Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3-8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.

OBJECTIVES:We evaluate the effect of myosteatosis on new-onset diabetes mellitus after kidney transplantation. METHODS:Consecutive patients who had renal transplant between 2006 and 2021 were reviewed, and 219 patients were finally included. Psoas muscle index was used to evaluate sarcopenia and average total psoas density (calculated by computed tomography before surgery) for myosteatosis. We used Cox proportional regression analyses in investigation of whether skeletal muscle depletion before surgery inclusive of sarcopenia and myosteatosis is a new additional predictor of new-onset diabetes mellitus. RESULTS:Median recipient age and body mass index were 45 years and 21.1 kg/m2 , respectively, and 123 patients (56%) were male. Preoperative impaired glucose tolerance was present in 58 patients (27%) and new-onset diabetes mellitus in 30 patients (14%), with median psoas muscle index of 6 cm2 /m2 and average total psoas density of 41 Hounsfield Unit. In multivariate analysis, significant risk factors were body mass index ≥25 kg/m2 (p < 0.01), impaired glucose tolerance (p < 0.01), and average total psoas density < 41.9 Hounsfield Unit (p = 0.03). New-onset diabetes mellitus had incidence rates of 3.7% without risk factors, 10% with a single risk factor, 33% with two, and 60% with three. Patients with new-onset diabetes mellitus were effectively stratified by the number of risk factors (p < 0.01). CONCLUSIONS:Myosteatosis could be a new risk factor used to predict new-onset diabetes mellitus.

BACKGROUND:Sarcopenia is defined as the loss of skeletal muscle mass and function and is associated with increased mortality. Certain genetic polymorphisms represent risk factors used to assess the incidence of sarcopenia; however, few studies have evaluated the association between genetic polymorphisms and sarcopenia after kidney transplantation (KTx). We examined single-nucleotide polymorphisms (SNPs) in the genes involved in sarcopenia after KTx. METHODS:Sixty-five patients who underwent KTx were enrolled in this study. We used the psoas mass index (PMI; the cross-sectional area of the bilateral psoas muscle/height) as a surrogate marker for assessing the extent of sarcopenia. We determined the PMI before KTx and 1 year after KTx, and we identified 5 SNPs in 5 genes associated with sarcopenia in the general population. Finally, the link between the changes in PMI 1 year after KTx and each SNP was examined. RESULTS:The median PMI before KTx and 1 year after KTx was 7.4 (4.6-13.2) and 7.0 (3.6-13.6), respectively. The PMI decreased in 43 patients (66.2%). The alpha-actinin-3 rs1815739 genotype was associated with changes in PMI; the distribution of CT+TT genotypes in the PMI decrease group was significantly higher than that of the CC genotype (odds ratio, 4.23; 95% CI 0.05-0.97; P = 0.025). Moreover, the T allele frequency was significantly higher in the PMI decrease group than in the PMI increase group (odds ratio, 2.34; 95% CI 0.18-0.950; P = 0.025). CONCLUSION:The alpha-actinin-3 rs1815739 genotype may represent a genetic risk factor for sarcopenia after KTx.

Background. Despite a growing need for everolimus (EVR) to reduce calcineurin inhibitor toxicity in kidney transplantation (KTx), the influence of EVR on the pharmacokinetics of mycophenolic acid (MPA), a mycophenolate mofetil (MMF) active metabolite, is obscure, and no suitable limited sampling strategy (LSS) for MPA when EVR is concomitantly present exists. We aimed to investigate the influence of EVR on MPA pharmacokinetics in KTx.Materials and Methods. This study complied with all principles of the Declaration of Helsinki. Twenty patients were initially administered tacrolimus, MMF, and methylprednisolone and then received EVR 4 months after KTx. Approximately 4 weeks before and after EVR administration, the estimated value of the area under the concentration-time curve for MPA from 0 to 12 hours (MPA-AUC0-12) was calculated using MPA blood concentration just before and 1, 2, 4, and 6 hours after MMF administration. We compared several MPA pharmacokinetics parameters before and after EVR addition and determined the best estimation equation for LSS of MPA-AUC0-12.Results. Although MPA-C6 per dose (MPA-C6/D) significantly decreased after EVR addition (from 3.4 [+/- 2.2] ng/mL/g to 2.5 [+/- 0.9] ng/mL/g), MPA-C0/D,-C1/D,-C2/D,-C4/D, and MPAAUC0-12/D showed no significant change. MPA-AUC0-12/D did not correlate with EVRAUC0-12/D. The best estimation equation for LSS of MPA-AUC0-12 by 2 time points was [(2.94 x C2) + (5.09 x C4) + 5.32] (R-2 = 0.73) and [(5.70 x C0) + (1.39 x C1) + 22.45] (R-2 = 0.72) before and after EVR addition, respectively.Conclusions. EVR can be safely combined with MMF after KTx once our results have been reevaluated.

