Search

Your search keyword '"Köttgen, A"' showing total 2,495 results
Start Over Author "Köttgen, A"
2,495 results on '"Köttgen, A"'

52. A slit-diaphragm-associated protein network for dynamic control of renal filtration

Author

Kocylowski, Maciej K., Aypek, Hande, Bildl, Wolfgang, Helmstädter, Martin, Trachte, Philipp, Dumoulin, Bernhard, Wittösch, Sina, Kühne, Lukas, Aukschun, Ute, Teetzen, Carolin, Kretz, Oliver, Gaal, Botond, Kulik, Akos, Antignac, Corinne, Mollet, Geraldine, Köttgen, Anna, Göcmen, Burulca, Schwenk, Jochen, Schulte, Uwe, Huber, Tobias B., Fakler, Bernd, and Grahammer, Florian

Published
2022
Full Text
View/download PDF

53. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author

Wielscher, Matthias, Mandaviya, Pooja R., Kuehnel, Brigitte, Joehanes, Roby, Mustafa, Rima, Robinson, Oliver, Zhang, Yan, Bodinier, Barbara, Walton, Esther, Mishra, Pashupati P., Schlosser, Pascal, Wilson, Rory, Tsai, Pei-Chien, Palaniswamy, Saranya, Marioni, Riccardo E., Fiorito, Giovanni, Cugliari, Giovanni, Karhunen, Ville, Ghanbari, Mohsen, Psaty, Bruce M., Loh, Marie, Bis, Joshua C., Lehne, Benjamin, Sotoodehnia, Nona, Deary, Ian J., Chadeau-Hyam, Marc, Brody, Jennifer A., Cardona, Alexia, Selvin, Elizabeth, Smith, Alicia K., Miller, Andrew H., Torres, Mylin A., Marouli, Eirini, Gào, Xin, van Meurs, Joyce B. J., Graf-Schindler, Johanna, Rathmann, Wolfgang, Koenig, Wolfgang, Peters, Annette, Weninger, Wolfgang, Farlik, Matthias, Zhang, Tao, Chen, Wei, Xia, Yujing, Teumer, Alexander, Nauck, Matthias, Grabe, Hans J., Doerr, Macus, Lehtimäki, Terho, Guan, Weihua, Milani, Lili, Tanaka, Toshiko, Fisher, Krista, Waite, Lindsay L., Kasela, Silva, Vineis, Paolo, Verweij, Niek, van der Harst, Pim, Iacoviello, Licia, Sacerdote, Carlotta, Panico, Salvatore, Krogh, Vittorio, Tumino, Rosario, Tzala, Evangelia, Matullo, Giuseppe, Hurme, Mikko A., Raitakari, Olli T., Colicino, Elena, Baccarelli, Andrea A., Kähönen, Mika, Herzig, Karl-Heinz, Li, Shengxu, Conneely, Karen N., Kooner, Jaspal S., Köttgen, Anna, Heijmans, Bastiaan T., Deloukas, Panos, Relton, Caroline, Ong, Ken K., Bell, Jordana T., Boerwinkle, Eric, Elliott, Paul, Brenner, Hermann, Beekman, Marian, Levy, Daniel, Waldenberger, Melanie, Chambers, John C., Dehghan, Abbas, and Järvelin, Marjo-Riitta

Published
2022
Full Text
View/download PDF

54. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author

Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.

Published
2022
Full Text
View/download PDF

56. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author

Matthias Wielscher, Pooja R. Mandaviya, Brigitte Kuehnel, Roby Joehanes, Rima Mustafa, Oliver Robinson, Yan Zhang, Barbara Bodinier, Esther Walton, Pashupati P. Mishra, Pascal Schlosser, Rory Wilson, Pei-Chien Tsai, Saranya Palaniswamy, Riccardo E. Marioni, Giovanni Fiorito, Giovanni Cugliari, Ville Karhunen, Mohsen Ghanbari, Bruce M. Psaty, Marie Loh, Joshua C. Bis, Benjamin Lehne, Nona Sotoodehnia, Ian J. Deary, Marc Chadeau-Hyam, Jennifer A. Brody, Alexia Cardona, Elizabeth Selvin, Alicia K. Smith, Andrew H. Miller, Mylin A. Torres, Eirini Marouli, Xin Gào, Joyce B. J. van Meurs, Johanna Graf-Schindler, Wolfgang Rathmann, Wolfgang Koenig, Annette Peters, Wolfgang Weninger, Matthias Farlik, Tao Zhang, Wei Chen, Yujing Xia, Alexander Teumer, Matthias Nauck, Hans J. Grabe, Macus Doerr, Terho Lehtimäki, Weihua Guan, Lili Milani, Toshiko Tanaka, Krista Fisher, Lindsay L. Waite, Silva Kasela, Paolo Vineis, Niek Verweij, Pim van der Harst, Licia Iacoviello, Carlotta Sacerdote, Salvatore Panico, Vittorio Krogh, Rosario Tumino, Evangelia Tzala, Giuseppe Matullo, Mikko A. Hurme, Olli T. Raitakari, Elena Colicino, Andrea A. Baccarelli, Mika Kähönen, Karl-Heinz Herzig, Shengxu Li, BIOS consortium, Karen N. Conneely, Jaspal S. Kooner, Anna Köttgen, Bastiaan T. Heijmans, Panos Deloukas, Caroline Relton, Ken K. Ong, Jordana T. Bell, Eric Boerwinkle, Paul Elliott, Hermann Brenner, Marian Beekman, Daniel Levy, Melanie Waldenberger, John C. Chambers, Abbas Dehghan, and Marjo-Riitta Järvelin

Subjects
Science
Abstract

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.

Published
2022
Full Text
View/download PDF

59. SLC26A1 is a major determinant of sulfate homeostasis in humans

Author

Anja Pfau, Karen I. López-Cayuqueo, Nora Scherer, Matthias Wuttke, Annekatrin Wernstedt, Daniela González Fassrainer, Desiree E.C. Smith, Jiddeke M. van de Kamp, Katharina Ziegeler, Kai-Uwe Eckardt, Friedrich C. Luft, Peter S. Aronson, Anna Köttgen, Thomas J. Jentsch, and Felix Knauf

Subjects
Genetics, Nephrology, Medicine
Abstract

Sulfate plays a pivotal role in numerous physiological processes in the human body, including bone and cartilage health. A role of the anion transporter SLC26A1 (Sat1) for sulfate reabsorption in the kidney is supported by the observation of hyposulfatemia and hypersulfaturia in Slc26a1-knockout mice. The impact of SLC26A1 on sulfate homeostasis in humans remains to be defined. By combining clinical genetics, functional expression assays, and population exome analysis, we identify SLC26A1 as a sulfate transporter in humans and experimentally validate several loss-of-function alleles. Whole-exome sequencing from a patient presenting with painful perichondritis, hyposulfatemia, and renal sulfate wasting revealed a homozygous mutation in SLC26A1, which has not been previously described to the best of our knowledge. Whole-exome data analysis of more than 5,000 individuals confirmed that rare, putatively damaging SCL26A1 variants were significantly associated with lower plasma sulfate at the population level. Functional expression assays confirmed a substantial reduction in sulfate transport for the SLC26A1 mutation of our patient, which we consider to be novel, as well as for the additional variants detected in the population study. In conclusion, combined evidence from 3 complementary approaches supports SLC26A1 activity as a major determinant of sulfate homeostasis in humans. In view of recent evidence linking sulfate homeostasis with back pain and intervertebral disc disorder, our study identifies SLC26A1 as a potential target for modulation of musculoskeletal health.

