Skip to content
2000
image of Do SGLT2 Inhibitors Protect the Kidneys? An Alternative Explanation

Abstract

SGLT2 inhibitors are a family of drugs that were developed to treat diabetes mellitus. In randomized controlled trials, SGLT2 inhibitors seem to prevent kidney deterioration in patients with nephropathies, both diabetic and non-diabetic. However, in contrast to biochemical/physiological results (proteinuria and serum creatinine levels) that improve in all studies, the clinical results (all-cause mortality, cardiovascular death, need for dialysis, or renal transplant) do not consistently improve. In this article, the author would like to suggest that SGLT2 inhibitors do not, in fact, prevent the progression of renal diseases but rather alter laboratory results. This study will present a theory that gives an alternative explanation for the findings in the studies that would explain the above discrepancy between biochemical/physiological and clinical results. In general, the author claims that SGLT2 inhibitors change the kinetics of renal creatinine and microalbumin excretion but do not prevent parenchymal adverse changes in kidneys. This causes a dissociation between renal function markers (such as serum creatinine level and urinary protein) and the real kidney function. Thus, the clinical renal prognosis does not improve despite seemingly better laboratory results.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/emiddt/10.2174/0118715303355221241021050443
2025-01-08
2025-11-01
Loading full text...

Full text loading...

/deliver/fulltext/emiddt/10.2174/0118715303355221241021050443/BMS-EMIDDT-2024-349.html?itemId=/content/journals/emiddt/10.2174/0118715303355221241021050443&mimeType=html&fmt=ahah

References

  1. Musso G. Gambino R. Cassader M. Pagano G. A novel approach to control hyperglycemia in type 2 diabetes: Sodium glucose co-transport (SGLT) inhibitors. Systematic review and meta-analysis of randomized trials. Ann. Med. 2012 44 4 375 393 10.3109/07853890.2011.560181 21495788
    [Google Scholar]
  2. Braunwald E. Gliflozins in the management of cardiovascular disease. N. Engl. J. Med. 2022 386 21 2024 2034 10.1056/NEJMra2115011 35613023
    [Google Scholar]
  3. Seidu S. Alabraba V. Davies S. Newland-Jones P. Fernando K. Bain S.C. Diggle J. Evans M. James J. Kanumilli N. Milne N. Viljoen A. Wheeler D.C. Wilding J.P.H. SGLT2 inhibitors – the new standard of care for cardiovascular, renal and metabolic protection in type 2 Diabetes: A narrative review. Diabetes Ther. 2024 15 5 1099 1124 10.1007/s13300‑024‑01550‑5 38578397
    [Google Scholar]
  4. Olanrewaju O.A. Sheeba F. Kumar A. Ahmad S. Blank N. Kumari R. Kumari K. Salame T. Khalid A. yousef N. Varrassi G. Khatri M. Kumar S. Mohamad T. Novel therapies in Diabetes: A comprehensive narrative review of glp-1 receptor agonists, sglt2 inhibitors, and beyond. Cureus 2023 15 12 e51151 10.7759/cureus.51151 38283440
    [Google Scholar]
