Renal Autotransplantation and Extracorporeal Nephron-Sparing Surgery for De Novo Renal Cell Carcinoma in a Kidney Allograft.
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ABSTRACT:
SUBMITTER: Ono S
PROVIDER: S-EPMC5540622 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary.A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared.The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m² and 67.4 mL/min/1.73 m², p<0.001). One graft loss was reported in the control group, and no patient deaths were reported in either group. The incidence of BCAR of the investigational group was 8.7%, compared to 18.8% in the control group (p=0.137), during the study period. There were no significant differences (p>0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups.CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues.
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Project description:A patient with germline von Hippel-Lindau (VHL) gene alteration and history of multiple tumors present with classical paraneoplastic syndrome (PNS) associated with renal cell carcinoma (RCC). She underwent open nephron sparing surgery with resolution of symptoms. She remained without recurrence of RCC for the initial 2 years of her follow-up. To the best of our knowledge, this case represents the first in which PNS was specifically resolved using a partial nephrectomy in a patient with VHL. This case report provides initial evidence for the potential role of nephron sparing surgery in the management of paraneoplastic symptoms associated with hereditary RCC.
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Project description:PurposeTo evaluate the oncologic efficacy and feasibility of nephron-sparing surgery (NSS) in adult Xp11.2 translocation renal cell carcinoma (RCC).Patients and methodsSeventy patients with Xp11.2 translocation RCC and 273 with conventional RCC from five institutions in Nanjing were retrospectively studied. All patients were older than 18 years and were categorized into clinical T1 (cT1) stage using preoperative imaging. Using the preoperative imaging and electronic medical records, anatomical and pathological features were collected and analyzed.ResultsAmong patients with Xp11.2 translocation RCC, 18/36 (50.0%) with cT1a and 12/34 (35.3%) with cT1b tumors underwent NSS. The respective proportions in the conventional RCC group were 121/145 (83.4%) and 93/128 (72.7%). Among cT1a tumors, the Xp11.2 translocation RCCs tended to be adjacent to the collecting system, sinus, and axial renal midline compared with conventional RCCs. Patients with Xp11.2 translocation RCCs who underwent NSS had comparable progression-free survival (PFS) and overall survival to radical nephrectomy (RN) patients (P > 0.05). Among cT1b tumors, surgical margin positivity and pelvicalyceal, vascular, and region lymphatic involvement were more likely to occur in the Xp11.2 translocation RCCs (P < 0.05). Patients with Xp11.2 translocation RCC who underwent RN had a more favorable PFS than those who underwent NSS (P = 0.048). However, multivariate analysis of PFS did not identify surgical method as a risk factor (P = 0.089).ConclusionsAmong adults with Xp11.2 translocation RCC, NSS can be an alternative for patients with cT1a tumor but should be performed with more deliberation in patients with cT1b tumors.
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Project description:C1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity >6237 and >10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P<0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.
| S-EPMC4731103 | biostudies-literature
Project description:Human pluripotent stem cell-derived kidney organoids recapitulate developmental processes and tissue architecture, but intrinsic limitations, such as lack of vasculature and functionality, have greatly hampered their application. Here we establish a versatile protocol for generating vascularized three-dimensional (3D) kidney organoids. We employ dynamic modulation of WNT signaling to control the relative proportion of proximal versus distal nephron segments, producing a correlative level of vascular endothelial growth factor A (VEGFA) to define a resident vascular network. Single-cell RNA sequencing identifies a subset of nephron progenitor cells as a potential source of renal vasculature. These kidney organoids undergo further structural and functional maturation upon implantation. Using this kidney organoid platform, we establish an in vitro model of autosomal recessive polycystic kidney disease (ARPKD), the cystic phenotype of which can be effectively prevented by gene correction or drug treatment. Our studies provide new avenues for studying human kidney development, modeling disease pathogenesis, and performing patient-specific drug validation.
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Project description:PurposeTo develop a preoperative prediction model using a computer-assisted volumetric assessment of potential spared parenchyma to estimate the probability of chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) 6 months from extirpative renal surgery (nephron-sparing surgery [NSS] or radical nephrectomy [RN]).Patients and methodsRetrospective analysis of patients who underwent NSS or RN at our institution from January 2000 to June 2013 with a compatible CT scan 6-month renal function follow-up was performed. Primary outcome was defined as the accuracy of 6-month postoperative eGFR compared with actual postoperative eGFR based on root mean square error (RMSE). Models were constructed using renal volumes and externally validated. A clinical tool was developed on the best model after a given surgical procedure using area under the curve (AUC).ResultsWe identified 130 (51 radical, 79 partial) patients with a median age of 58 years (interquartile range [IQR] 48-67) and preoperative eGFR of 82.1 (IQR 65.9-104.3); postoperative CKD (eGFR <60) developed in 42% (55/130). We performed various linear regression models to predict postoperative eGFR. The Quadratic model was the highest performing model, which relied only on preoperative GFR and the volumetric data for a RMSE of 15.3 on external validation corresponding to a clinical tool with an AUC of 0.89.ConclusionVolumetric-based assessment provides information to predict postoperative eGFR. A tool based on this equation may assist surgical counseling regarding renal functional outcomes before renal tumor surgical procedures.
