Mediators of the effects of canagliflozin on kidney protection in patients with type 2 diabetes
Open accessAbstract
Canagliflozin reduced kidney disease progression in participants with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program. This analysis explored potential mediators of the effects of canagliflozin on kidney outcomes. The percent mediating effect of 18 biomarkers indicative of disease was determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the average post-randomization level of each biomarker. Multivariable analyses assessed the joint effects of biomarkers that mediated most strongly in univariable analyses. The kidney outcome was defined as a composite of 40% estimated glomerular filtration rate decline, end-stage kidney disease, or death due to kidney disease. Nine biomarkers (systolic blood pressure [8.9% of effect explained], urinary albumin:creatinine ratio [UACR; 23.9%], gamma glutamyltransferase [4.1%], hematocrit [51.1%], hemoglobin [41.3%], serum albumin [19.5%], erythrocytes [56.7%], serum urate [35.4%], and urine pH [7.5%]) individually mediated the effect of canagliflozin on the kidney outcome. In a parsimonious multivariable model, erythrocyte concentration, serum urate, and systolic blood pressure maximized cumulative mediation (115%). Mediating effects of UACR, but not other mediators, were highly dependent upon the baseline level of UACR: UACR mediated 42% and 7% of the effect in those with baseline UACR 30 mg/g or more and under 30 mg/g, respectively. The identified mediators support existing hypothesized mechanisms for the prevention of kidney outcomes with sodium glucose co-transporter 2 inhibitors. Thus, the disparity in mediating effects across baseline UACR subgroups suggests that the mechanism for kidney protection with canagliflozin may vary across patient subgroups.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Both SGLT2 inhibitors and finerenone have shown that the majority of their beneficial effect is mediated by reduction in albuminuria.
“Reduction in albuminuria is also important to evaluate the efficacy of medications prescribed for kidney protection, as both SGLT2 inhibitors and finerenone have shown that the majority of their beneficial effect is mediated by reduction in albuminuria (42,43).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [43]
The ‘Mediating effects in patient subgroups’ section reports that albuminuria (UACR) mediated an estimated 7.4% or 42.3% of canagliflozin’s kidney benefit, depending on baseline UACR—not a majority in either subgroup. The paper studies canagliflozin, not finerenone; the finerenone portion may be covered by the sentence’s other citation. (LLM, conf=0.90)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes
Neal, B., Perkovic, V., Mahaffey, K. W., de Zeeuw, D., Fulcher, G., Erondu, N., Shaw, W., Law, G., Desai, M., & Matthews, D. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611925 · Cited by 7,830 · see citing works
Self-citationCanagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811744 · Cited by 6,189 · see citing works
Self-citationMacKinnon, D. P., Fairchild, A. J., & Fritz, M. S. (2007) · Annual Review of Psychology · doi:10.1146/annurev.psych.58.110405.085542 · Cited by 5,688 · see citing works
Introduction to Statistical Mediation Analysis
MacKinnon, D. P. (2012) · doi:10.4324/9780203809556 · Cited by 5,618 · see citing works
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
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. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1515920 · Cited by 3,655 · see citing works
Zelniker, T. A., Wiviott, S. D., Raz, I., Im, K., Goodrich, E. L., Bonaca, M. P., Mosenzon, O., Kato, E. T., Cahn, A., Furtado, R. H. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32590-x · Cited by 2,845 · cited 1× · see citing works
“T he CANagliflozin cardioVascular Assessment Study (CANVAS) Program reported that the sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin reduces the risk of clinically important kidney outcomes in patients with type 2 diabetes with established cardiovascular disease or those at high cardiovascular risk.(1)…”
BackgroundSurrogate End Points in Clinical Trials: Are We Being Misled?
