1. A pre-specified analysis of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial on the incidence of abrupt declines in kidney function
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Hiddo J.L. Heerspink, David Cherney, Douwe Postmus, Bergur V. Stefánsson, Glenn M. Chertow, Jamie P. Dwyer, Tom Greene, Mikhail Kosiborod, Anna Maria Langkilde, John J.V. McMurray, Ricardo Correa-Rotter, Peter Rossing, C. David Sjöström, Robert D. Toto, David C. Wheeler, Glenn Chertow, Fan Fan Hou, John McMurray, Robert Toto, Bergur Stefansson, L.E. Maffei, P. Raffaele, S.E. Solis, C.A. Arias, D. Aizenberg, C. Luquez, C. Zaidman, N. Cluigt, M. Mayer, A. Alvarisqueta, A. Wassermann, R. Maldonado, J. Bittar, M. Maurich, L.E. Gaite, N. Garcia, L. Sivak, P.O. Ramallo, J.C. Santos, R. Garcia Duran, J.A. Oddino, A. Maranon, L.N. Maia, D.D. Avila, E.J.G. Barros, M.H. Vidotti, D. Panarotto, I.D.L. Noronha, L.A.A. Turatti, L. Deboni, M.E. Canziani, M.C. Riella, M.R. Bacci, R.P. Paschoalin, R.J. Franco, J.C. Goldani, E. St-Amour, A.W. Steele, R. Goldenberg, S. Pandeya, H. Bajaj, D. Cherney, S.M. Kaiser, J.R. Conway, S.S. Chow, G. Bailey, J. Lafrance, J. Winterstein, S. Cournoyer, D. Gaudet, F. Madore, R.L. Houlden, A. Dowell, M. Langlois, N. Muirhead, H. Khandwala, A. Levin, F. Hou, Y. Xue, L. Zuo, C. Hao, Z. Ni, C. Xing, N. Chen, Y. Dong, R. Zhou, X. Xiao, Y. Zou, C. Wang, B. Liu, Q. Chen, M. Lin, Q. Luo, D. Zhang, J. Wang, M. Chen, X. Wang, A. Zhong, J. Dong, C. Zhu, T. Yan, P. Luo, Y. Ren, P. Pai, D. Li, R. Zhang, J. Zhang, M. Xu, Y. Zhuang, Y. Kong, X. Yao, X. Peng, F.I. Persson, T.K. Hansen, R. Borg, U. Pedersen Bjergaard, D. Hansen, M. Hornum, H. Haller, G. Klausmann, D. Tschope, T. Kruger, P. Gross, C. Hugo, N. Obermuller, L. Rose, P. Mertens, H. Zeller-Stefan, A. Fritsche, L. Renders, J. Muller, K. Budde, B. Schroppel, I. Wittmann, P. Voros, M. Dudas, G.A. Tabak, R. Kirschner, A. Letoha, I. Balku, Z. Hermanyi, G. Zakar, I. Mezei, G.G. Nagy, J. Lippai, A. Nemeth, D. Khullar, P.K. Gowdaiah, E. Fernando Mervin, V.A. Rao, D. Dewan, K. Goplani, V.S.K. Maddi, M.S. Vyawahare, R.K. Pulichikkat, R. Pandey, S.K. Sonkar, V.K. Gupta, S. Agarwal, A.J. Asirvatham, A. Ignatius, S. Chaubey, S. Melemadathil, H. Alva, Y. Kadam, H. Shimizu, A. Sueyoshi, H. Takeoka, Y. Abe, T. Imai, Y. Onishi, Y. Fujita, Y. Tokita, M. Oura, Y. Makita, A. Idogaki, R. Koyama, H. Kikuchi, N. Kashihara, T. Hayashi, Y. Ando, T. Tanaka, M. Shimizu, S. Hidaka, T. Gohda, K. Tamura, M. Abe, Y. Kamijo, T. Imasawa, Y. Takahashi, M. Nakayama, M. Tomita, F. Hirano, Y. Fukushima, A. Kiyosue, S. Kurioka, E. Imai, K. Kitagawa, M. Waki, J. Wada, K. Uehara, H. Iwatani, K. Ota, S. Shibazaki, K. Katayama, I. Narita, M. Iinuma, S. Matsueda, S. Sasaki, A. Yokochi, T. Tsukamoto, T. Yoshimura, S. Kang, S. Lee, C.S. Lim, H. Chin, K.W. Joo, S.Y. Han, T.I. Chang, S. Park, H. Park, C.W. Park, B.G. Han, D.R. Cha, S.A. Yoon, W. Kim, S.W. Kim, D. Ryu, R. Correa