Orthotopic Robot-assisted Kidney Transplantation: Surgical Technique and Preliminary Results.

BACKGROUND AND OBJECTIVE: Orthotopic kidney transplantation (KT) has been proposed as an option for patients ineligible for heterotopic KT. In this scenario, orthotopic robot-assisted KT (oRAKT) represents a novel, minimally invasive alternative to the open approach. Here we describe the largest oRAKT series of patients, with a focus on the surgical technique, perioperative surgical outcomes, and functional results. METHODS: We queried prospectively maintained databases from three referral centers to identify patients who underwent oRAKT and evaluated surgical and functional outcomes. KEY FINDINGS AND LIMITATIONS: Overall, 16 oRAKT procedures were performed between January 2020 and August 2023. These involved four donors after cardiovascular death, five donors after brain death, and seven living donors. All oRAKT procedures were carried out in the left renal fossa. The indication for oRAKT was extensive calcification of the external iliac vessels (100%), frequently associated with prior KT (31%). The median operative time was 295 min (interquartile range [IQR] 268-360) and the median rewarming time 48 min (IQR 40-54). Conversion to open surgery occurred in two cases (12%), and delayed graft function was observed in two cases (12%). Postoperative complications occurred in 11 patients (69%) and three (18%) experienced Clavien-Dindo grade >II complications. At median follow-up of 9 mo (IQR 7-17), 14 patients had a functioning graft and median creatinine of 1.49 mg/dl (IQR 1.36-1.72). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although oRAKT is a challenging procedure, it represents a feasible option for individuals ineligible for heterotopic KT and yields favorable perioperative and mid-term functional outcomes. PATIENT SUMMARY: We evaluated outcomes of orthotopic robot-assisted kidney transplantation (KT), in which the native kidney is removed and the donor kidney is transplanted into its place, in patients who are not eligible for heterotopic KT, in which the native kidney is left in place and the donor kidney is transplanted into a new location. We found that robot-assisted surgery is a safe and feasible alternative to traditional open surgery for orthotopic KT.

Delayed sequential abdominal wall closure in pediatric liver transplantation to overcome "large for size" scenarios.

BACKGROUND: Primary abdominal wall closure after pediatric liver transplantation (PLT) is neither always possible nor advisable, given the graft-recipient size discrepancy and its potential large-for-size scenario. Our objective was to report the experience accumulated with delayed sequential closure (DSC) guided by Doppler ultrasound control. METHODS: Retrospective analysis of DSC performed from 2013 to March 2020. RESULTS: Twenty-seven DSC (26.5%) were identified out of 102 PLT. Transplant indications and type of grafts were similar among both groups. In patients with DSC, mean weight and GRWR were 9.4 ± 5.5 kg (3.1-26 kg) and 4.7 ± 2.4 (1.9-9.7), significantly lower and higher than the primary closure cohort, respectively. The median time to achieve definitive closure was 6 days (range 3-23 days), and the median number of procedures was 4 (range 2-9). Patients with DSC had longer overall PICU (22.5 ± 16.9 vs. 9.1 ± 9.7 days, p < .05) and hospital stay (33.4 ± 19.1 vs 23, 9 ± 19.8 days (p < .05). These differences are less remarkable if the analysis is performed in a subgroup of patients weighing less than 10 kg. Two patients presented vascular complications (7.4%) within DSC group. No differences were seen when comparing overall, 3-year graft and patient survival (96% and 96% in the DSC group). CONCLUSIONS: DSC is a simple and safe technique to ensure satisfactory clinical outcomes to overcome "large for size" scenarios in PLT. In addition, we were able to avoid using a permanent biological material for closing the abdomen.

[Kidney transplant pathology.] / Histología del trasplante.

Renal biopsy procedure is used prior to insertion and at follow-up on a daily basis. The main donor renal biopsy indication is for evaluation of renal graft with expanded criteria, which have demonstrated heir utility for renal transplant decisions.Other indications include evaluation of donors on acuterenal failure; indeterminate lesions evaluation on renal parenchyma or evaluation prior to clinical trial evaluation.How the renal biopsy is performed is also importanton its evaluation, and evaluation of glomerularlesions, tubule-interstitial and vascular lesions. All those determine renal graft evaluation, survival and chronic renal disease during follow-up. The main indication for renal biopsy on the recipientis the differential diagnosis of rejection when clinically suspicious or on patients with high- immunologicalrisk where subclinical reject is important. In high 0riskpatients, such as sensitized patients or living-donor recipients with ABO incompatibility, protocol biopsies are evaluated without guideline consensus. For that procedure,an automatic punch 16G needle is used, generally associated with low complication rates.

