The use of SGLT2 Inhibitors in Peritoneal Dialysis Patients: a Shade of Light on Dapagliflozin

Al-Hwiesh, Abdullah K; Al-Wa, Ibrahiem Sarah; Abdul-Rahman, Saeed; Nasreldin, Mohammed Ahmad; Mohammed, Abdelgalil Moaz; Al-Oudah, Suzan; Al-Thwainy, Reem; AlAwal, Ayat; Alsenpisi, Zahra; Abdulrahman, Abdulla

doi:10.26502/anu.2644-2833047

Cited by 12 publications

(10 citation statements)

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“…If SGLT2 plays a role in glucose absorption from the PD solution, SGLT2 inhibitors might enhance the ultrafiltration volume by preserving the glucose gradient across the peritoneum membrane. Although animal studies have yielded inconsistent results [ 7 , 9 , 10 ], recent human case series reported the positive effects of SGLT2 inhibitors on the ultrafiltration volume [ 19 , 20 ]. Therefore, we planned to conduct a clinical trial evaluating the impact of SGLT2 inhibitors on the ultrafiltration volume.…”

Section: Discussionmentioning

confidence: 99%

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)

Doi,

Shinzawa,

Arisato

et al. 2024

Clin Exp Nephrol

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Background Volume overload is common and associated with high mortality in patients on peritoneal dialysis (PD). Traditional strategies including diuretics, water/salt restriction, and icodextrin-based solutions cannot always fully correct this condition, necessitating novel alternative strategies. Recent studies confirmed the expression of sodium–glucose cotransporter 2 (SGLT2) in the human peritoneum. Experimental data suggest that SGLT2 inhibitors decrease glucose absorption from the PD solution, thereby increasing the ultrafiltration volume. This trial aims to assess whether SGLT2 inhibitors increase the ultrafiltration volume in patients on PD. Methods The EMPOWERED trial (trial registration: jRCTs051230081) is a multicenter, randomized, double-blind, placebo-controlled, crossover trial. Patients with clinically diagnosed chronic heart failure are eligible regardless of the presence of diabetes if they use at least 3 L/day glucose-based PD solutions. Participants will be randomly assigned (1:1) to receive empagliflozin 10 mg once daily and then placebo or vice versa. Each treatment period will last 8 weeks with a 4-week washout period. This study will recruit at least 36 randomized participants. The primary endpoint is the change in the daily ultrafiltration volume from baseline to week 8 in each intervention period. The key secondary endpoints include changes in the biomarkers of drained PD solutions, renal residual function, and anemia-related parameters. Conclusions This trial aims to assess the benefit of SGLT2 inhibitors in fluid management with a novel mechanism of action in patients on PD. It will also provide insights into the effects of SGLT2 inhibitors on solute transport across the peritoneal membrane and residual renal function.

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Section: Discussionmentioning

confidence: 99%

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)

Doi,

Shinzawa,

Arisato

et al. 2024

Clin Exp Nephrol

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“…Recent preliminary studies have examined the clinical application of dapagliflozin in PD patients. Fifty type-2 diabetic patients on automated PD received oral dapagliflozin 10 mg daily for 6 months [ 104 ]. Treatment was associated with a significant improvement in urine volume, peritoneal UF, and mean systolic blood pressure.…”

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

“…Peritoneal transport status did not change. Significant improvements in fasting blood sugar and glycated hemoglobin with reduced insulin requirement were also observed [ 104 ]. Other authors evaluated the effects of oral dapagliflozin 5 mg daily in four incident PD patients (3 of them diabetic) with fluid overload [ 105 ].…”

