Robotic kidney transplantation.

Kidney transplantation is the best treatment option for patients with end-stage renal disease owing to improved survival and quality of life compared with dialysis. The surgical approach to kidney transplantation has been somewhat stagnant in the past 50 years, with the open approach being the only available option. In this scenario, evidence of reduced surgery-related morbidity after the introduction of robotics into several surgical fields has induced surgeons to consider robot-assisted kidney transplantation (RAKT) as an alternative approach to these fragile and immunocompromised patients. Since 2014, when the RAKT technique was standardized thanks to the pioneering collaboration between the Vattikuti Urology Institute and the Medanta hospital (Vattikuti Urology Institute-Medanta), several centres worldwide implemented RAKT programmes, providing interesting results regarding the safety and feasibility of this procedure. However, RAKT is still considered an alternative procedure to be offered mainly in the living donor setting, owing to various possible drawbacks such as prolonged rewarming time, demanding learning curve, and difficulties in carrying out this procedure in challenging scenarios (such as patients with obesity, severe atherosclerosis of the iliac vessels, deceased donor setting, or paediatric recipients). Nevertheless, the refinement of robotic platforms through the implementation of novel technologies as well as the encouraging results from multicentre collaborations under the umbrella of the European Association of Urology Robotic Urology Section are currently expanding the boundaries of RAKT, making this surgical procedure a real alternative to the open approach.

Step-by-step Development of a Cold Ischemia Device for Open and Robotic-assisted Renal Transplantation.

BACKGROUND: Kidney transplantation (KT) is the best renal replacement treatment. The rewarming time is associated with ischemia/reperfusion damage. In both the open (open KT [OKT]) and the robotic (robotic-assisted KT [RAKT]) approaches, ice slush is used to maintain graft temperature (T°) below 20 °C. This may result in nonhomogeneous graft T° maintenance and, particularly during RAKT where the graft is completely inside the abdominal cavity, rises concerns regarding systemic hypothermia. OBJECTIVE: To design a cold ischemia device (CID) to maintain a constant and homogeneous low graft T° during surgery. DESIGN, SETTING, AND PARTICIPANTS: In IDEAL phase 0, a CID was developed and tested to determine its cooling effect on the kidney inside a closed system at 37.5 °C, by comparing it with kidney alone versus a gauze-jacket filled with ice slush. The CID was evaluated in pigs undergoing OKT and RAKT, assessing feasibility and adverse reactions. In IDEAL phase 1, the CID was tested in human OKT and RAKT. SURGICAL PROCEDURE: OKT and RAKT. MEASUREMENTS: In all phases, T° was evaluated at scheduled time points. RESULTS AND LIMITATIONS: In the preliminary tests of IDEAL phase 0, the CID was able to maintain a low graft T° and superiority to other groups (p = 0.002). In the in vivo animal model, the CID maintained a low and constant graft T° in OKT (n = 3) and RAKT (n = 3), with a mean T° at 50 min of 10.8 °C and 14.9 °C, respectively. IDEAL phase 1 demonstrated feasibility of both approaches (OKT, n = 2 and RAKT, n = 3) using the CID, and graft T° never exceeded 20 °C (mean T°: OKT 15.7 °C vs RAKT 18.3 °C). No complications were recorded. The main limitation consists in the low number of participants. CONCLUSIONS: The CID assured a constant low graft T° during rewarming time, in both OKT and RAKT. PATIENT SUMMARY: A cold ischemia device (CID) is the first step toward a feasible, safe, and reproducible method to maintain a low graft temperature during surgery. The employment of a CID may optimize the functional outcomes.

Pretransplant CMV-Specific T-Cell Immunity But Not Dose of Antithymocyte Globulin Is Associated With Recovery of Specific Immunity After Kidney Transplantation.

BACKGROUND: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. METHODS: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI. RESULTS: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL. CONCLUSIONS: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.

Clinical and pathological outcomes of renal cell carcinoma (RCC) in native kidneys of patients with end-stage renal disease: a long-term comparative retrospective study with RCC diagnosed in the general population.

