Looking after the kidneys and heart in type 2 diabetes: the latest
Chronic kidney disease (CKD) and heart failure in type 2 diabetes were under discussion at the recent Primary Care Diabetes Europe conference. Screening and implementing the latest research need to be prioritised in primary care to improve the prognosis for those living with cardiorenal complications. Dr Susan Aldridge reports.
Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function that are present for three months or more and, in diabetes, is characterised by a urine albumin-creatinine ratio (UACR) of ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) of ≤ 60 ml/min/1.73 m2. Professor Per-Henrik Groop from the Department of Nephrology at Helsinki University Hospital said: “Kidney disease is so important. It’s so common and the consequences are grim. Convey this to all your friends and colleagues because GPs are the ones that should take care of this. If a patient has to see me, it’s too late, for I’m a nephrologist – and nephrologists are interested in dialysis and transplantation.”
Prevalence, consequences and management of CKD
In a study in which 27,000 people with type 2 diabetes worldwide were screened at random, at least half of them had CKD. “So it’s extremely important to screen for the presence of CKD,” said ProfessorGroop. “The majority of people you see in the clinic are microalbuminuric and these can be handled very nicely by GPs, but stages 3, 4 and 5 of CKD will have to involve the nephrologist.”
Screening rates around the world vary and are less than optimal everywhere. And the consequences of not detecting CKD early are grim, according to Professor Groop. These include increased risk of premature death, end-stage kidney disease (ESKD), cardiovascular events and hospitalisation for heart failure. For instance, years of life lost for diabetes alone, diabetes plus cardiovascular disease, and diabetes, cardiovascular disease and CKD are six, 12 and 16 years, respectively.
Professor Groop reiterated the ‘Five-Finger Rule’ for managing CKD. The five components are: optimise blood glucose, use an ACE inhibitor or angiotensin receptor blocker (ARB), control blood pressure, manage lipids and stop smoking. Research shows that achieving these multiple treatment targets is associated with a lower risk of death and end-stage kidney disease (ESKD) than achieving three or fewer. “This standard of care does work, but one of the problems is that we don’t always provide the optimal standard of care,” he said. So, for example, one study shows that 42% of people in the USA with CKD do not receive the standard of care – many still do not receive ACE inhibitors or ARBs, despite these drugs being introduced in the 1980s, and only a minority are receiving more recent therapies, such as SGLT-2 inhibitors.
Recent clinical trials have shown the value of SGLT-2 inhibitors in CKD. For example, the EMPA-REG cardiovascular outcomes trial showed a 39% reduction in composite kidney outcomes and a slowing of the natural decline in eGFR with empagliflozin. There have also been dedicated kidney trials, such as CREDENCE, which involved patients with albuminuria and had a primary composite end point of ESKD, doubling of serum creatinine, kidney or cardiovascular death. The findings of a 30% reduction in this endpoint were “absolutely wonderful,” according to Professor Groop.
Meanwhile, DAPA-CKD involved patients who did not have type 2 diabetes. Then there was EMPA-KIDNEY, with 6609 participants of whom 54% did not have diabetes, 27% had cardiovascular disease and 35% had an eGFR of less than 30. In this trial, empagliflozin led to a 28% reduction in the primary endpoint of kidney-disease progression or cardiovascular death. With these kind of results, Professor Groop noted that dialysis could be postponed by as much as 10 years with an SGLT-2 inhibitor.
Then there is finerenone, a non-steroidal mineralocorticoid receptor antagonist, which can offer extra protection to the kidney. FIDELITY is a large, pooled, pre-specified data analysis of the FIDELIO-DKD and FIGARO-DKD trials on finerenone involving 13,171 participants, which includes patients with microalbuminuria and those with relatively preserved kidney function. “These are like the majority of people you have in your clinic,” noted Professor Groop. “This is why I say primary care physicians are the ones that should pick up these patients and start to treat them.” FIDELITY showed that finerenone, compared with placebo, reduced cardiovascular and renal outcomes in patients with type 2 diabetes and all stages of kidney disease.
