Biomechanical properties of the ex vivo porcine trachea: A benchmark for three-dimensional bioprinted airway replacements.

PURPOSE: Combining tissue engineering and three-dimensional (3D) printing may allow for the introduction of a living functional tracheal replacement graft. However, defining the biomechanical properties of the native trachea is a key prerequisite to clinical translation. To achieve this, we set out to define the rotation, axial stretch capacity, and positive intraluminal pressure capabilities for ex vivo porcine tracheas. STUDY DESIGN: Animal study. MATERIALS AND METHODS: Six full-length ex vivo porcine tracheas were bisected into 5.5 cm segments. Maximal positive intraluminal pressure was measured by sealing segment ends with custom designed 3D printed caps through which a pressure transducer was introduced. Axial stretch capacity and rotation were evaluated by stretching and rotating the segments along their axis between two clamps, respectively. RESULTS: Six segments were tested for axial lengthening and the average post-stretch length percentage was 148.92% (range 136.81-163.48%, 95% CI 153-143%). The mean amount of length gain achieved per cartilaginous ring was 7.82% (range 4.71-10.95%, 95% CI 6.3-9.35%). Four tracheal segments were tested for maximal positive intraluminal pressure, which was over 400 mmHg. Degree of rotation testing found that the tracheal segments easily transformed 180° in anterior-posterior bending, lateral bending, and axial rotational twisting. CONCLUSIONS: We define several biomechanical properties of the ex vivo porcine trachea by reporting the rotation, axial stretch capacity, and positive intraluminal pressure capabilities. We hope that this will aid future work in the clinical translation of 3D bioprinted airway replacement grafts and ensure their compatibility with native tracheal properties.

A prediction model of delayed graft function in deceased donor for renal transplant: a multi-center study from China.

BACKGROUND: Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. METHODS: This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. RESULTS: The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. CONCLUSIONS: Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

Predictors of Hyperuricemia after Kidney Transplantation: Association with Graft Function.

BACKGROUND: In kidney transplant recipients (KTR), hyperuricemia (HU) is a commonly-observed phenomenon, due to calcineurin inhibitors and reduced kidney graft function. Factors predicting HU, and its association with graft function, remains equivocal. METHODS: We conducted a retrospective longitudinal study to assess factors associated with HU in KTR, and to determine risk factors associated with graft function, measured as glomerular filtration rate (GFR). Moreover, GFR > 60 mL/min/1.73 m2 was considered normal. HU was defined as a serum uric acid level of > 416 µmol/L (4.70 mg/dL) in men and >357 µmol/L (4.04 mg/dL) in women, or xanthine-oxidase inhibitor use. We built multiple logistic regression models to assess predictors of HU in KTR, as well as the association of demographic, clinical, and biochemical parameters of patients with normal GFR after a three-year follow-up. We investigated the effect modification of this association with HU. RESULTS: There were 144 patients (mean age 46.6 ± 13.9), with 42.4% of them having HU. Predictors of HU in KTR were the presence of cystic diseases (OR = 9.68 (3.13; 29.9)), the use of diuretics (OR = 4.23 (1.51; 11.9)), and the male gender (OR = 2.45 (1.07; 5.56)). Being a younger age, of female gender, with a normal BMI, and the absence of diuretic medications increased the possibility of normal GFR. HU was the effect modifier of the association between demographic, clinical, and biochemical factors and a normal GFR. CONCLUSIONS: Factors associated with HU in KTR: Presence of cystic diseases, diuretic use, and male gender. HU was the effect modifier of the association of demographic, clinical, and biochemical factors to GFR.

Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens' longitudinal development.

BACKGROUND: Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/-pancreas transplant recipients. Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth. METHODS: All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months. RESULTS: Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24-38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively. CONCLUSION: Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted.

Impact of acute kidney injury in expanded criteria deceased donors on post-transplant clinical outcomes: multicenter cohort study.

