Data from the EMPA-KIDNEY study, initiated by Prof. Dr. Christoph Wanner of the University Hospital of Würzburg with the University of Oxford, expand the spectrum for the administration of SGLT2 inhibitors in chronic kidney disease, regardless of diabetes status, albuminuria, or renal function.
The presentation of the results was not a sensation, because the clinical benefit of the two SGLT2 inhibitors dapagliflozin and canagliflozin in the treatment of chronic kidney disease has already been proven in previous studies. SGLT2 inhibitors inhibit the renal sodium-dependent glucose transporter SGLT-2 (sodium dependent glucose co-transporter 2) and cause increased sugar to be excreted in the urine. This lowers blood sugar levels and may cause a slight decrease in weight and blood pressure. At the same time, the kidneys and circulation are relieved. However, the efficiency of the active ingredient empagliflozin caused a surprise, even for Prof. Dr. Christoph Wanner. The head of nephrology at Würzburg University Hospital was one of the first to publish the potential of SGLT2 inhibitors in the treatment of diabetes, cardiovascular and renal diseases back in 2015 in the EMPA-REG OUTCOME study and came up with the idea for the EMPA-KIDNEY study, the results of which were published in the New England Journal of Medicine alongside ASN’s Kidney Week.
28 percent risk reduction compared to placebo
The study team, led by the University of Oxford in cooperation with the University Medical Center Würzburg, had assumed a risk reduction of 18 percent at the beginning of the studies. The risk included a combination of the primary endpoints of death from heart disease and kidney failure, i.e., the need for dialysis or a kidney transplant, or a drop in kidney function, known as the glomerular filtration rate (GFR), of 40 percent or more. “However, the fact that the administration of empagliflozin achieves a 28 percent risk reduction compared with placebo, and does so in a broad population of patients with chronic kidney disease, is sensational,” commented Christoph Wanner. “We observed the beneficial effects on cardioprotection and renal protection independent of diabetes status or urinary albumin levels.” Empagliflozin also showed a significant result with regard to hospitalization rates. The number of hospitalizations decreased by 14 percent, regardless of the reason for hospitalization. “I was also pleasantly surprised that empagliflozin was still effective even at a glomerular filtration rate (GFR) of 20 milliliters per minute.”
Empagliflozin suitable for different disease profiles
This means that empagfliflozin can be used in chronic kidney disease without diabetes and without albuminuria, or in concomitant heart failure and even in low renal function. This will make prescribing practices much easier for office-based physicians, Wanner said. According to Wanner, however, it is important to diagnose and thus assess the risk of heart and kidney disease, ideally according to the ABCDE scheme: A stands for albuminuria, an increased albumin excretion in the urine indicates kidney damage very early on, long before the effects of kidney weakness are even noticeable. In a healthy person, the concentration of albumin in urine is less than 30 milligrams. B stands for blood pressure, C for cholesterol, D for diabetes, and E for eGFR status. The e stands for estimated, English for appreciated. Glomerular filtration rate is estimated from serum creatinine, age, sex, and skin color. The normal value of primary urine filtered from the blood is 90 to 130 milliliters per minute.
Meta-analysis confirms results of EMPA-KIDNEY study
The results of the EMPA-KIDNEY study were also included and confirmed in a meta-analysis of a total of 13 SGLT2 studies involving a total of 90,309 subjects with diabetes and 15,605 without diabetes. In the analysis, which has now appeared in the prestigious journal The Lancet , various clinical trial leaders, known as principal investigators, specifically examined the impact of diabetes in terms of the effect of SGLT2 inhibitors on kidney levels and cardiovascular disease. Christoph Wanner, who was active in both the writing committee and the so-called SMART-c consortium of the meta-analysis, summarizes, “The data support the use of SGLT2 inhibitors to reduce the risk for progression of kidney disease and acute kidney injury – regardless of diabetes risk.”
Original publication:
Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. The Lancet, VOLUME 400, ISSUE 10365, P1788-1801, NOVEMBER 19; DOI: https://doi.org/10.1016/S0140-6736(22)02074-8
