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Publication Metadata only Application of HLA molecular mismatch algorithms to predict primary alloimmunity risk and rejection in paediatric kidney transplantation(Springer, 2023) Kim, Jon Jin; Fichtner, Alexander; Copley, Hannah; Krupka, Kai; Pape, Lars; Toenshoff, Burkhard; Kosmoliaptsis, Vasilis; Süsal, Caner; Koç Üniversitesi Organ Nakli İmmünoloji Araştırma Mükemmeliyet Merkezi (TIREX) / Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University Hospital[No abstract available]Publication Metadata only Assessment of HLA incompatibility at the molecular compared to antigenic HLA level enables better prediction of graft function deterioration in paediatric kidney transplantation(Springer, 2023) Kim, Jon Jin; Fichtner, Alexander; Copley, Hannah; Susal, Caner; Krupka, Kai; Pape, Lars; Burkhard, Toenshoff; Kosmoliaptsis, Vasilis; Süsal, Caner; Koç Üniversitesi Organ Nakli İmmünoloji Araştırma Mükemmeliyet Merkezi (TIREX) / Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University Hospital[No abstract available]Publication Metadata only Can we predict and manage persistent storage and voiding LUTS following bladder outflow resistance reduction surgery in men? ICI-RS 2023(Wiley, 2024) Hashim, Hashim; Malde, Sachin; Sinha, Sanjay; Sahai, Arun; Selai, Caroline; Agro, Enrico Finazzi; Abrams, Paul; Wein, Alan; Tarcan, Tufan; Acar, Ömer; ; School of Medicine;Aims Lower urinary tract symptoms (LUTS) persist in up to 50% of patients after bladder outflow resistance reduction surgery (BORRS) in men. Our think tank aims to address the predictive factors for persistent LUTS after BORRS and to propose the recommendations for future research to enable improved better patient counseling and selection by more accurate prediction of treatment outcome.MethodsA think tank of ICI-RS gathered in 2023, Bristol, UK, to discuss the pre and postsurgical clinical and urodynamic evaluation of men undergoing BORRS and whether it is possible to predict which men will have persistent LUTS after BORRS.ResultsOur think tank agrees that due to the multifactorial, and still not fully understood, etiology of male LUTS it is not possible to precisely predict in many men who will have persistent LUTS after BORRS. However, severe storage symptoms (overactive bladder, OAB) in association with low volume and high amplitude detrusor overactivity and low bladder capacity in preoperative urodynamics, increase the likelihood of persistent OAB/storage symptoms after BORRS. Furthermore, patients who are clearly obstructed and have good bladder contractility on preoperative pressure flow studies do better postoperatively compared to their counterparts. However, the benefit of pressure flow studies is decreased in patients who do not acceptably void during the study. Poor voiding after BORRS may occur due to persistent obstruction or detrusor underactivity.ConclusionFuture research is needed to increase our understanding of why male LUTS persist after surgery, and to enable better patient selection and more precise patient counseling before BORRS.Publication Metadata only Can we predict whether a man with acute or chronic urinary retention will void after bladder outflow resistance reduction surgery? ICI-RS 2023(Wiley, 2024) Malde, Sachin; Sinha, Sanjay; Sahai, Arun; Perrouin-Verbe, Marie-Aimee; Hashim, Hashim; Agro, Enrico Finazzi; Wein, Alan; Abrams, Paul; Tarcan, Tufan; Acar, Ömer; ; School of Medicine;Aims To address the predictive factors of a successful voiding after bladder outflow resistance reduction surgery (BORRS) in men presenting with acute or chronic urinary retention (UR).MethodsA think tank (TT) of ICI-RS was gathered in 2023, Bristol, UK, to discuss several aspects of the problem, such as the pathophysiology of UR, the clinical and urodynamic evaluation of men with UR and whether it is possible to predict which men will be able to successfully void after treatment with contemporary surgical options.ResultsThe TT agreed that successful voiding after BORRS depends on several factors but that a strong recommendation cannot be made regarding preoperative evaluation and whether there are predictive factors of success because of the heterogeneity of patients and methodology in published trials. The diagnosis of obstruction in men with UR may be challenging when there is apparent reduced detrusor contraction during urodynamic studies. Even in the absence of bladder contractility there is documentation of such cases that have voided adequately after BORRS. Still, detrusor underactivity and inadequate relief of prostatic obstruction are the main causes of an unsuccessful voiding after BORRS. Conventional resection and enucleation methods remain the most successful surgeries in relieving UR in men, whereas the efficacy of minimally invasive surgical treatments needs to be assessed further.ConclusionResearch is needed to understand the pathophysiology of UR and the predictors of successful voiding after different types of BORRS in men with UR.Publication Metadata only Clinicopathologic correlations of urinary proteomic and metabolomic analysis in patients with renal aa amyloidosis and membranous nephropathy(Oxford Univ Press, 2023) Ozbek, Deniz Aral; Koc, Sila; Yet, Idil; Kablan, Sevilay; Uner, Meral; Lay, Incilay; Yıldırım, Tolga; Yılmaz, Seref Rahmi; Altun, Bulent; Küçük, Nazlı