BACKGROUND: The problem of organ shortage is an important issue in kidney transplantation, but the effect of kidney donation on AKI is unclear. The aim of this study was to investigate the impact of acute kidney injury (AKI) on post-transplant clinical outcomes for deceased donor kidney transplantation (DDKT) using standard criteria donors (SCDs) versus expanded criteria donors (ECDs). METHODS: Five-hundred nine KT recipients receiving kidneys from 386 deceased donors (DDs) were included from three transplant centers. Recipients were classified into the SCD-KT or ECD-KT group according to corresponding DDs and both groups were divided into the AKI-KT or non-AKI-KT subgroups according to AKI in donor. We compared the clinical outcomes among those four groups and investigated the interaction between AKI in donors and ECD on allograft outcome. RESULTS: The incidence of delayed allograft function was higher when the donors had AKI within SCD-KT and ECD-KT groups. In allograft biopsies within 3 months, chronic change was more significant in the AKI-ECD-KT subgroup than in the non-AKI-ECD-KT subgroup, but it did not differ between AKI-SCD-KT and non-AKI-SCD-KT group. AKI-ECD-KT showed higher risk for death-censored allograft failure than the other three groups and a significant interaction was observed between AKI in donors and ECD on the allograft outcome. CONCLUSIONS: The presence of AKI in ECDs significantly impacted the long-term allograft outcomes of kidney transplant recipients, but it did not in SCDs.

Pre-donation BMI and preserved kidney volume can predict the cohort with unfavorable renal functional compensation at 1-year after kidney donation.

BACKGROUND: The magnitude of renal function recovery after kidney donation differs in donors with a heterogeneous background. Preoperative assessment of candidates with potentially unfavorable renal functional compensation is critical when baseline kidney function is marginal. We explored the significance of preserved kidney volume (PKV) and known preoperative risk factors for the prediction of unfavorable renal function compensation. METHODS: We enrolled 101 living donors for whom a 1-mm sliced enhanced computed tomography scan was performed preoperatively and clinical data could be collected up to 1 year after donation. The donors whose estimated glomerular filtration rate (eGFR) at 1 year after donation was 70% or higher of baseline eGFR were assigned to the "favorable renal compensation" group and the others to the "unfavorable renal compensation" group. RESULTS: Age, sex, and preoperative serum uric acid level were not significant predictors for "unfavorable renal compensation." Multivariable logistic regression analysis revealed that body mass index (BMI) and body surface area (BSA)-adjusted PKV were independent preoperative risk factors for "unfavorable renal compensation" (adjusted odds ratio, 1.342 and 0.929, respectively). Hypertension and preoperative eGFR were not independent predictors when adjusted with BMI and BSA-adjusted PKV. Receiver operative characteristic analysis revealed that the predictive equation with the two independent predictors yielded a good accuracy to detect donor candidates with unfavorable renal functional compensation (area under the curve = 0.803), and the optimal cut-off values were identified as 23.4 kg/m2 for BMI and 107.3 cm3/m2 for BSA-adjusted PKV. CONCLUSIONS: BMI and BSA-adjusted PKV may be useful to select candidates with potentially unfavorable renal function compensation before kidney donation.

Inferior graft maturity in the PL bundle after autograft hamstring double-bundle ACL reconstruction.

PURPOSE: The purpose of this study was to evaluate the signal/noise quotient (SNQ) for graft maturation and the serial changes observed in the magnetic resonance imaging (MRI) findings after double-bundle (DB) anterior cruciate ligament (ACL) reconstruction using a hamstring tendon autograft at a minimum of 5 years after surgery. METHODS: Forty-five patients who underwent DB ACL reconstruction between 2007 and 2010 were included in this prospective study. All participants underwent postoperative MRI at 3 weeks and 3, 6, 9 and 12, 18, 24, 36, 48 and 50 months. The signal intensity (SI) characteristics of the reconstructed graft were evaluated on oblique axial proton density-weighted MR imaging (PDWI) perpendicular to the grafts. The signal/noise quotient (SNQ) was calculated to quantitatively determine the normalized SI. The SNQ of the AMB and PLB was evaluated separately. RESULTS: The mean SNQ of the AM bundle (AMB) continued to increase until 6 months after surgery (5.2 ± 1.2), and then gradually decreased and became well stabilized by 18 months (3.3 ± 0.5), after which it remained unchanged. On the other hand, the mean SNQ of the PL bundle (PLB) continued to increase until 9 months after surgery (6.2 ± 1.1), and then decreased incrementally and became well stabilized by 24 months (4.1 ± 0.5). The SI of PLB was significantly higher than that of AMB between 3 and 24 months (p = 0.04, 0.03, 0.01, 0.04, 0.02 and 0.03, respectively). CONCLUSIONS: These results indicate that at least 18 months is needed after ACL reconstruction to sufficiently restore the SI of the AMB, while at least 24 months are needed to for the PLB. The SI of the PLB was significantly higher than that of the AMB at 3-24 months after surgery, indicating that the PLB showed inferior graft maturity to the AMB until 24 months after surgery. For clinical relevance, the correct understanding of serial changes in graft maturation may potentially be used in decision-making regarding a return to sports. LEVEL OF EVIDENCE: Prospective case series, Level IV.