Fleming, T. R., & DeMets, D. L. (1996) · Annals of Internal Medicine · doi:10.7326/0003-4819-125-7-199610010-00011 · Cited by 1,651 · see citing works
Heerspink, H. J. L., Perkins, B. A., Fitchett, D. H., Husain, M., & Cherney, D. Z. I. (2016) · Circulation · doi:10.1161/circulationaha.116.021887 · Cited by 1,376 · see citing works
Self-citationPathophysiology of Progressive Nephropathies
Remuzzi, G., & Bertani, T. (1998) · New England Journal of Medicine · doi:10.1056/nejm199811123392007 · Cited by 1,258 · see citing works
CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis
Ferrannini, E., Mark, M., & Mayoux, E. (2016) · Diabetes Care · doi:10.2337/dc16-0330 · Cited by 975 · see citing works
Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes
Lambers Heerspink, H. J., de Zeeuw, D., Wie, L., Leslie, B., & List, J. (2013) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12127 · Cited by 837 · see citing works
Mediation analysis in epidemiology: methods, interpretation and bias
Richiardi, L., Bellocco, R., & Zugna, D. (2013) · International Journal of Epidemiology · doi:10.1093/ije/dyt127 · Cited by 780 · see citing works
Inzucchi, S. E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., Schmoor, C., Ohneberg, K., Johansen, O. E., George, J. T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1096 · Cited by 740 · see citing works
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., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30180-9 · Cited by 684 · see citing works
Self-citationRenal, metabolic and cardiovascular considerations of SGLT2 inhibition
DeFronzo, R. A., Norton, L., & Abdul‐Ghani, M. A. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.170 · Cited by 556 · see citing works
Effects of Allopurinol on the Progression of Chronic Kidney Disease
Badve, S. V., Pascoe, E. M., Tiku, A., Boudville, N. C., Brown, F. G., Cass, A., Clarke, P., Dalbeth, N., Day, R. O., de Zoysa, J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1915833 · Cited by 483 · see citing works
Self-citationHeerspink, H. J. L., Perco, P., Mulder, S., Leierer, J., Hansen, M. K., Heinzel, A., & Mayer, G. (2019) · Diabetologia · doi:10.1007/s00125-019-4859-4 · Cited by 457 · see citing works
Self-citationHeerspink, H. J. L., Greene, T., Tighiouart, H., Gansevoort, R. T., Coresh, J., Simon, A. L., Chan, T. M., Hou, F. F., Lewis, J. B., Locatelli, F., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30314-0 · Cited by 397 · see citing works
Self-citationSerum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes
Doria, A., Gałecki, A. T., Spino, C., Pop‐Busui, R., Cherney, D. Z. I., Lingvay, I., Parsa, A., Rossing, P. R., Sigal, R. J., Afkarian, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1916624 · Cited by 382 · see citing works
Solini, A., Giannini, L., Seghieri, M., Vitolo, E., Taddei, S., Ghiadoni, L., & Bruno, R. M. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0621-8 · Cited by 375 · see citing works
van Bommel, E. J. M., Muskiet, M. H. A., van Baar, M. J. B., Tonneijck, L., Smits, M. M., Emanuel, A. L., Bozovic, A., Danser, A. H. J., Geurts, F., Hoorn, E. J., et al. (2020) · Kidney International · doi:10.1016/j.kint.2019.09.013 · Cited by 363 · see citing works
Neal, B. C., Perkovic, V., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Stein, P., Desai, M. G., Shaw, W. C., Jiang, J., Vercruysse, F., et al. (2013) · American Heart Journal · doi:10.1016/j.ahj.2013.05.007 · Cited by 340 · see citing works
Self-citationPacker, M., Anker, S. D., Butler, J., Filippatos, G. S., & Zannad, F. M. (2017) · JAMA Cardiology · doi:10.1001/jamacardio.2017.2275 · Cited by 335 · see citing works
Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers
Dekkers, C. C. J., Petrykiv, S., Laverman, G. D., Cherney, D. Z., Gansevoort, R. T., & Heerspink, H. J. L. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13301 · Cited by 263 · see citing works
Self-citationImpact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes
Ferrannini, E., & DeFronzo, R. A. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv239 · Cited by 256 · see citing works
SAS Macro for Causal Mediation Analysis with Survival Data
Valeri, L., & VanderWeele, T. J. (2015) · Epidemiology · doi:10.1097/ede.0000000000000253 · Cited by 226 · see citing works
Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes
Daniele, G., Xiong, J., Solis‐Herrera, C., Merovci, A., Eldor, R., Tripathy, D., DeFronzo, R. A., Norton, L., & Abdul‐Ghani, M. A. (2016) · Diabetes Care · doi:10.2337/dc15-2688 · Cited by 215 · see citing works
ENDOTHELIN: AN IMPORTANT FACTOR IN ACUTE RENAL FAILURE?
