The primary aim of this study is to determine the safety and mechanisms of SGLT2 inhibition in individuals on peritoneal dialysis (PD) with residual kidney function (RKF).
The importance of RKF on the survival of patients on PD has been demonstrated in several observational studies. Despite this, there are limited pharmacological interventions available to slow the loss of RKF in these patients. There is an unmet need for novel cardiovascular and kidney protective strategies for patients on renal replacement therapies, including PD. SGLT2 inhibitors have been shown to have both cardiovascular and kidney protective effects in individuals with kidney disease, with and without diabetes. These benefits have been attributed to diverse mechanisms and kidney benefits have been largely attributed to reductions in intraglomerular pressure at the single nephron level, reversibly lowering GFR in the short-term with long-term benefits. However, the beneficial effects of SGLT2 inhibitors have never been studied in patients on dialysis. The CANARY study will provide insight into the safety and mechanisms of SGLT2 inhibitors in individuals on dialysis with RKF, with and without type 2 diabetes, over a period of 2 weeks. Demonstrating that protective mechanisms associated with SGLT2 inhibitors are intact in patients on PD with RKF would provide a strong rationale for a larger clinical trial to explore the use of these novel drugs in this unique clinical application. Additionally, our proposed study would provide timely mechanistic data to inform clinical decisions in the context of other large clinical trials such as EMPA-KIDNEY. These findings would help physicians make decisions on leaving patients on SGLT2 inhibitors even beyond end-stage kidney disease.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
PO once daily
Toronto General Hospital
Toronto, Ontario, Canada
RECRUITINGChange in measured GFR
GFR will be determined from the average of creatinine and urea clearance from a 24-hour urine collection.
Time frame: Before and 2 weeks after initiation of empagliflozin.
Rebound in GFR after Cessation of Therapy
A GFR measurement will be performed 2 weeks after cessation of empagliflozin, with the aim of capturing the reversible "rebound" in GFR after cessation of therapy.
Time frame: 2 weeks
Change in ultrafiltration volume
Time frame: 2 weeks
Change in fraction of glucose remaining in the dialysate
Time frame: 2 weeks
Change in dialysate/plasma creatinine
Time frame: 2 weeks
Change in dialysate/plasma urea
Time frame: 2 weeks
Change in sodium dialysate concentration
Time frame: 2 weeks
Change in glycated hemoglobin (HbA1c)
Time frame: 2 weeks
Change in systolic and diastolic blood pressure
Time frame: 2 weeks
Change in body weight
Time frame: 2 weeks
Change in body composition (percent body mass, body fat, and muscle mass)
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Bioimpedence measurements will be taken to study the effects of intervention on body composition.
Time frame: 2 weeks
Change in fractional urine excretion of sodium
Urinary analysis will be performed to quantify the amount of sodium excretion.
Time frame: 2 weeks
Change in fractional urine excretion of glucose
Urinary analysis will be performed to quantify the amount of glucose excretion.
Time frame: 2 weeks
Change in eGFRβ2-microglobulin
Blood sample analysis to assess middle molecule clearance.
Time frame: 2 weeks
Change in degree of albuminuria
Urinary analysis will be performed to determine if there has been any change in the severity of albuminuria
Time frame: 2 weeks
Change in BNP (NT-proB-type Natriuretic Peptide)
Time frame: 2 weeks
Change in markers of neurohumoral activation, erythropoiesis, and inflammation.
Time frame: 2 weeks
The safety of empaglifllozin use in PD patients with RKF with regard to anuria (<100cc/day), volume depletion, diabetic ketoacidosis, genito-urinary infections, PD peritonitis and death will be evaluated.
Time frame: 2 weeks