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Context: There is no high-level evidence regarding the risk factors of glomerular filtration rate (GFR) loss following radical cystectomy (RC) and survival outcomes of patients with chronic kidney disease (CKD) undergoing RC., Objective: To identify the risk factors of CKD in patients treated with RC for bladder cancer and to assess overall and oncological survival of patients with CKD who underwent RC., Evidence Acquisition: According to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, two systematic reviews were performed for studies published before September 30, 2022, assessing (1) risk factors of renal function (RF) decline following RC and (2) overall and oncological outcomes of CKD patients treated with RC., Evidence Synthesis: A total of 21 and 17 studies were included for qualitative and quantitative syntheses, respectively. The first meta-analysis of ten studies (15 502 patients) identified these factors to be significantly associated with GFR loss following RC: advanced age, lower baseline RF, higher Charlson Comorbidity Index (CCI), diabetes mellitus, hypertension, postoperative hydronephrosis, ureteroenteric stricture, and locally advanced disease (hazard ratios [HRs] 1.03, 1.22, 1.5, 1.27, 1.24, 1.69, 1.92, and 5.13, respectively), while sex, preoperative hydronephrosis, perioperative chemotherapy, and diversion type were not. The second meta-analysis of seven studies (6900 patients) demonstrated significantly worse metastasis-free, cancer-specific, and overall survival in patients with higher CKD stages than in those with lower stages (HRs 1.54, 2.09, and 1.47, respectively)., Conclusions: Current evidence suggests that older age, lower baseline RF, higher CCI, diabetes mellitus, hypertension, postoperative hydronephrosis, ureteroenteric stricture, and locally advanced disease are associated with long-term GFR loss following RC. In addition, patients with higher stages of CKD have worse long-term overall and oncological outcomes following RC. These data may help in counseling and decision-making regarding therapy and preventive measures., Patient Summary: Several factors have been identified that can help identify patients at risk for glomerular filtration rate loss after radical cystectomy (RC). Chronic kidney disease is associated with poor cancer- and non-cancer-specific outcomes following RC., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Seasonal influenza is a major global health problem causing substantial morbidity and health care costs. Yet, in many countries, the rates of influenza vaccination remain low. Chronic kidney or liver diseases (CKLD) predispose patients to severe influenza infections, but data on vaccination acceptance and status is limited in this risk population. We investigated the influenza vaccination awareness considering sociodemographic factors in CKLD patients., Patients and Methods: This cross-sectional, questionnaire-based study recruited CKLD patients managed at three Viennese tertiary care centers between July and October 2020. CKLD was defined as chronic kidney- (all stages) or compensated/decompensated liver disease, including kidney/liver transplant recipients. Questionnaires assessed sociodemographic and transplant- associated parameters, patients vaccination status and the individuals self-perceived risks of infection and associated complications., Results: In total 516 patients (38.1% female, mean age 56.4 years) were included. 43.9% of patients declared their willingness to be vaccinated in the winter season 2020/2021, compared to 25.4% in 2019/2020 and 27.3% in 2016-2018. Vaccination uptake was associated with the self-perceived risks of infection (OR: 2.8 (95%CI: 1.8-4.5), p<0.001) and associated complications (OR: 3.8 (95%CI: 2.3-6.3), p<0.001) as well as with previously received influenza vaccination (2019/2020: OR 17.1 (95%CI: 9.5-30.7), p<0.001; season 2016-2018: OR 8.9 (95%CI: 5.5-14.5), p<0.001). Most frequent reasons for not planning vaccination were fear of a) graft injury (33.3%), b) complications after vaccination (32.4%) and c) vaccine inefficiency (15.0%)., Conclusion: While influenza vaccination willingness in patients with CKLD is increasing in the 2020/2021 season, vaccination rates may still remain <50%. Novel co-operations with primary health care, active vaccination surveillance and financial reimbursement may substantially improve vaccination rates in high-risk CKLD patients., Competing Interests: The authors have no competing interests.