Firth, J. D., Raine, A. E. G., Ratcliffe, P. J., & Ledingham, J. G. G. (1988) · The Lancet · doi:10.1016/s0140-6736(88)90243-7 · Cited by 211 · see citing works
The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD
Sato, Y., Feig, D. I., Stack, A. G., Kang, D., Lanaspa, M. A., Ejaz, A. A., Sánchez‐Lozada, L. G., Kuwabara, M., Borghi, C., & Johnson, R. J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0174-z · Cited by 199 · see citing works
Neal, B., Perkovic, V., Matthews, D. R., Mahaffey, K. W., Fulcher, G., Meininger, G., Erondu, N., Desai, M., Shaw, W., Vercruysse, F., et al. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12829 · Cited by 174 · see citing works
Self-citationLim, V. G., Bell, R. M., Arjun, S., Kolatsi‐Joannou, M., Long, D. A., & Yellon, D. M. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2018.10.002 · Cited by 162 · see citing works
Petrykiv, S. I., Sjöström, C. D., Greasley, P. J., Xu, J., Persson, F., & Heerspink, H. J. L. (2017) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.10180916 · Cited by 151 · see citing works
Self-citationMediators of the Effects of Canagliflozin on Heart Failure in Patients With Type 2 Diabetes
Li, J., Woodward, M., Perkovic, V., Figtree, G. A., Heerspink, H. J. L., Mahaffey, K. W., de Zeeuw, D., Vercruysse, F., Shaw, W., Matthews, D. R., et al. (2020) · JACC: Heart Failure · doi:10.1016/j.jchf.2019.08.004 · Cited by 144 · see citing works
Self-citationNeuen, B. L., Ohkuma, T., Neal, B. C., Matthews, D. R., de Zeeuw, D., Mahaffey, K. W., Fulcher, G., Li, Q., Jardine, M., Oh, R., et al. (2019) · Journal of the American Society of Nephrology · doi:10.1681/asn.2019010064 · Cited by 132 · see citing works
Self-citationTsai, Y., Tsai, J., Chen, S., Chiu, Y., Hwang, S., Hung, C., Chen, T.-H., Kuo, M., & Chen, H. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.06.011 · Cited by 121 · see citing works
“Proportion explained”: a causal interpretation for standard measures of indirect effect?
Hafeman, D. M. (2009) · American Journal of Epidemiology · doi:10.1093/aje/kwp283 · Cited by 98 · see citing works
Natural Direct and Indirect Effects on the Exposed: Effect Decomposition under Weaker Assumptions
Vansteelandt, S., & VanderWeele, T. J. (2012) · Biometrics · doi:10.1111/j.1541-0420.2012.01777.x · Cited by 96 · see citing works
Yu, Q., Wu, X., Ли, Б., & Scribner, R. A. (2018) · Statistics in Medicine · doi:10.1002/sim.7977 · Cited by 95 · see citing works
Chang, Y., Lei, C., Lin, K., Chang, D., Hsieh, C., & Lee, Y. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2768 · Cited by 66 · see citing works
Effects of dapagliflozin on urinary metabolites in people with type 2 diabetes
Mulder, S., Heerspink, H. J. L., Darshi, M., Kim, J. J., Laverman, G. D., Sharma, K., & Pena, M. J. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13823 · Cited by 65 · see citing works
Self-citationFaucon, A., Flamant, M., Metzger, M., Boffa, J., Haymann, J., Houillier, P., Thervet, É., Vrtovsnik, F., Stengel, B., Géri, G., et al. (2019) · Kidney International · doi:10.1016/j.kint.2019.06.017 · Cited by 49 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function
Vallon, V., & Verma, S. (2020) · Annual Review of Physiology · doi:10.1146/annurev-physiol-031620-095920 · Cited by 520 · see citing works
Finerenone with empagliflozin in chronic kidney disease and type 2 diabetes
Agarwal, R., Green, J. B., Heerspink, H. J. L., Mann, J. F. E., McGill, J. B., Mottl, A. K., Rosenstock, J., Rossing, P., Vaduganathan, M., Brinker, M., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2410659 · Cited by 319 · see citing works
Self-citationZannad, F. M., Ferreira, J. P., Butler, J., Filippatos, G. S., Januzzi, J. L., Sumin, M., Zwick, M., Saadati, M., Pocock, S., Sattar, N. A., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac495 · Cited by 202 · see citing works
Apperloo, E. M., Neuen, B. L., Fletcher, R. A., Jongs, N., Anker, S. D., Bhatt, D. L., Butler, J., Cherney, D. Z. I., Herrington, W. G., Inzucchi, S. E., et al. (2024) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(24)00155-4 · Cited by 177 · see citing works
Self-citationA kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors
Sen, T., & Heerspink, H. J. L. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.02.016 · Cited by 161 · see citing works