PURPOSE: Patients with end-stage renal disease (ESRD) have an increased risk of developing renal cell carcinoma (RCC). This retrospective study compared clinical and pathological outcomes of RCC occurring in native kidneys of patients with ESRD (whether they underwent kidney transplantation or not) with those of renal tumors diagnosed in the general population. METHODS: The study included a total of 533 patients with RCC. The ESRD cohort included 92 patients with RCC in native kidneys. Of these, 58 and 34 cases were identified before (pre-Tx group) and after kidney transplantation (post-Tx group), respectively. The control group was composed of 441 RCCs diagnosed in the general population. Variables were compared by chi-square and Student's t tests. Cancer-specific survival was assessed by Kaplan-Meier and Cox methods. RESULTS: The ESRD groups had smaller (P = 0.001), lower-grade, and lower-stage tumors than the non-ESRD group (P = 0.001). The papillary RCC rate was higher in the ESRD groups (P = 0.01). Ten-year cancer-specific survivals were 94.5, 87.9, and 74.6 % in pre-Tx, post-Tx, and non-ESRD patients, respectively (P = 0.003). Mean follow-up was 90.2 months. At multivariate analysis, tumor size (HR = 1.10), pathological stage (HR = 1.46), presence of nodal (HR = 2.22) and visceral metastases (HR = 3.49), and Fuhrman grade (HR = 1.48) were independent adverse prognostic factors for cancer-specific survival. CONCLUSIONS: Native kidney RCCs arising in ESRD patients are lower stage and lower grade as compared to RCCs diagnosed in the general population, and these tumors exhibit favorable clinical and outcome features.

Renal sodium transporters are increased in urinary exosomes of cyclosporine-treated kidney transplant patients.

BACKGROUND/AIMS: Cyclosporine (CsA) is a calcineurin inhibitor widely used as an immunosuppressant in organ transplantation. Previous studies demonstrated the relationship between CsA and renal sodium transporters such as the Na-K-2Cl cotransporter in the loop of Henle (NKCC2). Experimental models of CsA-induced hypertension have shown an increase in renal NKCC2. METHODS: Using immunoblotting of urinary exosomes, we investigated in CsA-treated kidney transplant patients (n = 39) the excretion of NKCC2 and Na-Cl cotransporter (NCC) and its association with blood pressure (BP) level. We included 8 non-CsA-treated kidney transplant patients as a control group. Clinical data, immunosuppression and hypertension treatments, blood and 24-hour urine tests, and 24-hour ambulatory BP monitoring were recorded. RESULTS: CsA-treated patients tended to excrete a higher amount of NKCC2 than non-CsA-treated patients (mean ± SD, 175 ± 98 DU and 90 ± 70.3 DU, respectively; p = 0.05) and showed higher BP values (24-hour systolic BP 138 ± 17 mm Hg and 112 ± 12 mm Hg, p = 0.003; 24-hour diastolic BP, 83.8 ± 9.8 mm Hg and 72.4 ± 5.2 mm Hg, p = 0.015, respectively). Within the CsA-treated group, there was no correlation between either NKCC2 or NCC excretion and BP levels. This was confirmed by a further analysis including potential confounding factors. On the other hand, a significant positive correlation was observed between CsA blood levels and the excretion of NKCC2 and NCC. CONCLUSION: Overall, these results support the hypothesis that CsA induces an increase in NKCC2 and NCC in urinary exosomes of renal transplant patients. The fact that the increase in sodium transporters in urine did not correlate with the BP level suggests that in kidney transplant patients, other mechanisms could be implicated in CsA-induced hypertension.

Is it appropriate to implant kidneys from elderly donors in young recipients?