BACKGROUND:There are several psychosocial and ethical issues surrounding the decision making of living kidney transplant donors. This study aimed to determine what health care professionals (HPs) consider in their clinical practice and their attitudes toward donors' decision-making processes.METHODS:Face-to-face semistructured interviews were conducted with 15 HPs. A thematic analysis was performed to categorize the thematic elements of the transcripts. All procedures were approved by the relevant review board and conducted in accordance with the Declaration of Helsinki.RESULTS:Six main categories-maintaining family relationships, improving donor understanding, supporting voluntary decision making, setting the environment for the examination, having different attitudes toward the donor's intentions, and resisting confirmation of intent-were identified. The HPs provided diverse considerations to respect the donors' autonomy.CONCLUSION:In clinical practice, there is a lack of practical methods to confirm living donors' levels of understanding and spontaneity, suggesting that these methods need to be established. Factors related to family functioning may reflect the unique culture of Japan, and this may be indicative of the need to consider treatment based on cultural values.

BACKGROUND Although renoprotective effects of everolimus (EVR) in kidney transplantation (KTx) have been widely reported, its pathophysiological mechanism remains unclear. MATERIAL AND METHODS We compared changes in eGFR (ΔGFR, ml/min/1.73 m²) and the ratio of the fibrotic area in biopsy specimens (ΔFI,%) from 3 months to 3 years after KTx between the EVR+ group (EVR addition and Tac reduction early after KTx, n=32), and the EVR- group (normal Tac without EVR, n=28). We also immunohistochemically evaluated mTOR-related protein expression. RESULTS ΔGFR and ΔFI in the EVR+ vs. EVR- groups were -0.27±6.8 vs. -9.8±12.8 (p<0.001) and 2.4±4.9 vs. 9.5±10.5 (p<0.001), respectively. Phosphorylated mTOR and phosphorylated 4EBP1 expression at 3 years in the EVR+ group was significantly lower than that in the EVR- group. Moreover, in the subgroup analysis comparing ΔGFR and ΔFI among groups stratified by immunosuppressive regimen and mTOR signal enhancement, the ΔFI in patients with EVR+ with decreased mTOR signal enhancement was significantly milder than that in other patients. In addition, in the multivariate analysis, EVR addition was the only independent predictor for allograft fibrosis, whereas the Tac C₀ concentration at neither 1 nor 3 years proved to be a risk factor. CONCLUSIONS These results suggested that EVR addition and Tac reduction may attenuate kidney allograft fibrosis, and that the suppression of mTOR signaling process may be involved in the anti-fibrotic effect of this immunosuppressive regimen. These results provide suggestions of how to utilize EVR for patients with KTx and improve graft function.

INTRODUCTION AND OBJECTIVE: Although several clinical studies have reported that everolimus (EVR) has a favorable effect on kidney allografts, the pathophysiological mechanism remains unclear. In this study, we examined the effects of EVR on progression of allograft fibrosis and the consequent change in allograft function from the viewpoint of the suppression of mTOR-related protein expression. METHODS: Sixty patients underwent kidney transplantation (KTx) and subsequent allograft biopsy both 3 months and 3 years after KTx. Three months after KTx, EVR was added and tacrolimus (Tac) was reduced in 32 patients (EVR+ group), and 28 patients remained on conventional Tac-based immunosuppression without EVR (EVR- group). We defined Fibrosis Index (FI, %) as an index of the fibrosis extent obtained by digital image analysis of the biopsy specimen with Masson’s Trichrome staining. We compared changes in eGFR ([INCREMENT]eGFR, ml/min/1.73m2) and fibrosis index ([INCREMENT]FI, %), after 3 years between the two groups. In addition, we semi-quantitatively scored mTOR-related protein (p-Akt, Rheb, p-mTOR, p-p70S6K, and p-4EBP1) expression at 3 months and 3 years based on the result of immunohistochemical staining of the biopsy specimen, and determined the risk factors for allograft fibrosis and dysfunction, including EVR use, Tac C0 concentration, and other clinical parameters. RESULTS: [INCREMENT]GFR and [INCREMENT]FI in the EVR+ vs EVR- groups were -0.27±6.8 vs -9.8±12.8 (p<0.001) and 2.4±4.9 vs 9.5±10.5 (p<0.001), respectively. In EVR+ group, the progression of fibrosis was significantly less than that in EVR- group, and as a result, the allograft function was better preserved. p-mTOR and p- 4EBP1 expression at 3 years in EVR+ group was significantly lower than that in the EVR- group (Fig1). Finally, addition of EVR was the only independent predictor for allograft fibrosis and dysfunction, whereas neither Tac C0 concentration at 3 month nor at 3 years proved to be a risk factor based on multivariate analysis. CONCLUSIONS: These results suggest that preserved allograft function by EVR-based immunosuppression is attributed to direct anti-fibrotic effect of EVR itself via the mTOR-related protein regulation independent of reduction in Tac nephrotoxicity.Source of Funding: none.