Rotter, S.S. Irizar Santana, G. Hernandez Llamas, R. Valdez Ortiz, N.C. Secchi Nicolas, G. Gonzalez Galvez, J.R. Lazcano Soto, T. Bochicchio Riccardelli, E.A. Bayram Llamas, D.R. Ramos Ibarra, M.G.S. Melo, J.G. Gonzalez Gonzalez, J.H. Sanchez Mijangos, M. Madero Robalo, A. Garcia Castillo, H.A. Manrique, J.C. Farfan, R. Vargas, A. Valdivia, A. Dextre, E. Escudero, J.R. Calderon Ticona, L. Gonzales, J. Villena, L. Leon, G. Molina, A. Saavedra, E. Garrido, H. Arbanil, S. Vargas Marquez, J. Rodriguez, R. Isidto, A.J. Villaflor, M.A. Gumba, L. Tirador, R.S. Comia, R.A. Sy, M.L.V.V. Guanzon, G. Aquitania, N.C. De Asis, A.A. Silva, C.M. Romero, M.E. Lim, R.A. Danguilan, M. Nowicki, H. Rudzki, K. Landa, I. Kucharczyk-Bauman, B. Gogola-Migdal, M. Golski, A. Olech-Cudzik, T. Stompor, T. Szczepanik, B. Miklaszewicz, R. Sciborski, M. Kuzniewski, K. Ciechanowski, D. Wronska, W. Klatko, S. Mazur, G. Popenda, M. Myslicki, L.Z. Bolieva, S. Berns, A. Galyavich, T. Abissova, I. Karpova, D. Platonov, N. Koziolova, L. Kvitkova, R. Nilk, T. Medina, A. Rebrov, M. Rossovskaya, I. Sinitsina, E. Vishneva, N. Zagidullin, T. Novikova, N. Krasnopeeva, O. Magnitskaya, N. Antropenko, M. Batiushin, V. Escudero Quesada, C. Barrios Barrea, E. Espinel Garauz, J.M. Cruzado Garrit, C. Morales Portillo, J.L. Gorriz Teruel, S. Cigarran Guldris, M. Praga Terente, N.R. Robles Perez-Monteoliva, F.J. Tinahones Madueno, A. Soto Gonzalez, C. Diaz Rodriguez, H. Furuland, A. Saeed, K. Dreja, J. Spaak, A. Bruchfeld, M. Kolesnyk, O. Levchenko, N. Pyvovarova, V. Stus, V. Doretskyy, N. Korobova, O. Horoshko, I. Katerenchuk, Y.M. Mostovoy, M. Orynchak, O. Legun, I. Dudar, O. Bilchenko, S. Andreychyn, A. Levchenko, L. Zub, N. Tereshchenko, I. Topchii, T. Ostapenko, S. Bezuglova, M. Kopytsya, O. Turenko, P. Mark, J. Barratt, S. Bhandari, D. Fraser, P. Kalra, S.P. Kon, K. Mccafferty, A. Mikhail, O.P. Alvarado, R. Anderson, N.S. Andrawis, A. Arif, S.A. Benjamin, G. Bueso, R.S. Busch, K.W. Carr, P. Crawford, N. Daboul, G.M. De La Calle, B. Delgado, J. Earl, M.A. El-Shahawy, R.J. Graf, G. Greenwood, A. Guevara, E.M. Wendland, R.K. Mayfield, M. Montero, D.J. Morin, P. Narayan, V. Numrungroad, A.C. Reddy, R. Reddy, M.B. Samson, R. Trejo, M.B. Butcher, J.K. Wise, L.R. Zemel, M. Raikhel, D. Weinstein, P. Hernandez, A. Wynne, B.V. Khan, G.A. Sterba, A. Jamal, D. Ross, S.F. Rovner, A. Tan, F. Ovalle, R.J. Patel, J. Talano, D.R. Patel, A. Burgner, N. Aslam, M. Elliott, S. Goral, A. Jovanovich, J.A. Manley, K. Umanath, D. Waguespack, D. Weiner, M. Yu, L. Schneider, D. Jalal, T. Le, N. Nguyen, H. Nguyen, D. Nguyen, V. Nguyen, T. Do, P. Chu, D. Ta, N. Tran, B. Pham, Marc A. Pfeffer, Stuart Pocock, Karl Swedberg, Jean L. Rouleau, Nishi Chaturvedi, Peter Ivanovich, Andrew S. Levey, Heidi Christ-Schmidt, Claes Held, Christina Christersson, Johannes Mann, Christoph Varenhorst, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), and Value, Affordability and Sustainability (VALUE)