Self-citationIron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF
Docherty, K. F., Welsh, P. I., Verma, S., de Boer, R. A., O’Meara, E., Bengtsson, O., Køber, L., Kosiborod, M., Hammarstedt, A., Langkilde, A. M., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.060511 · Cited by 154 · see citing works
Ku, E., Vecchio, L. D., Eckardt, K., Haase, V. H., Johansen, K. L., Nangaku, M., Tangri, N., Waikar, S. S., Więcek, A., Cheung, M., et al. (2023) · Kidney International · doi:10.1016/j.kint.2023.05.009 · Cited by 156 · see citing works
Oshima, M., Neuen, B. L., Jardine, M. J., Bakris, G., Edwards, R., Levin, A., Mahaffey, K. W., Neal, B., Pollock, C., Rosenthal, N., et al. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30300-4 · Cited by 135 · see citing works
Self-citationPotential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis
Mann, J. F. E., Buse, J. B., Idorn, T., Leiter, L. A., Pratley, R. E., Rasmussen, S., Vilsbøll, T., Wolthers, B., & Perkovic, V. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14443 · Cited by 120 · see citing works
Self-citationSGLT2 Inhibition and Uric Acid Excretion in Patients with Type 2 Diabetes and Normal Kidney Function
Suijk, D. L. S., van Baar, M. J. B., van Bommel, E. J. M., Iqbal, Z., Krebber, M. M., Vallon, V., Touw, D. J., Hoorn, E. J., Nieuwdorp, M., Kramer, M. M. H., et al. (2022) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.11480821 · Cited by 111 · see citing works
11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026
American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s011 · Cited by 108 · see citing works
Badura, K., Janc, J. J., Wąsik, J., Gnitecki, S., Skwira, S., Młynarska, E., Rysz, J., & Franczyk, B. (2024) · Biomedicines · doi:10.3390/biomedicines12061191 · Cited by 106 · see citing works
State-of-the-Art-Review: Mechanisms of Action of SGLT2 Inhibitors and Clinical Implications
Vallon, V. (2024) · American Journal of Hypertension · doi:10.1093/ajh/hpae092 · Cited by 115 · see citing works
Staplin, N., Haynes, R., Judge, P., Wanner, C., Green, J., Emberson, J., Preiss, D., Mayne, K., Ng, S., Sammons, E. L., et al. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00321-2 · Cited by 102 · see citing works
Self-citationRavindran, S., & Munusamy, S. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30621 · Cited by 96 · see citing works
Sen, T., Li, J., Neuen, B. L., Neal, B. C., Arnott, C. G., Parikh, C. R., Coca, S. G., Perkovic, V., Mahaffey, K. W., Yavin, Y., et al. (2021) · Diabetologia · doi:10.1007/s00125-021-05512-5 · Cited by 91 · see citing works
Self-citationHyperuricemia and Gout Reduction by SGLT2 Inhibitors in Diabetes and Heart Failure
Packer, M. (2024) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2023.10.030 · Cited by 80 · see citing works
Persson, F., Rossing, P., Vart, P., Chertow, G. M., Hou, F. F., Jongs, N., McMurray, J. J. V., Correa-Rotter, R., Bajaj, H. S., Stefansson, B. V., et al. (2021) · Diabetes Care · doi:10.2337/dc21-0300 · Cited by 78 · see citing works
Self-citationFrom Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options
Sharma, S., & Smyth, B. J. (2021) · Kidney & Blood Pressure Research · doi:10.1159/000516911 · Cited by 71 · see citing works
How do SGLT2 inhibitors protect the kidney? A mediation analysis of the EMPA-REG OUTCOME trial
Wanner, C., Nangaku, M., Kraus, B. J., Zinman, B., Mattheus, M., Hantel, S., Schumacher, M. C., Ohneberg, K., Schmoor, C., & Inzucchi, S. E. (2024) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfae032 · Cited by 54 · see citing works
Guedes, M. H., & Pecoits‐Filho, R. (2021) · Journal of Internal Medicine · doi:10.1111/joim.13424 · Cited by 51 · see citing works
Cherney, D. Z. I., Udell, J. A., & Drucker, D. J. (2021) · Med · doi:10.1016/j.medj.2021.10.004 · Cited by 52 · see citing works
Tian, Q., Guo, K., Deng, J., Zhong, Y., & Yang, L. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17115 · Cited by 51 · see citing works
Segar, M. W., Kolkailah, A. A., Frederich, R. C., Pong, A., Cannon, C. P., Cosentino, F., Dagogo-Jack, S. E., McGuire, D. K., Pratley, R. E., Liu, C., et al. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14769 · Cited by 43 · see citing works
