Researcher:
Güldan, Mustafa

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Undergraduate Student

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Mustafa

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Güldan

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Güldan, Mustafa

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Now showing 1 - 9 of 9
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    Publication
    Metabolically healthy obesity and chronic kidney disease risk: exploring the dynamics
    (Edizioni Minerva Medica, 2024) Covic, Adrian; Güldan, Mustafa; Özbek, Laşin; Topçu, Ahmet Umur;  ; School of Medicine;  
    Obesity represents a prevalent global health concern with significant implications for various diseases, including chronic kidney disease (CKD) Within this landscape, the phenomenon of metabolically healthy obesity has emerged, challenging traditional notions about the health risks as sociated with excess weight. While traditional CKD risk factors involve obesity, metabolic syndrome, diabetes, and hypertension, the metaboli cally healthy obese (MHO) subgroup disrupts these assumptions. Our main objective in this study is to integrate existing literature on CKD i MHO individuals. In this endeavor, we delve into the pathophysiological foundations, the transition between obesity phenotypes and their impac on renal health, examine the implications of their metabolic resilience on mortality within a renal context, and explore potential managemen strategies specifically designed for MHO individuals. Offering a comprehensive overview of the pathophysiology, we cover various factor contributing to the risk of CKD in the metabolically healthy obese setting, including inflammation, cytokines, hemodynamics, and the renin angiotensin-aldosterone system, gastrointestinal microbiota, diet, exercise, adipose distribution, and lipotoxicity. Through this synthesis, we aim to provide a comprehensive understanding of the risk of CKD in those classified as MHO. © 2024 EDIZIONI MINERVA MEDICA.
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    Prognostic impact of post-transplant diabetes mellitus in kidney allograft recipients: a meta-analysis
    (Oxford Univ Press, 2024) Siriopol D.; Siriopol I.; Tuttle K.; Güldan, Mustafa; Özbek, Laşin; Topçu, Ahmet Umur;  ; School of Medicine;  
    Background Post-transplant diabetes mellitus (PTDM) is a complex condition arising from various factors including immunosuppressive medications, insulin resistance, impaired insulin secretion and inflammatory processes. Its impact on patient and graft survival is a significant concern in kidney transplant recipients. PTDM's impact on kidney transplant recipients, including patient and graft survival and cardiovascular mortality, is a significant concern, given conflicting findings in previous studies. This meta-analysis was imperative not only to incorporate emerging evidence but also to delve into cause-specific mortality considerations. We aimed to comprehensively evaluate the association between PTDM and clinical outcomes, including all-cause and cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and graft loss, in kidney transplant recipients. Methods PubMed, Ovid/Medline, Web of Science, Scopus and Cochrane Library databases were screened and studies evaluating the effect of PTDM on all-cause mortality, cardiovascular mortality, sepsis-related mortality, malignancy-related mortality and overall graft loss in adult kidney transplant recipients were included. Results Fifty-three studies, encompassing a total of 138 917 patients, evaluating the association between PTDM and clinical outcomes were included. Our analysis revealed a significant increase in all-cause mortality [risk ratio (RR) 1.70, 95% confidence interval (CI) 1.53 to 1.89, P < .001] and cardiovascular mortality (RR 1.86, 95% CI 1.36 to 2.54, P < .001) among individuals with PTDM. Moreover, PTDM was associated with a higher risk of sepsis-related mortality (RR 1.96, 95% CI 1.51 to 2.54, P < .001) but showed no significant association with malignancy-related mortality (RR 1.20, 95% CI 0.76 to 1.88). Additionally, PTDM was linked to an increased risk of overall graft failure (RR 1.33, 95% CI 1.16 to 1.54, P < .001). Conclusion These findings underscore the importance of comprehensive management strategies and the need for research targeting PTDM to improve outcomes in kidney transplant recipients.
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    Native nephrectomy in polycystic kidney disease patients on transplant lists: how and when?
    (Springer Heidelberg, 2024) Çöpür, Sidar; Özbek, Laşin; Güldan, Mustafa; Topçu, Ahmet Umur; Kanbay, Mehmet; School of Medicine
    Autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney disease, accounts for approximately 10% of the patients on kidney transplantation waitlists. High rates of complications including hemorrhage, infections, nephrolithiasis and kidney size-related compressive complaints have been reported among ADPKD patients. Therefore, the need for routine native nephrectomy and timing of such procedure in ADPKD patients being prepared for transplantation are debated. Even though pre-transplant nephrectomy has the potential to provide fewer infectious complications due to lack of immunosuppressive medication use, such procedure has been associated with longer hospital stay, loss of residual kidney function and need for dialysis. Although simultaneous nephrectomy and transplantation could potentially lead to longer perioperative duration, perioperative complications and need for blood transfusions, this was not confirmed in cohort studies. Therefore, some institutions routinely perform simultaneous unilateral nephrectomy and kidney transplantation. In this narrative review, our aim is to evaluate the current evidence regarding the need and timing of nephrectomy in ADPKD patients in relation to kidney transplantation.