La utilización de las biopsias renales tanto preimplantacional como en el seguimiento de los pacientes trasplantados está dentro de la práctica habitual. La principal indicación para realizar la biopsia renal en el donante es para la valoración de los injertos de donantes con criterios expandidos, lo que ha demostrado su utilidad para decidir si un injerto es apto o no paraser trasplantado. Otras indicaciones incluyen la valoración de donantes con fracaso renal agudo, la valoración de lesiones dudosas a nivel del parénquima renal o como información basal necesaria en ensayos clínicos. La forma en que la biopsia de realiza tiene importancia en su valoración, y la valoración de las lesiones glomerulares, túbulointersticiales y vasculares del donante condicionan laevolución del injerto renal, tanto en la supervivencia del injerto, como en el daño renal crónico que presenten en el seguimiento.La principal indicación para realización de biopsias enel receptor es el despistaje de rechazo tanto cuando existe sospecha clínica o en los casos de alto riesgo inmunológico donde resulta fundamental el diagnóstico de rechazo subclínico.En los pacientes de alto riesgo, como son los pacientes sensibilizados o los receptores de trasplante de vivo ABO incompatible, se plantea la planificación de biopsias de protocolo, sin existir un claro consenso entre diferentes centros. Para el procedimiento se utiliza una pistola automática con una aguja de 16 Gauge,y se relaciona con un porcentaje muy bajo de complicaciones.

Histología del trasplante / Transplant histology

La utilización de las biopsias renales tantopreimplantacional como en el seguimiento de los pacientes trasplantados está dentro de la práctica habitual. La principal indicación para realizar la biopsia renal enel donante es para la valoración de los injertos de do-nantes con criterios expandidos, lo que ha demostradosu utilidad para decidir si un injerto es apto o no paraser trasplantado. Otras indicaciones incluyen la valoración de donantescon fracaso renal agudo, la valoración de lesiones dudosas a nivel del parénquima renal o como informaciónbasal necesaria en ensayos clínicos. La forma en que labiopsia de realiza tiene importancia en su valoración, y la valoración de las lesiones glomerulares, túbulointersticiales y vasculares del donante condicionan laevolución del injerto renal, tanto en la supervivencia delinjerto, como en el daño renal crónico que presenten enel seguimiento. La principal indicación para realización de biopsias enel receptor es el despistaje de rechazo tanto cuandoexiste sospecha clínica o en los casos de alto riesgoinmunológico donde resulta fundamental el diagnósticode rechazo subclínico. En los pacientes de alto riesgo, como son los pacientes sensibilizados o los receptores de trasplante devivo ABO incompatible, se plantea la planificación debiopsias de protocolo, sin existir un claro consenso entre diferentes centros. Para el procedimiento se utilizauna pistola automática con una aguja de 16 Gauge,y se relaciona con un porcentaje muy bajo de complicaciones.(AU)

Renal biopsy procedure is used prior toinsertion and at follow-up on a daily basis. The maindonor renal biopsy indication is for evaluation of renalgraft with expanded criteria, which have demonstratedtheir utility for renal transplant decisions. Other indications include evaluation of donors on acuterenal failure; indeterminate lesions evaluation on renalparenchyma or evaluation prior to clinical trial evaluation. How the renal biopsy is performed is also important on its evaluation, and evaluation of glomerularlesions, tubule-interstitial and vascular lesions. All thosedetermine renal graft evaluation, survival and chronicrenal disease during follow-up. The main indication for renal biopsy on the recipientis the differential diagnosis of rejection when clinically suspicious or on patients with high- immunologicalrisk where subclinical reject is important. In high0riskpatients, such as sensitized patients or living-donor recipients with ABO incompatibility, protocol biopsies areevaluated without guideline consensus. For that procedure, an automatic punch 16G needle is used, generally associated with low complication rates.(AU)

Deciphering transplant outcomes of expanded kidney allografts donated after controlled circulatory death in the current transplant era. A call for caution.