The Banff antibody-mediated rejection (ABMR) classification is vulnerable to misinterpretation, but the reasons are unclear. To better understand this vulnerability, we evaluated how ABMR is diagnosed in practice. To do this, the Banff Antibody-Mediated Injury Workgroup electronically surveyed an international cohort of nephrologists/surgeons (n = 133) and renal pathologists (n = 99). Most providers (97%) responded that they use the Banff ABMR classification at least sometimes, but DSA information is often not readily available. Only 41.1% (55/133) of nephrologists/surgeons and 19.2% (19/99) of pathologists reported that they always have DSA results when the biopsy is available. Additionally, only 19.6% (26/133) of nephrologists/surgeons responded that non-HLA antibody or molecular transcripts are obtained when ABMR histologic features are present but DSA is undetected. Several respondents agreed that histologic features concerning for ABMR in the absence of DSA and/or C4d are not well accounted for in the current classification [31.3% (31/99) pathologists and 37.6% (50/133) nephrologist/surgeons]. The Banff ABMR classification appears widely accepted, but efforts to improve the accessibility of DSA information for the multidisciplinary care team are needed. Further clarity is also needed in Banff ABMR nomenclature to account for the spectrum of ABMR and for histologic features suspicious for ABMR when DSA is absent., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Novel tools are needed to improve diagnostic accuracy and risk prediction in BK virus nephropathy (BKVN). We assessed the utility of intragraft gene expression testing for these purposes. Eight hundred genes were measured in 110 archival samples, including a discovery cohort of native kidney BKVN (n = 5) vs pure T cell-mediated rejection (TCMR; n = 10). Five polyomavirus genes and seven immune-related genes (five associated with BKVN and two associated with TCMR) were significantly differentially expressed between these entities (FDR < 0.05). These three sets of genes were further evaluated in samples representing a spectrum of BK infection (n = 25), followed by a multicenter validation cohort of allograft BKVN (n = 60) vs TCMR (n = 10). Polyomavirus 5-gene set expression reliably distinguished BKVN from TCMR (validation cohort AUC = 0.992), but the immune gene sets demonstrated suboptimal diagnostic performance (AUC ≤ 0.720). Within the validation cohort, no significant differences in index biopsy gene expression were identified between BKVN patients demonstrating resolution (n = 35), persistent infection (n = 14) or de novo rejection (n = 11) 6 months following a standardized reduction in immunosuppression. These results suggest that, while intragraft polyomavirus gene expression may be useful as an ancillary diagnostic for BKVN, assessment for concurrent TCMR and prediction of clinical outcome may not be feasible with current molecular tools., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell-mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation., (© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: Antibody-mediated rejection (ABMR) is an important cause of kidney allograft injury. In the last two decades, detection of complement split product C4d along transplant capillaries, a footprint of antibody-mediated classical complement activation, has evolved as a useful diagnostic marker of ABMR. While it was recognized that ABMR may occur also in the absence of C4d, numerous studies have shown that C4d deposition may indicate a more severe rejection phenotype associated with poor graft survival. Such studies suggest a possible diagnostic benefit of ex vivo monitoring the complement-activating capability of circulating alloantibodies., Design and Methods: We reviewed the literature between 1993 and 2015, focusing on in vivo (biopsy work-up) and in vitro detection (modified bead array technology) of HLA antibody-triggered classical complement activation in kidney transplantation., Results: Precise HLA antibody detection methods, in particular Luminex-based single antigen bead (SAB) assays, have provided a valuable basis for the design of techniques for in vitro detection of HLA antibody-triggered complement activation reflected by C1q, C4 or C3 split product deposition to the bead surface. Establishing such assays it was recognized that deposition of complement products to SAB, which critically depends on antibody binding strength, may be a cardinal trigger of the prozone effect, a troublesome in vitro artifact caused by a steric interference with IgG detection reagents. False-low IgG results, especially on SAB with extensive antibody binding, have to be considered when interpreting studies analyzing the diagnostic value of complement in relation to standard IgG detection. Levels of complement-fixing donor-specific antibodies (DSA) were shown to correlate with the results of standard crossmatch tests, suggesting potential application for crossmatch prediction. Moreover, while the utility of pre-transplant complement detection, at least in crossmatch-negative transplant recipients, is controversially discussed, a series of studies have shown that the appearance of post-transplant complement-fixing DSA may be associated with C4d deposition in transplant capillaries and a particular risk of graft failure., Conclusions: The independent value of modified single antigen bead assays, as compared to a careful analysis of standard IgG detection, which may be affected considerably by complement dependent artifacts, needs to be clarified. Whether they have the potential to improve the predictive accuracy of our current diagnostic repertoire warrants further study., (Copyright © 2015. Published by Elsevier Inc.)