Ezgi Özkan; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); ;Background and Aims AA Amyloidosis is a multisystemic amyloidosis subtype that develops on the background of various chronic inflammatory etiologies. Urinary omics studies have become a promising tool for elucidating pathophysiology and prognosis of glomerular diseases. However, no urinary omics analysis has been performed focusing on renal AA amyloidosis in literature to the best of our knowledge. Our main aim in this study is to perform a comparative urine proteomic and metabolomic analysis of recently diagnosed renal AA amyloidosis and to investigate the correlation of bioinformatic results with clinical and pathological data. Method Urine samples of 8 recently diagnosed AA amyloidosis (AA), 8 membranous nephropathy (MN) and 6 healthy control group patients were collected before kidney biopsy procedure. Proteomic analyzes were performed with nLC/Q-TOF MS/MS and metabolomic analyzes were performed by GC/MS in all patients. Biopsy specimens were scored according to glomerulosclerosis (G), tubular atrophy (TA) and interstitial fibrosis (IF) grades by two pathologists. Raw spectroscopic data was analyzed using MaxQuant and MS-DIAL programs for proteomic and metabolomic studies, respectively. Statistical analysis of the differences in molecules between study groups were performed with ANOVA and HSD-Tukey tests. Principal component (PCA) and heatmap analyzes were made in R language, while gene ontology (GO), network and functional enrichment analysis of bioinformatic results were performed with PANTHER, STRING and MetaboAnalyst databases. Results In comparison between AA and MN groups, median eGFR values tend to be lower in the AA group (67.6 vs 112 ml/min/1.73 m2 respectively, p = 0.08). Median 24-hour urine protein levels did not show statistically significant difference (9499 vs 9512 mg/day respectively, p = 0.9). Percentage of patients with moderate/severe IF/TA was higher and G score was tend to be in AA group compared to MN group (p values 0.02 and 0.07 for IF/TA and G scores, respectively). As a result of proteomic analysis, a total of 859 proteins were determined. Statistical analysis showed 51 proteins that were significantly differ in AA group compared to the control group. GO and functional enrichment analyzes showed that statistically most significant sub-domains were mainly related with cell-cell adhesion (Figure 1 & 2). In comparative analysis between AA and MN patients, uromodulin (UMOD) was lower in the AA group than in the MN group (log2FC -3.37), whereas ribonuclease 1 (RNASE1) and α-1-microglobulin/bikunin precursor protein (AMBP) were higher in the AA group (log2FC 3.41 and 3.07, respectively). In Spearman correlation analyzes, significant negative correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and between AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed 9 metabolites that were significantly different between AA and other study groups. Myo-inositol and urate were higher in AA group compared to MN group, while D-mannitol and N-acetylglutamate were higher in AA group compared to the control group. Significant positive correlation independent of GFR was detected between RNASE1 and urate (r = 0.63, p = 0.01).Publication Metadata only Evaluation of new treatments for benign prostatic obstruction: ICI-RS 2023(Wiley, 2023) Hashim, Hashim; Acar, Omer; Malde, Sachin; Wein, Alan; Abrams, Paul; Tarcan, Tufan; ; School of Medicine;Aims To address how invasive therapies for benign prostatic obstruction (BPO) have been evaluated, what their effect is on BPO, if they can prevent progression to BPO and how new therapies need to be evaluated before implementation into clinical practice.MethodsThe think tank conducted a literature review and looked at the previous and current American Urological Association, European Association of Urology and the International Consultation on Urological Diseases guidelines to see what procedures have been used to treat BPO. They then assessed whether trials have been conducted before implementation of the procedures and whether they have been compared to a "gold" standard treatment. The use of urodynamics has also been addressed in the think tank in relation the clinical trials as well as terminology.ResultsGuidelines vary in the use of terminology when it comes to BPO with some continuing to use the term benign prostatic hyperplasia (BPH). There are several procedures for example, TUNA, which have become obsolete although continues to be mentioned in the guidelines until recently. Majority of procedures have been introduced without comparing to "gold" standard treatment and without any long-term data. There continues to be many unknowns with regard to the success of some of the BPO procedures and why some of the adverse events develop.ConclusionThere needs to be more robust long-term clinical trials conducted of new BPO therapies, with men who have both lower urinary tract symptoms and urinary retention, before introduction into clinical practice.Publication Metadata only Glomerular hyperfiltration as a therapeutic target for CKD(Oxford Univ Press, 2024) Covic, Adrian; Ortiz, Alberto; Tuttle, Katherine R.; Kanbay, Mehmet; Bakır, Çiçek Nur; Çöpür, Sidar; ; School of Medicine;The global burden of chronic kidney disease (CKD) is high and increasing. Early diagnosis