9 research outputs found
Serikbol Qondıbay’ın “Arğıkazak Mifologiyası” Adlı Eserinde Mit Kavramsallaşması ve Kazak Mitoloji Tasarımı
No full textABSTRACT
CAYNAK, Sebahat, Myth Conceptualization and Kazakh Mythology Design in Serikbol
Qondıbay's "Arğıkazak Mythology”, Master Thesis, Ankara, 2021.
The myth is about a comprehensible stereotype about the environment in which human
society lives in a particular geographic area, in a particular political, social, cultural and
economic situation, about how it arose and about the internal forces affecting people,
about the place and degree of society in the universe. The book we will use in this
study consists of four volumes. The books generally include the ways of reconstructing
the Kazakh language using the internal and external abilities and the development
order of the early stages of our history through mythology, astronomical mythological
subjects of the Kazakhs, the image of women in the Kazakhs, the cult of snakes and
dragons, some animal totems, the mythology of twins, the cult of swords. . Our thesis
consists of an introduction and three main chapters that follow. Subsequently, the
conclusion and bibliography sections follow. In the introduction part, after a brief
evaluation about Serikbol Qondıbay's life and works, the aim, subject, method and
sections of the thesis are explained. After the first part of the conceptual analysis of the
work, in the second part, the methods used by the author in the work he created are
discussed and an evaluation has been made on the examples regarding the similarities
and differences with René Guénon. In the third chapter, the translation of the first
volume is included in this four-volume work of Qondıbay. The study was analyzed by
document analysis method and interpreted with content analysis. In the study, the
mythological product was analyzed according to the study named "Text, Verbal Texture
and Context" of Alan Dundes, one of Context-Centered Folklore Theories.
Key Words
Kazakh, Kazakhstan, Myth, Mythology, Serikbol QondıbayÖZET
CAYNAK, Sebahat, Serikbol Qondıbay’ın “Arğıkazak Mifologiyası” Adlı Eserinde Mit
Kavramsallaşması Ve Kazak Mitoloji Tasarımı, Yüksek Lisans Tezi, Ankara, 2021
Mit, belirli bir tarihte, belirli bir coğrafi alanda, belirli bir politik, sosyal, kültürel ve
ekonomik durumda yaşayan insan toplumunun yaşadığı çevre hakkında, nasıl ortaya
çıktığı ve insanları etkileyen içsel kuvvetler hakkında, evrendeki toplumun yeri ve
derecesi hakkında anlaşılır bir klişe ile ilgilidir. Bu çalışmada kullanacağımız kitap, dört
ciltten oluşmaktadır. Kitaplarda genel olarak, Kazak dilinin iç ve dış yeteneklerini ve
mitoloji yoluyla tarihimizin ilk aşamalarının gelişim sırasını kullanarak yeniden
yapılandırma yolları, Kazakların gökbilimsel mitolojik konuları, Kazaklarda kadın imajı,
yılan ve ejderha kültü, bazı hayvan totemleri, ikizler mitolojisi, kılıç kültü gibi konular yer
almaktadır. Tezimiz, giriş ve onu takip eden üç ana bölümden oluşmaktadır. Akabinde
sonuç ve kaynakça bölümleri gelmektedir. Giriş bölümünde Serikbol Qondıbay’ın
hayatı, eserleri hakkında kısa bir değerlendirme yapıldıktan sonra tezin amacı, konusu,
yöntemi ve bölümleri anlatılmıştır. Eserin kavram incelemesinin yapıldığı birinci
bölümden sonra ikinci bölümde yazarın oluşturduğu eserde kullandığı yöntemler ele
alınmış ve René Guénon ile benzerlikleri ve farklılıkları ile ilgili örnekler üzerinden
değerlendirme yapılmıştır. Üçüncü bölümde Qondıbay’ın bu dört ciltlik eserinde birinci
cildin çeviri yazısına yer verilmiştir. Çalışma doküman incelemesi yöntemiyle incelenip
içerik analizi ile yorumlanmıştır. Çalışmada mitolojik ürün, Bağlam Merkezli Halkbilim
Kuramlarından Alan Dundes’in “Metin, Sözel Doku ve Bağlam” adlı çalışmasına göre
analiz edilmiştir.
Anahtar Sözcükler
Kazak, Kazakistan, Mit, Mitoloji, Serikbol Qondıba
Reading Paulo Freire’s Pedagogy of the Oppressed: Why did it feel empowering to me?