Aroda, V. R., & Eckel, R. H. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14830 · Cited by 38 · see citing works
Koshino, A., Neuen, B. L., Jongs, N., Pollock, C. A., Greasley, P. J., Andersson, E.-M., Hammarstedt, A., Karlsson, C., Langkilde, A. M., Wada, T., et al. (2023) · Cardiovascular Diabetology · doi:10.1186/s12933-023-02027-8 · Cited by 40 · see citing works
Self-citationSen, T., Li, J., Neuen, B. L., Arnott, C. G., Neal, B., Perkovic, V., Mahaffey, K. W., Shaw, W., Canovatchel, W., Hansen, M. K., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.121.021661 · Cited by 35 · see citing works
Self-citationVallon, V. (2024) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfae060 · Cited by 37 · see citing works
Girardi, A. C. C., Polidoro, J. Z., Castro, P. C., Pio-Abreu, A., Noronha, I. L., & Drager, L. F. (2024) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00143.2024 · Cited by 32 · see citing works
Natale, P., Tunnicliffe, D. J., Toyama, T., Palmer, S. C., Saglimbene, V. M., Ruospo, M., Gargano, L., Stallone, G., Gesualdo, L., & Strippoli, G. F. (2024) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd015588.pub2 · Cited by 35 · see citing works
A meta-analysis of albuminuria as a surrogate endpoint for kidney failure
Heerspink, H. J. L., Collier, W., Chaudhari, J., Miao, S., Tighiouart, H., Appel, G. B., Caravaca‐Fontán, F., Floege, J., Hannedouche, T. P., Imai, E., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-04057-z · Cited by 31 · see citing works
Self-citationHare, G. M. T., Zhang, Y., Chin, K., Thai, K., Jacobs, E., Cazorla‐Bak, M. P., Nghiem, L., Wilson, D. F., Vinogradov, S. A., Connelly, K. A., et al. (2021) · Physiological Reports · doi:10.14814/phy2.14890 · Cited by 31 · see citing works
Agarwal, R., Green, J. B., Heerspink, H. J. L., Mann, J. F. E., McGill, J. B., Mottl, A. K., Rosenstock, J., Rossing, P. R., Vaduganathan, M., BRINKER, M. D., et al. (2025) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfaf022 · Cited by 32 · see citing works
Self-citationSen, T., Koshino, A., Neal, B. C., Bijlsma, M. J., Arnott, C. G., Li, J., Hansen, M. K., Ix, J. H., & Heerspink, H. J. L. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14779 · Cited by 29 · see citing works
Self-citationRenal Tubular Handling of Glucose and Fructose in Health and Disease
Vallon, V., & Nakagawa, T. (2021) · Comprehensive physiology · doi:10.1002/cphy.c210030 · Cited by 45 · see citing works
Sridhar, V. S., Limonte, C. P., Groop, P., Heerspink, H. J. L., Pratley, R. E., Rossing, P. R., Skyler, J. S., & Cherney, D. Z. I. (2023) · Diabetologia · doi:10.1007/s00125-023-06015-1 · Cited by 31 · see citing works
Self-citationAssociation between urinary uric acid excretion and kidney outcome in patients with CKD
Asahina, Y., Sakaguchi, Y., Oka, T., Hattori, K., Kawaoka, T., Doi, Y., Yamamoto, R., Matsui, I., Mizui, M., Kaimori, J., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-55809-9 · Cited by 27 · see citing works
Mayne, K. J., Sardell, R. J., Staplin, N., Judge, P. K., Zhu, D., Sammons, E. L., Cherney, D. Z. I., Green, J. B., Levin, A., Pontremoli, R., et al. (2024) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfae203 · Cited by 29 · see citing works
Self-citationThe Pathophysiological Basis of Diabetic Kidney Protection by Inhibition of SGLT2 and SGLT1
Oe, Y., & Vallon, V. (2022) · Kidney and Dialysis · doi:10.3390/kidneydial2020032 · Cited by 27 · see citing works
Renoprotective Effects of SGLT2 Inhibitors
Vallon, V. (2022) · Heart Failure Clinics · doi:10.1016/j.hfc.2022.03.005 · Cited by 27 · see citing works
Gohda, T., & Murakoshi, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213749 · Cited by 25 · see citing works
McCormick, N., Yokose, C., Lu, N., Wexler, D. J., Aviña-Zubieta, J. A., Vera, M. A. D., Chigurupati, S., Tan, K., Chen, C., McCoy, R. G., et al. (2024) · BMJ · doi:10.1136/bmj-2024-080035 · Cited by 24 · see citing works
Sinha, F., Federlein, A., Biesold, A., Schwarzfischer, M., Krieger, K., Schweda, F., & Tauber, P. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1118358 · Cited by 23 · see citing works
Cardiorenal Protection in Diabetic Kidney Disease
Lee, J. F., Berzan, E., Sridhar, V. S., Odutayo, A., & Cherney, D. Z. I. (2021) · Endocrinology and Metabolism · doi:10.3803/enm.2021.987 · Cited by 21 · see citing works
