Robot-assisted kidney transplantation with regional hypothermia using grafts with Multiple Vessels After Extracorporeal Vascular Reconstruction: results from the European Association of Urology Robotic Urology Section Working Group

Background: Kidney transplantation using grafts with multiple vessels (GMVs) is technically demanding and may be associated with increased risk of complications or suboptimal graft function. To date, no studies have reported on robot-assisted kidney transplantation (RAKT) using GMVs. Objective: To report our experience with RAKT using GMVs from living donors, focusing on technical feasibility and early postoperative outcomes. Design, setting, and participants: We reviewed the multi-institutional, prospectively collected European Association of Urology (EAU) Robotic Urology Section (ERUS)-RAKT database to select consecutive patients undergoing RAKT from living donors using GMVs between July 2015 and January 2018. Patients undergoing RAKT using grafts with single vessels (GSVs) served as controls. In case of GMVs, ex vivo vascular reconstruction techniques were performed during bench surgery according to the case-specific anatomy. Intervention: RAKT with regional hypothermia. Outcome measurements and statistical analysis: Intraoperative outcomes and early (30 d) postoperative complications and functional results were the main study endpoints. Multivariable logistic regression analysis evaluated potential predictors of suboptimal renal function at 1 mo. Results and limitations: Overall, 148 RAKTs were performed during the study period. Of these, 21/148 (14.2%) used GMVs; in all cases, single arterial and venous anastomoses could be performed after vascular reconstruction. Median anastomoses and rewarming times did not differ significantly between the GMV and GSV groups. Total and cold ischemia times were significantly higher in the GMV cohort (112 vs 88 min, p = 0.004 and 50 vs 34 min, p = 0.003, respectively). Overall complication rate and early functional outcomes were similar among the two groups. No major intra-or postoperative complications were recorded in the GMV cohort. At multivariable analysis, use of GMVs was not significantly associated with suboptimal renal function at 1 mo. Small sample size and short follow-up represent the main study limitations. Conclusions: RAKT using GMVs from living donors is technically feasible and achieved favorable perioperative and short-term functional outcomes. Larger studies with longer follow-up are needed to confirm our findings. Patient summary: In this study, we evaluated for the first time in literature the results of RAKT from living donors using kidneys with multiple arteries and veins. We found that, in experienced centers, RAKT using kidneys with multiple vessels is feasible and achieves optimal results in terms of postoperative kidney function with a low number of postoperative complications. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved

Robot-assisted Kidney Transplantation: The European Experience.

BACKGROUND: Robot-assisted kidney transplantation (RAKT) has recently been introduced to reduce the morbidity of open kidney transplantation (KT). OBJECTIVE: To evaluate perioperative and early postoperative RAKT outcomes. DESIGN, SETTING AND PARTICIPANTS: This was a multicenter prospective observational study of 120 patients who underwent RAKT, predominantly with a living donor kidney, in eight European institutions between July 2015 and May 2017, with minimum follow-up of 1 mo. The robot-assisted surgical steps were transperitoneal dissection of the external iliac vessels, venous/arterial anastomosis, graft retroperitonealization, and ureterovesical anastomosis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analysis of surgical data and their correlations with functional outcomes. RESULTS AND LIMITATIONS: The median operative and vascular suture time was 250 and 38min, respectively. The median estimated blood loss was 150ml. No major intraoperative complications occurred, although two patients needed open conversion. The median postoperative estimated glomerular filtration rate was 21.2, 45.0, 52.6, and 58.0ml/min on postoperative day 1, 3, 7, and 30, respectively. Both early and late graft function were not related to overall operating time or rewarming time. Five cases of delayed graft function (4.2%) were reported. One case (0.8%) of wound infection, three cases (2.5%) of ileus, and four cases of bleeding (3.3%; three of which required blood transfusion), managed conservatively, were observed. One case (0.8%) of deep venous thrombosis, one case (0.8%) of lymphocele, and three cases (2.5%) of transplantectomy due to massive arterial thrombosis were recorded. In five cases (4.2%), surgical exploration was performed for intraperitoneal hematoma. Limitations of the study include selection bias, the lack of an open control group, and failure to report on patient cosmetic satisfaction. CONCLUSIONS: When performed by surgeons with robotic and KT experience, RAKT is safe and reproducible in selected cases and yields excellent graft function. PATIENT SUMMARY: We present the largest reported series on robot-assisted kidney transplantation. Use of a robotic technique can yield low complication rates, rapid recovery, and excellent graft function. Further investigations need to confirm our promising data

Treatment of early borderline lesions in low immunological risk kidney transplant patients : a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study