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Project description:Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop de novo DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR (n=205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had de novo DSA. Compared with patients with preexisting DSA ABMR, patients with de novo DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. De novo DSA ABMR was characterized by increased expression of IFN?-inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the de novo DSA ABMR (63% versus 34% at 8 years after rejection, respectively; P<0.001). After adjusting for clinical, histologic, and immunologic characteristics and treatment, we identified de novo DSA ABMR (hazard ratio [HR], 1.82 compared with preexisting DSA ABMR; 95% confidence interval [95% CI], 1.07 to 3.08; P=0.03); low eGFR (<30 ml/min per 1.73 m2) at diagnosis (HR, 3.27; 95% CI, 1.48 to 7.23; P<0.001); ?0.30 g/g urine protein-to-creatinine ratio (HR, 2.44; 95% CI, 1.47 to 4.09; P<0.001); and presence of cg lesions (HR, 2.25; 95% CI, 1.34 to 3.79; P=0.002) as the main independent determinants of allograft loss. Our findings support the transplant of kidneys into highly sensitized patients and should encourage efforts to monitor patients for de novo DSA.
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Project description:PurposeRENAL nephrometry score (RNS) was devised for deciding the approach for renal tumors. It is increasingly used in predicting perioperative outcomes with variable results. The actual difficulty encountered during surgery depends on a number of other variables. The main purpose of this prospective study was to identify these variables which are not addressed by current RNS.Materials and methodsForty-nine patients undergoing robotic nephron sparing surgery from January 2015 onward were included. RNS was calculated from the imaging. Operating surgeon rated each surgery on a Likert scale of 0-4 after the completion of the procedure. The questionnaire was pre-validated in 5 cases before administration. The correlation between the surgeon rating and RNS with perioperative parameters and trifecta outcomes were calculated.ResultsForty-seven percent surgeries were rated easy, and 53.0% were rated as difficult. Surgeries for hilar, posterior location and presence of supernumerary vessels were found to be the a cause of difficulty. Trifecta outcomes were achieved in 37/49 patients (75.5%). The mean rating was 2.580±0.900 in trifecta negative patients while it was 1.410±0.832 in trifecta positive patient (p<0.0001). Surgeon's rating correlated positively with trifecta outcomes (likelihood ratio=15.75, p=0.006).ConclusionsThe RNS remained a useful tool for determining renal tumor complexity. The intraoperative difficulty faced by the surgeon can be rated which can better predict perioperative trifecta outcomes. A useful predicting tool can be developed using the two parameters (RNS and surgeon rated difficulty).
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Project description:We prospectively evaluated the general and cancer specific quality of life, and psychosocial adjustment of patients with a renal mass treated with radical vs partial nephrectomy via a laparoscopic or an open approach.A total of 172 patients with renal tumors completed questionnaires before surgery, and 3 weeks, and 2, 3, 6 and 12 months postoperatively. We assessed general quality of life using SF-36™ and cancer specific quality of life using the Cancer Rehabilitation Evaluation System-Short Form, in addition to intrusive thoughts, avoidance behaviors and fear of recurrence. We used mixed model regression analysis to compare these measures across surgery types during the study course, adjusted for tumor size, histology, stage and renal function.The SF-36 physical component score differed significantly by surgery type with time (p = 0.04). Patients treated with laparoscopy improved by month 2 while those treated with open surgery had poorer quality of life until month 3. Better cancer specific quality of life was reported in patients who underwent radical vs partial nephrectomy. Age also had a significant effect on outcomes.We report one of the most comprehensive patient reported prospective quality of life studies in patients with renal cell carcinoma. There were significant differences in quality of life and psychosocial adjustment outcomes during 1 year among patients treated with 1 of 4 commonly accepted surgical renal procedures. These outcomes must be evaluated in the context of tumor characteristics, cancer specific outcomes and renal function. These quality of life issues may be important to consider when choosing surgical procedures for patients with renal tumors.
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Project description:PurposeStereotactic body radiation therapy (SBRT) treatment planning for renal cell carcinoma requires accurate delineation of tumor from normal tissue due to the radiosensitivity of normal renal cortical tissue. Tc-99m dimercapto succinic acid (DMSA) renal imaging is a functional imaging technique that precisely differentiates normal renal cortical tissue from tumor. There are no prior publications reporting using this imaging modality for SBRT treatment planning.Methods and materialsA 59-year-old female with stage IV renal cell carcinoma progressed on systemic therapy and was dispositioned to primary cytoreduction with SBRT. She had baseline renal dysfunction and her tumor was 9 cm without clear delineation from normal tissue on conventional imaging. DMSA-single-photon emission computerized tomography (SPECT)/computed tomography (CT) was used for treatment planning.ResultsDMSA-SPECT/CT precisely delineated normal renal cortical tissue from tumor. Three months after treatment, labs were stable and DMSA-SPECT/CT was unchanged. The treated lesion had markedly decreased positron emission tomography avidity.ConclusionsDMSA-SPECT or SPECT/CT can be incorporated into radiation therapy planning for renal lesions to improve target delineation and better preserve renal function.
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