An unbalanced monocyte macrophage polarization in the bone marrow microenvironment of patients with poor graft function after allogeneic haematopoietic stem cell transplantation.

Poor graft function (PGF) is a severe complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). Murine studies have demonstrated that effective haematopoiesis depends on the specific bone marrow (BM) microenvironment. Increasing evidence shows that BM macrophages (MФs), which constitute an important component of BM immune microenvironment, are indispensable for the regulation of haematopoietic stem cells (HSCs) in the BM. However, little is known about the number and function of BM MФs or whether they directly interact with HSCs in PGF patients. In the current prospective case-control study, PGF patients showed a significant increase in classically activated inflammatory MФs (M1; 2·18 ± 0·11% vs. 0·82 ± 0·06%, P < 0·0001), a striking reduction in alternatively activated anti-inflammatory MФs (M2; 3·02 ± 0·31% vs. 21·89 ± 0·90%, P < 0·0001), resulting in a markedly increased M1/M2 ratio (0·82 ± 0·06 vs. 0·06 ± 0·002; P < 0·0001) in the BM compared with good graft function patients. Meanwhile, standard monocyte subsets were altered in PGF patients. Dysfunctional BM MФs, which were characterized by reduced proliferation, migration and phagocytosis, were evident in PGF patients. Furthermore, BM MФs from PGF patients with high tumour necrosis factor-α and interleukin 12 levels and low transforming growth factor-ß levels, led to impaired BM CD34+ cell function. In summary, our data indicate that an unbalanced BM M1/M2 ratio and dysfunctional MФs may contribute to the occurrence of PGF following allo-HSCT.

Preserved Vasoconstriction and Relaxation of Saphenous Vein Grafts Obtained by a No-Touch Technique for Coronary Artery Bypass Grafting.

BACKGROUND: To obtain a saphenous vein graft (SVG) for coronary artery bypass grafting (CABG), the benefit of using a no-touch (NT) technique in vascular function has not been fully investigated. Methods and Results: The pathological and physiological functions of human SVGs with a NT technique to preserve the perivascular adipose tissue (PVAT) and ones obtained by using a conventional (CON) technique removing PVAT, were examined. Immunohistochemistry of the section of SVGs showed that the phosphorylation of endothelial nitric oxide synthase in the endothelium of the NT group was more responsive to vascular endothelial growth factor. A myograph of SVGs showed greater contraction with phenylephrine in the NT group. However, the strong contraction was eliminated in SVGs taken by electrocautery. In the 10 patients whose SVGs were taken without electrocautery, endothelial-dependent relaxation with bradykinin was apparently increased in the CON group more than in the NT group. Smooth muscle relaxation with nitroprusside was higher in the CON group at the lower concentrations; however, the relaxation became greater in the NT group at the high concentrations. Therefore, the effect of neutralizing PVAT-released factors in the both groups was further examined. After medium of NT and CON were exchanged in half, relaxation of SVGs was immediately restored in the NT group. CONCLUSIONS: The results suggest that the NT technique preserves the functions of vasoconstriction and relaxation. Also, the presence of PVAT-released vasoconstrictive factors was suspected.

Time-intensity curve analysis of contrast-enhanced ultrasound is unable to differentiate renal dysfunction in the early post-transplant period - a prospective study.