The final message on CKD
It is imperative to screen for the presence of CKD. The SGLT-2 inhibitors and finerenone are effective tools for improving the prognosis of patients with type 2 diabetes and CKD on top of the standard of care because they reduce the risk of adverse cardiac and kidney outcomes. And the GLP-1 receptor agonists reduce albuminuria, while providing cardioprotection. “My humble wish to all of you is – screen, screen, screen, implement, implement, implement,” he concluded. “As Anton Chekhov said, ‘knowledge is of no value unless you put it into practice’.”
Diabetes and the heart
Heart failure has reached pandemic proportions and is now affecting 64 million people around the world. This number is likely to increase as the population ages and rates of type 2 diabetes increase. Heart failure is a leading complication of type 2 diabetes, where it is more common than either myocardial infarction or stroke.
Francesco Cosentino, Professor of Cardiology at the Karolinska Institute, spoke about the concept of the cardiovascular continuum, a chain of events that starts with diabetes and other risk factors such as hypertension and obesity, and progresses ultimately to ESKD, heart failure and cardiovascular death. “This concept is clinically very relevant because interruption anywhere can provide cardiorenal protection,” he said. “A major paradigm shift has taken place in the management of cardiovascular risk in type 2 diabetes because of the increase in the evidence base for new treatments.”
For example, following findings on SGLT-2 inhibitors from cardiovascular outcome trials, these are now recommended to patients with cardiovascular risk and type 2 diabetes. “Looking at the hospitalisation for heart failure outcomes in the cardiovascular outcome trials, the intervention and placebo curves diverge very early on,” he noted. “These are stunning results.” A meta-analysis also came up with very consistent findings of a reduction of around 32% in time to hospitalisation for heart failure (HHF) with SGLT-2 inhibitors.
The results of recent and upcoming heart failure trials are likely to move the treatment landscape on even further, added Professor Cosentino. These include DAPA-HF, which shows a relative risk reduction of 26% in cardiovascular death and HHF with dapagliflozin in nearly 5000 patients with heart failure with reduced ejection fraction (HFrEF), an effect independent of diabetes status – and there were similar findings in the EMPEROR-Reduced trial. Then there is the SOLOIST-WHF trial, which has shown that sotagliflozin reduces cardiovascular death and HHF compared with placebo in people with type 2 diabetes and worsening heart failure.
Heart failure with preserved ejection fraction
Until recently, there was little clinical trial evidence for the management of heart failure with preserved ejection fraction (HFpEF), so this was basically diuretics and management of comorbidities. Then the EMPEROR-Preserved trial showed a 21% reduction in the composite endpoint of cardiovascular death and HHF with empagliflozin and there were comparable results for dapagliflozin in the DELIVER trial. “So we can now say ‘one size fits all’ across the spectrum of left ventricular ejection fraction,” said Professor Cosentino.
Analysis of the data across EMPEROR, DELIVER, DAPA-HF and SOLOIST-WHF, covering 22,000 patients, shows combined cardiovascular death/HHF down by 23%. “The data points to a consistent signal of efficacy with SGLT-2 inhibitors,” said Professor Cosentino. “So basically we have been witnessing an evolving role of SGLT-2 inhibitors in cardiorenal protection.”
The results support European Society of Cardiology guidelines to prioritise the use of SGLT-2 inhibitors, independent of blood-glucose control considerations, in patients with or at high risk of cardiovascular and renal complications. “There has been a shift in trials to a cardiorenal focus and adequate management of this type of patient is only possible by building bridges aimed at improving collaboration between cardiology, diabetology, primary care and patients,” Professor Cosentino concluded.
To hear more from Professor Groop, listen to ‘The Briefing Room’ in which five leading experts discuss cardiorenal metabolic challenges in type 2 diabetes.
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.