  5. Wiviott S.D. Raz I. Bonaca M.P. Mosenzon O. Kato E.T. Cahn A. Silverman M.G. Zelniker T.A. Kuder J.F. Murphy S.A. Bhatt D.L. Leiter L.A. McGuire D.K. Wilding J.P.H. Ruff C.T. Gause-Nilsson I.A.M. Fredriksson M. Johansson P.A. Langkilde A.M. Sabatine M.S. Dapagliflozin and cardiovascular outcomes in type 2 Diabetes. N. Engl. J. Med. 2019 380 4 347 357 10.1056/NEJMoa1812389 30415602
    [Google Scholar]
  6. Neal B. Perkovic V. Mahaffey K.W. de Zeeuw D. Fulcher G. Erondu N. Shaw W. Law G. Desai M. Matthews D.R. Canagliflozin and cardiovascular and renal events in type 2 Diabetes. N. Engl. J. Med. 2017 377 7 644 657 10.1056/NEJMoa1611925 28605608
    [Google Scholar]
  7. Zinman B. Wanner C. Lachin J.M. Fitchett D. Bluhmki E. Hantel S. Mattheus M. Devins T. Johansen O.E. Woerle H.J. Broedl U.C. Inzucchi S.E. Empagliflozin, cardiovascular outcomes, and mortality in Type 2 Diabetes. N. Engl. J. Med. 2015 373 22 2117 2128 10.1056/NEJMoa1504720 26378978
    [Google Scholar]
  8. Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. Chertow G.M. Greene T. Hou F.F. Mann J.F.E. McMurray J.J.V. Lindberg M. Rossing P. Sjöström C.D. Toto R.D. Langkilde A.M. Wheeler D.C. Dapagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 2020 383 15 1436 1446 10.1056/NEJMoa2024816 32970396
    [Google Scholar]
  9. Heerspink H.J.L. Sjöström C.D. Jongs N. Chertow G.M. Kosiborod M. Hou F.F. McMurray J.J.V. Rossing P. Correa-Rotter R. Kurlyandskaya R. Stefansson B.V. Toto R.D. Langkilde A.M. Wheeler D.C. Heerspink H.J.L. Wheeler D.C. Chertow G. Correa-Rotter R. Greene T. Fan Hou F. McMurray J. Rossing P. Toto R. Stefansson B. Maria Langkilde A. Maffei L.E. Raffaele P. Solis S.E. Arias C.A. Aizenberg D. Luquez C. Zaidman C. Cluigt N. Mayer M. Alvarisqueta A. Wassermann A. Maldonado R. Bittar J. Maurich M. Gaite L.E. Garcia N. Sivak L. Ramallo P.O. Santos J.C. Garcia Duran R. Oddino J.A. Maranon A. Maia L.N. D Avila D. Barros E.J.G. Vidotti M.H. Panarotto D. Noronha I.D.L. Turatti L A A. Deboni L. Canziani M.E. Riella M.C. Bacci M.R. Paschoalin R.P. Franco R.J. Goldani J.C. St-Amour E. Steele A.W. Goldenberg R. Pandeya S. Bajaj H. Cherney D. Kaiser S.M. Conway J.R. Chow S.S. Bailey G. Lafrance J. Winterstein J. Cournoyer S. Gaudet D. Madore F. Houlden R.L. Dowell A. Langlois M. Muirhead N. Khandwala H. Levin A. Hou F. Xue Y. Zuo L. Hao C. Ni Z. Xing C. Chen N. Dong Y. Zhou R. Xiao X. Zou Y. Wang C. Liu B. Chen Q. Lin M. Luo Q. Zhang D. Wang J. Chen M. Wang X. Zhong A. Dong J. Zhu C. Yan T. Luo P. Ren Y. Pai P. Li D. Zhang R. Zhang J. Xu M. Zhuang Y. Kong Y. Yao X. Peng X. Persson F.I. Hansen T.K. Borg R. Pedersen Bjergaard U. Hansen D. Hornum M. Haller H. Klausmann G. Tschope D. Kruger T. Gross P. Hugo C. Obermuller N. Rose L. Mertens P. Zeller-Stefan H. Fritsche A. Renders L. Muller J. Budde K. Schroppel B. Wittmann I. Voros P. Dudas M. Tabak G.A. Kirschner R. Letoha A. Balku I. Hermanyi Z. Zakar G. Mezei I. Nagy G.G. Lippai