Chronic kidney disease (CKD) is a major public health problem because of its rising prevalence internationally (Yang et al, 2020). Much of this increase in prevalence, especially in high income countries, is associated with CKD that develops as a result of diabetes mellitus (DM) and/or hypertension (HT), both of which are linked to sedentary lifestyles and sub-optimal diets (Winocour, 2018; Pugh et al, 2019).
Not only are DM and HT risk factors for the development of CKD but they also contribute to the development of cardiovascular disease (CVD), including coronary artery disease (CAD), both in people living with CKD and those without (Naito and Miyauchi, 2017; National Institute for Health and Care Excellence (NICE), 2022a). As well as the excess risk of CAD from these well-known risk factors, people living with CKD experience a heightened risk of CAD arising from uraemia (including inflammation), an altered calcium-phosphate metabolism and oxidative stress (Sarnak et al, 2019). This risk dramatically increases as the individual’s kidney function declines (Sarnak et al, 2019), putting people living with CKD and diabetes in an especially high-risk group for all forms of CVD, including CAD.
Managing the CAD risk in people living with CKD, and associated morbidities, eg diabetes, is complex, not least of all because of the comorbidities themselves and the increased risks these pose, but also because of issues arising from the side effects of the treatments and polypharmacy (Kimura et al, 2021).
There is increasing interest in what is termed cardio-renal-metabolic (CaReMe) management for people affected by this triumvirate of diseases that share many predisposing factors, as well as common management pathways (Arnold et al, 2018). This article seeks to identify some of the strategies nurses in general practice should be aware of when working with people living with CKD and DM, together with CAD, as well as considering the lifestyle advice and support they might share with these individuals in the primary care setting.
General practice nurses should note that while most people with DM and CKD will have diabetic kidney disease (DKD) – CKD caused by the diabetes – some will have CKD from other causes. On the whole, the treatment of these individuals does not differ, except that some of the other causes of CKD may require additional or alternative management strategies, eg immunosuppression for autoimmune diseases affecting the kidneys, such as lupus nephritis and Goodpasture’s syndrome.
Medical management of blood pressure
Whatever the cause of an individual’s CKD, there is a universal emphasis on HT control (Pugh et al, 2019); HT being both a cause and symptom of CKD. NICE (2021) guidance for blood pressure control is for:
- A systolic blood pressure of less than 140 mmHg in patients with an albumin to creatine ratio (ACR) under 70mg/mmol
- A systolic blood pressure of less than 130 mmHg in patients with an ACR over 70mg/mmol.
Blood pressure control is generally achieved using angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) at the highest dose that is tolerable to the patient and always as the first-line antihypertensives in people living with type 2 diabetes (NICE, 2019).
ACEI and ARBs should be used with caution if the patient has an elevated serum potassium. The general practice nurse should ensure that the estimated glomerular filtration rate (eGFR) of any patient starting an ACEI or ARB is monitored and the drug stopped immediately if they suffer a decrease in their eGFR of 25% or more which is unexplained by another cause.
All the guidelines caution against the prescription of more than one ACEI or ARB in people with CKD as there is no additional benefit to be had, but there is an increased risk of causing acute kidney injury (Tomson et al, 2021).
There are no further guidelines for the use of pharmaceutical agents in the management of HT associated with CKD over and above those recommended by NICE (2019) in their Hypertension in adults: diagnosis and management guidelines.
General practice nurses should be alert to the fact that most people with CKD, perhaps especially those with CKD and DM, will require more than one antihypertensive medication in order to attain good blood pressure control.
Diuretic therapy in patients with CKD can reduce volume overload, and hence blood volume, ventricular stroke volume, blood pressure and, therefore, CVD risk. In patients with CKD and no proteinuria, a thiazide, or thiazide-like diuretic, can provide first-line treatment with drugs like furosemide, often in high doses in people with advanced CKD, having a role to play in managing hypertension associated with fluid overload (Pugh et al, 2019). General practice nurses caring for people taking diuretics for this indication should be alert to the possibility of fluid depletion in some patients treated with high-dose diuretics and will need to counsel patients about the timing of the medication and its impact on their toilet habits.
Calcium channel blockers (CCBs), eg amlodipine, while having no beneficial effects in patients with proteinuria on their own, can serve to aid HT control when used with an ACEI or ARB without impacting their effect on proteinuria (Pugh et al, 2019). General practice nurses should note that CCBs can worsen peripheral oedema, especially in people with CKD.