BACKGROUND: Contrast enhanced ultrasonography (CEUS) assessment of kidney allografts mainly focuses on graft rejection. However, studies on delayed graft function (DGF) without acute rejection are still lacking. The aim of this study was to build a time-intensity curve (TIC) using CEUS in non-immunological DGF to understand the utility of CEUS in early transplantation. METHODS: Twenty-eight patients in the short-term postoperative period (<14 days) were divided according to the need for dialysis (early graft function [EGF] and [DGF]) and 37 subjects with longer than 90 days follow-up were divided into creatinine tertiles. Time to peak [TTP] and rising time [RT were compared between groups. RESULTS: EGF and DGF were similar, except for creatinine. In comparison to the late group, medullary TTP and RT were shorter in the early group as well as the delay regarding contrast arrival in the medulla (in relation to cortex) and reaching the medullary peak (in relation to artery and cortex). In the late group, patients with renal dysfunction showed shorter temporal difference to reach medullary peak in relation to artery and cortex. CONCLUSIONS: Although it was not possible to differentiate EGF and DGF using TIC, differences between early and late groups point to blood shunting in renal dysfunction.

Comparison of graft bending angle during knee motion after outside-in, trans-portal and trans-tibial anterior cruciate ligament reconstruction.

PURPOSE: To determine graft bending angle (GBA) during knee motion after anatomic anterior cruciate ligament (ACL) reconstruction and to clarify whether surgical techniques affect GBA. Our hypotheses were that the graft bending angle would be highest at knee extension and the difference of surgical techniques would affect the bending steepness. METHODS: Eight healthy volunteers with a mean age of 29.3 ± 3.0 years were recruited and 3D MRI knee models were created at three flexion angles (0°, 90° and 130°). Surgical simulation of the tunnel drilling was performed with anatomic tunnel position using each outside-in (OI), trans-portal (TP) and trans-tibial (TT) techniques on the identical cases. The models were matched to other knee positions and the GBA in 3D was measured using computational software. Double-bundle ACL reconstruction was analysed first, and single-bundle reconstruction was also analysed to evaluate its effect to reduce GBA. A repeated-measures ANOVA was used to compare GBA difference at three flexion angles, by three techniques or of three bundles. RESULTS: GBA changed substantially with knee motion, and it was highest at full extension (p < 0.001) in each surgical technique. OI technique exhibited highest GBA for anteromedial bundle (94.3° ± 5.2°) at extension, followed by TP (83.1° ± 6.5°) and TT (70.0° ± 5.2°) techniques (p < 0.01). GBA for posterolateral bundle at extension were also high in OI (84.6° ± 7.4°), TP (83.0° ± 6.3°) and TT (77.2° ± 7.0°) techniques (n.s.). Single-bundle grafts did not decrease GBA compared with double-bundle grafts. In OI technique, a more proximal location of the femoral exit reduced GBA of each bundle at extension and 90° flexion. CONCLUSION: A significant GBA change with knee motion and considerably steep bending at full extension, especially with OI and TP techniques, were simulated. Although single-bundle technique did not reduce GBA as seen in double-bundle technique, proximal location of femoral exits by OI technique, with tunnels kept in anatomic position, was effective in decreasing GBA at knee extension and flexion. For clinical relevance, high stress on graft and bone interface has been suggested by steep GBA at full extension after anatomic ACL reconstruction. LEVEL OF EVIDENCE: Therapeutic study (prospective comparative study), Level II.

Glomerulopatí del trasplante. Resultados clínicos y seguimiento de casos.

OBJECTIVE: We describe the evolution of graft function in patients with transplant glomerulopathy measure by levels of serum creatinine, proteinuria and estimated glomerular filtration rate. METHOD: Cross-sectional study conducted in the Regional General Hospital No. 46 IMSS. Included patients with kidney allograft and diagnosis of renal biopsy of transplant glomerulopathy grafting between January 1, 2006 to April 31, 2013 serum creatinine, proteinuria and estimated glomerular filtration rate at diagnosis, 6, 12 and 24 was recorded months. The results are shown with numbers, percentages and standard deviations. RESULTS: 42 patients were included. At 6 months of diagnosis, 14% decline in graft function and 7.1% graft loss. At 12 months, 17.9% graft loss, and at 24 months 36.3% had chronic graft dysfunction and graft loss as return to dialysis. CONCLUSIONS: Evolution in our patients seems to be better to other series of cases reported in the literature.