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II (MP52)1 Apr 2020MP52-09 CARDIAC FUNCTION IMPROVEMENT IN KIDNEY TRANSPLANTS PATIENTS AFTER THE EARLY ADDITION OF EVEROLIMUS WITH CALCINEURIN INHIBITOR MINIMIZATION Naoki Yokoyama*, Takeshi Ishimura, Takahito Endo, Shun Nishioka, Teruyuki Oda, Satoshi Ogawa, and Masato Fujisawa Naoki Yokoyama*Naoki Yokoyama* More articles by this author , Takeshi IshimuraTakeshi Ishimura More articles by this author , Takahito EndoTakahito Endo More articles by this author , Shun NishiokaShun Nishioka More articles by this author , Teruyuki OdaTeruyuki Oda More articles by this author , Satoshi OgawaSatoshi Ogawa More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000914.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In patients with chronic kidney disease, cardiac function has been shown to improve after kidney transplantation (KTx) in accordance with kidney function recovery. In contrast, KTx patients are exposed to de novo risk factors for cardiac dysfunction such as calcineurin inhibitors (CNIs). Recently, everolimus (EVR)-based CNI-minimization regimens have been reported to reduce cardiac abnormalities during heart transplants. Moreover, EVR itself has been reported to confer direct cardioprotective effects. However, the details concerning the long-term effects of KTx have not been elucidated. METHODS: This study included 75 patients who underwent KTx and were initially treated with CNI, mycophenolate mofetil, and methylprednisolone between 2010 and 2016. Thirty-seven patients started to receive EVR along with a CNI reduction 3 months after KTx (EVR group) and 38 patients were continued on CNI-based immunosuppression without EVR (CNI group). All patients underwent echocardiography before, and at 3 months and 3 years after KTx. We analyzed several parameters such as ejection fraction (EF), left ventricular diastolic diameter (LVDd), and left ventricular mass index (LVMI, g/m2) and compared these parameters between groups. Additionally, we regarded patients who had an LVMI≥125 and ≥110 in male and females, respectively, as having left ventricular hypertrophy (LVH). The prevalence of LVH was also compared between the EVR and CNI groups. RESULTS: The EF and LVDd did not show any apparent changes from pre-KTx to 3 years after KTx. The mean LVMI before, and at 3 months and 3 years after KTx were 118.7 ± 54.7, 102.1 ± 23.3, and 100.6 ± 23.7, respectively. We observed significant improvements in LVMI values from pre-KTx to 3 months after KTx (p=0.02). The change in LVMI values and prevalence of LVH did not show any differences between the EVR and CNI groups. Since the change in LVMI values of patients who already had LVH 3 months after KTx tended to be considerably affected by kidney function improvements regardless of immunosuppressant, we performed a subgroup analysis on 62 patients without LVH at 3 months after KTx. The LVMI in the EVR group showed greater improvement than the CNI group (-1.7 ± 21.5 vs 9.2 ± 18.4, p=0.03) and the ratio of patients with LVH was significantly higher in the EVR group than in the CNI group 3 years after KTx (5.8% vs 21.4%, p=0.05). CONCLUSIONS: The early addition of EVR and reduction of CNI after KTx may reduce myocardial hypertrophy and improve long-term cardiac function. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e775-e775 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Naoki Yokoyama* More articles by this author Takeshi Ishimura More articles by this author Takahito Endo More articles by this author Shun Nishioka More articles by this author Teruyuki Oda More articles by this author Satoshi Ogawa More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery III (MP59)1 Apr 2020MP59-19 ANTI-ATHEROSCLEROTIC EFFECT OF EVEROLIMUS IN KIDNEY-TRANSPLANTED PATIENTS Takeshi Ishimura*, Takahito Endo, Shun Nishioka, Naoki Yokoyama, Teruyuki Oda, Satoshi Ogawa, and Masato Fujisawa Takeshi Ishimura*Takeshi Ishimura* More articles by this author , Takahito EndoTakahito Endo More articles by this author , Shun NishiokaShun Nishioka More articles by this author , Naoki YokoyamaNaoki Yokoyama More articles by this author , Teruyuki OdaTeruyuki Oda More articles by this author , Satoshi OgawaSatoshi Ogawa More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000928.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cardiovascular disease (CVD) is the major cause of death after kidney transplantation (KTx). Everolimus (EVR) is an immunosuppressive agent now widely used in KTx that is also known for its anti-atherosclerotic effect. The Ankle–Brachial Index (ABI), Carotid Artery Intima–Media Thickness (IMT), and Cardioankle Vascular Index (CAVI) provide indicators of atherosclerosis and are utilized as surrogate CVD markers in many diseases such as chronic kidney disease and diabetes. In this study, we explored the potential anti-atherosclerotic effect of EVR in KTx by sequentially assessing the ABI, IMT, and CAVI. METHODS: This study included 107 patients who recently underwent KTx with triple immunosuppression therapy consisting of calcineurin inhibitor (CNI, either tacrolimus or cyclosporine), mycophenolate mofetil, and methylprednisolone. Three months after KTx, EVR was added in 52 patients (EVR+ group), and 55 patients remained on conventional CNI-based immunosuppression therapy without EVR (EVR- group). The ABI, IMT (mm), and CAVI were examined 3 months and 1 year after KTx, and the mean of the right and left values of each test were regarded as an index of atherosclerosis. The changes in the values of each test from 3 months to 1 year were compared between the EVR+ and EVR- groups. Additionally, we determined the prognostic significance of EVR use in the progression of atherosclerosis as well as other clinical parameters. RESULTS: Overall, the mean ABI, IMT, and CAVI 3 months and 1 year after KTx were 1.125 ± 0.087 (n=107) and 1.137 ± 0.091 (n=100), 0.650 ± 0.199 (n=107) and 0.633 ± 0.310 (n=92), and 7.579 ± 1.348 (n=70) and 7.493± 1.623 (n=63), respectively; no significant differences from 3 months to 1 year were observed in each test. The changes in the ABI, IMT, and CAVI in the EVR+ vs. EVR- groups were 0.044 ± 0.093 vs. -0.011 ± 0.087 (p=0.003), -0.022 ± 0.127 vs. 0.033 ± 0.361, and 0.023 ± 1.487 vs. -0.173 ± 1.322, respectively. The ABI in the EVR- group showed a significant reduction from 3 months to 1 year than that in the EVR+ group. Furthermore, EVR non-use, high total cholesterol 3 months after KTx, and cyclosporine use were revealed as prognostic factors for a reduction in the ABI; however, the only independent prognostic factor determined on multivariate analysis was high total cholesterol 3 months after KTx. CONCLUSIONS: The results suggest that the early addition of EVR may prevent atherosclerosis progression after KTx. Further studies in more patients with a longer observation period may provide evidence of the anti-atherosclerotic effect of EVR. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e888-e888 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takeshi Ishimura* More articles by this author Takahito Endo More articles by this author Shun Nishioka More articles by this author Naoki Yokoyama More articles by this author Teruyuki Oda More articles by this author Satoshi Ogawa More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF downloadLoading ...