J. Nemeth A. Khullar D. Gowdaiah P.K. Fernando Mervin E. Rao V.A. Dewan D. Maddi V.S.K. Vyawahare M.S. Pulichikkat R.K. Sonkar S.K. Gupta V.K. Agarwal S. Asirvatham A.J. Ignatius A. Chaubey S. Melemadathil S. Alva H. Kadam Y. Shimizu H. Sueyoshi A. Takeoka H. Abe Y. Imai T. Onishi Y. Fujita Y. Tokita Y. Makita Y. Idogaki A. Koyama R. Kikuchi H. Kashihara N. Hayashi T. Ando Y. Tanaka T. Shimizu M. Hidaka S. Gohda T. Tamura K. Abe M. Kamijo Y. Imasawa T. Takahashi Y. Nakayama M. Tomita M. Hirano F. Nakayama M. Fukushima Y. Kiyosue A. Kurioka S. Imai E. Kitagawa K. Waki M. Wada J. Uehara K. Iwatani H. Ota K. Shibazaki S. Tamura K. Katayama K. Narita I. Iinuma M. Matsueda S. Sasaki S. Yokochi A. Tsukamoto T. Yoshimura T. Kang S. Lee S. Lim C.S. Chin H. Joo K.W. Han S.Y. Chang T.I. Park S. Park H. Park C.W. Han B.G. Cha D.R. Yoon S.A. Kim W. Kim S.W. Ryu D. Correa Rotter R. Irizar Santana S.S. Hernandez Llamas G. Valdez Ortiz R. Secchi Nicolas N.C. Gonzalez Galvez G. Lazcano Soto J.R. Bochicchio Riccardelli T. Bayram Llamas E.A. Ramos Ibarra D.R. Melo M.G.S. Gonzalez Gonzalez J.G. Sanchez Mijangos J.H. Madero Robalo M. Garcia Castillo A. Manrique H.A. Farfan J.C. Vargas R. Valdivia A. Dextre A. Escudero E. Calderon Ticona J.R. Gonzales L. Villena J. Leon L. Molina G. Saavedra A. Garrido E. Arbanil H. Vargas Marquez S. Rodriguez J. Isidto R. Villaflor A.J. Gumba M.A. Tirador L. Comia R.S. Sy R.A. Guanzon M.L.V.V. Aquitania G. De Asis N.C. Silva A.A. Lim M.E. Danguilan R.A. Nowicki M. Rudzki H. Landa K. Kucharczyk-Bauman I. Gogola-Migdal B. Golski M. Olech-Cudzik A. Stompor T. Szczepanik T. Miklaszewicz B. Sciborski R. Kuzniewski M. Ciechanowski K. Wronska D. Klatko W. Mazur S. Popenda G. Myslicki M. Bolieva L.Z. Berns S. Galyavich A. Abissova T. Karpova I. Platonov D. Koziolova N. Kvitkova L. Nilk R. Medina T. Rebrov A. Rossovskaya M. Sinitsina I. Vishneva E. Zagidullin N. Novikova T. Krasnopeeva N. Magnitskaya O. Antropenko N. Batiushin M. Escudero Quesada V. Barrios Barrea C. Espinel Garauz E. Cruzado Garrit J.M. Morales Portillo C. Gorriz Teruel J.L. Cigarran Guldris S. Praga Terente M. Robles Perez-Monteoliva N.R. Infanta Cristina H. Tinahones Madueno F.J. Soto Gonzalez A. Diaz Rodriguez C. Furuland H. Saeed A. Dreja K. Spaak J. Bruchfeld A. Kolesnyk M. Levchenko O. Pyvovarova N. Stus V. Doretskyy V. Korobova N. Horoshko O. Katerenchuk I. Mostovoy Y.M. Orynchak M. Legun O. Dudar I. Bilchenko O. Andreychyn S. Levchenko A. Zub L. Tereshchenko N. Topchii I. Ostapenko T. Bezuglova S. Kopytsya M. Turenko O. Mark P. Barratt J. Bhandari S. Fraser D. Kalra P. Kon S.P. Mccafferty K. Mikhail A. Kon S.P. Alvarado O.P. Anderson R. Andrawis N.S. Arif A. Benjamin S.A. Bueso G. Busch R.S. Carr K.W. Carr K.W. Crawford P. Daboul N. De La Calle G.M. Delgado B. Earl J. El-Shahawy M.A. Graf R.J. Greenwood G. Guevara A. Wendland E.M. Mayfield R.K. Montero M. Morin D.J. Narayan P. Numrungroad V. Reddy A.C. Reddy R. Samson