Rodriguez‐Valadez, J. M., Tahsin, M., Masharani, U. B., Park, M., Hunink, M. G. M., Yeboah, J., Li, L., Weber, E. S., Berkalieva, A., Avezaat, L., et al. (2024) · Journal of the American Heart Association · doi:10.1161/jaha.123.032463 · Cited by 21 · see citing works
Sodium–glucose cotransporter 2 inhibitors: renal outcomes according to baseline albuminuria
Delanaye, P., Wissing, K. M., & Scheen, A. J. (2021) · Clinical Kidney Journal · doi:10.1093/ckj/sfab096 · Cited by 21 · see citing works
SGLT2 inhibitors as metabolic modulators: beyond glycemic control in type 2 diabetes
Wu, Q., Zhang, J., Zhang, F., & Li, D. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1601633 · Cited by 20 · see citing works
Scheen, A. J., & Delanaye, P. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2022.2014322 · Cited by 18 · see citing works
Canagliflozin may increase thromboembolic events in males with erythrocytosis but not in females
Doi, Y., Hamano, T., Yamaguchi, O., & Isaka, Y. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016320 · Cited by 18 · see citing works
Dapagliflozin for the treatment of chronic kidney disease
Kurata, Y., & Nangaku, M. (2022) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2022.2099373 · Cited by 19 · see citing works
Ferrannini, E., Solini, A., Baldi, S., Scozzaro, T., Polidori, D., Natali, A., & Hansen, M. K. (2023) · Diabetes · doi:10.2337/db23-0448 · Cited by 18 · see citing works
Renal Tubular Handling of Glucose and Fructose in Health and Disease
Vallon, V., & Nakagawa, T. (2022) · Comprehensive physiology · doi:10.1002/j.2040-4603.2022.tb00207.x · Cited by 17 · see citing works
Sridhar, V. S., Heerspink, H. J. L., Davies, M. J., Banks, P. L., Girard, M., Garg, S. K., & Cherney, D. Z. I. (2023) · Diabetes Care · doi:10.2337/dc23-0129 · Cited by 16 · see citing works
Self-citationShenoy, S. V., Nagaraju, S. P., Bhojaraja, M. V., Prabhu, R., Rangaswamy, D., & Rao, I. R. (2021) · Nephrology · doi:10.1111/nep.13917 · Cited by 16 · see citing works
Recent evidence on the effect of urate-lowering treatment on the progression of kidney disease
Tiku, A., Johnson, D. W., & Badve, S. V. (2021) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000699 · Cited by 15 · see citing works
Sridhar, V. S., Ambinathan, J. P. N., Gillard, P., Mathieu, C., Cherney, D. Z. I., Lytvyn, Y., & Singh, S. K. (2021) · Transplantation · doi:10.1097/tp.0000000000003919 · Cited by 15 · see citing works
Liu, H., Sridhar, V. S., Perkins, B. A., Rosenstock, J., & Cherney, D. Z. I. (2022) · Current Diabetes Reports · doi:10.1007/s11892-022-01471-2 · Cited by 14 · see citing works
Cases, A., Cigarrán, S., Górriz, J. L., & Núñez, J. E. (2023) · Nefrología · doi:10.1016/j.nefro.2023.11.001 · Cited by 14 · see citing works
Effect of SGLT2 inhibitors on anemia and their possible clinical implications
Cases, A., Cigarrán, S., Górriz, J. L., & Núñez, J. E. (2024) · Nefrología (English Edition) · doi:10.1016/j.nefroe.2024.03.011 · Cited by 15 · see citing works
Heerspink, H. J. L., Stack, A. G., Terkeltaub, R. A., Greene, T., Inker, L. A., Bjursell, M. K., Perl, S., Rikte, T., Erlandsson, F., & Perkovic, V. (2021) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfab237 · Cited by 13 · see citing works
Self-citationDoi, Y., Hamano, T., Yamaguchi, S., Sakaguchi, Y., Kaimori, J., & Isaka, Y. (2023) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15191 · Cited by 13 · see citing works
Budoff, M. J., Davis, T. M. E., Palmer, A. G., Frederich, R. C., Lawrence, D. E., Liu, J., Gantz, I., & Derosa, G. (2021) · Diabetes Therapy · doi:10.1007/s13300-021-01033-x · Cited by 12 · see citing works
Tye, S. C., de Vries, S. T., Wanner, C., Denig, P., & Heerspink, H. J. L. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.786706 · Cited by 11 · see citing works
Self-citationLi, J., Arnott, C. G., Heerspink, H. J. L., MBiostat, Q. L., Cannon, C. P., Wheeler, D. C., Charytan, D. M., Barraclough, J., Figtree, G. A., Agarwal, R., et al. (2022) · Journal of the American Heart Association · doi:10.1161/jaha.121.025045 · Cited by 11 · see citing works
Self-citationSGLT2i in Patients with Type 1 Diabetes: Benefits, Risks, and Preventive Strategies