Published
2023
Full Text
View/download PDF

60. Grams ME, Sang Y, Ballew SH, et al, for the Chronic Kidney Disease Prognosis Consortium. Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int. 2018;93:1442–1451

Author

Astor, Brad, Appel, Lawrence J, Levin, Adeera, Tang, Mila, Djurdjev, Ognjenka, Navaneethan, Sankar D, Jolly, Stacey E, Schold, Jesse D, Nally, Joseph V, Wheeler, David C, Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I, Hsu, Chi-yuan, Lash, James P, Kalra, Philip A, Ritchie, James P, Maharajan, Raman, Middleton, Rachel J, O’Donoghue, Donal J, Eckardt, Kai-Uwe, Schneider, Markus P, Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R, Green, Jamie A, Kirchner, H Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J, Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Wang, Angela Yee-Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Garg, Amit X, McArthur, Eric, Nash, Danielle M, Shalev, Varda, Chodick, Gabriel, Blankestijn, Peter J, Wetzels, Jack FM, van Zuilen, Arjan D, van den Brand, Jan A, Levey, Andrew S, Inker, Lesley A, Sarnak, Mark J, Tighiouart, Hocine, Zhang, Haitao, Stengel, Benedicte, Metzger, Marie, Flamant, Martin, Houillier, Pascal, Haymann, Jean-Philippe, Rios, Pablo G, Mazzuchi, Nelson, Gadola, Liliana, Lamadrid, Verónica, Sola, Laura, Collins, John F, Elley, C Raina, Kenealy, Timothy, Moranne, Olivier, Couchoud, Cecile, Vigneau, Cecile, Brunskill, Nigel J, Major, Rupert W, Shepherd, David, Medcalf, James F, Kovesdy, Csaba P, Kalantar-Zadeh, Kamyar, Molnar, Miklos Z, Sumida, Keiichi, Potukuchi, Praveen K, Heerspink, Hiddo JL, de Zeeuw, Dick, Brenner, Barry, Carrero, Juan Jesus, Gasparini, Alessandro, Qureshi, Abdul Rashid, Elinder, Carl-Gustaf, Visseren, Frank LJ, van der Graaf, Yolanda, Evans, Marie, Stendahl, Maria, Schön, Staffan, Segelmark, Mårten, Prütz, Karl-Göran, Naimark, David M, Tangri, Navdeep, and Mark, Patrick B

Subjects
Renal and urogenital, Chronic Kidney Disease Prognosis Consortium, Clinical Sciences, Urology & Nephrology
Abstract

The Chronic Kidney Disease (CKD) Prognosis Consortium is a collaborative author of the above-mentioned article. The CKD Prognosis Consortium investigators/collaborators are as follows: • African American Study of Kidney Disease and Hypertension (AASK): Brad Astor, Lawrence J. Appel; Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT): Adeera Levin, Mila Tang, Ognjenka Djurdjev; Cleveland Clinic CKD Registry Study (CCF): Sankar D. Navaneethan, Stacey E. Jolly, Jesse D. Schold, Joseph V. Nally Jr.; Chronic Renal Impairment in Birmingham (CRIB): David C. Wheeler, Jonathan Emberson, John Townend, Martin Landray; Chronic Renal Insufficiency Cohort Study (CRIC): Harold I. Feldman, Chi-yuan Hsu, James P. Lash, Lawrence J. Appel; Chronic Renal Insufficiency Standards Implementation Study (CRISIS): Philip A. Kalra, James P. Ritchie, Raman Maharajan, Rachel J. Middleton, Donal J. O'Donoghue; German Chronic Kidney Disease Study (GCKD): Kai-Uwe Eckardt, Markus P. Schneider, Anna Köttgen, Florian Kronenberg, Barbara Bärthlein; Geisinger Health System: Alex R. Chang, Jamie A. Green, H. Lester Kirchner, Kevin Ho; Grampian Laboratory Outcomes, Morbidity and Mortality Studies – 2 (GLOMMS2): Angharad Marks, Corri Black, Gordon J. Prescott, Nick Fluck; Gonryo Study: Masaaki Nakayama, Mariko Miyazaki, Tae Yamamoto, Gen Yamada; Hong Kong CKD Studies: Angela Yee-Moon Wang, Sharon Cheung, Sharon Wong, Jessie Chu, Henry Wu; Ontario Institute for Clinical Evaluative Sciences, Provincial Kidney, Dialysis and Transplantation program (ICES KDT): Amit X. Garg, Eric McArthur, Danielle M. Nash; Maccabi Health System: Varda Shalev, Gabriel Chodick; Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of a Nurse Practitioner (MASTERPLAN): Peter J. Blankestijn, Jack F.M. Wetzels, Arjan D. van Zuilen, Jan A. van den Brand; Modification of Diet in Renal Disease Study (MDRD): Andrew S. Levey, Lesley A. Inker, Mark J. Sarnak, Hocine Tighiouart; Nanjing CKD Network Cohort Study (Nanjing CKD): Haitao Zhang; NephroTest Study (NephroTest): Benedicte Stengel, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann; National Renal Healthcare Program – Uruguay (NRHP-URU): Pablo G. Rios, Nelson Mazzuchi, Liliana Gadola, Verónica Lamadrid, Laura Sola; New Zealand Diabetes Cohort Study (NZDCS): John F. Collins, C. Raina Elley, Timothy Kenealy; Parcours de Soins des Personnes Agées (PSPA): Olivier Moranne, Cecile Couchoud, Cecile Vigneau; Primary-Secondary Care Partnership to Prevent Adverse Outcomes in Chronic Kidney Disease (PSP CKD): Nigel J. Brunskill, Rupert W. Major, David Shepherd, James F. Medcalf; Racial and Cardiovascular Risk Anomalies in CKD Cohort (RCAV): Csaba P. Kovesdy, Kamyar Kalantar-Zadeh, Miklos Z. Molnar, Keiichi Sumida, Praveen K. Potukuchi; Reduction of Endpoints in Non-insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL): Hiddo J.L. Heerspink, Dick de Zeeuw, Barry Brenner; Stockholm CREAtinine Measurements Cohort (SCREAM): Juan Jesus Carrero, Alessandro Gasparini, Abdul Rashid Qureshi, Carl-Gustaf Elinder; Second Manifestations of ARTerial Disease Study (SMART): Frank L.J. Visseren, Yolanda van der Graaf; Swedish Renal Registry CKD Cohort (SRR CKD): Marie Evans, Maria Stendahl, Staffan Schön, Mårten Segelmark, Karl-Göran Prütz; Sunnybrook Cohort: David M. Naimark, Navdeep Tangri; West of Scotland CKD Study: Patrick B. Mark, Jamie P. Traynor, Colin C. Geddes, Peter C. Thomson.• CKD Prognosis Consortium Steering Committee: Alex R. Chang, Josef Coresh (Chair), Ron T. Gansevoort, Morgan E. Grams, Anna Köttgen, Andrew S. Levey, Kunihiro Matsushita, Mark Woodward, Luxia Zhang.• CKD Prognosis Consortium Data Coordinating Center: Shoshana H. Ballew (Assistant Project Director), Jingsha Chen (Programmer), Josef Coresh (Principal Investigator), Morgan E. Grams (Director of Nephrology Initiatives), Lucia Kwak (Programmer), Kunihiro Matsushita (Director), Yingying Sang (Lead Programmer), Aditya Surapaneni (Programmer), Mark Woodward (Senior Statistician).• Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Prognosis and Optimal Management of Patients with Advanced CKD: Kai-Uwe Eckardt (Conference Co-Chair), Brenda R. Hemmelgarn (Conference Co-Chair), David C. Wheeler (KDIGO Co-Chair), Wolfgang C. Winkelmayer (KDIGO Co-Chair), John Davis (CEO), Danielle Green (Managing Director), Michael Cheung (Chief Scientific Officer), Tanya Green (Communications Director), Melissa McMahan (Programs Director).

Published
2018

61. Evans M, Grams ME, Sang Y, et al., for the Chronic Kidney Disease Prognosis Consortium. Risk factors for prognosis in patients with severely decreased GFR. Kidney Int Rep. 2018;3:625–637

Author

Astor, Brad, Appel, Lawrence J, Levin, Adeera, Djurdjev, Ognjenka, Tang, Mila, Navaneethan, Sankar D, Jolly, Stacey E, Schold, Jesse D, Nally, Joseph V, Wheeler, David C, Emberson, Jonathan, Townend, John, Landray, Martin, Feldman, Harold I, Hsu, Chi-yuan, Lash, James P, Kalra, Philip A, Ritchie, James P, Maharajan, Raman, Alderson, Helen, Lane, Beverly, Eckardt, Kai-Uwe, Schneider, Markus P, Köttgen, Anna, Kronenberg, Florian, Bärthlein, Barbara, Chang, Alex R, Green, Jamie A, Kirchner, H Lester, Ho, Kevin, Marks, Angharad, Black, Corri, Prescott, Gordon J, Fluck, Nick, Nakayama, Masaaki, Miyazaki, Mariko, Yamamoto, Tae, Yamada, Wang, Angela Yee-Moon, Cheung, Sharon, Wong, Sharon, Chu, Jessie, Wu, Henry, Shalev, Varda, Chodick, Gabriel, Blankestijn, Peter J, Wetzels, Jack FM, van Zuilen, Arjan D, van den Brand, Jan A, Levey, Andrew S, Inker, Lesley A, Sarnak, Mark J, Tighiouart, Hocine, Zhang, Haitao, Stengel, Benedicte, Rios, Pablo G, Mazzuchi, Nelson, Gadola, Liliana, Lamadrid, Verónica, Sola, Laura, Collins, John F, Elley, C Raina, Kenealy, Timothy, Moranne, Olivier, Couchoud, Cecile, Vigneau, Cecile, Brunskill, Nigel J, Major, Rupert W, Shepherd, David, Medcalf, James F, Kovesdy, Csaba P, Kalantar-Zadeh, Kamyar, Molnar, Miklos Z, Sumida, Keiichi, Potukuchi, Praveen K, Heerspink, Hiddo JL, de Zeeuw, Dick, Brenner, Barry, Carrero, Juan Jesus, Barany, Peter, Qureshi, Abdul Rashid, Elinder, Carl-Gustaf, Visseren, Frank LJ, van der Graaf, Yolanda, Evans, Marie, Stendahl, Maria, Schön, Staffan, Segelmark, Mårten, Prütz, Karl-Göran, Naimark, David M, Tangri, Navdeep, Mark, Patrick B, Traynor, Jamie P, Geddes, Colin C, Thomson, Peter C, and Coresh, Josef