Subclinical inflammation, including borderline lesions (BL), is very common (30-40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function. The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression. This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL. : NCT04936282. Registered June 23, 2021, . Protocol Version 2 of 21 January 2022. Sponsor: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). [email protected]

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología

Introduction: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated.Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis.Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis.Results: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 +/- 0.8, 2.1 +/- 1.2 and 1.8 +/- 1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant.Conclusions: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Avaluació del filtrat glomerular en el donant viu renal

Fer una correcta avaluació de la funció renal del potencial donant renal viu té moltes implicacions a la pràctica clínica. Davant la impossibilitat de fer una mesura directe del filtrat glomerular (FG), els nefròlegs es basen en estimacions mitjançant equacions basades habitualment en creatinina o utilitzen mètodes de referència que fan més complexa l’avaluació del donant. Molts nefròlegs estan preocupats per les limitacions d’aquests mètodes. I encara més, un altre factor limitant és que les equacions d’estimació es desenvolupen i validen en poblacions concretes i que demogràficament o clínicament poden ser molt diferents de la nostra. L’objectiu del treball ha estat conèixer el comportament i les limitacions de les equacions d’estimació a la nostra població, així com valorar la certesa de basar-nos en l’estimació del FG per a seleccionar els donants, analitzant el comportament de les equacions també en subpoblacions definides segons paràmetres demogràfics com edat, gènere o índex de massa corporal. També s’ha valorat el comportament de la depuració de creatinina en orina de 24 hores com estimador del FG. S’han avaluat prospectivament 219 potencials donants que disposen de mesura del FG per mètode de referència, 51Cr-EDTA. 174 donants consecutius disposen també de mesura de Cistatina C. A l’any de la nefrectomia ha estat possible avaluar amb 51Cr-EDTA 110 donants. S’ha analitzat el percentatge de recuperació de la funció renal després de la nefrectomia, en situació renal estable. Les conclusions permeten afirmar que l’estimació del FG per CKD-EPI creatinina és molt exacte en l’avaluació del donant viu i pot substituir la mesura del FG, mentre que els errors associats a la col·lecció d’orina descarten la depuració de creatinina en orina de 24 hores com a mètode vàlid per avaluar el donant renal. En relació a la determinació de Cistatina C, s’ha vist que no comporta una millora significativa en el comportament en les equacions d’estimació. En relació a la funció renal post-nefrectomia, destaca una infraestimació del FG amb totes les equacions que pot fer classificar incorrectament en relació a la funció renal residual a aquest grup poblacional.Kidney donor renal function evaluation has important implications in daily clinical practice. Despite this, an accurate measurement is truly challenging. A direct measure of the glomerular filtration rate (GFR) is not feasible, therefore most nephrologists base their decision on GFR estimations. These are usually based on creatinine levels, or reference methods which are inaccurate. Most nephrologists are concerned about the limitations of all these methods. Furthermore the estimation equations to calculate GFR have been developed in specific populations which can be demographically or clinically very different from ours. The goal of this study has been to learn how the equations behave in our population and what limitations they may present. Also, to evaluate the security on the estimation of the GFR when selecting donors, by analyzing the accuracy of the equations in subpopulations using demographic parameters such us age, gender or body mass index. The 24 hour creatinine clearance in urine as estimator of the GFR has also been evaluated. 219 potencial living kidney donors have been included in this study. GFR has been measured as the clearance of a exogenous filtration marker (51Cr-EDTA). 174 of them have Cystatin C as an endogenous marker to estimate GFR in addition to creatinine. One year after nephrectomy 110 donors have measured GFR based on the reference method. We evaluated percentages of base line kidney function compensation 12 months after-nephrectomy. Conclusions allow to confirm that CKD-EPI GFR estimation accuracy is sufficient to avoid GFR measurement in living kidney donor evaluation. Errors related to most donors incorrect 24-hour urine collections make this method unreliable in this setting. When adding Cystatin C to creatinine in estimation GFR equacions no accuracy or behavior improvement has been achieved. Related to kidney function follow up after nephrectomy, it is to mention that an important infraestimation of GFR occurs with the use of the majority of creatinine estimation equations, which leads to misclassified residual kidney function in this population

