Effects of the SGLT‐2 inhibitor dapagliflozin on glomerular and tubular injury markers

Dekkers, Claire C J; Petrykiv, S.; Laverman, Gozewijn D.; Cherney, David Z.I.; Gansevoort, Ron T.; Heerspink, Hiddo J L

doi:10.1111/dom.13301

Cited by 212 publications

(194 citation statements)

References 22 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…In RCTs, dapagliflozin consistently reduced AER by 36‐40% irrespective of therapy with ACE inhibitors or ARBs . In our study, AER declined by 37% in patients taking, and by 45% in patients not taking ACEi/ARBs.…”

Section: Discussionsupporting

confidence: 58%

Effectiveness of dapagliflozin versus comparators on renal endpoints in the real world: A multicentre retrospective study

Fadini

Solini

Manca

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 58%

Effectiveness of dapagliflozin versus comparators on renal endpoints in the real world: A multicentre retrospective study

Fadini

Solini

Manca

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…SGLT2is induced an initial and small reduction in eGFR during the early treatment period, which was noted at 1‐6 weeks and gradually narrowed over time, with, finally, a long‐term protection from eGFR decline. Recent studies exploring the effects of SGLT2is on inflammatory and kidney injury markers have observed no correlation between early changes in indicators of renal function and changes in kidney injury markers (KIM‐1, IL‐6 et al); these studies and further pointed out that the early transient changes in eGFR were not associated with an excess risk of renal adverse events. We considered the initial drop in eGFR to be attributed to the amelioration of volume overload related to an osmotic diuresis that is consistent with an increased incidence of adverse events, potentially indicative of volume depletion which also begins early after initiating therapy, as well as with tubule‐glomerular feedback with increased sodium delivery to the juxtaglomerular apparatus.…”

Section: Discussionmentioning

confidence: 93%

The renoprotective effects of sodium‐glucose cotransporter 2 inhibitors versus placebo in patients with type 2 diabetes with or without prevalent kidney disease: A systematic review and meta‐analysis

Wang

Zhou

Kong

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims:We undertook a systematic review and meta-analysis to assess the efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) concerning kidney outcomes in patients with type 2 diabetes mellitus (T2DM), with or without prevalent kidney disease.Materials and Methods: PubMed, Web of science, Embase and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) to assess the efficacy and safety of treatment with SGLT2is versus placebo in patients with T2DM. The weighted mean difference (WMD) and its 95% confidence interval (CI) were applied for continuous variables, and the risk ratio (RR) and corresponding 95% CI were used for dichotomous outcomes. Patients were categorized according to whether the baseline mean estimated glomerular filtration rate (eGFR) was less or was more than 60 mL/min/1.73 m 2 .Results: A total of 25 eligible studies with 43 721 participants were included. There was an initial and small decrease in eGFR during the early treatment period (WMD, −4.63; 95% CI, −6.08 to −3.19 mL/min/1.73 m 2 ), which was noted at 1-6 weeks and gradually narrowed over time, with a decline in protection from eGFR in the long term (WMD, 3.82; 95% CI, 2.80-4.85 mL/min/1.73 m 2 ).SGLT2is significantly delayed albuminuria progression (RR, 0.71; 95% CI, 0.66-0.76), promoted albuminuria regression (RR,1.71; 95% CI, 1.54-1.90), improved the composite of ≥40% decrease in eGFR, in the need for renal-replacement and in death from renal causes (RR, 0.57; 95% CI, 0.49-0.66), and reduced all-cause mortality (RR, 0.84; 95% CI, 0.75-0.94). At the same time, they significantly increased the risk of genital infection (RR, 3.43; 95% CI, 2.87-4.10) vs placebo in patients with T2DM. Meta-regression analyses showed that eGFR-preservation effects were not significantly associated with basic patient characteristics (age, BMI, HbA1c, eGFR level), but were influenced by drug administration (treatment duration, type, dosage of SGLT2is). Subgroup analyses showed that the relative effects on renal outcomes of SGLT2is vs placebo were similar across eGFR subgroups (P heterogeneity >0.05).Conclusions: SGLT2is slowed eGFR decline, lowered albuminuria progression, improved adverse renal endpoints and reduced all-cause mortality, but increased risk of genital infections vs placebo in patients with T2DM. The indication of consistent renal benefits across categories of baseline eGFR levels may allow additional individuals to benefit from SGLT2is therapy.

show abstract

“…Dapagliflozin treatment reduced urinary Kidney Injury Molecule-1 (KIM-1) excretion by 22.6% (0.3–39.8%; p = 0.05), reduced urinary IL-6 excretion by 23.5% (1.4–40.6%; p = 0.04) [37]. KIM-1 is a marker for hypoxic injury to proximal tubular cells, which would suggest that Dapagliflozin reduces proximal tubular cell injury.…”

Section: Hypotheses Of Different Sglt2 Inhibitors In Acute Kidney Injurymentioning

confidence: 99%

The SGLT2 Inhibitor Empagliflozin Might Be a New Approach for the Prevention of Acute Kidney Injury

Chu

et al. 2019

Kidney Blood Press Res

View full text Add to dashboard Cite

Three randomized control trials (Canagliflozin Cardiovascular Assessment Study, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients [EMPA-REG OUTCOME], and Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 [DECLARE-TIMI 58]) showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering drugs, are associated with a lower rate of adverse renal outcomes, such as need for renal replacement therapy, doubling of serum creatinine, and loss of glomerular filtration rate (GFR) compared to those in placebo groups. Besides, canagliflozin and empagliflozin also showed a lower risk of progression to macroalbuminuria. The EMPA-REG OUTCOME trial and DECLARE-TIMI 58 trial also indicated that these SGLT2 inhibitors might have beneficial effects on the prevention of acute kidney injury. The United States Food and Drug Administration (FDA) warned of the risk of acute kidney injury for canagliflozin and dapagliflozin. We compared canagliflozin, empagliflozin, and dapagliflozin with respect to chemical structure and pharmacological properties, to explain the observed differences in preventing acute kidney injury, and put forward the hypotheses of the potential mechanisms of different effects of SGLT2 inhibitors on acute kidney injury. Given the raising clinical use of SGLT2 inhibitors, our review should stimulate further basic science and clinical studies in order to definitively understand the role of SGLT2 inhibitors in acute kidney injury. A weakness of the clinical data obtained so far is the fact that the statements concerning acute kidney injury are just based on safety data – mainly creatine measurements. However, given the mode of action of SGLT2 blockers, initiation of a therapy with a SGLT2 blocker will cause an increase of creatine because of its effects on the tubuloglomerular feedback mechanisms/glomerular hemodynamics like RAAS blocking agents do. To really understand the potential effects of SGLT2 inhibitors, we need preclinical and clinical SGLT2 inhibitor studies focusing on all aspects of acute kidney injury – not just changes in GFR biomarkers.

show abstract

Effects of the SGLT‐2 inhibitor dapagliflozin on glomerular and tubular injury markers

Cited by 212 publications

References 22 publications

Effectiveness of dapagliflozin versus comparators on renal endpoints in the real world: A multicentre retrospective study

Effectiveness of dapagliflozin versus comparators on renal endpoints in the real world: A multicentre retrospective study

The renoprotective effects of sodium‐glucose cotransporter 2 inhibitors versus placebo in patients with type 2 diabetes with or without prevalent kidney disease: A systematic review and meta‐analysis

The SGLT2 Inhibitor Empagliflozin Might Be a New Approach for the Prevention of Acute Kidney Injury

Contact Info

Product

Resources

About