Beta-blockers, eg bisoprolol, lower blood pressure as well as having well documented cardioprotective effects (Jankowski et al, 2021), including improved kidney and patient survival. While beta-blockers do not offer the renoprotective effects of ACEI and ARBs, they can safely be used together, especially where the patient has known CVD (Pugh et al, 2019).
Similarly alpha-blockers, eg doxazosin, are widely used in combination with other antihypertensives as they do not need adjustment as the eGFR declines and they have some positive impact on glycaemic control (Pugh et al, 2019).
Medical management of glycaemic control
While not being able to divorce good glycaemic control from other aspects of the management of CKD progression entirely, there does remain a strong requirement for good glucose control, ie HbA1c <53 mmol/mol, in all patients with CKD and DM (Kidney Disease: Improving Global Outcomes: Diabetes Working Group (KDIGO:DWG), 2020). As a rule, except in a few cases, good glucose control is known to help prevent the progression of DKD (Leehey and Moinuddin, 2022).
DKD is the result of hyperglycaemia, which causes glomerular capillary hypertension and hyperfiltration. This further damages the glomerular capillaries, perpetuating the damage. This is paired with thickening of the glomerular basement membrane and changes to podocytes and the mesangial matrix. This damage leads to albuminuria and eventually proteinuria and a reduction in the individual’s glomerular filtration rate (GFR) (Lim, 2014).
In their Cochrane review into lowering blood glucose in people living with diabetes and CKD, Lo et al (2018) identified some evidence for the use of sodium-glucose co-transporter-2 (SGLT2) inhibitors, eg canagliflozin, dapagliflozin and empagliflozin, as well as for glucagonlike peptide-1 (GLP-1) receptor agonists, eg dulaglutide, liraglutide and semaglutide. However, Lo et al (2018) found no evidence to support the use of other glucoselowering pharmaceuticals, eg dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, saxagliptin and vildagliptin, in people living with DKD.
There remains some controversy around target HbA1c levels for patients with DKD, especially in those whose disease is progressing (Hahr and Mokitch, 2021). Therefore, it is advisable that general practice nurses discuss their management with nephrology colleagues. It is especially important that HbA1c targets are individualised so hypoglycaemic episodes are avoided, as these are associated with increased levels of mortality in patients with CKD and DM (Jankowski et al, 2021).
Medical management of CAD risk
As previously discussed, CVD, including CAD, is commonly experienced by people with CKD (Leehey and Moinuddin, 2022). In fact, the risk of CAD rises in a linear relationship with the decline of eGFR (Warrens et al, 2022), so that people with the most advanced CKD also have the highest risk of CAD.
As CAD is a known risk in CKD, NICE (2016) recommended the statin atorvastatin for both primary and secondary prevention of CVD for people living with CKD (NICE, 2016). Atorvastatin doses should be adjusted to achieve in excess of a 40% reduction in non-HDL cholesterol in patients whose eGFR is 30 ml/min/1.73 m2, or more, ie CKD stages 1–3b. Practice nurses should seek nephrologist advice for dosing in patients with an eGFR of less than 30 ml/min/1.73 m2, ie CKD stages 4 or 5.
‘Practice nurses are well placed to work with people affected by CKD, DM and CAD in both optimising their medical management and providing the sort of advice and support that this group of patients also need.‘
Notably, studies suggest that the benefits of lipid lowering as a primary preventor of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or coronary revascularisation are lost once a patient requires renal replacement therapy such as haemodialysis (Jankowski et al, 2021).
There may be some benefit to people with CKD from using a statin alongside ezetimibe, another cholesterol lowering agent, although further evidence is needed to prove this (Warrens et al, 2022).
The CaReMe partnership (British Cardiovascular Society, 2020) identify a cardioprotective role for both SGLT2 inhibitors and GLP-1 receptor agonists in people living with DM and CKD. SGLT2 inhibitors are said to have benefit for patients with concomitant left ventricular dysfunction, while GLP-1 receptor agonists have additional benefits in patients with DKD with CVD, as well as those classified as obese.
In patients with CAD and CKD, there is some evidence that antiplatelet therapy, widely beneficially used in people without CKD, may increase the risk of bleeding so that they are not beneficial (Palmer et al, 2012), although NICE (2021) advise their use with the caveat that prescribers should be aware of the increased bleeding risk. This is a decision to be taken with nephrology colleagues with patients on these regimes, requiring counselling on the potential effects and monitoring in primary care.