Avaluació del filtrat glomerular en el donant viu renal /

Fer una correcta avaluació de la funció renal del potencial donant renal viu té moltes implicacions a la pràctica clínica. Davant la impossibilitat de fer una mesura directe del filtrat glomerular (FG), els nefròlegs es basen en estimacions mitjançant equacions basades habitualment en creatinina o utilitzen mètodes de referència que fan més complexa l'avaluació del donant. Molts nefròlegs estan preocupats per les limitacions d'aquests mètodes. I encara més, un altre factor limitant és que les equacions d'estimació es desenvolupen i validen en poblacions concretes i que demogràficament o clínicament poden ser molt diferents de la nostra. L'objectiu del treball ha estat conèixer el comportament i les limitacions de les equacions d'estimació a la nostra població, així com valorar la certesa de basar-nos en l'estimació del FG per a seleccionar els donants, analitzant el comportament de les equacions també en subpoblacions definides segons paràmetres demogràfics com edat, gènere o índex de massa corporal. També s'ha valorat el comportament de la depuració de creatinina en orina de 24 hores com estimador del FG. S'han avaluat prospectivament 219 potencials donants que disposen de mesura del FG per mètode de referència, 51Cr-EDTA. 174 donants consecutius disposen també de mesura de Cistatina C. A l'any de la nefrectomia ha estat possible avaluar amb 51Cr-EDTA 110 donants. S'ha analitzat el percentatge de recuperació de la funció renal després de la nefrectomia, en situació renal estable. Les conclusions permeten afirmar que l'estimació del FG per CKD-EPI creatinina és molt exacte en l'avaluació del donant viu i pot substituir la mesura del FG, mentre que els errors associats a la col·lecció d'orina descarten la depuració de creatinina en orina de 24 hores com a mètode vàlid per avaluar el donant renal. En relació a la determinació de Cistatina C, s'ha vist que no comporta una millora significativa en el comportament en les equacions d'estimació. En relació a la funció renal post-nefrectomia, destaca una infraestimació del FG amb totes les equacions que pot fer classificar incorrectament en relació a la funció renal residual a aquest grup poblacional.Kidney donor renal function evaluation has important implications in daily clinical practice. Despite this, an accurate measurement is truly challenging. A direct measure of the glomerular filtration rate (GFR) is not feasible, therefore most nephrologists base their decision on GFR estimations. These are usually based on creatinine levels, or reference methods which are inaccurate. Most nephrologists are concerned about the limitations of all these methods. Furthermore the estimation equations to calculate GFR have been developed in specific populations which can be demographically or clinically very different from ours. The goal of this study has been to learn how the equations behave in our population and what limitations they may present. Also, to evaluate the security on the estimation of the GFR when selecting donors, by analyzing the accuracy of the equations in subpopulations using demographic parameters such us age, gender or body mass index. The 24 hour creatinine clearance in urine as estimator of the GFR has also been evaluated. 219 potencial living kidney donors have been included in this study. GFR has been measured as the clearance of a exogenous filtration marker (51Cr-EDTA). 174 of them have Cystatin C as an endogenous marker to estimate GFR in addition to creatinine. One year after nephrectomy 110 donors have measured GFR based on the reference method. We evaluated percentages of base line kidney function compensation 12 months after-nephrectomy. Conclusions allow to confirm that CKD-EPI GFR estimation accuracy is sufficient to avoid GFR measurement in living kidney donor evaluation. Errors related to most donors incorrect 24-hour urine collections make this method unreliable in this setting. When adding Cystatin C to creatinine in estimation GFR equacions no accuracy or behavior improvement has been achieved. Related to kidney function follow up after nephrectomy, it is to mention that an important infraestimation of GFR occurs with the use of the majority of creatinine estimation equations, which leads to misclassified residual kidney function in this population

Early Macrophage Infiltration and Sustained Inflammation in Kidneys From Deceased Donors Are Associated With Long-Term Renal Function

Kidney transplants from living donors (LDs) have a better outcome than those from deceased donors (DDs). Different factors have been suggested to justify the different outcome. In this study, we analyzed the infiltration and phenotype of monocytes/macrophages and the expression of inflammatory and fibrotic markers in renal biopsy specimens from 94 kidney recipients (60 DDs and 34 LDs) at baseline and 4 months after transplantation. We evaluated their association with medium- and long-term renal function. At baseline, inflammatory gene expression was higher in DDs than in LDs. These results were confirmed by the high number of CD68-positive cells in DD kidneys, which correlated negatively with long-term renal function. Expression of the fibrotic markers vimentin, fibronectin, and α-smooth muscle actin was more elevated in biopsy specimens from DDs at 4 months than in those from LDs. Gene expression of inflammatory and fibrotic markers at 4 months and difference between 4 months and baseline correlated negatively with medium- and long-term renal function in DDs. Multivariate analysis point to transforming growth factor-β1 as the best predictor of long-term renal function in DDs. We conclude that early macrophage infiltration, sustained inflammation, and transforming growth factor-β1 expression, at least for the first 4 months, contribute significantly to the difference in DD and LD transplant outcome