Background: The objective of this study was to assess the effect of everolimus (EVR) on the pharmacokinetic parameters of mycophenolate mofetil (MMF) in patients who underwent kidney transplantation (KTx). Methods: Ten patients underwent KTx under triple immunosuppression which comprised of tacrolimus (Tac), MMF, and methylprednisolone (mPSL), and EVR was added at 3–6 months after KTx. The EVR dose was 1.5 mg/day and was adjusted to maintain the targeted trough blood concentration (C0) of 3–8 ng/mL. At 4 weeks before and after the initiation of EVR, blood concentrations of Tac and MMF were measured before and 1, 2, 4, and 6 hours after administration, and the estimated value of the area under the concentration-time curve from 0 to 12 hours (AUC0–12) was calculated. We compared the C0 and AUC0–12 per dose of Tac and MMF before and after the initiation of EVR. We did not change the dose of Tac, MMF, and mPSL until 4 weeks after the initiation of EVR. Results: The C0 of EVR at 4 weeks after EVR addition was 5.1±1.3 ng/mL, which was within the targeted range in all patients. The mean estimated glomerular filtration rate at 4 weeks before and after the initiation of EVR was almost at the same level. The mean dose of Tac and dose per weight of MMF during the observation period were 7.2±4.2 mg/day and 19.0±6.5 mg/kg/day, respectively. The Tac C0 per dose and the Tac AUC per dose before and after EVR addition were 1.16±0.57 and 1.18±0.68 ng/mL/ mg and 46.3±18.0 and 48.1±22.9 ng·hr/mL/mg, respectively. The MMF C0 per dose and the MMF AUC per dose before and after EVR addition were 19.0±0.63 and 22.0±1.3 ng/mL/g and 43.0±20.0 and 51.0±15.0 ng·hr/mL/g, respectively. Conclusions: The EVR administration has no significant influence on the pharmacokinetics of MMF.