and intervention are key to improve outcomes. Single-nephron glomerular hyperfiltration is an early pathophysiologic manifestation of CKD that may result in absolute glomerular hyperfiltration, i.e. a high glomerular filtration rate (GFR), or be associated with normal or low GFR because of nephron loss (relative glomerular hyperfiltration). Even though compensatory glomerular hyperfiltration may contribute to maintain kidney function after the loss of kidney mass, the associated increased glomerular capillary pressure and glomerular and podocyte size drive podocyte loss, albuminuria and proximal tubular overload, contributing to CKD progression. In this regard, all kidney protective drugs in clinical use so far, from renin-angiotensin system blockers to mineralocorticoid receptor blockers to sodium-glucose co-transporter 2 inhibitors to tolvaptan, induce an early dip in glomerular filtration that is thought to represent reversal of hyperfiltration. As glomerular hyperfiltration may be present early in the course of kidney disease, its recognition may provide an effective intervention window that may predate current criteria based on high albuminuria or loss of GFR. Nevertheless, there is no diagnostic method with high sensitivity and specificity to identify single-nephron glomerular hyperfiltration, except when it leads to obvious absolute glomerular hyperfiltration, as observed in the early stages of diabetic kidney disease when nephron mass is still preserved. We now review the concept of glomerular hyperfiltration as an indicator of CKD risk, including definitions, challenges in diagnosis and evaluation, underlying pathophysiological mechanisms, potential therapeutic approaches and unanswered questions.Publication Metadata only How do we make progress in phenotyping patients with lower urinary tract such as overactive bladder and underactive detrusor, including using urine markers and microbiome data, to personalize therapy? ICI-RS 2023 - Part 2(Wiley, 2024) Agro, Enrico Finazzi; Rosato, Eleonora; Wagg, Adrian; Sinha, Sanjay; Fede Spicchiale, Claudia; Serati, Maurizio; Mancini, Vito; de Rijk, Mathijs; Wein, Alan; Abrams, Paul; Bou Kheir, George; Tarcan, Tufan; ; School of Medicine;IntroductionOveractive bladder (OAB) and underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction.ObjectivesThe aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment.MethodsA compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU using urodynamic tests, functional neuro-imaging, urinary markers, and microbiome.Results and ConclusionsThe article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract (LUT) symptoms, such as OAB and UAB. The intricate interplay between the LUT and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.Publication Metadata only How do we make progress in phenotyping patients with LUT such as OAB and underactive detrusor, including using urine markers and microbiome data, in order to personalize therapy? ICI-RS 2023 - Part 1(Wiley, 2024) Agro, Enrico Finazzi; Rosato, Eleonora; Wagg, Adrian; Sinha, Sanjay; Spicchiale, Claudia Fede; Serati, Maurizio; Mancini, Vito; de Rijk, Mathijs; Wein, Alan; Abrams, Paul; Kheir, George Bou; Tarcan, Tufan; ; School of Medicine;IntroductionOveractive bladder (OAB) and Underactive bladder (UAB) could be associated with metabolic syndrome, affective disorders, sex hormone deficiency, changes in urinary microbiota, functional gastrointestinal disorders, or autonomic nervous system dysfunction.ObjectivesThe aim of this Think Tank was to provide a guide on how to investigate OAB and/or detrusor underactivity (DU) patients to better clarify the underlying pathophysiology and possibly personalize the treatment.MethodsA compendium of discussion based on the current evidence related to phenotyping patients with OAB or DU investigating metabolic, neurogical, psychological and gastrointestinal aspects with the aim to personalize the treatment.Results and ConclusionsThe article emphasizes the critical significance of adopting a comprehensive yet tailored approach to phenotyping patients with lower urinary tract symptoms, such as OAB and UAB. The intricate interplay between the lower urinary tract and various factors, metabolic, neurological, psychological, and gastrointestinal can define unique LUT profiles, enabling personalized therapies to replace the one-size-fits-all approach.Publication Metadata only Kidney transplantation in children and adolescents with C3 glomerulopathy or immune complex membranoproliferative glomerulonephritis: a real-world study within the CERTAIN research network(Springer, 2024) Patry, Christian; Webb, Nicholas J. A.; Feisst, Manuel; Krupka, Kai; Becker, Jan; Bald, Martin; Antoniello, Benedetta; Gulhan, Bora; Hogan, Julien; Kanzelmeyer, Nele; Ozkaya, Ozan; Buescher, Anja; Sellier-Leclerc, Anne-Laure; Shenoy, Mohan; Weber, Lutz T.; Fichtner, Alexander; Hoecker, Britta; Meier, Matthias; Toenshoff, Burkhard; Bilge, İlmay; ; School of Medicine;BackgroundComplement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40-50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation.MethodsIn this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case-control group (n = 20).ResultsEleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective.ConclusionsThese data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information