Ma, Y., Zhao, Q., Peng, H., Nalisa, D. L., Shan, P., & Jiang, H. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2805098 · Cited by 11 · see citing works
Innovative therapeutics for renoprotection: Where we are
Cortinovis, M., Perico, N., & Remuzzi, G. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100060 · Cited by 10 · see citing works
Schwarz, Y., Klein, P., & Lev-Shalem, L. (2023) · Acta Diabetologica · doi:10.1007/s00592-023-02174-0 · Cited by 9 · see citing works
Bishr, A., El-Mokadem, B. M., & Gomaa, A. A. (2025) · Scientific Reports · doi:10.1038/s41598-024-82163-7 · Cited by 9 · see citing works
Wen, S., Yuan, Y., Li, Y., Xu, C., Chen, L., Ren, Y., Wang, C., He, Y., Li, X., Gong, M., et al. (2025) · BMC Endocrine Disorders · doi:10.1186/s12902-025-01985-2 · Cited by 11 · see citing works
The future of Diabetic Kidney Disease management: reducing the unmet need
de Zeeuw, D. (2020) · Journal of Nephrology · doi:10.1007/s40620-020-00820-2 · Cited by 9 · see citing works
Pollock, C. A., & Neuen, B. L. (2021) · Advances in Chronic Kidney Disease · doi:10.1053/j.ackd.2021.02.006 · Cited by 9 · see citing works
Self-citationLiver function markers predict cardiovascular and renal outcomes in the CANVAS Program
Ferrannini, G., Rosenthal, N. R., Hansen, M. K., & Ferrannini, E. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01558-w · Cited by 9 · see citing works
Sridhar, V. S., Cosentino, F., Dagogo-Jack, S. E., McGuire, D. K., Pratley, R. E., Cater, N. B., Essex, M. N., Mancuso, J. P., Zhao, Y., & Cherney, D. Z. I. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15895 · Cited by 8 · see citing works
van Mil, D., Kieneker, L. M., Harms, E., Prins, G. H., van Geer-Postmus, I., Mepschen, M., Leving, M. T., Stoker, N., Kocks, J. W. H., Gansevoort, R. T., et al. (2025) · EClinicalMedicine · doi:10.1016/j.eclinm.2025.103185 · Cited by 8 · see citing works
Self-citationBonnet, F., Vaduva, P., Halimi, J., Dosda, A., Ducluzeau, P., Koppe, L., & Fauchier, L. (2025) · Cardiovascular Diabetology · doi:10.1186/s12933-025-02930-2 · Cited by 8 · see citing works
Speedtsberg, E. S., & Tepel, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1281107 · Cited by 8 · see citing works
Yang, H., Yang, L., Jardine, M., Arnott, C. G., Neuen, B. L., Xu, K., Zhao, X., Qian, D., Cui, B., Qiu, Y., et al. (2024) · European journal of medical research · doi:10.1186/s40001-024-02214-7 · Cited by 8 · see citing works
Self-citationCardiorenal Protections of SGLT2 Inhibitors in the Treatment of Type 2 Diabetes
Nazari, S., & Mirkhani, H. (2022) · Current Diabetes Reviews · doi:10.2174/1573399819666221222160035 · Cited by 8 · see citing works
Cardiorenal protective effects of canagliflozin in CREDENCE according to glucose lowering
Charytan, D. M., Mahaffey, K. W., Jardine, M., Cannon, C. P., Neal, B. C., Heerspink, H. J. L., Agarwal, R., Bakris, G. L., de Zeeuw, D., Levin, A., et al. (2023) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2022-003270 · Cited by 10 · see citing works
Self-citationTesfaye, H., Wang, K. M., Zabotka, L. E., Wexler, D. J., Schmedt, N., Koeneman, L., SEMAN, L. J., Paik, J. M., & Patorno, E. (2024) · Journal of General Internal Medicine · doi:10.1007/s11606-024-08793-9 · Cited by 7 · see citing works
Chen, A., Fletcher, R., Neuen, B. L., Neal, B. C., & Arnott, C. G. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15751 · Cited by 8 · see citing works
Self-citationMatsubayashi, Y., Yoshida, A., Suganami, H., Oe, M., Sato, T., Yaguchi, Y., Fujihara, K., Yamada, T., Tanaka, S., Kaku, K., et al. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14836 · Cited by 7 · see citing works
Kidney involvement in glycogen storage disease type I: Current knowledge and key challenges
Schumann, A., Garbade, S. F., Beblo, S., Gautschi, M., Haas, D., Hochuli, M., Hoffmann, G. F., May, P., Merkel, M., Scholl‐Bürgi, S., et al. (2025) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2025.109054 · Cited by 6 · see citing works
Mechanistic evaluation of ertugliflozin in patients with type 2 diabetes and heart failure
Lytvyn, Y., Scholtes, R. A., Boorsma, E. M., Sridhar, V. S., Kugathasan, L., Liu, H., Lovblom, L. E., Handoko, M. L., Mosterd, C. M., Floras, J. S., et al. (2025) · Physiological Reports · doi:10.14814/phy2.70275 · Cited by 6 · see citing works