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    Understanding the role of sex hormones in cardiovascular kidney metabolic syndrome: toward personalized therapeutic approaches
    (MDPI, 2024) Gaipov, Abduzhappar; Covic, Andreea; Soler, Maria Jose; Covic, Adrian; Güldan, Mustafa; Ünlü, Selen; Abdel-Rahman, Sama Mahmoud; Özbek, Laşin; Kanbay, Mehmet; School of Medicine; Graduate School of Health Sciences
    Cardiovascular kidney metabolic (CKM) syndrome represents a complex interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic comorbidities, posing a significant public health challenge. Gender exerts a critical influence on CKM syndrome, affecting the disease severity and onset through intricate interactions involving sex hormones and key physiological pathways such as the renin-angiotensin system, oxidative stress, inflammation, vascular disease and insulin resistance. It is widely known that beyond the contribution of traditional risk factors, men and women exhibit significant differences in CKM syndrome and its components, with distinct patterns observed in premenopausal women and postmenopausal women compared to men. Despite women generally experiencing a lower incidence of CVD, their outcomes following cardiovascular events are often worse compared to men. The disparities also extend to the treatment approaches for kidney failure, with a higher prevalence of dialysis among men despite women exhibiting higher rates of CKD. The impact of endogenous sex hormones, the correlations between CKM and its components, as well as the long-term effects of treatment modalities using sex hormones, including hormone replacement therapies and gender-affirming therapies, have drawn attention to this topic. Current research on CKM syndrome is hindered by the scarcity of large-scale studies and insufficient integration of gender-specific considerations into treatment strategies. The underlying mechanisms driving the gender disparities in the pathogenesis of CKM syndrome, including the roles of estrogen, progesterone and testosterone derivatives, remain poorly understood, thus limiting their application in personalized therapeutic interventions. This review synthesizes existing knowledge to clarify the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. By addressing these knowledge gaps, this study aims to guide future research efforts and promote tailored approaches for effectively managing CKD syndrome.
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    Exploring the nexus: The place of kidney diseases within the cardiovascular-kidney-metabolic syndrome spectrum
    (Elsevier B.V., 2024) Covic, Andreea Simona; Covic, Adrian; Kanbay, Mehmet; Güldan, Mustafa; Özbek, Laşin; Çöpür, Sidar; School of Medicine
    Cardiovascular-kidney-metabolic (CKM) syndrome and chronic kidney disease (CKD) are two significant comorbidities affecting a large proportion of the general population with considerable crosstalk. In addition to substantial co-incidence of CKD and CKM syndrome in epidemiological studies, clinical and pre-clinical studies have identified similar pathophysiological pathways leading to both entities. Patients with CKM syndrome are more prone to develop acute kidney injury and CKD, while therapeutic alternatives and their success rates are considerably lower in such patient groups. Nevertheless, the association between CKM syndrome and CKD or ESKD is bidirectional rather than being a cause-effect relationship as patients with CKD are also prone to develop peripheral insulin resistance, high blood pressure, and dyslipidemia. Furthermore, such patients are less likely to receive kidney transplantation in addition to the higher allograft dysfunction risk. We hereby aim to evaluate the association in-between kidney diseases and CKM syndrome, including epidemiological data, pre-clinical studies with pathophysiological pathways, and potential therapeutic perspectives. © 2024 European Federation of Internal Medicine
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    Proximal tubule hypertrophy and hyperfunction: a novel pathophysiological feature in disease states
    (Oxford Univ Press, 2024) Covic, Adrian; Mallamaci, Francesca; Zoccali, Carmine; Kanbay, Mehmet; Çöpür, Sidar; Güldan, Mustafa; Özbek, Laşin; Hatipoğlu, Alper; School of Medicine
    The role of proximal tubules (PTs), a major component of the renal tubular structure in the renal cortex, has been examined extensively. Along with its physiological role in the reabsorption of various molecules, including electrolytes, amino acids and monosaccharides, transcellular transport of different hormones and regulation of homeostasis, pathological events affecting PTs may underlie multiple disease states. PT hypertrophy or a hyperfunctioning state, despite being a compensatory mechanism at first in response to various stimuli or alterations at tubular transport proteins, have been shown to be critical pathophysiological events leading to multiple disorders, including diabetes mellitus, obesity, metabolic syndrome and congestive heart failure. Moreover, pharmacotherapeutic agents have primarily targeted PTs, including sodium-glucose cotransporter 2, urate transporters and carbonic anhydrase enzymes. In this narrative review, we focus on the physiological role of PTs in healthy states and the current understanding of the PT pathologies leading to disease states and potential therapeutic targets.