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Renal and urogenital, Good Health and Well Being, Chronic Kidney Disease Prognosis Consortium, Biomedical and clinical sciences, Health sciences
Abstract

[This corrects the article DOI: 10.1016/j.ekir.2018.01.002.].

Published
2018

62. The mitochondrial transporter SLC25A25 links ciliary TRPP2 signaling and cellular metabolism.

Author

Hofherr, Alexis, Seger, Claudia, Fitzpatrick, Fiona, Busch, Tilman, Michel, Elisabeth, Luan, Jingting, Osterried, Lea, Linden, Frieder, Kramer-Zucker, Albrecht, Wakimoto, Barbara, Schütze, Conny, Wiedemann, Nils, Artati, Anna, Adamski, Jerzy, Walz, Gerd, Kunji, Edmund RS, Montell, Craig, Watnick, Terry, and Köttgen, Michael

Subjects
Cilia, Animals, Zebrafish, Humans, Drosophila melanogaster, Calcium, Calcium-Binding Proteins, Amino Acid Transport Systems, Acidic, Ion Channels, Calcium Channels, Antiporters, Mitochondrial Membrane Transport Proteins, Mitochondrial Proteins, Signal Transduction, Heterozygote, TRPP Cation Channels, Amino Acid Transport Systems, Acidic, Developmental Biology, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences
Abstract

Cilia are organelles specialized in movement and signal transduction. The ciliary transient receptor potential ion channel polycystin-2 (TRPP2) controls elementary cilia-mediated physiological functions ranging from male fertility and kidney development to left-right patterning. However, the molecular components translating TRPP2 channel-mediated Ca2+ signals into respective physiological functions are unknown. Here, we show that the Ca2+-regulated mitochondrial ATP-Mg/Pi solute carrier 25 A 25 (SLC25A25) acts downstream of TRPP2 in an evolutionarily conserved metabolic signaling pathway. We identify SLC25A25 as an essential component in this cilia-dependent pathway using a genome-wide forward genetic screen in Drosophila melanogaster, followed by a targeted analysis of SLC25A25 function in zebrafish left-right patterning. Our data suggest that TRPP2 ion channels regulate mitochondrial SLC25A25 transporters via Ca2+ establishing an evolutionarily conserved molecular link between ciliary signaling and mitochondrial metabolism.

Published
2018

63. Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

Author

Adrienne Tin, Pascal Schlosser, Pamela R. Matias-Garcia, Chris H. L. Thio, Roby Joehanes, Hongbo Liu, Zhi Yu, Antoine Weihs, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L. Min, Victoria L. Halperin Kuhns, Adebowale A. Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A. Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Jan Bressler, Monique M. B. Breteler, Cristian Carmeli, Layal Chaker, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R. Cox, Graciela E. Delgado, Kai-Uwe Eckardt, Arif B. Ekici, Karlhans Endlich, James S. Floyd, Eliza Fraszczyk, Xu Gao, Xīn Gào, Allan C. Gelber, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L. Grove, Sarah E. Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A. Hurme, Shih-Jen Hwang, Sharon L. R. Kardia, Silva Kasela, Marcus E. Kleber, Wolfgang Koenig, Jaspal S. Kooner, Florian Kronenberg, Brigitte Kühnel, Christine Ladd-Acosta, Terho Lehtimäki, Lars Lind, Dan Liu, Donald M. Lloyd-Jones, Stefan Lorkowski, Ake T. Lu, Riccardo E. Marioni, Winfried März, Daniel L. McCartney, Karlijn A. C. Meeks, Lili Milani, Pashupati P. Mishra, Matthias Nauck, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Scott M. Ratliff, Alex P. Reiner, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A. Smith, Nona Sotoodehnia, Hannah R. Stocker, Silvia Stringhini, Johan Sundström, Brenton R. Swenson, Joyce B. J. van Meurs, Jana V. van Vliet-Ostaptchouk, Andrea Venema, Uwe Völker, Juliane Winkelmann, Bruce H. R. Wolffenbuttel, Wei Zhao, Yinan Zheng, The Estonian Biobank Research Team, The Genetics of DNA Methylation Consortium, Marie Loh, Harold Snieder, Melanie Waldenberger, Daniel Levy, Shreeram Akilesh, Owen M. Woodward, Katalin Susztak, Alexander Teumer, and Anna Köttgen

Subjects
Science
Abstract

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Published
2021
Full Text
View/download PDF

64. Meta-analyses identify DNA methylation associated with kidney function and damage

Author

Pascal Schlosser, Adrienne Tin, Pamela R. Matias-Garcia, Chris H. L. Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L. Min, Adebowale A. Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A. Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M. B. Breteler, Cristian Carmeli, Layal Chaker, John C. Chambers, Shelley A. Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R. Cox, Niek de Klein, Graciela E. Delgado, Arce Domingo-Relloso, Kai-Uwe Eckardt, Arif B. Ekici, Karlhans Endlich, Kathryn L. Evans, James S. Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L. Grove, Sarah E. Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A. Hurme, Shih-Jen Hwang, Marjo-Riitta Jarvelin, Sharon L. R. Kardia, Silva Kasela, Marcus E. Kleber, Wolfgang Koenig, Jaspal S. Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M. Lloyd-Jones, Kurt Lohman, Stefan Lorkowski, Ake T. Lu, Riccardo E. Marioni, Winfried März, Daniel L. McCartney, Karlijn A. C. Meeks, Lili Milani, Pashupati P. Mishra, Matthias Nauck, Ana Navas-Acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Scott M. Ratliff, Alex P. Reiner, Sylvia E. Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A. Smith, Nona Sotoodehnia, Hannah R. Stocker, Silvia Stringhini, Johan Sundström, Brenton R. Swenson, Maria Tellez-Plaza, Joyce B. J. van Meurs, Jana V. van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M. Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H. R. Wolffenbuttel, Wei Zhao, Yinan Zheng, Estonian Biobank Research Team, Genetics of DNA Methylation Consortium, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, and Alexander Teumer

Subjects
Science
Abstract

Many genetic loci have been identified to be associated with kidney disease, but the molecular mechanisms are not well understood. Here, the authors perform epigenome-wide association studies on kidney function measures to identify epigenetic marks and pathways involved in kidney function.

Published
2021
Full Text
View/download PDF

67. Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease

Author

Clotet-Freixas, Sergi, primary, Zaslaver, Olga, additional, Kotlyar, Max, additional, Pastrello, Chiara, additional, Quaile, Andrew T., additional, McEvoy, Caitriona M., additional, Saha, Aninda D., additional, Farkona, Sofia, additional, Boshart, Alex, additional, Zorcic, Katarina, additional, Neupane, Slaghaniya, additional, Manion, Kieran, additional, Allen, Maya, additional, Chan, Michael, additional, Chen, Xuqi, additional, Arnold, Arthur P., additional, Sekula, Peggy, additional, Steinbrenner, Inga, additional, Köttgen, Anna, additional, Dart, Allison B., additional, Wicklow, Brandy, additional, McGavock, Jon M., additional, Blydt-Hansen, Tom D., additional, Barrios, Clara, additional, Riera, Marta, additional, Soler, María J., additional, Isenbrandt, Amandine, additional, Lamontagne-Proulx, Jérôme, additional, Pradeloux, Solène, additional, Coulombe, Katherine, additional, Soulet, Denis, additional, Rajasekar, Shravanthi, additional, Zhang, Boyang, additional, John, Rohan, additional, Mehrotra, Aman, additional, Gehring, Adam, additional, Puhka, Maija, additional, Jurisica, Igor, additional, Woo, Minna, additional, Scholey, James W., additional, Röst, Hannes, additional, and Konvalinka, Ana, additional