Cardiac abnormalities, including left ventricular hypertrophy and systolic dysfunction, are frequently observed among patients with CKD, including kidney transplant recipients; they are closely linked to cardiovascular disease and mortality. Although several studies have been performed for elucidating changes and mechanisms of cardiac abnormalities after kidney transplantation, details remain unclear. This study included 43 consecutive patients who underwent HD and received kidney transplantation between 2008 and 2012 at our institution. All subjects underwent echocardiography before and 1 year after kidney transplantation. One year after kidney transplantation, left ventricular mass index, cardiac chamber sizes, BP, and the number of antihypertensive agents were reduced. Although the percentage of patients with concentric hypertrophy did not change, the percentage of those with eccentric hypertrophy significantly decreased after kidney transplantation. Volume reduction due to the recovery of kidney function may be primarily attributed to the improvement of cardiac abnormalities, including left ventricular hypertrophy.

BackgroundTo assess whether application of a hyaluronic acid-carboxymethyl cellulose membrane (HA/CMC) to the prostate bed and neurovascular plate facilitated early return of continence after nerve-sparing robot-assisted radical prostatectomy (RARP).MethodsThe subjects were 183 consecutive patients with organ-confined prostate cancer who underwent unilateral or bilateral nerve-sparing RARP. After vesicourethral anastomosis, HA/CMC was placed to cover Denonvilliers' fascia (behind the anastomotic suture) and the preserved neurovascular plate. The time until complete continence after RARP and perioperative complications were compared between patients with or without HA/CMC.ResultsHA/CMC was applied in 13/46 patients (28.3%) receiving bilateral nerve-sparing surgery and 40/137 patients (29.2%) receiving unilateral nerve-sparing surgery. After bilateral nerve-sparing RARP, the median time until continence was significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 9.3months, respectively, p<0.01). After unilateral nerve-sparing RARP, the median time until continence was also significantly shorter in patients with HA/CMC than in those without HA/CMC (3.2 vs. 12.0months, respectively, p<0.01). Multivariate Cox proportional hazards regression analysis showed that an age<70years (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.12-2.80), institutional caseload >200, (HR: 1.64, 95%CI: 1.10-2.47), and use of HA/CMC (HR: 1.84, 95%CI: 1.22-2.76) were independent predictors of early postoperative continence. Complication rates, including urinary leakage, did not differ significantly between patients with or without HA/CMC.ConclusionApplication of HA/CMC to the prostate bed and neurovascular plate resulted in significantly faster postoperative return of continence after both unilateral and bilateral nerve-sparing RARP.

hyperfiltration.Although hyperfiltration is known to be associated with renal injury its effect on donors after nephrectomy is not well known.In this study we evaluated the occurrence of proteinuria in living kidney donors during the immediate postdonation period, aiming to determine its clinical significance in renal function recovery.METHODS: Urine protein-excretion-rate (PER) and albuminto-creatinine ratio(ACR) was prospectively collected in 909 living kidney donors.849 donors with predonation PER<150mg/24hr were enrolled in the study.Post-donation PER was studied at 4 days after nephrectomy.Donors with post-donation PER<150mg/24hr were included in the non-hyperfiltration group (n[244), and those with PER!150mg/24hr were included in the hyperfiltration group (n[605) RESULTS: Post-donation eGFR was not significantly different on day 3w5 after nephrectomy but was consistently lower in the hyperfiltration group at from 1week to 1year after nephrectomy.Estimated GFR (MDRD, ml/min/1.73m 2 ) at 1year after donation was 63.6AE12.1 in the hyperfiltration group and 68.6AE12.3 in the non-hyperfiltration group (p[0.001).On multivariable regression analysis presence of immediate post-donation hyperfiltration was an independent predictor of eGFR at 1-year postdonation( 2 (SE) [-2.68(1.15),p[0.02), along with predonation eGFR, age and gender.(Table1) Age and gender were independent predictors of immediate post-donation hyperfiltration on multivariable regression analysis.(Table2)CONCLUSIONS: Hyperfiltration after donor nephrectomy is associated with decreased recovery of renal function.Donors who are older and male are more likely to undergo immediate hyperfiltration after donation.

