Table 4.
Studies included in this narrative review.
| A: Original research articles | ||
|---|---|---|
| Author (Ref) | Publication year Study design | Main findings |
| Cherney et al. (15) | 2020 RCT Dpagliflozin |
No reduction in proteinuria. Reversible decline of eGFR. |
| Heerspink et al. (16) | 2016 RCT Dapagliflozin |
Reduction in albuminuria independent of changes in HbA1c, systolic blood pressure, bodyweight and eGFR. |
| Nojima et al. (17) | 2020 RCT Tofogliflozin | Lowered heart rate, improved insulin resistance. |
| Cherney et al. (18) | 2014 Dapagliflozin |
Attenuation of renal hyperfiltration. |
| Van Bommel et al. (19) | 2020 RCT Dapagliflozin |
Reduction of GFR in patients with DM. |
| Li et al. (20) | 2020 Canagliflozin |
Reduced urinary pH indicate blockade of sodium-proton-exchanger 3 |
| Rajasekeran et al. (21) | 2018 Dapagliflozin | Decreased expression of SGLT2 mRNA in patients with FSGS |
| Antlanger et al. (22) | 2022 RCT Empagliflozin |
Empagliflozin on top of an Angiotensin-Converting-Enzyme-Inhibitor (ACEi) induced activation of the vasodilating and anti-inflammatory alternative pathways in diabetic patients. |
| Yoshimoto et al. (23) | 2017 Case study | Limited effect of SGLT2i to activate RAAS in diabetic patients. |
| Heise et al. (24) | 2016 RCT Empagliflozin |
No changes in plasma renin or serum aldosterone. |
| Heerspink et al. (25) | 2013 RCT Dapagliflozin |
Increase of hematocrit and hemoglobin. |
| Laursen et al. (26) | 2021 RCT Dapagliflozin |
Reduciton of renal resistance. |
| Liu et al. (27) | 2021 RCT Ertugliflozin | Reduction of kidney injury molecule 1. |
| Dekkers et al. (28) | 2018 RCT Dapagliflozin |
Reducito of kidney injury molecule 1. |
| Wang et al. (29) | 2017 Case control | Increased expression of SGLT2 mRNA and protein in biopsies from patients with type 2 DM and CKD. |
| Rahmoune et al. (30) | 2005 Case control | Increased expression of SGLT2 mRNA and protein, in renal tubular cells in urine samples from diabetic patients. |
| Solini et al. (31) | 2017 Case control | Increased expression of SGLT2 mRNA and protein in nondiabetic patients. |
| Sridhar et al. (32) | 2019 Cross control | Reduced renal SGLT2 mRNA expression in diabetic patients. |
| B: Reviews including diabetic patients | ||
| Author (Ref) | Publication year | Main findings |
|---|---|---|
| Vallon et al. ( 14 ) | 2021 | Upregulation of SGLT2 in diabetic CKD. Upregulation of Sodium-Hydrogen-Exchanger type 3 (NHE3). |
| Zhao et al. (33) | 2018 | Reduction of plasma uric acid. |
| Gillard et al. (34) | 2020 | Hyperglycemia increases urinary inflammatory markers and may lead to RAAS activation. |
| Rocha et al. (35) | 2018 | Reduction of blood pressure reduction without compensatory increase in heart rate. |
| Liu et al. (36) | 2022 | Restoration of TGF. |
| Kanduri et al. (37) | 2020 | Restoration of TGF. Downregulation of NHE3. |
| Packer ( 38 ) | 2021 | Upregulating of oxygen delivery and downregulation of oxygen demand. |
| Gnudi et al. (39) | 2016 | Restoration of TGF. Increased vasodilating and anti-inflammatory alternative pathways. |
| Packer ( 40 ) | 2020 | Stimulation of transcription factors resulting in ketogenesis, erythropoiesis and autophagia. |
| Brown et al. (41) | 2019 | Reduced blood glucose, reduced secretion of insulin and increased secretion of glucagon. |
| Ito et al. (42) | 2018 | Reduced oxygen consumption due to ketogenesis. |
| Hesp et al. (43) | 2020 | Enhanced energy consumption through upregulation of SGLT2. |