Published
2024
Full Text
View/download PDF

68. The Role of the Co-Chaperone DNAJB11 in Polycystic Kidney Disease: Molecular Mechanisms and Cellular Origin of Cyst Formation

Author

Busch, Tilman, primary, Neubauer, Björn, additional, Schmitt, Lars, additional, Cascante, Isabel, additional, Knoblich, Luise, additional, Wegehaupt, Oliver, additional, Schöler, Felix, additional, Tholen, Stefan, additional, Hofherr, Alexis, additional, Schell, Christoph, additional, Schilling, Oliver, additional, Westermann, Lukas, additional, and Köttgen, Michael, additional

Published
2024
Full Text
View/download PDF

69. High detection rate for disease-causing variants in a cohort of 30 Iranian pediatric steroid resistant nephrotic syndrome cases

Author

Maryam Najafi, Korbinian M. Riedhammer, Aboulfazl Rad, Paria Najarzadeh Torbati, Riccardo Berutti, Isabel Schüle, Sophie Schroda, Thomas Meitinger, Jasmina Ćomić, Simin Sadeghi Bojd, Tayebeh Baranzehi, Azadeh Shojaei, Anoush Azarfar, Mahmood Reza Khazaei, Anna Köttgen, Rolf Backofen, Ehsan Ghayoor Karimiani, Julia Hoefele, and Miriam Schmidts

Subjects
nephrotic syndrome, Iran, SRNS, ARHGDIA, NUP205, COQ6, Pediatrics, RJ1-570
Abstract

BackgroundSteroid resistant nephrotic syndrome (SRNS) represents a significant renal disease burden in childhood and adolescence. In contrast to steroid sensitive nephrotic syndrome (SSNS), renal outcomes are significantly poorer in SRNS. Over the past decade, extensive genetic heterogeneity has become evident while disease-causing variants are still only identified in 30% of cases in previously reported studies with proportion and type of variants identified differing depending on the age of onset and ethnical background of probands. A genetic diagnosis however can have implications regarding clinical management, including kidney transplantation, extrarenal disease manifestations, and, in some cases, even causal therapy. Genetic diagnostics therefore play an important role for the clinical care of SRNS affected individuals.Methodology and resultsHere, we performed NPHS2 Sanger sequencing and subsequent exome sequencing in 30 consanguineous Iranian families with a child affected by SRNS with a mean age of onset of 16 months. We identified disease-causing variants and one variant of uncertain significance in 22 families (73%), including variants in NPHS1 (30%), followed by NPHS2 (20%), WT1 (7%) as well as in NUP205, COQ6, ARHGDIA, SGPL1, and NPHP1 in single cases. Eight of these variants have not previously been reported as disease-causing, including four NPHS1 variants and one variant in NPHS2, ARHGDIA, SGPL1, and NPHP1 each.ConclusionIn line with previous studies in non-Iranian subjects, we most frequently identified disease-causing variants in NPHS1 and NPHS2. While Sanger sequencing of NPHS2 can be considered as first diagnostic step in non-congenital cases, the genetic heterogeneity underlying SRNS renders next-generation sequencing based diagnostics as the most efficient genetic screening method. In accordance with the mainly autosomal recessive inheritance pattern, diagnostic yield can be significantly higher in consanguineous than in outbred populations.

Published
2022
Full Text
View/download PDF

70. Frequent LPA KIV-2 Variants Lower Lipoprotein(a) Concentrations and Protect Against Coronary Artery Disease

Author

Eckardt, Kai-Uwe, Meiselbach, Heike, Schneider, Markus P., Schiffer, Mario, Prokosch, Hans-Ulrich, Bärthlein, Barbara, Beck, Andreas, Reis, André, Ekici, Arif B., Becker, Susanne, Becker-Grosspitsch, Dinah, Alberth-Schmidt, Ulrike, Hausknecht, Birgit, Weigel, Anke, Walz, Gerd, Köttgen, Anna, Schultheiß, Ulla T., Kotsis, Fruzsina, Meder, Simone, Mitsch, Erna, Reinhard, Ursula, Floege, Jürgen, Saritas, Turgay, Schaeffner, Elke, Baid-Agrawal, Seema, Theisen, Kerstin, Haller, Hermann, Menne, Jan, Zeier, Martin, Sommerer, Claudia, Theilinger, Johanna, Wolf, Gunter, Busch, Martin, Paul, Rainer, Sitter, Thomas, Wanner, Christoph, Krane, Vera, Börner-Klein, Antje, Bauer, Britta, Kronenberg, Florian, Raschenberger, Julia, Kollerits, Barbara, Forer, Lukas, Schönherr, Sebastian, Weissensteiner, Hansi, Oefner, Peter, Gronwald, Wolfram, Schmid, Matthias, Nadal, Jennifer, Schachtl-Riess, Johanna F., Kheirkhah, Azin, Grüneis, Rebecca, Di Maio, Silvia, Schoenherr, Sebastian, Streiter, Gertraud, Losso, Jamie Lee, Paulweber, Bernhard, Lamina, Claudia, and Coassin, Stefan

Published
2021
Full Text
View/download PDF

72. Identification of pathological transcription in autosomal dominant polycystic kidney disease epithelia

Author

Sebastian Friedrich, Hannah Müller, Caroline Riesterer, Hannah Schüller, Katja Friedrich, Carlotta Leonie Wörner, Tilman Busch, Amandine Viau, E. Wolfgang Kuehn, Michael Köttgen, and Alexis Hofherr

Subjects
Medicine, Science
Abstract

Abstract Autosomal dominant polycystic kidney disease (ADPKD) affects more than 12 million people worldwide. Mutations in PKD1 and PKD2 cause cyst formation through unknown mechanisms. To unravel the pathogenic mechanisms in ADPKD, multiple studies have investigated transcriptional mis-regulation in cystic kidneys from patients and mouse models, and numerous dysregulated genes and pathways have been described. Yet, the concordance between studies has been rather limited. Furthermore, the cellular and genetic diversity in cystic kidneys has hampered the identification of mis-expressed genes in kidney epithelial cells with homozygous PKD mutations, which are critical to identify polycystin-dependent pathways. Here we performed transcriptomic analyses of Pkd1- and Pkd2-deficient mIMCD3 kidney epithelial cells followed by a meta-analysis to integrate all published ADPKD transcriptomic data sets. Based on the hypothesis that Pkd1 and Pkd2 operate in a common pathway, we first determined transcripts that are differentially regulated by both genes. RNA sequencing of genome-edited ADPKD kidney epithelial cells identified 178 genes that are concordantly regulated by Pkd1 and Pkd2. Subsequent integration of existing transcriptomic studies confirmed 31 previously described genes and identified 61 novel genes regulated by Pkd1 and Pkd2. Cluster analyses then linked Pkd1 and Pkd2 to mRNA splicing, specific factors of epithelial mesenchymal transition, post-translational protein modification and epithelial cell differentiation, including CD34, CDH2, CSF2RA, DLX5, HOXC9, PIK3R1, PLCB1 and TLR6. Taken together, this model-based integrative analysis of transcriptomic alterations in ADPKD annotated a conserved core transcriptomic profile and identified novel candidate genes for further experimental studies.

Published
2021
Full Text
View/download PDF

73. Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals

Author

Kira J. Stanzick, Yong Li, Pascal Schlosser, Mathias Gorski, Matthias Wuttke, Laurent F. Thomas, Humaira Rasheed, Bryce X. Rowan, Sarah E. Graham, Brett R. Vanderweff, Snehal B. Patil, VA Million Veteran Program, Cassiane Robinson-Cohen, John M. Gaziano, Christopher J. O’Donnell, Cristen J. Willer, Stein Hallan, Bjørn Olav Åsvold, Andre Gessner, Adriana M. Hung, Cristian Pattaro, Anna Köttgen, Klaus J. Stark, Iris M. Heid, and Thomas W. Winkler

Subjects
Science
Abstract

Identifying causal variants and genes in genome-wide association studies remains a challenge, an issue that is ameliorated with larger sample sizes. Here the authors meta-analyze kidney function genome-wide association studies to identify new loci and fine-map loci to home in on variants and genes involved in kidney function.

