renal de donador vivo.

INTRODUCTION: Donor-to-recipient gender match and mismatch may be a potential prognostic factor for living donor renal graft function. METHODS: A retrospective review of donor-to-recipient pairs undergoing living donor kidney transplantation was done. They were classified according to gender match as: male-to-male, female-to-female, male-to-female, and female-to-male. Serum creatinine was recorded during one year for donors and for up to four years for recipients. Renal function was evaluated by estimating the glomerular filtration rate with the Chronic Kidney Disease-Epidemiology Collaboration formula. A comparative statistical analysis was performed. RESULTS: The analysis included 217 donor-to-recipient pairs. No significant differences across the four groups in estimated glomerular filtration rate and serum creatinine at any cut-off time point except at day one serum creatinine were found. Recipients had a significant difference in serum creatinine up to the first year of follow-up, with higher values for male recipients; no significant differences were found during the second through fourth year of follow-up. A significant difference was observed in estimated glomerular filtration rate throughout all follow-ups among the four groups, favoring female recipients of male kidneys. CONCLUSIONS: Donor-recipient mismatch may have a deleterious effect over long-term graft function. Female recipients of male kidneys have the best prognosis.

[Donor/recipient age index (DoRAIn) as an independent predictor of long-term living-donor renal graft function]. / Índice de edad donador/receptor (DoRAIn) como un predictor independiente de la función del injerto de donante vivo renal a largo plazo.

PROBLEM: The effect of donor/recipient age disparity on living-donor renal graft function is controversial. The objective of this study is to find new clinical predictors of renal graft function and evaluate the effect of donor/recipient age disparity in our series. METHODS: A retrospective review of our institutional renal transplantation database was performed. We calculated the glomerular filtration rate of our patients with the Chronic Kidney Disease Epidemiology Collaboration formula. Our receptors were categorized using a cut-off of 60 ml/min calculated glomerular filtration rate. An index called "Donor/Recipient Age Index" was created based on the interaction between donor/recipient ages. Univariable and multivariable regression analysis were performed. The Mantel-Cox model was used for statistical analysis. RESULTS: A total of 220 donor/recipient pairs were selected from January 2005 to August 2013. Only 186 pairs completed the one-year follow-up. The mean age of the donors was 35.3 ± 10.4 years and 31.6 ± 11.7 years for the recipients. The Donor/Recipient Age Index significantly predicted a glomerular filtration rate < 60 ml/min at one-year follow-up in univariable (p = 0.02) and multivariable (p = 0.033) regression models. CONCLUSION: We propose the Donor/Recipient Age Index as a significant predictor of long-term graft function.

Tempering allorecognition to induce transplant tolerance with chemically modified apoptotic donor cells.

The development of organ transplantation as a therapy for end-stage organ failure is among the most significant achievements of 20th century medicine, but chronic rejection remains a barrier to achieving long-term success. Current therapeutic regimens consist of immunosuppressive drugs that are efficient at delaying rejection but are associated with significant risks such as opportunistic infections, toxicity, and malignancy. Thus, the induction of specific immune tolerance to transplant antigens is the coveted aim of researchers. The use of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (ECDI)-treated, autoantigen-coupled syngeneic leukocytes has been developed as a specific immunotherapy in preclinical models of autoimmunity and is currently in a phase II clinical trial for the treatment of multiple sclerosis. In this review, we discuss the use of allogeneic ECDI-treated apoptotic donor leukocytes (allo-ECDI-SP) as a strategy for inducing antigen-specific tolerance in allogeneic transplantation. Allo-ECDI-SP therapy induces long-term systemic immune tolerance to transplant antigens by subverting alloimmune recognition and exploiting apoptotic cell uptake pathways to recapitulate innate mechanisms of peripheral tolerance. Lastly, we discuss potential indications and challenges for transitioning allo-ECDI-SP therapy into clinical practice.