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    PublicationOpen Access
    Imlifidase in kidney transplantation
    (Oxford Univ Press, 2024) Callemeyn, Jasper; Segelmark, Marten; Kanbay, Mehmet; Çöpür, Sidar; Güldan, Mustafa; Topçu, Ahmet Umur; Özbek, Laşin; Hasbal, Nuri Barış; Süsal, Caner; Koçak, Burak; Koç University Transplant Immunology Research Centre of Excellence (TIREX); School of Medicine; Koç University Hospital
    Kidney transplantation, the gold-standard therapeutic approach for patients with end-stage kidney disease, offers improvement in patient survival and quality of life. However, broad sensitization against human leukocyte antigens often resulting in a positive crossmatch against the patient's living donor or the majority of potential deceased donors in the allocation system represents a major obstacle due to a high risk for antibody-mediated rejection, delayed graft function and allograft loss. Kidney-paired donation and desensitization protocols have been established to overcome this obstacle, with limited success. Imlifidase, a novel immunoglobulin G (IgG)-degrading enzyme derived from Streptococcus pyogenes and recombinantly produced in Escherichia coli, is a promising agent for recipients with a positive crossmatch against their organ donor with high specificity towards IgG, rapid action and high efficacy in early pre-clinical and clinical studies. However, the rebound of IgG after a few days can lead to antibody-mediated rejection, making the administration of potent immunosuppressive regimens in the early post-transplant phase necessary. There is currently no comparative study evaluating the efficiency of imlifidase therapy compared with conventional desensitization protocols along with the lack of randomized control trials, indicating the clear need for future large-scale clinical studies in this field. Besides providing a practical framework for the clinical use of the agent, our aim in this article is to evaluate the underlying mechanism of action, efficiency and safety of imlifidase therapy in immunologically high-risk kidney transplant recipients.
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    Antibacdus-pan: antibacterial utilization among adult patients at Koc University Hospital before and during COVID-19 pandemic within 12-months period: a hospital pharmacoepidemiology study
    (Wiley, 2022) Gülmez, Sinem Ezgi; Güldan, Mustafa; Uçar, Ege Anıl; Karakuş, Mehmet Batuhan; Şahin, Selin Merve; Şişman, Uluman; Baygül, Arzu Eden; Faculty Member; Undergraduate Student; Undergraduate Student; Undergraduate Student; Undergraduate Student; Undergraduate Student; Undergraduate Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; School of Medicine; 281312; N/A; N/A; N/A; N/A; N/A; 272290
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    PublicationOpen Access
    Antipacdus-pan: antibacterial utilization among adult patients before and during COVID-19 Pandemic within 12-months period: a tertiary hospital pharmacoepidemiology study
    (Design Oriented Community (DOC), 2022) Uçar, Ege Anıl; Karakuş, Mehmet Batuhan; Güldan, Mustafa; Şahin, Selin Merve; Şişman, Uluman; Baygül, Arzu Eden; Gülmez, Sinem Ezgi; Undergraduate Student; Undergraduate Student; Undergraduate Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; N/A; N/A; N/A; N/A; N/A; 272290; 281312
    Objective: irrational use of antibacterials is a concern during the COVID-19 pandemic. Hospital pharmacoepidemiology studies are important for evaluating the rational use of medicines, especially antibacterials, during pandemics. Defined daily doses (DDD) and drug utilization 90% (DU90%) are established methods for the evaluation of drug utilization. We aimed to evaluate antibacterial utilization in a tertiary hospital setting at Koç University Hospital (KUH). Materials and methods: this cross-sectional, descriptive study was retrospectively conducted with data extracted from KUH Inpatient Electronic Order System (CP) and was carried out for a period of one year. Antibacterial utilization of adult (aged ? 18 years) inpatients, who were prescribed at least one type of systemic antibacterial (ATC code J01), was evaluated using the recommended parameter DDD/100 admission and compared between 6 months before COVID-19 and during COVID-19 periods. March 11, 2020, the very first COVID-19 diagnosed case in Turkey, was set as the cutoff date of the 6-month period for the selection of the compared antibacterials using the DU90% method. Results: finally, 3280 of 5942 and 2605 of 4942 prescriptions for pre-COVID-19 and COVID-19 periods were included, respectively. Antibacterial utilization according to DDD/100 admissions increased from 193.96 to 201.26 DDD/100 admissions after the initiation of COVID-19 pandemic. The most utilized antibacterials were piperacillin and enzyme inhibitors in pre-COVID-19 period, whereas meropenem was utilized the most during COVID-19 period. Azithromycin utilization increased by 656.24%, whereas clarithromycin utilization decreased by 52.12%. Antibacterials were utilized most in general surgery department, with an increase of 17.57%. Conclusion: there is an increase in antibacterial utilization in KUH during COVID-19 pandemic, especially reserved antibacterials, which is a concern for antibacterial resistance.