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multicenter cohort of 1161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n = 1585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (log-rank < 0.001). Besides standard ECD classification, dialysis vintage, older age, and previous cardiovascular recipient events together with low class-II-HLA match, long cold ischemia time and combining a diabetic donor with a cDCD predicted graft loss (C-Index 0.715, 95% CI 0.675-0.755). External validation showed good prediction accuracy (C-Index 0.697, 95%CI 0.643-0.741). Recipient older age, male gender, dialysis vintage, previous cardiovascular events, and receiving a cDCD independently predicted patient death. Benefit/risk assessment of undergoing KT was compared with concurrent waitlisted candidates, and despite the fact that undergoing KT outperformed remaining waitlisted, remarkably high mortality rates were predicted if KT was undertaken under the worst risk-prediction model. Strategies to increase the donor pool, including cDCD transplants with highly expanded donor and recipient candidates, should be performed with caution.

Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial.

BACKGROUND: Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies. METHODS: This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy. RESULTS: Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]). CONCLUSIONS: Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation. CLINICAL TRIALS REGISTRATION: NCT02550639.

Antibiotic Treatment Versus No Treatment for Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Multicenter Randomized Trial.

BACKGROUND: Whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. METHODS: In this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. RESULTS: We enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40-4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50-8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P = .030), amoxicillin-clavulanic (P < .001) resistance, and extended-spectrum ß-lactamase production (P = .044) were more common in KT recipients receiving antibiotic treatment for AB. CONCLUSIONS: Antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed.

Residual urinary volume is a risk factor for primary nonfunction in kidney transplantation.

Primary nonfunction is a severe complication after kidney transplantation. Residual renal function could be a risk factor for this complication in the current era of kidney transplantation from extended criteria donors (ECD). This is a single-center case-control study. Between 2000 and 2012, 1112 patients received a kidney transplant from a deceased donor. We identified 56 cases of early graft loss (kidney that never recover renal function and/or graft thrombosis <48 h after kidney transplantation). As controls we used patients receiving the contralateral kidney. Donor age was 55 ± 17 years with 57% fulfilling ECD criteria. Among the 56 cases, 14 were due to vascular rejection and 42 to primary nonfunction. Risk factors for early graft loss due to vascular rejection were previous transplant, time on dialysis, and HLA sensitization. Risk factors for primary nonfunction were first transplant, short period on dialysis, mainly peritoneal dialysis, and a residual urinary volume ≥500 ml/24 h. Conditional logistic regression analysis showed that residual urinary volume (OR = 20.01) rather than the dialysis modality was a major risk factor for primary nonfunction. In conclusion, residual urinary volume seems to be a risk factor for primary nonfunction in the current era of kidney transplantation.

CT diagnosis of chronic pulmonary thromboembolism.

Chronic pulmonary thromboembolism is mainly a consequence of incomplete resolution of pulmonary thromboembolism. Increased vascular resistance due to obstruction of the vascular bed leads to pulmonary hypertension. Chronic thromboembolic pulmonary hypertension is clearly more common than previously was thought, and misdiagnosis is common because patients often present with nonspecific symptoms related to pulmonary hypertension. Computed tomography (CT) is a useful alternative to conventional angiography not only for diagnosing chronic pulmonary thromboembolism but also for determining which cases are treatable with surgery and confirming technical success postoperatively. The vascular CT signs include direct pulmonary artery signs (complete obstruction, partial obstruction, eccentric thrombus, calcified thrombus, bands, webs, poststenotic dilatation), signs related to pulmonary hypertension (enlargement of main pulmonary arteries, atherosclerotic calcification, tortuous vessels, right ventricular enlargement, hypertrophy), and signs of systemic collateral supply (enlargement of bronchial and nonbronchial systemic arteries). The parenchymal signs include scars, a mosaic perfusion pattern, focal ground-glass opacities, and bronchial anomalies. The presence of one or more of these radiologic signs arouses suspicion and allows diagnosis of this entity. Early recognition of chronic pulmonary thromboembolism may help improve the outcome, since the condition is potentially curable with pulmonary thromboendarterectomy.

Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1.

Specific deletion of Notch1 and RBPjkappa in the mouse results in abrogation of definitive haematopoiesis concomitant with the loss of arterial identity at embryonic stage. As prior arterial determination is likely to be required for the generation of embryonic haematopoiesis, it is difficult to establish the specific haematopoietic role of Notch in these mutants. By analysing different Notch-ligand-null embryos, we now show that Jagged1 is not required for the establishment of the arterial fate but it is required for the correct execution of the definitive haematopoietic programme, including expression of GATA2 in the dorsal aorta. Moreover, successful haematopoietic rescue of the Jagged1-null AGM cells was obtained by culturing them with Jagged1-expressing stromal cells or by lentiviral-mediated transduction of the GATA2 gene. Taken together, our results indicate that Jagged1-mediated activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse.