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Adult ,medicine.medical_specialty ,Urology ,Renal function ,Placebo ,Kidney ,chemistry.chemical_compound ,Glucosides ,medicine ,Humans ,Cardiac and Cardiovascular Systems ,Dapagliflozin ,Benzhydryl Compounds ,Renal Insufficiency, Chronic ,Sodium-Glucose Transporter 2 Inhibitors ,Creatinine ,Kardiologi ,business.industry ,Incidence ,Hazard ratio ,Acute kidney injury ,dapagliflozin ,medicine.disease ,chemistry ,acute kidney injury ,Diabetes Mellitus, Type 2 ,Nephrology ,Albuminuria ,medicine.symptom ,business ,chronic kidney disease ,SGLT2 inhibitors ,Kidney disease ,Glomerular Filtration Rate - Abstract
This pre-specified analysis of DAPA-CKD assessed the impact of sodium-glucose cotransporter 2 inhibition on abrupt declines in kidney function in high-risk patients based on having chronic kidney disease (CKD) and substantial albuminuria. DAPA-CKD was a randomized, double-blind, placebo-controlled trial that had a median follow-up of 2.4 years. Adults with CKD (urinary albumin-to-creatinine ratio 200-5000 mg/g and estimated glomerular filtration rate 25-75 mL/min/1.73m2) were randomized to dapagliflozin 10 mg/day matched to placebo (2152 individuals each). An abrupt decline in kidney function was defined as a pre-specified endpoint of doubling of serum creatinine between two subsequent study visits. We also assessed a post-hoc analysis of investigator-reported acute kidney injury-related serious adverse events. Doubling of serum creatinine between two subsequent visits (median time-interval 100 days) occurred in 63 (2.9%) and 91 (4.2%) participants in the dapagliflozin and placebo groups, respectively (hazard ratio 0.68 [95% confidence interval 0.49, 0.94]). Accounting for the competing risk of mortality did not alter our findings. There was no heterogeneity in the effect of dapagliflozin on abrupt declines in kidney function based on baseline subgroups. Acute kidney injury-related serious adverse events were not significantly different and occurred in 52 (2.5%) and 69 (3.2%) participants in the dapagliflozin and placebo groups, respectively (0.77 [0.54, 1.10]). Thus, in patients with CKD and substantial albuminuria, dapagliflozin reduced the risk of abrupt declines in kidney function. HJLH and DC are co-primary authors. The DAPA-CKD Trial Committees and Investigators are listed in the Appendix.
- Published
- 2021
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