M.B. Trejo R. Butcher M.B. Wise J.K. Zemel L.R. Raikhel M. Weinstein D. Hernandez P. Wynne A. Khan B.V. Sterba G.A. Jamal A. Ross D. Rovner S.F. Tan A. Ovalle F. Patel R.J. Talano J. Patel D.R. Burgner A. Aslam N. Elliott M. Goral S. Jovanovich A. Umanath K. Waguespack D. Weiner D. Yu M. Schneider L. Le T. D T. Nguyen N. Nguyen H. Nguyen D. Nguyen V. Do T. Chu P. Ta D. Tran N. Nguyen D. Pfeffer M.A. Pocock S. Swedberg K. Rouleau J.L. Chaturvedi N. Ivanovich P. Levey A.S. Held C. Christersson C. Mann J. Varenhorst C. Effects of dapagliflozin on mortality in patients with chronic kidney disease: A pre-specified analysis from the DAPA-CKD randomized controlled trial. Eur. Heart J. 2021 42 13 1216 1227 10.1093/eurheartj/ehab094 33792669
    [Google Scholar]
  10. Mosenzon O. Wiviott S.D. Cahn A. Rozenberg A. Yanuv I. Goodrich E.L. Murphy S.A. Heerspink H.J.L. Zelniker T.A. Dwyer J.P. Bhatt D.L. Leiter L.A. McGuire D.K. Wilding J.P.H. Kato E.T. Gause-Nilsson I.A.M. Fredriksson M. Johansson P.A. Langkilde A.M. Sabatine M.S. Raz I. Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: An analysis from the DECLARE–TIMI 58 randomised trial. Lancet Diabetes Endocrinol. 2019 7 8 606 617 10.1016/S2213‑8587(19)30180‑9 31196815
    [Google Scholar]
  11. Perkovic V. de Zeeuw D. Mahaffey K.W. Fulcher G. Erondu N. Shaw W. Barrett T.D. Weidner-Wells M. Deng H. Matthews D.R. Neal B. Canagliflozin and renal outcomes in type 2 diabetes: Results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018 6 9 691 704 10.1016/S2213‑8587(18)30141‑4 29937267
    [Google Scholar]
  12. Perkovic V. Jardine M.J. Neal B. Bompoint S. Heerspink H.J.L. Charytan D.M. Edwards R. Agarwal R. Bakris G. Bull S. Cannon C.P. Capuano G. Chu P.L. de Zeeuw D. Greene T. Levin A. Pollock C. Wheeler D.C. Yavin Y. Zhang H. Zinman B. Meininger G. Brenner B.M. Mahaffey K.W. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N. Engl. J. Med. 2019 380 24 2295 2306 10.1056/NEJMoa1811744 30990260
    [Google Scholar]
  13. Bhatt D.L. Szarek M. Pitt B. Cannon C.P. Leiter L.A. McGuire D.K. Lewis J.B. Riddle M.C. Inzucchi S.E. Kosiborod M.N. Cherney D.Z.I. Dwyer J.P. Scirica B.M. Bailey C.J. Díaz R. Ray K.K. Udell J.A. Lopes R.D. Lapuerta P. Steg P.G. Sotagliflozin in patients with diabetes and chronic kidney disease. N. Engl. J. Med. 2021 384 2 129 139 10.1056/NEJMoa2030186 33200891
    [Google Scholar]
  14. Cannon C.P. Pratley R. Dagogo-Jack S. Mancuso J. Huyck S. Masiukiewicz U. Charbonnel B. Frederich R. Gallo S. Cosentino F. Shih W.J. Gantz I. Terra S.G. Cherney D.Z.I. McGuire D.K. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N. Engl. J. Med. 2020 383 15 1425 1435 10.1056/NEJMoa2004967 32966714
    [Google Scholar]
  15. Wanner C. Inzucchi S.E. Lachin J.M. Fitchett D. von Eynatten M. Mattheus M. Johansen O.E. Woerle H.J. Broedl U.C. Zinman B. Empagliflozin and progression of kidney disease in type 2 Diabetes. N. Engl. J. Med. 2016 375 4 323 334 10.1056/NEJMoa1515920 27299675