Background: Despite major advances in transplant medicine, improvements in long-term kidney allograft survival have not been commensurate with those observed shortly after transplantation. The formation of donor-specific antibodies (DSA) and ongoing antibody-mediated rejection (AMR) processes may critically contribute to late graft loss. However, appropriate treatment for late AMR has not yet been defined. There is accumulating evidence that the proteasome inhibitor bortezomib may substantially affect the function and integrity of alloantibody-secreting plasma cells. The impact of this agent on the course of late AMR has not so far been systematically investigated., Methods/design: The BORTEJECT Study is a randomized controlled trial designed to clarify the impact of intravenous bortezomib on the course of late AMR. In this single-center study (nephrological outpatient service, Medical University Vienna) we plan an initial cross-sectional DSA screening of 1,000 kidney transplant recipients (functioning graft at ≥180 days; estimated glomerular filtration rate (eGFR) >20 ml/minute/1.73 m2). DSA-positive recipients will be subjected to kidney allograft biopsy to detect morphological features consistent with AMR. Forty-four patients with biopsy-proven AMR will then be included in a double-blind placebo-controlled intervention trial (1:1 randomization stratified for eGFR and the presence of T-cell-mediated rejection). Patients in the active group will receive two cycles of bortezomib (4 × 1.3 mg/m2 over 2 weeks; 3-month interval between cycles). The primary end point will be the course of eGFR over 24 months (intention-to-treat analysis). The sample size was calculated according to the assumption of a 5 ml/minute/1.73 m2 difference in eGFR slope (per year) between the two groups (alpha: 0.05; power: 0.8). Secondary endpoints will be DSA levels, protein excretion, measured glomerular filtration rate, transplant and patient survival, and the development of acute and chronic morphological lesions in 24-month protocol biopsies., Discussion: The impact of anti-humoral treatment on the course of late AMR has not yet been systematically investigated. Based on the hypothesis that proteasome inhibition improves the outcome of DSA-positive late AMR, we suggest that our trial has the potential to provide solid evidence towards the treatment of this type of rejection., Trial Registration: Clinicaltrials.gov: NCT01873157.

Background and Objectives: Dialysis patients are at high risk for low-trauma bone fracture. Bone density measurements using dual-energy x-ray absorptiometry (DXA) do not reliably differentiate between patients with and without fractures. The aim of this study was to identify differences in bone microarchitecture between patients with and without a history of fracture using high-resolution peripheral quantitative computed tomography (HR-pQCT)., Design, Setting, Participants, & Measurements: Seventy-four prevalent hemodialysis patients were recruited for measurements of areal bone mineral density (aBMD) by DXA and bone microarchitecture by HR-pQCT. Patients with a history of trauma-related fracture were excluded. Forty healthy volunteers served as controls. Blood levels of parathyroid hormone, vitamin D, and markers of bone turnover were determined., Results: Dialysis patients, particularly women, had markedly impaired bone microarchitecture. Patients with fractures had significantly reduced cortical and trabecular microarchitecture compared with patients without fractures. aBMD tended to be lower in patients with fractures, but differences were statistically not significant. The strongest determinant of fracture was the HR-pQCT-measured trabecular density of the tibia, which also had the highest discriminatory power to differentiate patients according to fracture status. Radial DXA had a lower discriminatory power than trabecular density., Conclusions: Bone microarchitecture is severely impaired in dialysis patients and even more so in patients with a history of fracture. HR-pQCT can identify dialysis patients with a history of low-trauma fracture.

Background: Type I allergies have repeatedly been reported after solid organ transplantation despite T cell-targeted immunosuppressive therapy. A causal relationship with tacrolimus has been proposed., Objective: The present study directly compared the occurrence of allergic sensitization and disease under tacrolimus- vs. cyclosporin A-based immunosuppressive therapy., Methods: The prevalences of IgE-mediated sensitization and allergy were assessed in a cross-sectional study of kidney-transplanted adults receiving tacrolimus (n = 100) or cyclosporin A (n = 100)., Methods: included a standardized questionnaire, skin prick test and measurement of total and specific IgE against common nutritive and inhalant allergens. Results The prevalence of sensitization was significantly higher in the tacrolimus- than in the cyclosporin A-treated group (34%, n = 34, vs. 20%, n = 20; P = 0.026). The rate of clinically relevant allergy in patients receiving tacrolimus was twice that in patients receiving cyclosporin A (15%, n = 15, vs. 8%, n = 8; P = 0.12). No other factor (age, serum drug level, concomitant immunosuppressive medication, time since transplantation, underlying disease) was found to have an influence on sensitization or allergy prevalence (logistic regression)., Conclusion and Clinical Relevance: Our results suggest that post-transplant immunosuppression with tacrolimus is associated with an increased occurrence of IgE-mediated sensitization and probably manifestation of allergic disease, which has to be treated specifically despite immunosuppressive therapy., (© 2011 Blackwell Publishing Ltd.)