Section: Combating Pd-solution Associated Toxicitymentioning

confidence: 99%

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

Bonomini,

Masola,

Monaco

et al. 2024

IJMS

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Peritoneal dialysis (PD) is a home-based efficacious modality for the replacement of renal function in end-stage kidney failure patients, but it is still under-prescribed. A major limitation is the durability of the dialytic technique. Continuous exposure of the peritoneum to bioincompatible conventional glucose-based solutions is thought to be the main cause of the long-term morpho-functional peritoneal changes that eventually result in ultrafiltration failure. Poor PD solution biocompatibility is primarily related to the high glucose content, which is not only detrimental to the peritoneal membrane but has many potential metabolic side effects. To improve the clinical outcome and prolong the survival of the treatment, PD-related bioincompatibility urgently needs to be overcome. However, combining dialytic and osmotic efficacy with a satisfactory biocompatible profile is proving to be quite difficult. New approaches targeting the composition of the PD solution include the replacement of glucose with other osmotic agents, and the addition of cytoprotective or osmo-metabolic compounds. Other strategies include the infusion of mesenchymal cells or the administration of orally active agents. In the present article, we review the current evidence on efforts to improve the biocompatible and functional performance of PD, focusing on studies performed in vivo (animal models of PD, human subjects on PD).

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“…Over the last decade, SGLT2is have been shown to reduce major kidney events (MAKEs) by 40% in people with or without diabetes ( Kanda and Nangaku, 2019 ; Suzuki et al, 2022 ). Whether this benefit can be extended to other more specific kidney conditions, such as kidney transplantation ( Pham and Pham, 2022 ), glomerular diseases such as IgA nephropathy, focal and segmental glomerulopathy ( Morales and Galindo, 2022 ), acute cardiorenal syndrome ( Schulze et al, 2022 ; Voors et al, 2022 ), or unusual pathologies such as Alport syndrome ( Ge et al, 2023 ), and even to people on dialysis ( Alhwiesh et al, 2022 ; De La Flor et al, 2023 ), is currently being explored. In specific scenarios, such as hospitalized critically ill patients or those with acute kidney injury (AKI), the nephrology community has been more cautious because SGLT2is are considered “sick day” drugs ( Watson et al, 2023 ), which means that during critical illness or AKI, SGLT2is should not be administered or need to be suspended due to the reasonable risk of non-hyperglycemic ketoacidosis ( Palmer and Clegg, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

SGLT2i treatment during AKI and its association with major adverse kidney events

Alcantar-Vallin,

Zaragoza,

Díaz-Villavicencio

et al. 2024

Front. Pharmacol.

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BackgroundThe association between the administration of sodium–glucose cotransporter 2 inhibitors (SGLT2is) during acute kidney injury (AKI) and the incidence of major adverse kidney events (MAKEs) is not known.MethodsThis retrospective cohort study included patients with AKI and compared the outcomes for those who were treated with SGLT2is during hospitalization and those without SGLT2i treatment. The associations of SGLT2i use with MAKEs at 10 and 30–90 days, each individual MAKE component, and the pre-specified patient subgroups were analyzed.ResultsFrom 2021 to 2023, 374 patients were included in the study—316 without SGLT2i use and 58 with SGLT2i use. Patients who were treated with SGLT2is were older; had a greater prevalence of diabetes, hypertension, chronic heart failure, and chronic kidney disease; required hemodialysis less often; and presented stage 3 AKI less frequently than those who were not treated with SGLT2is. Logistic regression analysis with nearest-neighbor matching revealed that SGLT2i use was not associated with the risk of MAKE10 (OR 1.08 [0.45–2.56]) or with MAKE30–90 (OR 0.76 [0.42–1.36]). For death, the stepwise approach demonstrated that SGLT2i use was associated with a reduced risk (OR 0.08; 0.01–0.64), and no effect was found for kidney replacement therapy (KRT). The subgroups of patients who experienced a reduction in the risk of MAKEs in patients with AKI treated with SGLT2is were those older than 61 years, those with an eGFR >81, and those without a history of hypertension or DM (p ≤ 0.05 for all).ConclusionThe use of SGLT2is during AKI had no effect on short- or medium-term MAKEs, but some subgroups of patients may have experienced benefits from SGLT2i treatment.

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The use of SGLT2 Inhibitors in Peritoneal Dialysis Patients: a Shade of Light on Dapagliflozin

Cited by 12 publications

References 0 publications

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)

Effects of sodium-glucose co-transporter 2 inhibitors on ultrafiltration in patients with peritoneal dialysis: a protocol for a randomized, double-blind, placebo-controlled, crossover trial (EMPOWERED)

Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge

SGLT2i treatment during AKI and its association with major adverse kidney events

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