BACKGROUND: Kidneys from elderly donors tend to be implanted in recipients who are also elderly. We present the results obtained after 10 years of evolution on transplanting elderly kidneys into young recipients. METHODS: Ninety-one consecutive transplants are studied, carried out in our center with kidneys from cadaver donors older than 60 years implanted in recipients younger than 60 years. The control group is made up of 91 transplants, matched with those from the study group, whose donor and recipient were younger than 60 years. RESULTS: There were no differences between groups with regard to recipient age, sex, cause of death and renal function of the donor, hepatitis C and cytomegalovirus serologies, cold ischemia time, tubular necrosis, immediate diuresis, need for dialysis, human leukocyte antigen incompatibilities, hypersensitized patients, acute rejection, waiting time on dialysis, and days of admission. Survival in both groups at 1, 5, and 10 years was 97.6%, 87.2%, and 76.6% vs. 98.8%, 87.5%, and 69.5% for the patient (P=0.642), 92.9%, 81.3%, and 64.2% vs. 93.9%, 76.4%, and 69.5% for the graft (P=0.980), and 94.4%, 92.6%, and 77.4% vs. 94.3%, 86.7%, and 84.4% for the graft with death censured (P=0.747), respectively. Creatininaemias at 1, 5, and 10 years were 172, 175, and 210 vs. 139, 134, and 155 (P<0.05). CONCLUSIONS: We conclude that patient and graft survival on transplanting kidneys from elderly donors to young recipients is superimposable on that obtained with young donors. However, renal function is better in the group of young donors.

Tacrolimus/mycophenolate mofetil-based immunosuppression in aged kidney transplant. A prospective study.

BACKGROUND: At the moment, controversy has arisen about immunosuppression in aged kidney transplant recipients. We present our results on the efficacy and safety of induction treatment based on tacrolimus (FK506) and mycophenolate mofetil (MMF). MATERIAL AND METHOD: We performed 72 transplants in patients of 60 years or older. Induction treatment consisted on (FK 506) 0.1 mg/kg/day and MMF 2 gr/day. Antilymphocyte serum was administered with delayed graft function. A total of 54 patients received kidneys from donors over 60 years old. RESULTS: Cold ischemia time was 16.4 h (S=5.7). Delayed graft function occurred in 35 patients (48.6%). Acute rejection was observed in nine patients (12.5%). Opportunistic infections were found in 19 patients (26.4%). Seven patients died due to sudden death (1), acute myocardial infarction (1), stroke (1), infection (3), and neoplasm (1). At 1, 2, and 3 years, serum creatinine was 145, 163, and 156 mmol/l; patient survival 93%, 90%, and 90%; graft survival 93%, 90%, and 87%; and death-censored graft survival 100%, 100%, and 97%, respectively. CONCLUSION: These immunosuppressive guidelines appear to be efficacious and safe in kidney transplant in elderly recipients.

Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis.

BACKGROUND: No precise studies have been performed on cutaneous leukocytoclastic vasculitis (LV) to establish whether it is better to obtain a skin biopsy from lesional or from perilesional skin for direct immunofluorescence (DIF). There is no agreement on the immunoglobulins most frequently detected and the value of DIF for the classification of cutaneous vasculitis. METHODS: A prospective study of DIF in lesional and perilesional skin was performed in 50 leukocytoclastic vasculitis patients and 15 nonvasculitis patients. RESULTS: We detected a higher level of positivity in involved skin than in uninvolved skin for IgG, IgA, IgM, C3 and fibrinogen but not for C1q. In vasculitic patients, IgA was the immunoglobulin most frequently detected in lesional (82%) and perilesional skin (68%), followed by IgM (56 and 34%, respectively) and IgG (20 and 8%, respectively). Only IgA deposits were associated with the diagnosis of vasculitis, with a sensitivity of 82% in lesional and 68% in perilesional skin, and with a specificity of 73 and 66.7%, respectively. The presence of IgA in lesional skin was associated with renal involvement but there was no association with severity. The presence of IgG or IgM, or the absence of IgA in perilesional skin was related to the presence of cryoglobulins. The absence of IgA in lesional and perilesional skin was also related to hepatitis C virus infection. CONCLUSIONS: DIF findings in involved skin are more closely related to the diagnosis of vasculitis and can give more information about overall renal involvement than findings in uninvolved skin. However, findings in uninvolved skin are more closely related to the pathogenic factors that trigger the development of vasculitis.