Regulation of ubiquitous 6-phosphofructo-2-kinase by the ubiquitin-proteasome proteolytic pathway during myogenic C2C12 cell differentiation.

6-Phosphofructo-2-kinase catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, activator of phosphofructokinase-1 and inhibitor of fructose 1,6-bisphosphatase. These properties confer to this bifunctional enzyme a key role in the control of glycolysis and gluconeogenesis. Several mammalian isozymes generated by alternative splicing from four genes, designated pfkfb1-4, have been identified. The results presented in this study demonstrate the expression of the pfkfb3 gene in C2C12 cells and its downregulation during myogenic cell differentiation. We also show that the decrease of ubiquitous 6-phosphofructo-2-kinase isozyme levels, product of pfkfb3 gene, is due to its enhanced degradation through the ubiquitin-proteasome proteolytic pathway.

Calcineurin inhibitor-free immunosuppression based on antithymocyte globulin and mycophenolate mofetil in cadaveric kidney transplantation: results after 5 years.

Kidney grafts from suboptimal donors are more likely to suffer the nephrotoxic side-effects of cyclosporine than kidneys from standard donors. In an attempt to avoid the use of cyclosporine, we carried out a prospective study in low-immunological risk recipients of suboptimal kidneys, using an immunosuppressive protocol combining Thymoglobuline in induction with a bi-therapy of mycophenolate mofetil (MMF) and steroids. Patients with panel reactive antibodies (PRA) <50% receiving a first renal transplant from a suboptimal donor (age >or=50, non heart beating, arterial hypertension, or acute renal failure) or a kidney at risk of delayed graft function (DGF) because of a prolonged cold ischaemia time (CIT) of 24 h or more, were eligible for this trial. Between September 1996 and December 1999, 30 patients were enrolled for the trial and treated with MMF 2 g orally, pre-operatively, and 3 g daily, post-operatively; Thymoglobuline 2 mg/kg IV pre-operatively, 1.5 mg/kg IV the next day, and for doses of 1 mg/kg IV given on alternate days; and prednisolone 0.25 mg/kg per day, reduced progressively from the end of the first month to 0.1 mg/kg per day by 3 months post-transplant. Cyclosporine was added only if rejection grade II or higher, or a reduction in MMF below 1 g daily, occurred. Ten patients (30%) suffered from DGF, and one kidney suffered primary non function. Seven patients (24%) suffered acute rejection (six were biopsy proven, 3 grade I and 3 grade II). MMF dosage was reduced in 28 patients because of adverse events, and calcineurin inhibitors were introduced in 16 patients. There were 14 episodes of opportunistic infection (cytomegalovirus (CMV 10), Herpes zoster 2, Listeria monocytogenes 1, Pseudomonas aeuruginosa 1), and 7 malignancies (skin 2, thyroid 1, lung 1, Kaposi's sarcoma 2, post-transplantation lymphoproliferative disorder 1). Mean serum creatinine was 178, 199, 213, and 218 micromol/l at 1, 2, 3 and 5 years after transplantation, respectively. Actuarial patient and graft (after censoring for death) survival was 94% and 83% after 1 year and 79% and 65% after 5 years, respectively. These results show that with the combination of MMF, Thymoglobuline and steroids the use of cyclosporine can be delayed, and in a few cases completely avoided, with good efficacy in terms of prevention of rejection and recovery of renal function. Regardless of acceptable patient and graft survival, side-effects of MMF at the doses used in this protocol were common and led to overimmunosuppression in the long-term. Starting MMF at low dose, MPA monitoring and probably CMV prophylaxis may improve the results of this regimen.

Insulin induces PFKFB3 gene expression in HT29 human colon adenocarcinoma cells.

Fructose 2,6-bisphosphate is present at high concentrations in many established lines of transformed cells. It plays a key role in the maintenance of a high glycolytic rate by coupling hormonal and growth factor signals with metabolic demand. The concentration of fructose 2,6-bisphosphate is controlled by the activity of the homodimeric bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2). We report here the PFKFB-3 gene expression control by insulin in the human colon adenocarcinoma HT29 cell line. The incubation of these cells with 1 microM insulin resulted in an increase in the PFK-2 mRNA level after 6 h of treatment, this effect being blocked by actinomycin D. Furthermore, insulin induced ubiquitous PFK-2 protein levels, that were evident after a lag of 3 h and could be inhibited by incubation with cycloheximide.