    [Google Scholar]
  16. Anker S.D. Butler J. Filippatos G. Ferreira J.P. Bocchi E. Böhm M. Brunner-La Rocca H.P. Choi D.J. Chopra V. Chuquiure-Valenzuela E. Giannetti N. Gomez-Mesa J.E. Janssens S. Januzzi J.L. Gonzalez-Juanatey J.R. Merkely B. Nicholls S.J. Perrone S.V. Piña I.L. Ponikowski P. Senni M. Sim D. Spinar J. Squire I. Taddei S. Tsutsui H. Verma S. Vinereanu D. Zhang J. Carson P. Lam C.S.P. Marx N. Zeller C. Sattar N. Jamal W. Schnaidt S. Schnee J.M. Brueckmann M. Pocock S.J. Zannad F. Packer M. Empagliflozin in heart failure with a preserved ejection fraction. N. Engl. J. Med. 2021 385 16 1451 1461 10.1056/NEJMoa2107038 34449189
    [Google Scholar]
  17. Packer M. Anker S.D. Butler J. Filippatos G. Pocock S.J. Carson P. Januzzi J. Verma S. Tsutsui H. Brueckmann M. Jamal W. Kimura K. Schnee J. Zeller C. Cotton D. Bocchi E. Böhm M. Choi D.J. Chopra V. Chuquiure E. Giannetti N. Janssens S. Zhang J. Gonzalez Juanatey J.R. Kaul S. Brunner-La Rocca H.P. Merkely B. Nicholls S.J. Perrone S. Pina I. Ponikowski P. Sattar N. Senni M. Seronde M.F. Spinar J. Squire I. Taddei S. Wanner C. Zannad F. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 2020 383 15 1413 1424 10.1056/NEJMoa2022190 32865377
    [Google Scholar]
  18. Packer M. Butler J. Zannad F. Pocock S.J. Filippatos G. Ferreira J.P. Brueckmann M. Jamal W. Zeller C. Wanner C. Anker S.D. Empagliflozin and major renal outcomes in heart failure. N. Engl. J. Med. 2021 385 16 1531 1533 10.1056/NEJMc2112411 34449179
    [Google Scholar]
  19. Herrington W.G. Staplin N. Wanner C. Green J.B. Hauske S.J. Emberson J.R. Preiss D. Judge P. Mayne K.J. Ng S.Y.A. Sammons E. Zhu D. Hill M. Stevens W. Wallendszus K. Brenner S. Cheung A.K. Liu Z.H. Li J. Hooi L.S. Liu W. Kadowaki T. Nangaku M. Levin A. Cherney D. Maggioni A.P. Pontremoli R. Deo R. Goto S. Rossello X. Tuttle K.R. Steubl D. Petrini M. Massey D. Eilbracht J. Brueckmann M. Landray M.J. Baigent C. Haynes R. Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 2023 388 2 117 127 10.1056/NEJMoa2204233 36331190
    [Google Scholar]
  20. Solomon S.D. McMurray J.J.V. Claggett B. de Boer R.A. DeMets D. Hernandez A.F. Inzucchi S.E. Kosiborod M.N. Lam C.S.P. Martinez F. Shah S.J. Desai A.S. Jhund P.S. Belohlavek J. Chiang C.E. Borleffs C.J.W. Comin-Colet J. Dobreanu D. Drozdz J. Fang J.C. Alcocer-Gamba M.A. Al Habeeb W. Han Y. Cabrera Honorio J.W. Janssens S.P. Katova T. Kitakaze M. Merkely B. O’Meara E. Saraiva J.F.K. Tereshchenko S.N. Thierer J. Vaduganathan M. Vardeny O. Verma S. Pham V.N. Wilderäng U. Zaozerska N. Bachus E. Lindholm D. Petersson M. Langkilde A.M. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N. Engl. J. Med. 2022 387 12 1089 1098 10.1056/NEJMoa2206286 36027570
    [Google Scholar]
  21. Prandi F.R. Barone L. Lecis D. Belli M. Sergi D. Milite M. Lerakis S. Romeo F. Barillà F. Biomolecular mechanisms of cardiorenal protection with sodium-glucose co-transporter 2 inhibitors. Biomolecules 2022 12 10 1349 10.3390/biom12101349 36291558