No full textCelebrating the work of Paulo Freire for his healing influence, this paper gives an auto-ethnographic account of the author’s personal, pedagogical and political liberation process reading Paulo Freire’s Pedagogy of the Oppressed. Raised in a conservative patriarchal middle-class atmosphere in central Turkey, the author analyzes her own story of liberation as a woman, as a young scholar, as nonnative English-speaking language educator and a citizen of a democratic republic. The author describes how she realized her own subjugation by reading Freire (2005) at a time of personal and political crisis and how she tried hard to find her personal voice. She also depicts the impact of the book on her pedagogy, on her relationships with students and on her liberatory praxis. Finally, the author tells how she transformed her understanding of the dynamics of social transformation reading Freire’s dialogic, problem-posing pedagogy of the oppressed
Türk resim sanatında (1908 - 1930) Erken Cumhuriyet Dönemine kadar ilk ve öncü kadın ressamlar
No full textAkçay, Sebahat (Dogus Author)Kadının konumu, toplum içerisinde yüklenmesi gereken sorumlulukları ve görevleri, dönemden döneme ve toplum anlayışlarına göre farklılıklar göstermiştir. Teokratik bir yapıya sahip olan Osmanlı İmparatorluğu döneminde, Tanzimat'tan 1.Dünya Savaşı sonuna kadar geçen dönemde, kadın sorununa ilişkin gelişmeler, toplumun her kesimindeki kadını kapsar nitelikte değildir. Bu gelişmelerin ancak büyük kent kadınlarının çok sınırlı bir kesimine yönelik olduğu görülmektedir. Bu dönemde, kadınların büyük bir bölümü tarımda çalışırken, büyük kentlerde de çok az sayıda kadın öğrenim olanaklarına sahip idi. Birinci Dünya Savaşıyla birlikte Müslüman Türk kadınlar fabrikalarda çalışmaya başladılar. Bu fabrikaların bazıları; İstanbul İplik ve Kibrit Fabrikaları, Adana bölgesinde de Mavrumati fabrikasıdır. Fabrikalarda çalışan işçi kadınlar da çok düşük ücret karşılığı çalışmaktaydı. Tanzimat Fermanı'nın içeriğinde; halkın güvenliği, hukuk, vergi adaleti, askerlik, mülkiyet güvencesi gibi konuların yer almasına rağmen kadınlara bir hak tanınmamıştı. Kadın statüsünün bu durağan hali, Tanzimat döneminden itibaren tartışılmaya başlanmıştır. Resim sanatı, Tazimattan sonra başlamış, Türk kızlarının sanat eğitimi ile tanışması da "İnas Sanayi-i Nefise Mektebi"nin açılması ile başlamıştır. Bu okuldan önce resmî anlamda kız çocuklarına sanat eğitimi veren bir devlet kurumu mevcut değildi. Sanat eğitimi, ailelerin kız çocuklarına özel dersler aldırmasıyla gerçekleştiriliyor; bu çocuklar daha sonra eğitimlerine yurtdışındaki okullarda devam ediyorlardı. 1914 yılında İnas Sanayi-i Nefise Mektebinin kuruluşu ile kadın ilk defa sanat alanında eğitimi görmeye başladı. 1916 yılında başlayan "Galatasaray" Sergilerinde ilk kez kadın ressamlar da eserlerini sergileme imkanı buldu. Ardından devlet tarafından verilen burslarla, ilk kadın ressamlarımızdan olan "Belkıs Mustafa" gibi bazı kadın sanatçılar, yurt dışında eğitim görme fırsatı elde ettiler. Önceleri gerçekçi ve natüralist üslupta çalışmalar yapan ilk kadın ressamlar Avrupa'da aldıkları eğitimin ardından yeni sanat akımlarını çalışmalarına uyguladılar. Temalarının çoğunu güncel konular, yeni yaşam tarzı, portre ve peyzajlar oluşturuyorlardı. Bu kadın sanatçıların genelinin çalışmalarına baktığımızda kadın portreleri, günlük yaşam ve modern kadın imgesinin ağırlıklı olarak kullanıldığını görürüz. Dönemin toplumsal ve siyasi koşulları göz önünde bulundurulduğunda, model olarak yakın çevrelerini kullanmaları kaçınılmaz bir durumdur. Yaşadıkları dönem itibarıyla kadın ressamların ortak özelliklerinden biri de hepsinin kültürlü, aydın ve aristokrat ailelerin kızları olmalarıdır. Osmanlı toplumu, sanat ve sanat eğitimi ile ilgili gelişmelere kapılarını Batı'ya göre epey geç açmıştır. Dolayısıyla sanatın, toplumun tüm kesimlerinde kabul görmesi de zaman almıştır. Cumhuriyet'in kuruluşundan sonra Türkiye Cumhuriyeti Devleti her sınıftan bireyine, sanatı tanıma ve sanatla ilgilenme imkanı sağlamıştır. Toplumsal kesimlerin üst ve aşağı gelir düzeyi arasındaki uyuşmazlığa "Halkçılık" ilkesiyle Cumhuriyet yönetimi son vermiştir. Türkiye Cumhuriyetinin temel ilkelerinden olan "Halkçılık" ve bunun doğal sonucu olan ulusal egemenlik, kültür ve sanat politikasının da gelişimini belirlemiştir. Cumhuriyetin kuruluşuyla kadının yaşamında birçok olumlu değişiklikler yapılmış, kadın yasalar karşısında erkekle eşit konuma sahip olmuştur. Aynı şekilde kadına sanat yaşamına adım atma ve bu alanda erkeklerle eşit sanat eğitimi görme fırsatı verilmiş, erkeklerle aynı sergilerde yer alabilmişlerdir. Kadın sanatçılar da erkek sanatçılar gibi kişisel sergi açma olanaklarını elde edebilmişlerdir.Women's