Objective: To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease., Patients and Methods: We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant., Results: The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages (P = 0.040), were smaller (P = 0.027), of lower grades (P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age (P = 0.022). After a median follow-up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival., Conclusions: Most RCCs in renal transplant recipients are incidental low-stage, low-grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated.

Objectives: The impact and outcome of holmium:YAG-laser (Ho:YAG) ureterolithotripsy in treating proximal and distal ureteral stones was investigated., Methods: A total of 543 patients harbouring proximal (n=194) or distal (n=349) ureteral stones underwent semirigid Ho:YAG ureterolithotripsy. The degree of hydronephrosis; stone size, location, impaction, and composition; and complication and stone-free rates were recorded., Results: Mean stone size for proximal and distal stones was 7.1+/-3.6 mm and 6.2+/-2.5 mm, respectively. The stone-free rate on the first postoperative day was 79.4% for proximal and 96.8% for distal stones (p<0.0001). For proximal stones <10mm and > or =10mm, respectively, the stone-free rate was 80.5% and 74.3% (p=0.4) and for distal stones 97.3% and 94.3% (p=0.2). Stone-free rates for radio-opaque versus radiolucent stones in proximal stones were 79.6% versus 77.9% (p=0.8) and 97.6% versus 96.2% in distal stones (p=0.5). Impaction correlated significantly with stone-free rates (p<0.0001). Stone-free rates for nonimpacted versus impacted proximal stones were 85.8% versus 67.2% (p=0.003) and for distal stones 99.2% versus 91.4% (p<0.003), respectively. The presence or degree of hydronephrosis did not correlate with treatment success (p=0.4, p=0.8). The presence of intraoperative complications correlated significantly with proximal compared to distal ureteral stone location (p=0.004). Auxiliary measures in proximal versus distal stones were performed in 20.6% versus 2.9% (p<0.0001)., Conclusions: In this series, stone-free rates in Ho:YAG ureterolithotripsy were significantly higher in distal and nonimpacted stones but were independent of stone size and composition and the degree of hydronephrosis. Ureterolithotripsy in proximal stones was associated with higher intraoperative complication and retreatment rates compared to distal stones.

Objectives: In delayed extracorporeal shock wave lithotripsy (ESWL) treatment, increasing stone impaction is associated with delayed stone clearance. Whether colic patients treated by rapid ESWL have the same time to stone clearance as noncolic patients, which supports the thesis that stones in both groups are nonimpacted, has not been investigated yet, and was the objective of this study., Methods: A total of 82 patients were prospectively enrolled and treated with piezoelectric ESWL for a solitary proximal ureteral stone. Of these, 56 patients experienced at least one colic episode compared with 26 noncolic patients. Hydronephrosis has been assessed with the use of ultrasound and intravenous urography (IVU). Time to stone clearance after the first ESWL and stone-free rates after a follow-up period of 3 mo were recorded., Results: In colic and noncolic patients, mean stone size was 7.8mm (p=0.7). Ultrasound-detected hydronephrosis was present in 88% versus 39% (p<0.0001), whereas IVU-detected hydronephrosis was present in 60% versus 7.7% (p=0.0001). Mean number of impulses applied was 8000+/-4000 versus 6700+/-3400 (p=0.1). Mean time to stone clearance was 9.5+/-12.1 d versus 4.6+/-3.8 d (p=0.1). Colic and noncolic patients were considered as treatment success in 83% and 81% after 3 mo of follow-up (p=0.9)., Conclusions: Treatment outcome and time to stone clearance after rapid ESWL in colic patients compared with noncolic patients is comparable and independent of concomitant hydronephrosis. This finding suggests an absence of significant impaction in proximal ureteral stones treated within 24h after a first colic episode, enforcing the concept of performing rapid ESWL in patients harbouring proximal ureteral stones.