    [Google Scholar]
  22. Wright E.M. SGLT2 inhibitors: Physiology and pharmacology. Kidney360 2021 2 12 2027 2037 10.34067/KID.0002772021 35419546
    [Google Scholar]
  23. Ojha U. Reyes L. Eyenga F. Oumbe D. Watkowska J. Saint-Jacques H. Diabetes, heart failure and beyond: Elucidating the cardioprotective mechanisms of Sodium Glucose Cotransporter 2 (SGLT2) inhibitors. Am. J. Cardiovasc. Drugs 2022 22 1 35 46 10.1007/s40256‑021‑00486‑6 34189716
    [Google Scholar]
  24. Yau K. Dharia A. Alrowiyti I. Cherney D.Z.I. Prescribing SGLT2 inhibitors in patients with CKD: Expanding indications and practical considerations. Kidney Int. Rep. 2022 7 7 1463 1476 10.1016/j.ekir.2022.04.094 35812300
    [Google Scholar]
  25. Davies M.J. Aroda V.R. Collins B.S. Gabbay R.A. Green J. Maruthur N.M. Rosas S.E. Del Prato S. Mathieu C. Mingrone G. Rossing P. Tankova T. Tsapas A. Buse J.B. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2022 65 12 1925 1966 10.1007/s00125‑022‑05787‑2 36151309
    [Google Scholar]
  26. Heidenreich P.A. Bozkurt B. Aguilar D. Allen L.A. Byun J.J. Colvin M.M. Deswal A. Drazner M.H. Dunlay S.M. Evers L.R. Fang J.C. Fedson S.E. Fonarow G.C. Hayek S.S. Hernandez A.F. Khazanie P. Kittleson M.M. Lee C.S. Link M.S. Milano C.A. Nnacheta L.C. Sandhu A.T. Stevenson L.W. Vardeny O. Vest A.R. Yancy C.W. 2022 AHA/ACC/HFSA guideline for the management of heart failure: Executive summary: A report of the american college of cardiology/american heart association joint committee on clinical practice guidelines. Circulation 2022 145 18 e876 e894 10.1161/CIR.0000000000001062 35363500
    [Google Scholar]
  27. Sheikh O. Nashawi M. Battisha A. Chilton R. A focused review of cardiovascular guideline related recommendations for the primary care physician in the USA. Cardiovasc. Endocrinol. Metab. 2020 9 2 36 41 10.1097/XCE.0000000000000192 32537563
    [Google Scholar]
  28. Stevens L.A. Coresh J. Greene T. Levey A.S. Assessing kidney function--measured and estimated glomerular filtration rate. N. Engl. J. Med. 2006 354 23 2473 2483 10.1056/NEJMra054415 16760447
    [Google Scholar]
  29. Musso C.G. Michelángelo H. Vilas M. Martinez B. Bonetto A. Jauregui R. Algranati L. Renal creatinine handling in very old patients with chronic renal disease. Int. Urol. Nephrol. 2011 43 3 899 902 10.1007/s11255‑010‑9886‑5 21190081
    [Google Scholar]
  30. Dekkers C.C.J. Sjöström C.D. Greasley P.J. Cain V. Boulton D.W. Heerspink H.J.L. Effects of the sodium-glucose co-transporter-2 inhibitor dapagliflozin on estimated plasma volume in patients with type 2 diabetes. Diabetes Obes. Metab. 2019 21 12 2667 2673 10.1111/dom.13855 31407856
    [Google Scholar]
  31. Mordi N.A. Mordi I.R. Singh J.S. McCrimmon R.J. Struthers A.D. Lang C.C. Renal and cardiovascular effects of SGLT2 inhibition in combination with loop diuretics in patients with type 2 diabetes and chronic heart failure. Circulation 2020 142 18 1713 1724 10.1161/CIRCULATIONAHA.120.048739 32865004