[EBV-positive central nervous system lymphoproliferative disease associated with immunosuppression after organ transplantation: Long-term remission without chemotherapy]. / Limfoproliferativnoe EBV-pozitivnoe zabolevanie s porazheniem tsentral'noi nervnoi sistemy, assotsiirovannoe s immunosupressiei posle organnoi transplantatsii: dlitel'naia remissiia posle khimioterapevticheskogo lecheniia.

Primary central nervous system (CNS) lymphomas account for 13-20% of the posttransplant lymphoproliferative disorders (PTLD) and rank among the most aggressive conditions. Reduction of immunosuppressive therapy should be mandatory to treat PTLD, but this is rarely used as the only therapy option. Chemotherapy regimens for PTLD involving the CNS most commonly include high-dose rituximab and high-dose methotrexate and/or cytarabine. The efficiency only of discontinuation of immunosuppressive therapy for PTLD does not exceed 5-10%, but there are no literature data on its efficiency for PTLD involving the CNS. The paper describes a clinical case of achieving long-term remission in a female patient with Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma involving the central nervous system, associated with immunosuppression after kidney transplantation from a related donor, in the absence of chemotherapy during immunosuppressive therapy discontinuation and transplantectomy.

Is HRQOL in dialysis associated with patient survival or graft function after kidney transplantation?

BACKGROUND: Health related quality of life (HRQOL) is patient-reported, and an important treatment outcome for patients undergoing renal replacement therapy. Whether HRQOL in dialysis can affect mortality or graft survival after renal transplantation (RTX) is not determined. The aims of the present study were to investigate whether pretransplant HRQOL is associated with post-RTX patient survival or graft function, and to assess whether improvement in HRQOL from dialysis to RTX is associated with patient survival. METHODS: In a longitudinal prospective study, HRQOL was measured in 142 prevalent dialysis patients (67 % males, mean age 51 ± 15.5 years) who subsequent underwent renal transplantation. HRQOL could be repeated in 110 transplant patients 41 (IQR 34-51) months after RTX using the self-administered Kidney Disease and Quality of Life Short Form (KDQOL-SF) measure. Kaplan-Meier plots were utilized for survival analyses, and linear regression models were used to address HRQOL and effect on graft function. RESULTS: Follow-up time was 102 (IQR 97-108) months after RTX. Survival after RTX was higher in patients who perceived good physical function (PF) in dialysis compared to patients with poorer PF (p = 0.019). Low scores in the domain mental health measured in dialysis was associated with accelerated decline in graft function (p = 0.048). Improvements in the kidney-specific domains "symptoms" and "effect of kidney disease" in the trajectory from dialysis to RTX were associated with a survival benefit (p = 0.007 and p = 0.02, respectively). CONCLUSION: HRQOL measured in dialysis patients was associated with survival and graft function after RTX. These findings may be useful in clinical pretransplant evaluations. Improvements in some of the kidney-specific HRQOL domains from dialysis to RTX were associated with lower mortality. Prospective and interventional studies are warranted.

[Evaluation of markers for renal graft dysfunction in patients with type 1 diabetes mellitus after kidney transplantation and simultaneous pancreas-kidney transplantation]. / Otsenka markerov disfunktsii pochechnogo transplantata u patsientov s sakharnym diabetom 1-go tipa posle transplantatsii pochki i sochetannoi transplantatsii pochki i podzheludochnoi zhelezy.