Published
2021
Full Text
View/download PDF

74. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author

Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Snieder, Harold, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Abecasis, Goncalo, Baras, Aris, Cantor, Michael, Coppola, Giovanni, Economides, Aris, Lotta, Luca A., Overton, John D., Reid, Jeffrey G., Shuldiner, Alan, Beechert, Christina, Forsythe, Caitlin, Fuller, Erin D., Gu, Zhenhua, Lattari, Michael, Lopez, Alexander, Schleicher, Thomas D., Padilla, Maria Sotiropoulos, Toledo, Karina, Widom, Louis, Wolf, Sarah E., Pradhan, Manasi, Manoochehri, Kia, Ulloa, Ricardo H., Bai, Xiaodong, Balasubramanian, Suganthi, Barnard, Leland, Blumenfeld, Andrew, Eom, Gisu, Habegger, Lukas, Hawes, Alicia, Khalid, Shareef, Maxwell, Evan K., Salerno, William, Staples, Jeffrey C., Jones, Marcus B., Mitnaul, Lyndon J., Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H.L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O’Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W.J.H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.

Published
2021
Full Text
View/download PDF

75. Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action

Author

Bello, Aminu K, Alrukhaimi, Mona, Ashuntantang, Gloria E, Basnet, Shakti, Rotter, Ricardo C, Douthat, Walter G, Kazancioglu, Rumeyza, Köttgen, Anna, Nangaku, Masaomi, Powe, Neil R, White, Sarah L, Wheeler, David C, and Moe, Orson

Subjects
Kidney Disease, Cardiovascular, Prevention, Renal and urogenital, Good Health and Well Being, CKD, complications, knowledge gaps, management, mechanisms, Other Medical and Health Sciences
Abstract

The International Society of Nephrology has adopted a proactive approach to defining the current state of kidney care and unmet needs through a multifaceted Closing the Gaps initiative. As part of this initiative, the International Society of Nephrology convened a meeting of experts to develop an approach to tackle acute kidney injury and chronic kidney disease (CKD). This manuscript expands on the recently published International Society of Nephrology CKD Roadmap and reports on the discussions of the working group assigned to the task of reviewing the global impact of complication of CKD. The working group defined the following goals: Goal 1: Optimize the management of anemia and endocrine and metabolic abnormalities associated with CKD. The impact of these conditions at a global level is not well understood, particularly in regions where renal replacement therapy is not readily available. Some treatment regimens may be affordable in low- and middle-income countries and if implemented, could have an impact on the burden of suffering associated with CKD. Goal 2: Improve the prevention and management of cardiovascular complications linked to CKD. Most research on cardiovascular complications of CKD has focused on atherosclerotic diseases (myocardial infarction, ischemic stroke, and peripheral gangrene). There has been growing recognition that other forms of cardiovascular diseases, such as heart failure, valvular disease and arrhythmias, have a major impact on patient outcomes. Much less is known about the mechanisms and treatment of these non-atherosclerotic complications. Goal 3: Improve the diagnosis and management of symptoms associated with CKD. Symptom management is one of the greatest challenges in the management of CKD, with limited knowledge about the mechanisms associated with the development of these common problems and how best to characterize them into usable clinical phenotypes. Improved understanding of the complications of CKD may alleviate suffering and prolong life among millions of people worldwide both in developed countries and in regions where renal replacement therapy is not widely available.

Published
2017

76. Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data

Author

Matsushita, Kunihiro, Ballew, Shoshana H, Coresh, Josef, Arima, Hisatomi, Ärnlöv, Johan, Cirillo, Massimo, Ebert, Natalie, Hiramoto, Jade S, Kimm, Heejin, Shlipak, Michael G, Visseren, Frank LJ, Gansevoort, Ron T, Kovesdy, Csaba P, Shalev, Varda, Woodward, Mark, Kronenberg, Florian, Chalmers, John, Perkovic, Vlado, Grams, Morgan E, Sang, Yingying, Schaeffner, Elke, Martus, Peter, Levin, Adeera, Djurdjev, Ognjenka, Tang, Mila, Heine, Gunnar, Seiler, Sarah, Zawada, Adam, Emrich, Insa, Sarnak, Mark, Katz, Ronit, Brenner, Hermann, Schöttker, Ben, Rothenbacher, Dietrich, Saum, Kai-Uwe, Köttgen, Anna, Schneider, Markus, Eckardt, Kai-Uwe, Green, Jamie, Kirchner, H Lester, Chang, Alex R, Black, Corri, Marks, Angharad, Prescott, Gordon, Clark, Laura, Fluck, Nick, Jee, Sun Ha, Mok, Yejin, Chodick, Gabriel, Wetzels, Jack FM, Blankestijn, Peter J, van Zuilen, Arjan D, Bots, M, Peralta, Carmen, Hiromoto, Jade, Bottinger, Erwin, Nadkarni, Girish N, Ellis, Stephen B, Nadukuru, Rajiv, Kenealy, Timothy, Elley, C Raina, Collins, John F, Drury, Paul L, Bakker, Stephan JL, Heerspink, Hiddo J Lambers, Jassal, Simerjot K, Bergstrom, Jaclyn, Ix, Joachim H, Barrett-Connor, Elizabeth, Kalantar-Zadeh, Kamyar, Carrero, Juan J, Gasparini, Alessandro, Qureshi, Abdul Rashid, Barany, Peter, Algra, Ale, van der Graaf, Yolanda, Evans, Marie, Segelmark, Mårten, Stendahl, Maria, Schön, Staffan, Tangri, Navdeep, Sud, Maneesh, Naimark, David, Lannfelt, Lars, Larsson, Anders, Hallan, Stein, Levey, Andrew S, Chen, Jingsha, and Kwak, Lucia

Subjects
Clinical Research, Kidney Disease, Prevention, Renal and urogenital, Good Health and Well Being, Adult, Aged, Albuminuria, Creatinine, Databases, Factual, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Peripheral Arterial Disease, Renal Insufficiency, Chronic, Risk Factors, Chronic Kidney Disease Prognosis Consortium, Medical Biochemistry and Metabolomics, Clinical Sciences, Public Health and Health Services
Abstract

BackgroundSome evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.MethodsIn this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.FindingsWe analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR

Published
2017

77. Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study.

Author

Gruber, Ida, Kollerits, Barbara, Forer, Lukas, Di Maio, Silvia, Schachtl‐Riess, Johanna F., Kheirkhah, Azin, Schönherr, Sebastian, Schultheiss, Ulla T., Köttgen, Anna, Eckardt, Kai‐Uwe, Coassin, Stefan, Lamina, Claudia, and Kronenberg, Florian

Abstract

Background: Lipoprotein(a) (Lp(a)) is a causal, genetically determined risk factor for cardiovascular disease (CVD) in the general population. Patients with chronic kidney disease (CKD) have an increased CVD risk and elevated Lp(a) concentrations. Only a few studies on Lp(a) were performed in persons with mild‐to‐moderate CKD; none of them used genetic variants to explore potential causal associations. Objectives: This study aims to investigate the association of measured and genetically predicted Lp(a) concentrations on prevalent and incident CVD events in the German Chronic Kidney Disease (GCKD) study. Methods: The study included 5043 participants of European ancestry with an estimated glomerular filtration rate (eGFR) between 30 and 60 mL/min/1.73 m2 or an eGFR >60 mL/min/1.73 m2 in the presence of overt albuminuria with a follow‐up of 6.5 years. Results: With each 10 mg/dL higher Lp(a) concentration, odds for prevalent CVD (1290 events) increased 1.065‐fold (95%CI: 1.042–1.088, p < 0.001). The risk was significantly higher in patients with Lp(a) ≥50 mg/dL but most pronounced in Lp(a) ≥70 mg/dL (odds ratio = 1.775 [1.409–2.231], p < 0.001) compared to Lp(a) <30 mg/dL. Each 10 mg/dL higher Lp(a) concentration and Lp(a) ≥70 mg/dL increased the risk for incident 3‐point major adverse cardiovascular events (MACEs) (474 events): hazard ratio [HR] = 1.037 [1.009–1.067], p = 0.009 and HR = 1.335 [1.001–1.781], p = 0.050), respectively. Similar results were obtained for 4‐point MACE (653 events). Analyses based on apo(a) isoforms and genetically predicted Lp(a) concentrations led to even stronger associations. Conclusions: In patients with mild‐to‐severe CKD, elevated Lp(a) concentrations and genetic determinants of Lp(a) concentrations are significantly associated with CVD at baseline and during follow‐up, independent of traditional risk factors. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

78. New insights into the hypothalamic–pituitary–thyroid axis:a transcriptome- and proteome-wide association study

Author

Monteiro-Martins, Sara, Sterenborg, Rosalie B.T.M., Borisov, Oleg, Scherer, Nora, Cheng, Yurong, Medici, Marco, Köttgen, Anna, Teumer, Alexander, Monteiro-Martins, Sara, Sterenborg, Rosalie B.T.M., Borisov, Oleg, Scherer, Nora, Cheng, Yurong, Medici, Marco, Köttgen, Anna, and Teumer, Alexander