Similarly, surgical interventions for revascularisation in patients with high CAD risk carries dangers, such as the potential for acute kidney injury and creating issues for subsequent dialysis access creation, with no apparent reduction in mortality risk (Sarnak et al, 2019). Some patients may fail to understand this and may require education and support regarding the risk/benefit calculation.
Of great interest is the registry observation that many patients with CKD who experience acute myocardial infarction do not receive the evidence-based therapies offered to most of the rest of the population, ie statins, beta-blockers and antiplatelet therapy (Washam et al, 2015). General practice nurses are well placed to address this health inequality in their general practice.
Mineralocorticoid receptor antagonists
As things stand currently, the mainstay of management of CKD in people with DM is good glycaemic control, good management of hypertension and lifestyle changes (KDIGO:DWG, 2020).
As well as the more standard medications used in the management of hypertension, cardiovascular disease and diabetes, there is increasing interest in mineralocorticoid receptor antagonists both steroidal, eg eplerenone, and non-steroidal, eg finerenone. Steroidal mineralocorticoid receptor antagonists have been shown in a meta-analysis of 19 trials (Currie et al, 2016) to reduce both blood pressure and proteinuria in patients already treated with a reninangiotensin system inhibitor, eg an ACEI or ARB.
Finerenone, a non-steroidal mineralocorticoid receptor antagonist, is said to block the activation of physiological pathways that lead to inflammation and kidney scarring. It is indicated for use in people with type 2 diabetes and moderate to severe CKD, which includes albuminuria. Finerenone is an adjunct to existing therapies and may be preferred in patients with CKD and DM as it provides better end organ damage protection and less in the way of electrolyte disturbance than steroidal mineralocorticoid receptor antagonists (Kolkhof et al, 2014).
Lifestyle changes
Practitioners are aware that diseases of chronicity are associated both with ageing as well as some of the lifestyle choices people make. This makes lifestyle advice in patients with CKD, DM and CAD important. Such questioning and advice may not only delay the progression of disease but can also prolong life.
In their guidelines for the management of blood glucose, NICE (2022b) identify, alongside medical management, the need for exercise, diet and weight loss advice. There is similar guidance from NICE (2019) when it comes to the management of hypertension, with an additional focus on the moderation of alcohol consumption and smoking cessation. There is also advice about reducing salt intake, as much hypertension in developed countries is salt-dependent, with some evidence that this relationship is increased in patients with diabetes (Uzu, 2017).
Guidelines from the influential KDIGO group (Tomson et al, 2021) on the management of blood pressure in people with CKD, suggests the need for a low sodium diet of less than 2g per day. They also caution against replacing this with potassium-based salt products because of the risks of hyperkalaemia in this population.
Such seemingly simplistic approaches to disease management are anything but, with good evidence underpinning the advice. In their guide to managing cardiovascular risk in patients with type 2 diabetes and atherosclerotic cardiovascular disease, the CaReMe partnership (British Cardiovascular Society, 2020), identify the need not only for lifestyle advice for those affected, but also for emotional and psychological support.
Practice nurses are well placed to work with people affected by CKD, DM and CAD in both optimising their medical management and providing the sort of advice and support that this group of patients also need.
Conclusions
Individually, CKD, CAD and DM are challenging enough to manage; taken together they represent what are globally three of the top ten causes of mortality (World Health Organization, 2020). While there is a lot of overlap in the strategies for management of each of these three diseases, the response to treatment of individual patients will vary as will their needs for lifestyle advice and emotional and psychosocial support, both in terms of adapting to a broad diagnosis of disease as well as any lifestyle changes which are being recommended.
CPD REFLECTIVE PRACTICE:
- How confident are you around management of chronic kidney disease (CKD), type 2 diabetes (DM) and coronary artery disease? How could you ensure you stay up to date?
- What lifestyle advice would you give to patients with these conditions?
- How will this article change your clinical practice?
KEY POINTS:
- Chronic kidney disease (CKD), type 2 diabetes (DM) and coronary artery disease (CAD) frequently affect the same individuals
- There is some overlap in the management of CKD, DM and CAD
- CKD, DM and CAD management requires both medication and lifestyle education
- The management of CKD, DM and CAD can be complicated and may require a multidisciplinary approach
- Practice nurses have an important role to play in educating and supporting people affected by CKD, DM and CAD