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II (MP70)1 Apr 2019MP70-15 CHANGE IN GLOMERULAR VOLUME AND ITS CLINICAL SIGNIFICANCE IN PROTOCOL BIOPSIES AFTER KIDNEY TRANSPLANTATION Satoshi Ogawa*, Takeshi Ishimura, Yuzo Nakano, and Masato Fujisawa Satoshi Ogawa*Satoshi Ogawa* More articles by this author , Takeshi IshimuraTakeshi Ishimura More articles by this author , Yuzo NakanoYuzo Nakano More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557107.16114.bdAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Glomerular enlargement caused by glomerular hyperfiltration is one of the etiologies that affects graft function after kidney transplantation (KTx). Although the glomerular volume in baseline biopsies is reported to be predictor of graft function, the significance of change in glomerular volume in long-term period after KTx is unclear. We investigated changes in glomerular volume in protocol biopsies obtained from patients who underwent KTx and examined its correlation with subsequent graft function and other clinical factors. METHODS: We enrolled 37 patients who underwent KTx between 2006 and 2012 at Kobe university hospital. All these patients underwent protocol biopsy at 1 hour, 1 year, and 5 years after KTx and had stable graft function with an estimated glomerular filtration rate (eGFR) > 30 mL/min at 5 years after KTx, and without an episode of rejection or any complications that affect graft function. Glomerular area (GA) was defined as the area described by the outer capillary loops of the tuft and was calculated by Image J software (National Institutes of Health, Bethesda, MD, USA) and the mean value of glomerular area in whole specimen was used for this study. Then mean glomerular volume (Vg) in the specimen of protocol biopsy at 1 hour, 1 year, and 5 years after KTx (Vg1h, Vg1y, Vg5y, respectively) was estimated according to the Weibel and Gomez method as: Vg=GA3/2×1.38/1.01 We evaluated the changes in Vg and investigated the correlation of Vg1h, Vg1y, Vg5y with eGFR and amount of daily proteinuria at 1week, 4 weeks, 1 year and 5 years after KTx. RESULTS: The Vg increased significantly after kidney transplantation (Vg1h = 4.3 ± 1.8 ± 106 μm3, Vg1y = 5.3 ± 2.1 ± 106 μm3 [p <0.001, Vg1h vs Vg1y], Vg5y = 6.1 ± 2.3 ± 106 μm3 [p < 0.001, in Vg1y vs Vg5y]). Neither Vg1y nor Vg5y was correlated with estimated glomerular filtration rate (eGFR) or proteinuria; Vg1h was correlated with eGFR at 1 week after KTx (R = 0.40, p = 0.016). CONCLUSIONS: After KTx, the transplanted glomerular volume was observed to increase over time. Glomerular volume at the time of transplantation was correlated to renal function at early transplantation. Source of Funding: None Kobe, Japan© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e1043-e1044 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Satoshi Ogawa* More articles by this author Takeshi Ishimura More articles by this author Yuzo Nakano More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement PDF downloadLoading ...