    [Google Scholar]
  32. Oshima M. Neuen B.L. Jardine M.J. Bakris G. Edwards R. Levin A. Mahaffey K.W. Neal B. Pollock C. Rosenthal N. Wada T. Wheeler D.C. Perkovic V. Heerspink H.J.L. Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: A post-hoc analysis from the CREDENCE trial. Lancet Diabetes Endocrinol. 2020 8 11 903 914 10.1016/S2213‑8587(20)30300‑4 33065060
    [Google Scholar]
  33. Packer M. Hyperuricemia and gout reduction by SGLT2 inhibitors in diabetes and heart failure. J. Am. Coll. Cardiol. 2024 83 2 371 381 10.1016/j.jacc.2023.10.030 38199714
    [Google Scholar]
  34. Chino Y. Samukawa Y. Sakai S. Nakai Y. Yamaguchi J. Nakanishi T. Tamai I. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria. Biopharm. Drug Dispos. 2014 35 7 391 404 10.1002/bdd.1909 25044127
    [Google Scholar]
  35. Shemesh O. Golbetz H. Kriss J.P. Myers B.D. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int. 1985 28 5 830 838 10.1038/ki.1985.205 2418254
    [Google Scholar]
  36. Choosongsang P. Soonthornpun S. Overestimation of glomerular filtration rate calculated from creatinine as compared with cystatin C in patients with type 2 diabetes receiving sodium-glucose cotransportor 2 inhibitors. Diabet. Med. 2022 39 1 e14659 10.1111/dme.14659 34309941
    [Google Scholar]
  37. van Ruiten C.C. van der Aart-van der Beek A.B. IJzerman R.G. Nieuwdorp M. Hoogenberg K. van Raalte D.H. Heerspink H.J.L. Effect of exenatide twice daily and dapagliflozin, alone and in combination, on markers of kidney function in obese patients with type 2 diabetes: A prespecified secondary analysis of a randomized controlled clinical trial. Diabetes Obes. Metab. 2021 23 8 1851 1858 10.1111/dom.14410 33908691
    [Google Scholar]
  38. Levey A.S. Gansevoort R.T. Coresh J. Inker L.A. Heerspink H.L. Grams M.E. Greene T. Tighiouart H. Matsushita K. Ballew S.H. Sang Y. Vonesh E. Ying J. Manley T. de Zeeuw D. Eckardt K.U. Levin A. Perkovic V. Zhang L. Willis K. Change in albuminuria and gfr as end points for clinical trials in early stages of ckd: A scientific workshop sponsored by the national kidney foundation in collaboration with the us food and drug administration and european medicines agency. Am. J. Kidney Dis. 2020 75 1 84 104 10.1053/j.ajkd.2019.06.009 31473020
    [Google Scholar]
  39. Afkarian M. Zelnick L.R. Hall Y.N. Heagerty P.J. Tuttle K. Weiss N.S. de Boer I.H. Clinical manifestations of kidney disease among us adults with Diabetes, 1988-2014. JAMA 2016 316 6 602 610 10.1001/jama.2016.10924 27532915
    [Google Scholar]
  40. An N. Wu B. Yang Y. Huang Z. Feng J. Re-understanding and focusing on normoalbuminuric diabetic kidney disease. Front. Endocrinol. (Lausanne) 2022 13 1077929 10.3389/fendo.2022.1077929 36531487
    [Google Scholar]