status and heavy responsibilities she took on her shoulders showed differences from time to time depending on the different perceptions of the society. The Ottoman Empire era with a theocratic structure, did not take hold of women issue during the time of Ottoman Reforms to the end of World War I. Progressions covered only those women who lived in modern cities. While most of the women worked in the fields, only a few women had the chance to be educated in the big cities. With the start of the World War I, Muslim Women started to work in the factories. Some of these factories were Thread and Match Factories in Istanbul and Mavrumati Factory in Adana. And the Turkish women were paid for such a poor amount of money. The content of the Imperial Edict of Reorganization (Tanzimat Fermanı) covered public security,justice, military rights, property insurance, trial and tax justice, but, did not include any rights for women. This stable situation in womens' status, were subject to discussion. Pictorial art, has started after the Tanzimat(Bunun ingilizcesine bakar mısın) and the Turkish girls met with the art education with the foundation of "Inas Sanayi-i Nefise Mektebi""Faculty of Arts". Before the establishment of this school, there weren't any government institutions providing art education for women. Art education was taking place with families providing private tuition for their children and these children were continuing their education abroad. With the foundation of Inas Sanayi-i Nefise Mektebi(Fine Arts Faculty) in 1914, women started to be educated in art. In 1916, women artists found the opportunity to display their work in "Galatasaray"Exhibitions. Scholarships provided by the state, some women artists as forerunners in art like "Belkıs Mustafa" were titled to the opportunity to study abroad. The forerunners of women artists, who were producing their work of art with realistic and naturalist styles before, started to reflect new understand in their work which they had faced in the foreign countries. Their themes were based on current topics as new life styles, portraits and landscapes. When we take a look at the works of these women artists, we see that women portraits and modern women imagery from the daily life were highly common. Considering the public and political events of the day, it was inevitable for them not to use their relatives as models. Considering the era that they were living in, another common feature they had was that they were all the daughters of well-educated and intellectual aristocrat families. Compared to the West, Ottoman Society adopted new understanding in art and art education reasonably late. Therefore, it took some time for the whole society to accept art itself. After the development of Republic of Democracy, the Republic of Turkey has provided the opportunity to discover and study art for each Turkish citizen of different social status. Keeping pace to (populism) factor, the inequality between the low income class and the upper class was ended. "Halkçılık" 'populism" which is one of the main principles of the Turkish Republic and as a natural consequence of belonging to the national sovereignty, determined the direction of cultural and art policies. With the foundation of the Republic of Democracy, many positive changes came along in women's lives and women were titled to have equal rights as men. Likewise, women were given the same opportunities as men to receive art education, taking part in the same exhibitions and the right to stand for solo exhibitions.ÖNSÖZ, I -- ÖZET, II -- ABSTRACT, IV -- İÇİNDEKİLER, VI -- RESİMLER LİSTESİ, VIII -- KISALTMALAR, XI -- 1. GİRİŞ, 1 -- 1.1. Problem Cümlesi, 2 -- 1.2. Alt Problemler, 2 -- 1.3. Çalışmanın Sınırlılıkları, 2 -- 1.4. Çalışmanın Amacı ve Kapsamı, 3 -- 1.5. Çalışmanın Araştırma Yöntemi, 4 -- 2. TÜRK RESİM SANATININ ERKEN CUMHURİYET DÖNEMİNE KADAR KISA TARİHİ, 5 -- 3. TÜRK KADINININ TARİHSEL SÜREÇ İÇERİSİNDE GELİŞİMİ, 11 -- 3.1.Osmanlı Toplumunda Kadın, 13 -- 3.2. Milli Mücadelede Türk Kadını, 18 -- 3.3. Atatürk ve Türk Kadını, 19 -- 4. TÜRK RESİM SANATINDA KADIN RESSAMLAR, 23 -- 5. TÜRK RESİM SANATINDA İLK ve ÖNCÜ KADIN RESSAMLAR, 25 -- 5.1.Mihri Müşfik (Rasim) (1886-1954), 25 -- 5.2.Müfide Kadri Hanım ( 1889-1912), 42 -- 5.3.Celile Uğuraldım (Hikmet) (1883-1956), 50 -- 5.4. Ayşe Yaltır’ın Portresinin Hikâyesi, 61 -- 5.5. Vildan Gizer ( 1889-1974), 64 -- 5.6. Emine Fuat Tugay (1897-1975), 69 -- 5.7. Sanatkâr Ana- Kız Naciye Tevfik – Meliha Zâfir, 71 -- 5.7.1. Naciye Tevfik (1878-1960), 71 -- 5.7.2. Meliha (Zafer) Yenerden (1896-1979), 72 -- 6. İNAS SANAYİ-İ NEFİSE MEKTEBİ, 74 -- 6.1. İnas Sanayi-i Nefise Mektebi’nde Yetişen Kadın Ressamlar, 81 -- 6.1.1. Müzdan Arel (1897-1986), 81 -- 6.1.2. Nazlı Ecevit (1900-1985), 84 -- 6.1.3. Güzin Duran (1898-1981), 91 -- 6.1.4. Melek Celal Sofu (1896-1976), 96 -- 6.1.5. Fahrünnisa Zeyd (1901-1991), 103 -- 6.1.6. Belkıs (Mustafa) Hanım (1896-1925), 122 -- 6.1.7. Sabiha Bozcalı (1903-1998), 128 -- 6.1.7.1. İllüstratör Sabiha Bozcalı, 132 -- 7. CUMHURİYETİN İLK SANATÇI GRUBU: MÜSTAKİL RESSAMLAR VE HEYKELTRAŞLAR BİRLİĞİ, 156 -- 7.1. Hale (Salih) Asaf ( 1905-1938), 157 -- 8. BASKI RESİM SANATINDA İLK KADIN SANATÇI, 166 -- 8.1. Aliye Berger (1903-1974), 166 -- 9. DEĞERLENDİRME VE SONUÇ, 195 -- 10. KAYNAKLAR, 197 -- 10. ÖZGEÇMİŞ, 20