Introduction and Objectives Pre-emptive kidney transplantation (PKT) has recently become more common, particularly in living-donor kidney transplantation (LDKT), as a treatment option for end-stage chronic kidney disease (CKD). The rate of PKT in total LDKT cases has been increasing and comprises approximately 25% of LDKT in Japan. Although PKT offers numerous advantages, it has been observed that in a few patients who are originally selected to undergo PKT, progression of kidney disease necessitates the institution of dialysis prior to undergoing LDKT. We aimed to determine the optimal timing at which a patient should be referred to a transplant center during the course of end-stage CKD to undergo a successful living-donor PKT. Methods Between 2006 and 2016, 61 end-stage CKD patients were referred to our department prior to institution of renal replacement therapy (RRT) and eventually underwent LDKT. We divided them into 2 groups-patients who successfully underwent PKT (PKT group) and those who required dialysis prior to LDKT (Non-PKT group). We compared the groups in terms of estimated glomerular filtration rate (eGFR) calculated using the Japanese formula at the first visit as well as in the interval between the first visit and the induction of RRT-either dialysis or a KT (Time to RRT). Eventually, we determined the cut-off value of eGFR and Time to RRT using the receiver operating characteristic curve (ROC) analysis to determine an optimal timing to refer end-stage CKD patients intending to undergo PKT to a transplant center. Results The PKT group comprised 49 patients, and the non-PKT group comprised 12. Median eGFR at the first visit in the PKT and non-PKT group was 10.9 mL/min/1.73m2 (4.4-27.3) and 6.7 mL/min.73m2 (4.3-16.9) and showed a significant difference between the groups (p < 0.01). ROC analysis determined that an eGFR level > 8.1 mL/min/1.73m2 at the first visit was a cutoff value to predict successful PKT, and area under the curve was 0.865. Time to RRT was significantly shorter in the non-PKT (median 75 days, 2-379) than in the PKT group (median 205 days, 55-1350). A cutoff point determined using ROC analysis was 116 days, and area under the curve was 0.745. Conclusion This study demonstrates that PKT from a living donor may be successfully performed if CKD patients are referred to a transplant center before their eGFR declines to < 8.7 mL/min/1.73m2. We propose that pre-transplant clinical examination of both the donor and the recipient be completed within 116 days.

Weight gain, and especially visceral fat gain early after kidney transplantation has a worse outcome for metabolic disorder, graft function, and cardiovascular disease. The mammalian target of rapamycin (mTOR) is a regulator of metabolism and associated with obesity. The aim of this study is to investigate the role of mTOR inhibition in post-transplant obesity and body composition change. Method This is single-center cohort study. We analyzed 96 healthy adult kidney transplant patients and they were divided 2 groups; (1) Everolimus (EVR: introduced 3-months after transplantation), mPSL, MMF and reduced tacrolimus (TAC) (n=48) (2) mPSL, MMF and normal tacrolimus (n=48. These patients were transplanted before EVR was approved in Japan). In this analysis, change of body weight and visceral fat area at 3-12 months were compared between two groups by using logistic regression adjusted propensity score analysis. Vital signs, lipid and glucose profile, such as parameters of metabolic syndrome were also analyzed. Results Mean increase in body weight from 3 to 12 months after transplantation ware 2.45±7.98 kg (EVR group) and 2.35±5.42 kg (control group), and there was no significant difference. Visceral fat area was significantly increased in control group (13.34±28.51 cm2, EVR group: 8.34±16.93 cm2). EVR and reduced TAC significantly reduced the risk of abdominal obesity (visceral fat area≧100cm2) at 12-months after transplantation (Odds ratio; EVR: 0.14 95% confidence interval (CI), 0.03-0.67, Age: 1.06 95% CI, 1.01-1.02, pre-transplant abdominal obesity: 16.50 95% CI, 3.88-70.27). There were no significant differences about kidney function, glucose metabolism and occurrence of metabolic syndrome between two groups. Dyslipidemia was highly occurred in EVR group. Conclusion EVR with reduced TAC regimen had a possibility to attenuate visceral fat gain early after kidney transplantation without graft dysfunction. There was no significant effect for metabolic syndrome and impaired glucose metabolism. Further analysis is required.

Introduction Live donor nephrectomy is considered to be a unique surgery performed on healthy donor, and should be convinced to provide an excellent graft outcome in a kidney recipient. Laparo-endoscopic single-site surgery has been reported to be a feasible and effective choice of treatment for several kidney diseases such as renal cancer, in terms of cosmetics and less invasiveness. In this study, we evaluated the clinical outcomes of laparo-endoscopic single-site live donor nephrectomy (LESS-DN) in comparison with those of mini-incision retroperitoneal live donor nephrectomy (Mini-DN). Methods Between 2009 and 2016, a total of 126 live donor nephrectomies were performed at the Kobe University. They were comprised of 61 cases performed as LESS-DN for the retrieval of left kidney grafts after 2013 (LESS-DN group), and 65 cases performed as Mini-DN for the retrieval of right kidney grafts after 2013 and all grafts before 2013 (Mini-DN group). We compared several clinical parameters such as total operation time (TOP), warm ischemia time (WIT), blood loss, length of hospital stay, complication rate, as well as the function of kidney graft. Results TOP and WIT of LESS-DN and Mini-DN group was 256.6±44.8 vs. 247.6±37.9 min, 4.2±1.4 vs. 4.0±1.2 min respectively, observed no significant difference between the groups. Blood loss was significantly less in LESS-DN group compared with that in Mini-DN group (57.1±183.3 vs. 471.5±274.3 ml, P < 0.01). No visceral injuries and intra-operative complications of Clavien-Dindo greater than Grade II was observed in both LESS-DN and Mini-DN group. The dose of analgesics required at discharge was significantly lower in LESS-DN group than that in Mini-DN group (104.9±22.7 vs. 222.9±25.6 mg/day, < 0.01), and the length of hospital stay was significantly shorter in LESS-DN group than that of Mini-DN group (7.1±1.4 vs. 9.3±3.3 days, P=0.04). Serum creatinine level of the recipient at 4 weeks after kidney transplantation was of no difference between the groups (1.11±0.45 vs. 1.18±0.35 mg/dl). Conclusion LESS-DN is a safe and feasible method for the retrieval of the graft in living donor kidney transplantation, giving the kidney donor a significantly shorter period of recovery, and also giving the recipient an excellent graft function, and thus, may be an attractive and recommendable procedures.