Abstract

Introduction: Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic–pituitary–thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels. Results: TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10−13, TWAS: P = 7.61 × 10−12 (whole blood), P = 6.40 × 10−13 (hypothalamus), P = 1.57 × 10−15 (pituitary), P = 4.27 × 10−15 (thyroid)), supported by colocalizations. Conclusion: Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein l

Published
2024

79. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, Medici, Marco, Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco

Abstract

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

80. Selective endocytosis controls slit diaphragm maintenance and dynamics in Drosophila nephrocytes

Author

Konrad Lang, Julian Milosavljevic, Helena Heinkele, Mengmeng Chen, Lea Gerstner, Dominik Spitz, Severine Kayser, Martin Helmstädter, Gerd Walz, Michael Köttgen, Andrew Spracklen, John Poulton, and Tobias Hermle

Subjects
nephrocyte, podocyte, endocytosis, nephrin, proteinuria, Drosophila, Medicine, Science, Biology (General), QH301-705.5
Abstract

The kidneys generate about 180 l of primary urine per day by filtration of plasma. An essential part of the filtration barrier is the slit diaphragm, a multiprotein complex containing nephrin as major component. Filter dysfunction typically manifests with proteinuria and mutations in endocytosis regulating genes were discovered as causes of proteinuria. However, it is unclear how endocytosis regulates the slit diaphragm and how the filtration barrier is maintained without either protein leakage or filter clogging. Here, we study nephrin dynamics in podocyte-like nephrocytes of Drosophila and show that selective endocytosis either by dynamin- or flotillin-mediated pathways regulates a stable yet highly dynamic architecture. Short-term manipulation of endocytic functions indicates that dynamin-mediated endocytosis of ectopic nephrin restricts slit diaphragm formation spatially while flotillin-mediated turnover of nephrin within the slit diaphragm is needed to maintain filter permeability by shedding of molecules bound to nephrin in endosomes. Since slit diaphragms cannot be studied in vitro and are poorly accessible in mouse models, this is the first analysis of their dynamics within the slit diaphragm multiprotein complex. Identification of the mechanisms of slit diaphragm maintenance will help to develop novel therapies for proteinuric renal diseases that are frequently limited to symptomatic treatment.

Published
2022
Full Text
View/download PDF

81. Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function

Author

Mathilda Bedin, Olivia Boyer, Aude Servais, Yong Li, Laure Villoing-Gaudé, Marie-Josephe Tête, Alexandra Cambier, Julien Hogan, Veronique Baudouin, Saoussen Krid, Albert Bensman, Florie Lammens, Ferielle Louillet, Bruno Ranchin, Cecile Vigneau, Iseline Bouteau, Corinne Isnard-Bagnis, Christoph J. Mache, Tobias Schäfer, Lars Pape, Markus Gödel, Tobias B. Huber, Marcus Benz, Günter Klaus, Matthias Hansen, Kay Latta, Olivier Gribouval, Vincent Morinière, Carole Tournant, Maik Grohmann, Elisa Kuhn, Timo Wagner, Christine Bole-Feysot, Fabienne Jabot-Hanin, Patrick Nitschké, Tarunveer S. Ahluwalia, Anna Köttgen, Christian Brix Folsted Andersen, Carsten Bergmann, Corinne Antignac, and Matias Simons

Subjects
Medicine
Published
2022
Full Text
View/download PDF

83. Integrating multiple kidney function markers to predict all-cause and cardiovascular disease mortality: prospective analysis of 366 758 UK Biobank participants.

Author

Fujii, Ryosuke, Melotti, Roberto, Köttgen, Anna, Teumer, Alexander, Giardiello, Daniele, and Pattaro, Cristian

Subjects
CARDIOVASCULAR disease related mortality, PROPORTIONAL hazards models, EXPLORATORY factor analysis, KIDNEY physiology, BLOOD urea nitrogen, CEREBROVASCULAR disease
Abstract

Background Reduced kidney function is a risk factor of cardiovascular and all-cause mortality. This association was demonstrated for several kidney function markers, but it is unclear whether integrating multiple measured markers may improve mortality risk prediction. Methods We conducted an exploratory factor analysis (EFA) of serum creatinine– and cystatin C–based estimated glomerular filtration rate [eGFRcre and eGFRcys; derived by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and European Kidney Function Consortium (EKFC) equations], blood urea nitrogen (BUN), uric acid and serum albumin among 366 758 participants in the UK Biobank without a history of kidney failure. Fitting Cox proportional hazards models, we compared the ability of the identified latent factors to predict overall mortality and mortality by cardiovascular disease (CVD), also considering CVD-specific causes like coronary heart disease (CHD) and cerebrovascular disease. Results During 12.5 years of follow-up, 26 327 participants died from any cause, 5376 died from CVD, 2908 died from CHD and 1116 died from cerebrovascular disease. We identified two latent factors, EFA1 and EFA2, both representing kidney function variations. When using the CKD-EPI equation, EFA1 performed like eGFRcys, with EFA1 showing slightly larger hazard ratios for overall and CVD-related mortality. At 10 years of follow-up, EFA1 and eGFRcys showed moderate discrimination performance for CVD-related mortality, outperforming all other kidney indices. eGFRcre was the least predictive marker across all outcomes. When using the EKFC equation, eGFRcys performed better than EFA1 while all other results remaining similar. Conclusions While EFA is an attractive approach to capture the complex effects of kidney function, eGFRcys remains the most practical and effective measurement for all-cause and CVD mortality risk prediction. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

84. Rare genetic variants affecting urine metabolite levels link population variation to inborn errors of metabolism

Author

Yurong Cheng, Pascal Schlosser, Johannes Hertel, Peggy Sekula, Peter J. Oefner, Ute Spiekerkoetter, Johanna Mielke, Daniel F. Freitag, Miriam Schmidts, GCKD Investigators, Florian Kronenberg, Kai-Uwe Eckardt, Ines Thiele, Yong Li, and Anna Köttgen

Subjects
Science
Abstract

Metabolites are indicators of health and disease; genetic studies can reveal variants influencing their levels. Here, the authors investigate the contribution of rare, exonic variants on the levels of urine metabolites and generate predictions on metabolic consequences underlying metabolic disease.

Published
2021
Full Text
View/download PDF

85. Genome-wide studies reveal factors associated with circulating uromodulin and its relationships to complex diseases

Author

Yong Li, Yurong Cheng, Francesco Consolato, Guglielmo Schiano, Michael R. Chong, Maik Pietzner, Ngoc Quynh H. Nguyen, Nora Scherer, Mary L. Biggs, Marcus E. Kleber, Stefan Haug, Burulça Göçmen, Marie Pigeyre, Peggy Sekula, Inga Steinbrenner, Pascal Schlosser, Christina B. Joseph, Jennifer A. Brody, Morgan E. Grams, Caroline Hayward, Ulla T. Schultheiss, Bernhard K. Krämer, Florian Kronenberg, Annette Peters, Jochen Seissler, Dominik Steubl, Cornelia Then, Matthias Wuttke, Winfried März, Kai-Uwe Eckardt, Christian Gieger, Eric Boerwinkle, Bruce M. Psaty, Josef Coresh, Peter J. Oefner, Guillaume Pare, Claudia Langenberg, Jürgen E. Scherberich, Bing Yu, Shreeram Akilesh, Olivier Devuyst, Luca Rampoldi, and Anna Köttgen

Subjects
Genetics, Nephrology, Medicine
Abstract

Uromodulin (UMOD) is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is highly abundant in urine and related to chronic kidney disease, hypertension, and pathogen defense. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin using complementary antibody-based and aptamer-based assays. We detected 3 and 10 distinct significant loci, respectively. Integration of antibody-based results at the UMOD locus with functional genomics data (RNA-Seq, ATAC-Seq, Hi-C) of primary human kidney tissue highlighted an upstream variant with differential accessibility and transcription in uromodulin-synthesizing kidney cells as underlying the observed cis effect. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same pathway as UMOD. Experimental validation of the third antibody-based locus, B4GALNT2, showed that the p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase had a loss-of-function effect leading to higher serum uromodulin levels. Aptamer-based results pointed to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation, suggesting that this assay permits investigating uromodulin’s complex glycosylation rather than its quantitative levels. Overall, our study provides insights into circulating uromodulin and its emerging functions.

