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.

Randomized clinical trial of non-antibiotic prophylaxis with d-Mannose plus Proanthocyanidins vs. Proanthocyanidins alone for urinary tract infections and asymptomatic bacteriuria in de novo kidney transplant recipients: The Manotras study.

BACKGROUND: Studies analyzing non-antibiotic alternatives in kidney transplant UTI's are lacking. d-Mannose, a simple sugar, inhibits bacterial attachment to the urothelium, as does Proanthocyanidins; both could act as a synergic strategy preventing UTI; nonetheless their efficacy and safety have not been evaluated in kidney transplant population yet. METHODS: This is a pilot prospective, double-blind randomized trial. Sixty de novo kidney transplant recipients were randomized (1:1) to receive a prophylactic strategy based on a 24-h prolonged release formulation of d-Mannose plus Proanthocyanidins vs. Proanthocyanidins (PAC) alone. The supplements were taken for the first 3 months after kidney transplant and then followed up for 3 months as well. The main objective of the study was to search if the addition of Mannose to PAC alone reduced the incidence of UTI and/or asymptomatic bacteriuria in the first 6 months post-transplantation. RESULTS: 27% of patients experienced one UTI episode (cystitis or pyelonephritis) while asymptomatic bacteriuria was very common (57%). Incidences according UTI type or AB were: 7% vs. 4% for cystitis episode (p 0.3), 4% vs. 5% for pyelonephritis (p 0.5) and 17% vs. 14% for asymptomatic bacteriuria (p 0.4) for patients in the Mannose+PAC group vs. PAC group respectively. The most frequent bacteria isolated in both groups was Escherichia coli (28% of all episodes), UTI or AB due to E. coli was not different according to study group (30% vs. 23% for Mannose+PAC vs. PAC alone p 0.37). CONCLUSIONS: Non-antibiotic therapy is an unmet need to prevent UTI after kidney transplantation; however, the use of d-Mannose plus PAC does not seem capable to prevent it.

[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.

Comparing the Behavioural Effects of Exogenous Growth Hormone and Melatonin in Young and Old Wistar Rats.

Growth hormone (GH) and melatonin are two hormones with quite different physiological effects. Curiously, their secretion shows parallel and severe age-related reductions. This has promoted many reports for studying the therapeutic supplementation of both hormones in an attempt to avoid or delay the physical, physiological, and psychological decay observed in aged humans and in experimental animals. Interestingly, the effects of the external administration of low doses of GH and of melatonin were surprisingly similar, as both hormones caused significant improvements in the functional capabilities of aged subjects. The present report aims at discerning the eventual difference between cognitive and motor effects of the two hormones when administered to young and aged Wistar rats. The effects were tested in the radial maze, a test highly sensitive to the age-related impairments in working memory and also in the rotarod test, for evaluating the motor coordination. The results showed that both hormones caused clear improvements in both tasks. However, while GH improved the cognitive capacity and, most importantly, the physical stamina, the effects of melatonin should be attributed to its antioxidant, anxiolytic, and neuroprotective properties.

Chronic melatonin treatment and its precursor L-tryptophan improve the monoaminergic neurotransmission and related behavior in the aged rat brain.

Melatonin has an important role in the aging process as a potential drug to relieve oxidative damage, a likely cause of age-associated brain dysfunction. As age advances, the nocturnal production of melatonin decreases potentially causing physiological alterations. The present experiments were performed to study in vivo the effects of exogenously administered melatonin chronically on monoaminergic central neurotransmitters serotonin (5-HT), dopamine (DA) and norepinephrine (NE) and behavioral tests in old rats. The accumulation of 5-hydroxy-tryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (DOPA) after decarboxylase inhibition was used as a measure of the rate of tryptophan and tyrosine hydroxylation in rat brain. Also neurotransmitters 5-HT, DA and NE and some metabolites were quantified by HPLC. In control rats, an age-related decline was observed in neurochemical parameters. However, chronic administration of melatonin (1 mg/kg/day, diluted in drinking water, 4 wk) significantly reversed the age-induced deficits in all the monoaminergic neurotransmitters studied. Also, neurochemical parameters were analyzed after administration of melatonin biosynthesis precursor L-tryptophan (240 mg/kg/day, i.p., at night for 4 wk) revealing similar improvement effects to those induced by melatonin. Behavioral data corresponded well with the neurochemical findings since spatial memory test in radial-maze and motor coordination in rota-rod were significantly improved after chronic melatonin treatment. In conclusion, these in vivo findings suggest that melatonin and L-tryptophan treatments exert a long-term effect on the 5-HT, DA and NE neurotransmission by enhancing monoamine synthesis in aged rats, which might improve the age-dependent deficits in cognition and motor coordination.