Introduction and Objectives Congenital renal hypoplasia/dysplasia (CRH) is the most common cause of end stage renal disease (ESRD) in patients who undergo kidney transplantation (KTx) at a young age in Japan. In some cases of CRH, bladder capacity is large and disproportionate to their physique. Although patients with true neurogenic bladder may require intermittent self-catheterization (CIC) or urinary tract diversion to protect graft function after KTx, few patients need to undergo these procedures in our experience. In this study, we evaluated the voiding function as well as the graft function in patients with CRH after KTx, especially in cases with abnormality of bladder capacity. Methods Among 310 patients who underwent KTx between 1985 and 2017 at Kobe University, CRH was the primal renal disease of ESRD in 26 patients. Bladder capacity and volume of residual urine after voiding (RU) were assessed preoperatively by voiding cystourethrography (VCUG). We defined flaccid bladder (FB) as the maximum desire to void (MDV) (mL) / body surface area (BSA; m2) >300 (mL/m2). The patients with RU in VCUG underwent urodynamic study (UDS). Postoperatively, we measured RU by ultrasonography at least 3 times and the mean value was used in this study. We also evaluated estimated glomerular filtration rate (eGFR; ml/min/1.73m2) by Japanese fomula and the analysis of urine sediment (Ux) at 3 months after KTx. Results Overall, 7 (27%) patients, including 5 women and 2 man, met the inclusion criteria for FB. The median age of the patients at the time of KTx was 11 years (7-43). Preoperative median MDV was 250 mL (range, 200-400), median MDV/BSA 302 mL/m2 (range, 300-337), and median RU 0 mL (range, 0- 150). One patient had Grade 1 VUR, 1 patients had Grade 3 VUR, and 1 patient, Grade 4. Two patients with RU underwent UDS. Although both of these 2 patients had very weak sense of micturition after saline > 500 mL was injected in the bladder, the compliance of their bladder wall was good and observed no RU in UDS. All patients underwent KTx with the informed consent about the possibility of need to perform CIC if they had RU post-operatively. Patients with Grade 4 VUR also underwent nephrectomy simultaneously with KTx. All patients were indicated of schedule urination after removal of urinary catheter. Median RU was 3 mL (range, 0-49) after KTx and no patients required CIC. Ux was normal at 3 months follow-up in all cases; and median eGFR was 68.4 mL/min/1.73 m2 (range, 54.3-92.9). Conclusion Although some of the patients with CRH who undergo KTx had bladder capacity abnormality, few patients need CIC with adequate indication of scheduled urination after KTx.

To investigate the efficacy and safety of first-line Pazopanib advanced or metastatic renal cell carcinoma (RCC): a single-institution study. (Patients and methods) We gathered 23 RCC patients treated between April 2014 and February 2018 in our institution and examined the treatments outcome and adverse events (AEs). (Results) Their risk criteria were categorized as follows: Favorable (n=2), Intermediate (n=12) and Poor (n=9) by International mRCC Database Consortion (IMDC). Median progression free survival (PFS) was 8.6 months and median overall survival (OS) was unreached. Best response (BR) of Pazopanib was partial response (PR): n=10, 50.0%, stable disease (SD): n=8, 40.0% and progression disease (PD): n=2, 10.0% (Three patients had no evaluable data,). AEs of Grade3 had liver dysfunction (n=3), thrombocytopenia (n=2), hand-foot syndrome (n=1), vomiting (n=1) and bowel bleeding (n=1). (Conclusion) The fist-line pazopanib demonstrated good clinical benefit with well-tolerance.