AIM: To study the markers of renal graft dysfunction in patients with type 1 diabetes mellitus (T1DM) after kidney transplantation (KT) and simultaneous pancreas-kidney transplantation (SPKT). SUBJECTS AND METHODS: The investigation enrolled 20 patients after successful SPKT and 41 patients after KT (of them 21 received continuous subcutaneous insulin infusion with an insulin doser; 20 had multiple insulin injections). The periods after KT and SPKT at patient inclusion were 8 (7; 8) and 11 (8; 18) months, respectively. A control group comprised 15 patients with T1DM without diabetic nephropathy. The patients were matched for gender, age, and T1DM duration. At a 9-month follow-up, the main biomarkers of kidney graft dysfunction were identified using the standard kits: Cystatin C (Cys C; serum; urine), NGAL, KIM-1, Podocin, Nephrin, IL-18, MMP-9 (urine), TGF-ß1, VEGF-A, and Osteopontin (OPN; serum). Fasting blood was taken; a morning urinary portion was examined. RESULTS: The posttransplantation glomerular filtration rate (GFR) in the patients corresponded to Stage C2; albuminuria did to Category A1 chronic kidney disease. Despite successful SPKT in the group of patients with T1DM, as in that of patients after isolated KT, there was a statistically significant increase in the level of kidney dysfunction markers (Cys C, NGAL, Podocin, and OPN) versus the control group regardless of the compensation for glucose metabolism. compensation. It was found that the level of Cys C was high and correlated negatively with GFR (r=-0.36; p<0.05) and positively with the level of albuminuria (r=0.40; p<0.05). There was also a direct correlation of urinary podocin concentrations with blood creatinine levels (r=0.35; p<0.05) and that of NGAL with albuminuria (r=0.35; p<0.05) in recipients after transplantation. CONCLUSION: The high levels of biomarkers for kidney graft dysfunction in the examinees (including subjects after SPKT) reflect the persistence of graft microstructural injuries in clinically stable function.

How to increase the utilization of donor hearts?

Cardiac transplantation is the best treatment available for patients with end-stage cardiomyopathy. Shortage of donor hearts is the main factor limiting the use of this treatment. Many donor hearts are rejected for transplantation because of left ventricular (LV) systolic dysfunction and/or wall motion abnormalities. While some donors have true cardiomyopathy, a significant proportion has reversible LV dysfunction due to neurogenic stunned myocardium. This condition is triggered by excess of catecholamines, which is typical for brain-dead donors. If given time to recover, LV function may improve, and the heart will be suitable for transplantation. Moreover, limiting of exogenous catecholamines may facilitate the recovery. In this review, we summarize the data on LV dysfunction/wall motion abnormalities in heart donors and propose the strategy to increase the utilization of donor hearts.

Renal function decline in recipients and donors of kidney grafts: role of aortic stiffness.

BACKGROUND/AIMS: Renal function decreases over time as a result of reduction in the number of functioning nephrons with age. In recipients and donors of kidney grafts, renal function decline may be linked differently to various parameters, namely arterial stiffness. METHODS: We conducted a prospective cohort study including 101 recipients of kidney grafts and their donors aiming at determining the factors correlated to the renal function decline over time. Aortic stiffness was evaluated by the non-invasive measurement of aortic pulse wave velocity. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) equation and the annualized change was determined. RESULTS: Decline in renal function was estimated at 1-year post-transplantation and annually thereafter (median follow-up 8 years, range 3.6-18.3), as the mean of the annualized decrease in the glomerular filtration rate. In recipients, filtration rate decreased by 4.8 ± 19.7 ml/min/1.73 m(2) the first post-transplant year and at a yearly rate of 2.2 ± 3.8 ml/min/1.73 m(2) thereafter. The first-year decline was related to smoking and acute rejection. Later decline was significantly associated with donor age and aortic stiffness. In living donors, renal function decline after the first year corresponded to 0.7 ml/min/1.73 m(2), was significantly lower than that of recipients (p < 0.001), and was determined by donor age at nephrectomy. CONCLUSION: Recipients of kidney grafts show a glomerular filtration rate decline over time that is significantly associated with donor age and aortic stiffness after the first post-transplant year, while donors demonstrate a lower decline that is mostly determined by age at nephrectomy.

Fate of atrioventricular valve function of the transplanted heart.