Published
2022
Full Text
View/download PDF

88. Results from the German Chronic Kidney Disease (GCKD) study support association of relative telomere length with mortality in a large cohort of patients with moderate chronic kidney disease

Author

Eckardt, Kai-Uwe, Meiselbach, Heike, Schneider, Markus, Dienemann, Thomas, Prokosch, Hans-Ulrich, Bärthlein, Barbara, Beck, Andreas, Ganslandt, Thomas, Reis, André, Ekici, Arif B., Avendaño, Susanne, Becker-Grosspitsch, Dinah, Alberth-Schmidt, Ulrike, Hausknecht, Birgit, Zitzmann, Rita, Weigel, Anke, Walz, Gerd, Köttgen, Anna, Schultheiß, Ulla T., Kotsis, Fruzsina, Meder, Simone, Mitsch, Erna, Reinhard, Ursula, Floege, Jürgen, Schlieper, Georg, Saritas, Turgay, Ernst, Sabine, Beaujean, Nicole, Schaeffner, Elke, Baid-Agrawal, Seema, Theisen, Kerstin, Haller, Hermann, Menne, Jan, Zeier, Martin, Sommerer, Claudia, Woitke, Rebecca, Wolf, Gunter, Busch, Martin, Fuß, Rainer, Sitter, Thomas, Blank, Claudia, Wanner, Christoph, Krane, Vera, Börner-Klein, Antje, Bauer, Britta, Kronenberg, Florian, Raschenberger, Julia, Kollerits, Barbara, Forer, Lukas, Schönherr, Sebastian, Weissensteiner, Hansi, Oefner, Peter, Gronwald, Wolfram, Zacharias, Helena, Schmid, Matthias, Nadal, Jennifer, Fazzini, Federica, Lamina, Claudia, Schultheiss, Ulla T., and Steinbrenner, Inga

Published
2020
Full Text
View/download PDF

89. Mapping of the gene network that regulates glycan clock of ageing

Author

Frkatović-Hodžić, Azra, primary, Mijakovac, Anika, additional, Miškec, Karlo, additional, Nostaeva, Arina, additional, Sharapov, Sodbo Z., additional, Landini, Arianna, additional, Haller, Toomas, additional, Akker, Erik van den, additional, Sharma, Sapna, additional, Cuadrat, Rafael R. C., additional, Mangino, Massimo, additional, Li, Yong, additional, Keser, Toma, additional, Rudman, Najda, additional, Štambuk, Tamara, additional, Pučić-Baković, Maja, additional, Trbojević-Akmačić, Irena, additional, Gudelj, Ivan, additional, Štambuk, Jerko, additional, Pribić, Tea, additional, Radovani, Barbara, additional, Tominac, Petra, additional, Fischer, Krista, additional, Beekman, Marian, additional, Wuhrer, Manfred, additional, Gieger, Christian, additional, Schulze, Matthias B., additional, Wittenbecher, Clemens, additional, Polasek, Ozren, additional, Hayward, Caroline, additional, Wilson, James F., additional, Spector, Tim D., additional, Köttgen, Anna, additional, Vučković, Frano, additional, Aulchenko, Yurii S., additional, Vojta, Aleksandar, additional, Krištić, Jasminka, additional, Klarić, Lucija, additional, Zoldoš, Vlatka, additional, and Lauc, Gordan, additional

Published
2023
Full Text
View/download PDF

91. Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT).

Author

Riedhammer, Korbinian M., primary, Nguyen, Thanh-Minh T., additional, Koşukcu, Can, additional, Calzada-Wack, Julia, additional, Li, Yong, additional, Batzir, Nurit Assia, additional, Saygılı, Seha, additional, Wimmers, Vera, additional, Kim, Gwang-Jin, additional, Chrysanthou, Marialena, additional, Bakey, Zeineb, additional, Sofrin-Drucker, Efrat, additional, Kraiger, Markus, additional, Sanz-Moreno, Adrián, additional, Amarie, Oana V., additional, Rathkolb, Birgit, additional, Klein-Rodewald, Tanja, additional, Garrett, Lillian, additional, Hölter, Sabine M., additional, Seisenberger, Claudia, additional, Haug, Stefan, additional, Schlosser, Pascal, additional, Marschall, Susan, additional, Wurst, Wolfgang, additional, Fuchs, Helmut, additional, Gailus-Durner, Valerie, additional, Wuttke, Matthias, additional, Hrabe de Angelis, Martin, additional, Ćomić, Jasmina, additional, Doğan, Özlem Akgün, additional, Özlük, Yasemin, additional, Taşdemir, Mehmet, additional, Ağbaş, Ayşe, additional, Canpolat, Nur, additional, Orenstein, Naama, additional, Çalışkan, Salim, additional, Weber, Ruthild G., additional, Bergmann, Carsten, additional, Jeanpierre, Cecile, additional, Saunier, Sophie, additional, Lim, Tze Y., additional, Hildebrandt, Friedhelm, additional, Alhaddad, Bader, additional, Basel-Salmon, Lina, additional, Borovitz, Yael, additional, Wu, Kaman, additional, Antony, Dinu, additional, Matschkal, Julia, additional, Schaaf, Christian W., additional, Renders, Lutz, additional, Schmaderer, Christoph, additional, Rogg, Manuel, additional, Schell, Christoph, additional, Meitinger, Thomas, additional, Heemann, Uwe, additional, Köttgen, Anna, additional, Arnold, Sebastian J., additional, Ozaltin, Fatih, additional, Schmidts, Miriam, additional, and Hoefele, Julia, additional

Published
2023
Full Text
View/download PDF

92. Investigation of a nonsense mutation located in the complex KIV-2 copy number variation region of apolipoprotein(a) in 10,910 individuals

Author

Silvia Di Maio, Rebecca Grüneis, Gertraud Streiter, Claudia Lamina, Manuel Maglione, Sebastian Schoenherr, Dietmar Öfner, Barbara Thorand, Annette Peters, Kai-Uwe Eckardt, Anna Köttgen, Florian Kronenberg, and Stefan Coassin

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Background The concentrations of the highly atherogenic lipoprotein(a) [Lp(a)] are mainly genetically determined by the LPA gene locus. However, up to 70% of the coding sequence is located in the complex so-called kringle IV type 2 (KIV-2) copy number variation, a region hardly accessible by common genotyping and sequencing technologies. Despite its size, little is known about genetic variants in this complex region. The R21X variant is a functional variant located in this region, but it has never been analyzed in large cohorts. Methods We typed R21X in 10,910 individuals from three European populations using a newly developed high-throughput allele-specific qPCR assay. R21X allelic location was determined by separating the LPA alleles using pulsed-field gel electrophoresis (PFGE) and typing them separately. Using GWAS data, we identified a proxy SNP located outside of the KIV-2. Linkage disequilibrium was determined both statistically and by long-range haplotyping using PFGE. Worldwide frequencies were determined by reanalyzing the sequencing data of the 1000 Genomes Project with a dedicated pipeline. Results R21X carriers (frequency 0.016–0.021) showed significantly lower mean Lp(a) concentrations (− 11.7 mg/dL [− 15.5; − 7.82], p = 3.39e−32). The variant is located mostly on medium-sized LPA alleles. In the 1000 Genome data, R21X mostly occurs in Europeans and South Asians, is absent in Africans, and shows varying frequencies in South American populations (0 to 0.022). Of note, the best proxy SNP was another LPA null mutation (rs41272114, D′ = 0.958, R 2 = 0.281). D′ was very high in all 1000G populations (0.986–0.996), although rs41272114 frequency varies considerably (0–0.182). Co-localization of both null mutations on the same allele was confirmed by PFGE-based long-range haplotyping. Conclusions We performed the largest epidemiological study on an LPA KIV-2 variant so far, showing that it is possible to assess LPA KIV-2 mutations on a large scale. Surprisingly, in all analyzed populations, R21X was located on the same haplotype as the splice mutation rs41272114, creating “double-null” LPA alleles. Despite being a nonsense variant, the R21X status does not provide additional information beyond the rs41272114 genotype. This has important implications for studies using LPA loss-of-function mutations as genetic instruments and emphasizes the complexity of LPA genetics.