SaO010STANDARDIZED CLINICAL FOOT EXAMINATION IN PREVALENT DIABETIC HEMODIALYSIS PATIENTS - A EUROPEAN MULTICENTER ANALYSIS
No full textRegulation of Natural Food Additives
No full textThe use of natural ingredients in food formulation has been facing an increasing demand worldwide. Aiming to preserve the consumer’s health and provide better guidance to the food industry, regulatory agencies must propose precise definitions and establish safe limits of use for additives of natural origin. In this book chapter, we discuss the lack of specific regulations for natural additives and list the substances currently approved by two important regulatory agencies in the globe: the European Food Safety Authority (EFSA) and the Food and Drug Administration (FDA) from the United States. Other regulatory documents from Asia, Australia, and South America are briefly mentioned. Clearly, there is a need for an international regulatory consensus to minimize ambiguity around the term ʼnatural’ with a better understanding of what the term “natural” meant and how it can be applied to food labelling and international trade. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
Determination Of The Efficiency Of Menstruation Hygiene Training Given To Trainable Intellectual Disability Adolescent Girls
No full textObjectives: This study aimed to evaluate the efficiency of menstruation hygiene training given to trainable intellectual disability adolescent girls. Materials and Methods: The study was conducted as a pretest-posttest quasi-experimental study. It was carried out with educable intellectual disability adolescent girls attending a Special Education and Application Center (School) located in the central county of Ankara province. The study was completed with 25 participants. Data were collected through a “personal information form” and “menstrual skills assessment form”. The researchers given education to participants to gain sanitary pad replacement skills. The menstrual pad replacement skills of them were followed before and after the training. The follow-ups were extended to the first and the sixth month after the training. Data were evaluated by computer. Results: The mean age of the participants in the study was 16.56 ± 1.00 (14-18). All of them had already got periods. Their menstrual process was found to be in the normal cycle. The median score for pre-interventional pad replacement skill was 16.00 (minimum: 0- maximum: 36). The post-interventional score for the first follow-up was 36.00 (minimum: 22- maximum: 36), it was 36.00 (minimum: 24- maximum: 36) in the second follow-up, and the difference was found strong evidence in support of the alternative hypothesis (p0.001). Conclusion: It was revealed that the training given trainable intellectual disability adolescent girls by nurses by using video and dolls was an effective method for having intellectual disability adolescents gain pad replacement skills. © 2020 by the Author(s)
Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial
No full textBackground: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to 1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial
No full textBackground: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.
Methods: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.
Findings: Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2·7 mL/min per 1·73 m2 per year versus -3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1-week 110) was -2·9 mL/min per 1·73 m2 per year versus -3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI -0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (-42·8%, 95% CI -49·8 to -35·0, with sparsentan versus -4·4%, -15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.
Interpretation: Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function
Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial
No full textBackground
Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis.
Methods
PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850.
Findings
Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals.
Interpretation
Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p