| Packer ( 44 ) | 2020 | Reduction of blood and urine biomarkers of autophagic proteins. |
| Yaribeygi et al. (45) | 2018 | Reduction of the inflammatory response. |
| Packer ( 46 ) | 2020 | Downregulation of SGLT2 and NHE3. Activation of transcription factors promoting autophagia. |
| Hattori ( 47 ) | 2021 | Restoration of TGF. Increased keton bodies. Inhibition of histone deacetylases and inflammasomes. |
| Gilbert ( 48 ) | 2014 | Reduction of plasma uric acid. |
| Cherney et al. (49) | 2014 | Better blood pressure control. |
| Heerspink et al. (50) | 2016 | Elevated RAAS metabolites in urine and blood from the vasoconstrictive and pro-inflammatory classical and vasodilating and anti-inflammatory alternative pathways. |
| Satirapoj (51) | 2017 | Reduction of inflammatory, oxidative, and fibrotic markers. |
| Van Bommel et al. (52) | 2017 | Multiple mechanisms underlying the nephroprotective effects. |
| Thomas et al. (53) | 2018 | Changes in solute, water and energy balance in the proximal tubule following SGLT2 inhibition. |
| Tsimihodimos et al. (54) | 2018 | Improvements in several pathways and metabolic variables. |
| Alicic et al. (55) | 2019 | Reduced glomerular hyperfiltration and hypertension. |
| Kuriyama (56) | 2019 | Attenuation of renal fluid congestion. |
| Sarafidis et al. (57) | 2019 | Amelioration of glomerular hyperfiltration. |
| Thomson et al. (58) | 2019 | Reduction of SGLT2 veractivity. |
| Hou et al. (59) | 2020 | Restoration of TGF. Arteriole constriction by adenosine and efferent arteriole dilatation by prostaglandins. |
| Kashihara et al. (60) | 2020 | Multiple mechanisms. |
| Packer ( 61 ) | 2020 | Upregulation of “starvation” transcription factors with increased ketogenesis. |
| Schnell et al. (62) | 2020 | Restoration of TGF. |
| Zelniker et al. (63) | 2020 | Multiple hemodynamic and metabolic changes. |
| Lee et al. (64) | 2021 | Multiple mechanisms including hemodynamic and non-hemodynamic mechanisms. |
| Onyali et al. (65) | 2021 | Benefits are independent of glycemic control. |
| Puglisi et al. (66) | 2021 | Increased angiotensin1-7. |
| Leoncini et al. (67) | 2021 | Multiple mechanisms. |
| Din et al. (68) | 2021 | Multiple mechanisms. |
| Provenzano et al. (69) | 2021 | Restoration of TGF. |
| Srinivas et al. (70) | 2021 | Reduction of interstitial fluid instead |
| Castañeda et al. (71) | 2021 | Attenuation of hyperfiltration. |
| Takata et al. (72) | 2021 | Pleiotropic effects. |
| C: Reviews including diabetic and nondiabetic patients | ||
| Author (Ref) | Publication year | Main findings |
|---|---|---|
| Pollock et al. (73) | 2021 | Multiple mechanisms. |
| Bailey ( 74 ) | 2019 | Reduction of plasma uric acid. Glucose and uric acid compete with the same transporter. |
| Yip et al. (75) | 2022 | Reduction of serum uric acid. |
| Dekkers et al. (76) | 2018 | Amelioration of glomerular hyperfiltration. |
| Nayak et al. (77) | 2021 | Inhibition of NHE3 plays an essential role in TGF activation in nondiabetics. Increased plasma and urinary ketones in nondiabetic patients. |
| Dekkers et al. (78) | 2020 | Restoration of TGF in type 1 DM. |
| Rajasekeran et al. (79) | 2017 | Natriuretic effects extend to nondiabetic CKD. |
| Ekanayake et al. (80) | 2022 | Lipolysis and ketogenesis. Ketones improve renal tissue oxygenation and show anti-inflammatory and antifibrotic properties. |
| Herrington et al. (81) | 2021 | Reduction of intraglomerular hypertension in CKD. |
| Oguz et al. (82) | 2021 | Amelioration of single nephron GFR. |