  41. Sehtman-Shachar D.R. Yanuv I. Schechter M. Fishkin A. Aharon-Hananel G. Leibowitz G. Rozenberg A. Mosenzon O. Normoalbuminuria-is it normal? The association of urinary albumin within the ‘normoalbuminuric’ range with adverse cardiovascular and mortality outcomes: A systematic review and meta‐analysis. Diabetes Obes. Metab. 2024 26 10 4225 4240 10.1111/dom.15752 39021242
    [Google Scholar]
  42. Jongs N. Greene T. Chertow G.M. McMurray J.J.V. Langkilde A.M. Correa-Rotter R. Rossing P. Sjöström C.D. Stefansson B.V. Toto R.D. Wheeler D.C. Heerspink H.J.L. Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: A prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 9 11 755 766 10.1016/S2213‑8587(21)00243‑6 34619106
    [Google Scholar]
  43. Roscioni S.S. Lambers Heerspink H.J. de Zeeuw D. Microalbuminuria: Target for renoprotective therapy PRO. Kidney Int. 2014 86 1 40 49 10.1038/ki.2013.490 24759154
    [Google Scholar]
  44. Heerspink H.J.L. Jongs N. Chertow G.M. Langkilde A.M. McMurray J.J.V. Correa-Rotter R. Rossing P. Sjöström C.D. Stefansson B.V. Toto R.D. Wheeler D.C. Greene T. Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: A prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol. 2021 9 11 743 754 10.1016/S2213‑8587(21)00242‑4 34619108
    [Google Scholar]
  45. Pollock C. Stefánsson B. Reyner D. Rossing P. Sjöström C.D. Wheeler D.C. Langkilde A.M. Heerspink H.J.L. Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): A randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2019 7 6 429 441 10.1016/S2213‑8587(19)30086‑5 30992195
    [Google Scholar]
  46. Wanner C. Lachin J.M. Inzucchi S.E. Fitchett D. Mattheus M. George J. Woerle H.J. Broedl U.C. von Eynatten M. Zinman B. Empagliflozin and clinical outcomes in patients with type 2 diabetes mellitus, established cardiovascular disease, and chronic kidney disease. Circulation 2018 137 2 119 129 10.1161/CIRCULATIONAHA.117.028268 28904068
    [Google Scholar]
  47. Packer M. Mechanisms of enhanced renal and hepatic erythropoietin synthesis by sodium–glucose cotransporter 2 inhibitors. Eur. Heart J. 2023 44 48 5027 5035 10.1093/eurheartj/ehad235 37086098
    [Google Scholar]
  48. Daugirdas J.T. Depner T.A. Inrig J. Mehrotra R. Rocco M.V. Suri R.S. Weiner D.E. Greer N. Ishani A. MacDonald R. Olson C. Rutks I. Slinin Y. Wilt T.J. Rocco M. Kramer H. Choi M.J. Samaniego-Picota M. Scheel P.J. Willis K. Joseph J. Brereton L. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update. Am. J. Kidney Dis. 2015 66 5 884 930 10.1053/j.ajkd.2015.07.015 26498416
    [Google Scholar]
  49. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 2013 3 1 150
    [Google Scholar]
/content/journals/emiddt/10.2174/0118715303355221241021050443
Loading
/content/journals/emiddt/10.2174/0118715303355221241021050443
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: Diabetes mellitus ; proteinuria ; SGLT2 ; microalbumin ; neuropathy ; renal failure
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test