Published
2020
Full Text
View/download PDF

93. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Author

Jingyuan Xie, Lili Liu, Nikol Mladkova, Yifu Li, Hong Ren, Weiming Wang, Zhao Cui, Li Lin, Xiaofan Hu, Xialian Yu, Jing Xu, Gang Liu, Yasar Caliskan, Carlo Sidore, Olivia Balderes, Raphael J. Rosen, Monica Bodria, Francesca Zanoni, Jun Y. Zhang, Priya Krithivasan, Karla Mehl, Maddalena Marasa, Atlas Khan, Fatih Ozay, Pietro A. Canetta, Andrew S. Bomback, Gerald B. Appel, Simone Sanna-Cherchi, Matthew G. Sampson, Laura H. Mariani, Agnieszka Perkowska-Ptasinska, Magdalena Durlik, Krzysztof Mucha, Barbara Moszczuk, Bartosz Foroncewicz, Leszek Pączek, Ireneusz Habura, Elisabet Ars, Jose Ballarin, Laila-Yasmin Mani, Bruno Vogt, Savas Ozturk, Abdülmecit Yildiz, Nurhan Seyahi, Hakki Arikan, Mehmet Koc, Taner Basturk, Gonca Karahan, Sebahat Usta Akgul, Mehmet Sukru Sever, Dan Zhang, Domenico Santoro, Mario Bonomini, Francesco Londrino, Loreto Gesualdo, Jana Reiterova, Vladimir Tesar, Claudia Izzi, Silvana Savoldi, Donatella Spotti, Carmelita Marcantoni, Piergiorgio Messa, Marco Galliani, Dario Roccatello, Simona Granata, Gianluigi Zaza, Francesca Lugani, GianMarco Ghiggeri, Isabella Pisani, Landino Allegri, Ben Sprangers, Jin-Ho Park, BeLong Cho, Yon Su Kim, Dong Ki Kim, Hitoshi Suzuki, Antonio Amoroso, Daniel C. Cattran, Fernando C. Fervenza, Antonello Pani, Patrick Hamilton, Shelly Harris, Sanjana Gupta, Chris Cheshire, Stephanie Dufek, Naomi Issler, Ruth J. Pepper, John Connolly, Stephen Powis, Detlef Bockenhauer, Horia C. Stanescu, Neil Ashman, Ruth J. F. Loos, Eimear E. Kenny, Matthias Wuttke, Kai-Uwe Eckardt, Anna Köttgen, Julia M. Hofstra, Marieke J. H. Coenen, Lambertus A. Kiemeney, Shreeram Akilesh, Matthias Kretzler, Lawrence H. Beck, Benedicte Stengel, Hanna Debiec, Pierre Ronco, Jack F. M. Wetzels, Magdalena Zoledziewska, Francesco Cucca, Iuliana Ionita-Laza, Hajeong Lee, Elion Hoxha, Rolf A. K. Stahl, Paul Brenchley, Francesco Scolari, Ming-hui Zhao, Ali G. Gharavi, Robert Kleta, Nan Chen, and Krzysztof Kiryluk

Subjects
Science
Abstract

Membranous nephropathy (MN) is a rare autoimmune disease of podocyte-directed antibodies, such as anti-phospholipase A2 receptor. Here, the authors report a genome-wide association study for MN and identify two previously unreported loci encompassing the NFKB1 and IRF4 genes and additional ancestry-specific effects.

Published
2020
Full Text
View/download PDF

94. Cardiovascular disease protein biomarkers are associated with kidney function: The Framingham Heart Study

Author

Amena Keshawarz, Shih-Jen Hwang, Gha Young Lee, Zhi Yu, Chen Yao, Anna Köttgen, and Daniel Levy

Subjects
Medicine, Science
Abstract

Background Biomarkers common to chronic kidney disease (CKD) and cardiovascular disease (CVD) may reflect early impairments underlying both diseases. Methods We evaluated associations of 71 CVD-related plasma proteins measured in 2,873 Framingham Heart Study (FHS) Offspring cohort participants with cross-sectional continuous eGFR and with longitudinal change in eGFR from baseline to follow-up (ΔeGFR). We also evaluated the associations of the 71 CVD proteins with the following dichotomous secondary outcomes: prevalent CKD stage ≥3 (cross-sectional), new-onset CKD stage ≥3 (longitudinal), and rapid decline in eGFR (longitudinal). Proteins significantly associated with eGFR and ΔeGFR were subsequently validated in 3,951 FHS Third Generation cohort participants and were tested using Mendelian randomization (MR) analysis to infer putatively causal relations between plasma protein biomarkers and kidney function. Results In cross-sectional analysis, 37 protein biomarkers were significantly associated with eGFR at FDRDiscussion/conclusions Eight protein biomarkers were consistently associated with eGFR in cross-sectional and longitudinal analysis in both cohorts and may capture early kidney impairment; others were implicated in association and causal inference analyses. A subset of CVD protein biomarkers may contribute causally to the pathogenesis of kidney impairment and should be studied as targets for CKD treatment and early prevention.

Published
2022

95. Meta-analyses identify DNA methylation associated with kidney function and damage

Author

Schlosser, Pascal, Tin, Adrienne, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Weihs, Antoine, Yu, Zhi, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Chambers, John C., Cole, Shelley A., Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., de Klein, Niek, Delgado, Graciela E., Domingo-Relloso, Arce, Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Evans, Kathryn L., Floyd, James S., Fornage, Myriam, Franke, Lude, Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Ghanbari, Mohsen, Ghasemi, Sahar, Gieger, Christian, Greenland, Philip, Grove, Megan L., Harris, Sarah E., Hemani, Gibran, Henneman, Peter, Herder, Christian, Horvath, Steve, Hou, Lifang, Hurme, Mikko A., Hwang, Shih-Jen, Jarvelin, Marjo-Riitta, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kramer, Holly, Kronenberg, Florian, Kühnel, Brigitte, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Liu, Yongmei, Lloyd-Jones, Donald M., Lohman, Kurt, Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Navas-Acien, Ana, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Rosas, Sylvia E., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., Tellez-Plaza, Maria, van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Verweij, Niek, Walker, Rosie M., Wielscher, Matthias, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Levy, Daniel, Waldenberger, Melanie, Susztak, Katalin, Köttgen, Anna, and Teumer, Alexander

Published
2021
Full Text
View/download PDF

96. Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

Author

Tin, Adrienne, Schlosser, Pascal, Matias-Garcia, Pamela R., Thio, Chris H. L., Joehanes, Roby, Liu, Hongbo, Yu, Zhi, Weihs, Antoine, Hoppmann, Anselm, Grundner-Culemann, Franziska, Min, Josine L., Kuhns, Victoria L. Halperin, Adeyemo, Adebowale A., Agyemang, Charles, Ärnlöv, Johan, Aziz, Nasir A., Baccarelli, Andrea, Bochud, Murielle, Brenner, Hermann, Bressler, Jan, Breteler, Monique M. B., Carmeli, Cristian, Chaker, Layal, Coresh, Josef, Corre, Tanguy, Correa, Adolfo, Cox, Simon R., Delgado, Graciela E., Eckardt, Kai-Uwe, Ekici, Arif B., Endlich, Karlhans, Floyd, James S., Fraszczyk, Eliza, Gao, Xu, Gào, Xīn, Gelber, Allan C., Ghanbari, Mohsen, Ghasemi, Sahar, Gieger, Christian, Greenland, Philip, Grove, Megan L., Harris, Sarah E., Hemani, Gibran, Henneman, Peter, Herder, Christian, Horvath, Steve, Hou, Lifang, Hurme, Mikko A., Hwang, Shih-Jen, Kardia, Sharon L. R., Kasela, Silva, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Kronenberg, Florian, Kühnel, Brigitte, Ladd-Acosta, Christine, Lehtimäki, Terho, Lind, Lars, Liu, Dan, Lloyd-Jones, Donald M., Lorkowski, Stefan, Lu, Ake T., Marioni, Riccardo E., März, Winfried, McCartney, Daniel L., Meeks, Karlijn A. C., Milani, Lili, Mishra, Pashupati P., Nauck, Matthias, Nowak, Christoph, Peters, Annette, Prokisch, Holger, Psaty, Bruce M., Raitakari, Olli T., Ratliff, Scott M., Reiner, Alex P., Schöttker, Ben, Schwartz, Joel, Sedaghat, Sanaz, Smith, Jennifer A., Sotoodehnia, Nona, Stocker, Hannah R., Stringhini, Silvia, Sundström, Johan, Swenson, Brenton R., van Meurs, Joyce B. J., van Vliet-Ostaptchouk, Jana V., Venema, Andrea, Völker, Uwe, Winkelmann, Juliane, Wolffenbuttel, Bruce H. R., Zhao, Wei, Zheng, Yinan, Loh, Marie, Snieder, Harold, Waldenberger, Melanie, Levy, Daniel, Akilesh, Shreeram, Woodward, Owen M., Susztak, Katalin, Teumer, Alexander, and Köttgen, Anna

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results