Self-citationZheng, T., Luo, L., Wang, X., Deng, X., & Xue, M. (2025) · Cellular Signalling · doi:10.1016/j.cellsig.2025.112038 · Cited by 6 · see citing works
Shi, Y., Dong, S., Xu, Y., Ji, D., Yang, L., & Zhao, R. (2024) · Acta Diabetologica · doi:10.1007/s00592-024-02252-x · Cited by 6 · see citing works
Effects of antidiabetic drugs on the level of serum uric acid in patients who have type 2 diabetes
Wang, G., & Wang, G. (2025) · Saudi Medical Journal · doi:10.15537/smj.2025.46.3.20240920 · Cited by 6 · see citing works
Patoulias, D., Eid, A. H., & Rizzo, M. (2023) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2023.108630 · Cited by 6 · see citing works
Berezin, A. Е., & Berezina, T. A. (2024) · Journal of International Medical Research · doi:10.1177/03000605241227659 · Cited by 6 · see citing works
Goodluck, H., Zemljic‐Harpf, A. E., Galdino, O. A., Kanoo, S., Lopez, N., Kim, Y., & Vallon, V. (2025) · Physiological Reports · doi:10.14814/phy2.70217 · Cited by 4 · see citing works
Weingold, R., Zinman, B., Mattheus, M., Ofstad, A. P., Steubl, D., Wanner, C., & Inzucchi, S. E. (2023) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2023.108628 · Cited by 5 · see citing works
Sodium glucose co-transporter 2 inhibitors (SGLT2i) for pediatric kidney disease: the future is near
Portalatin, G. M., Hong‐McAtee, I., Burgner, A. M., Gould, E. R., & Hunley, T. E. (2025) · Frontiers in Pediatrics · doi:10.3389/fped.2025.1521425 · Cited by 5 · see citing works
Emerging roles of Sodium-glucose cotransporter 2 inhibitors in Diabetic kidney disease
Gan, T., Song, Y., Guo, F., & Qin, G. (2022) · Molecular Biology Reports · doi:10.1007/s11033-022-07758-7 · Cited by 4 · see citing works
Georgianos, P. I., Koufakis, T., Arampatzis, S., & Liakopoulos, V. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70026 · Cited by 3 · see citing works
Chalès, G., Coiffier, G., & Robin, F. (2025) · EMC - Appareil locomoteur · doi:10.1016/s0246-0521(25)47868-1 · Cited by 3 · see citing works
Sridhar, V. S., Kugathasan, L., Lytvyn, Y., Deng, Y., Liu, H., Lovblom, L. E., TSE, J. M., Nardone, M., Floras, J. S., Osuntokun, T., et al. (2025) · Hypertension · doi:10.1161/hypertensionaha.125.25955 · Cited by 3 · see citing works
Self-citationMaruhashi, T., Tanaka, A., Takahashi, K., Higashi, Y., Node, K., & the PROCEED trial investigators (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15481 · Cited by 3 · see citing works
Steinmetz, T., Goldman, S. N., Kagan, K. B. T., Bielopolski, D., Buchrits, S., Schechter, A., Kushnir, S., Turjeman, ., Agur, T., Grossman, A., et al. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf184 · Cited by 3 · see citing works
Zheng, Q., Yan, Y., Xu, L., Lin, J., Shu, Z., Yan, D., Li, X., Liu, B., Chan, K. W., Fan, G., et al. (2025) · Phytomedicine · doi:10.1016/j.phymed.2025.157225 · Cited by 3 · see citing works
- Authors
- Li, J., Neal, B., Perkovic, V., de Zeeuw, D., Neuen, B. L., Arnott, C., Simpson, R., Oh, R., Mahaffey, K. W., & Heerspink, H. J. L.
- Affiliations
- Army Medical University (CN)
- The George Institute for Global Health (GB)
- UNSW Sydney (AU)
- Royal Prince Alfred Hospital (AU)
- Janssen Research & Development (United States) (US)
- Stanford Medicine (US)
- University Medical Center Groningen (NL)
- Corresponding author
- Heerspink, Hiddo J.L.
- ORCID
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 98
- Issue
- 3
- Pages
- 769-777
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W3029576443
- Cited by
- 130
- References
- 41
- Citations by year
- 2026: 8 · 2025: 30 · 2024: 25 · 2023: 21 · 2022: 22 · 2021: 21 · 2020: 3
- FWCI
- 10.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by)
- UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Funders
- Janssen Research & Development
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Keywords
- canagliflozin, type 2 diabetes, renal protection, kidney disease progression, SGLT2 inhibitors, mediation analysis, urinary albumin-creatinine ratio, erythrocyte concentration, serum uric acid, systolic blood pressure, estimated glomerular filtration rate decline, end-stage renal disease, CANVAS trial
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Humans, Kidney
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
