Heart failure is the leading cause of heart disease and death in dialysis patients, as well as fatigue, shortness of breath and hospital admissions. Impaired heart muscle function occurs in 40-70% of dialysis patients and is a strong predictor of mortality due to heart disease in dialysis patients. This reduced heart muscle function (HFpEF) is sometimes without symptoms and not detected on an ultrasound of the heart, since heart pump function or ejection fraction (HFrEF) can be normal.
SGLT2 inhibitors
There are currently no good treatment options for heart failure (both HFpEF and HFrEF) in dialysis patients. Possibly, the new SGLT2 inhibitors could change this. SGLT2 inhibitors were developed as a treatment for diabetes and, in large studies, caused a sharp decrease in cardiovascular death and hospital admissions that were due to heart failure. This was not explained by the drop in blood sugars, as SGLT2 inhibitors also worked well in people without diabetes. Moreover, patients with impaired kidney function seemed to benefit equally, and in some studies even more, from SGLT2 inhibitors. This can be explained if the mechanism of action is not (exclusively) via the kidneys, but (also) via the heart. Unfortunately, this has never been investigated in dialysis patients, although they might benefit from treatment with these SGLT2 inhibitors.
Large international study
The team of Dr. Lily Jakulj and Prof. Marc Vervloet will investigate this mechanism of action within a large international study investigating whether the SGLT2 inhibitor dapagliflozin reduces mortality and admissions for heart failure in patients with severe chronic kidney injury, including dialysis patients (Renal Lifecycle Trial). Additional measurements will be made in participants who undergo peritoneal dialysis (PD). It was initially chosen to investigate this mechanism of action in PD patients because of the more stable daily fluid withdrawal (ultrafiltration), compared to ultrafiltration in hemodialysis. It is hypothesized that SGLT2 inhibitors improve myocardial function in PD patients.
The study involves 100 patients treated with PD. They will be treated with dapagliflozin (1 tablet daily) or placebo within the Renal Lifecyle Trial for an extended period of time (about 2 years). At the start of the study and after 6 months, heart muscle function (GLS) will be measured in the hospital by ultrasound of the heart. In addition, an ECG, measurement of fluid status (BCM), a 6-minute walk test (fitness) and questionnaire focusing on specific symptoms appropriate to heart failure will be performed. Blood is also drawn and dialysate (outflow) and, if applicable, urine from the last 24 hours are collected.
At the end of the 6-month treatment period, the difference in GLS in patients treated with dapagliflozin compared with those who received placebo will be assessed. In addition, differences in: blood pressure, weight, fitness, symptoms consistent with heart failure, glucose regulation and excretion, ultrafiltration, and blood and dialysate values that may be associated with the development of heart failure will be looked at. After completion of the Renal Lifecycle Trial, the association between these outcomes and clinical outcomes, such as admissions for heart failure, may also be investigated.
Source: Dutch Kidney Foundation