BACKGROUND: Long-term echocardiographic data on quantitative assessment of tricuspid and mitral regurgitation after heart transplantation are scarce. METHODS AND RESULTS: From November 1992 to December 2008, the medical records for 201 patients (mean age, 42.8±12.4 years, 47 females) who underwent heart transplantation were reviewed. Quantitative assessment of mitral and tricuspid valve function was performed using transthoracic echocardiography through long-term follow-up. A total of 196 (97.5%) patients were evaluated with echocardiography for more than 6 months postoperatively. During a mean echocardiography follow-up duration of 89.9±54.3 months, 23 (11.4%) patients showed either tricuspid regurgitation (TR >mild; n=21, 10.4%) or mitral regurgitation (MR >mild; n=6, 3.0%); 4 (2.0%) patients experienced both significant TR and MR. Freedom from moderate-to-severe TR at 10 years was 85.5±5.1% and 93.4±2.2% for the standard and bicaval techniques, respectively (P=0.531). Freedom from moderate-to-severe MR at 10 years was 96.0±2.7% and 98.6±1.0%, respectively, for the 2 techniques (P=0.252). In multivariate analysis, older-age donor emerged as the only independent predictor of significant TR (hazard ratio 1.06, 95% confidence interval 1.01-1.12, P=0.012). CONCLUSIONS: The long-term results of atrioventricular function after heart transplantation in adults were excellent regardless of anastomotic technique. Older-age donor was significantly associated with the development of postoperative TR.

Lung transplantation in adults and children: putting lung function into perspective.

The number of lung transplants performed globally continues to increase year after year. Despite this growing experience, long-term outcomes following lung transplantation continue to fall far short of that described in other solid-organ transplant settings. Chronic lung allograft dysfunction (CLAD) remains common and is the end result of exposure to a multitude of potentially injurious insults that include alloreactivity and infection among others. Central to any description of the clinical performance of the transplanted lung is an assessment of its physiology by pulmonary function testing. Spirometry and the evaluation of forced expiratory volume in 1 s and forced vital capacity, remain core indices that are measured as part of routine clinical follow-up. Spirometry, while reproducible in detecting lung allograft dysfunction, lacks specificity in differentiating the different complications of lung transplantation such as rejection, infection and bronchiolitis obliterans. However, interpretation of spirometry is central to defining the different 'chronic rejection' phenotypes. It is becoming apparent that the maximal lung function achieved following transplantation, as measured by spirometry, is influenced by a number of donor and recipient factors as well as the type of surgery performed (single vs double vs lobar lung transplant). In this review, we discuss the wide range of variables that need to be considered when interpreting lung function testing in lung transplant recipients. Finally, we review a number of novel measurements of pulmonary function that may in the future serve as better biomarkers to detect and diagnose the cause of the failing lung allograft.

CXCR3 ligands are associated with the continuum of diffuse alveolar damage to chronic lung allograft dysfunction.

RATIONALE: After lung transplantation, insults to the allograft generally result in one of four histopathologic patterns of injury: (1) acute rejection, (2) lymphocytic bronchiolitis, (3) organizing pneumonia, and (4) diffuse alveolar damage (DAD). We hypothesized that DAD, the most severe form of acute lung injury, would lead to the highest risk of chronic lung allograft dysfunction (CLAD) and that a type I immune response would mediate this process. OBJECTIVES: Determine whether DAD is associated with CLAD and explore the potential role of CXCR3/ligand biology. METHODS: Transbronchial biopsies from all lung transplant recipients were reviewed. The association between the four injury patterns and subsequent outcomes were evaluated using proportional hazards models with time-dependent covariates. Bronchoalveolar lavage (BAL) concentrations of the CXCR3 ligands (CXCL9/MIG, CXCL10/IP10, and CXCL11/ITAC) were compared between allograft injury patterns and "healthy" biopsies using linear mixed-effects models. The effect of these chemokine alterations on CLAD risk was assessed using Cox models with serial BAL measurements as time-dependent covariates. MEASUREMENTS AND MAIN RESULTS: There were 1,585 biopsies from 441 recipients with 62 episodes of DAD. An episode of DAD was associated with increased risk of CLAD (hazard ratio, 3.0; 95% confidence interval, 1.9-4.7) and death (hazard ratio, 2.3; 95% confidence interval, 1.7-3.0). There were marked elevations in BAL CXCR3 ligand concentrations during DAD. Furthermore, prolonged elevation of these chemokines in serial BAL fluid measurements predicted the development of CLAD. CONCLUSIONS: DAD is associated with marked increases in the risk of CLAD and death after lung transplantation. This association may be mediated in part by an aberrant type I immune response involving CXCR3/ligands.