Cardiovascular complications of renal disease

Aetiology and management of risk factors for cardiovascular disease in patients with chronic kidney disease and the use of beta-blockers, statins, diuretics and anticoagulants in controlling progression of disease.

Chronic kidney disease (CKD) is common (up to 10% of the population) and was only really introduced to primary care in the UK in the last 15 years or so as a significant risk factor for cardiovascular disease (CVD).

The risk of a CVD complication worsens with time of CKD progression, from about 3-5 times the risk at stage G3a, when compared to the general non-affected population, to 20 times for patients on dialysis. In other words, a 25-year-old on dialysis has a higher statistical risk of CVD than an 85-year-old in normal health.

Even after a successful renal transplant in a young patient there remains a high risk, because the renal function will not fully recover, and ongoing medical treatment with immunosuppressants adversely affects the kidneys and metabolism in the long term.

One of the main overall causes of CKD is diabetes, which in itself further significantly increases cardiovascular risks through multiple mechanisms.

The major shift of understanding in the last few years has been that even 'mild' CKD increases CVD risks and should be identified and managed early, before additional features such as proteinuria/albuminuria emerge. These can be regarded as an early complication.

The degree of CKD is determined and classified by the albumin creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR), which should be regularly monitored. Figure 1 depicts the increased risk of adverse outcomes when considering both eGFR and ACR categories.1

Chronic kidney disease

Systemic impact of CKD

There is a close interaction of cause and effect between abnormal blood pressure control and abnormal renal function. A dysfunction of the renin-angiotensin-aldosterone system eventually leads to hypertension (through vasoconstriction, water retention and electrolyte disturbances such as sodium and phosphate), which then negatively affects the kidneys structurally, if not controlled well.

CKD contributes directly to atherosclerosis through calcification of blood vessels by a degree of hyperparathyroidism.

Studies on dialysis patients have demonstrated coronary multivessel narrowing through calcification in more than 50% of patients. There can be signs of this even on a simple ECG, whilst more advanced investigations such as an exercise ECG or angiography could be more complicated because of possibly reduced overall fitness of the patient, and the potential risks of causing harm by the physical strain or the nephrotoxicity of most contrast media presently used.

In advanced CKD the benefits of cardiac interventions, for example with angioplasty and stenting, are limited, with currently high restenosis rates (40% or more after six months).

Patients tend to die from CVD complications rather than CKD itself, typically through sudden death, various forms of potentially fatal arrhythmia, or progressive cardiac failure, rather than classic myocardial infarctions.

Once cardiac abnormalities are detected patients may need to be monitored with echocardiography or cardiac magnetic resonance imaging (MRI); if they are dialysis patients waiting for a transplant, then there appears to be a chance that some of these cardiac features may recover after the operation.

Patients with stage G3-G4 CKD are at an increased relative risk of both ischaemic and haemorrhagic stroke of about 1.4 times, and in dialysis patients the risk increases to about 5-10 times the general population, resulting in an overall stroke risk of 4% per year.

This is mostly due to atrial fibrillation (present in 15-20% of dialysis patients), which therefore requires the same intensity of proactive medical stroke prevention as for any other AF patient, regardless of their age at the time. NICE discusses the benefits and role of apixaban, as long as the patient’s eGFR is above 30ml/min/1.73m2, otherwise they may be prescribed warfarin or even aspirin.1

Management

Early detection

It is important to detect and systematically follow up incidental findings of abnormal renal function, which could be a sign of CKD. The clinical consultation systems used in general practice will provide tools for this, such as calculators and reminders. It is important to inform and involve patients early in this process to increase the chance for understanding and subsequent compliance.

 Important! Systematically follow up incidental findings of abnormal renal function, which could be a sign of CKD

Lifestyle and diabetes-related factors

Management of lifestyle risk factors is essential for all patients with CKD - particularly smoking cessation, weight loss, regular exercise, and a low salt diet. If the patient is diabetic, then this is particularly important, alongside reasonably (but realistically) tight glycaemic control.

Hypertension

Most patients with CKD will require and benefit from an angiotension converting enzyme (ACE) inhibitor, which offers direct renal protective effects, as well as the benefits from blood pressure control. An initially increasing creatinine/decreasing eGFR of up to 25% may be observed, and this is acceptable but needs to be monitored closely, particularly in the beginning of treatment. Deterioration beyond 25% should prompt an assessment by specialist services, for example for renal artery stenosis.

NICE recommends a target blood pressure for most CKD 1-4 patients of less than 140/90 mmHg, but for patients with diabetes or significant proteinuria (ACR greater than 70 mg/mmol) the target is less than 130/80 mmHg (see box).

The sequence and combination of antihypertensive drugs is the same as for the general population, but CKD patients frequently require three or four antihypertensive agents in combination to achieve target blood pressure control whilst minimising side effects or complications of treatment.

Blood pressure targets
Patient group Target blood pressure
All CKD G1-G4 (without other chronic health issues or complications) <140/90 mmHg
CKD and diabetes or CKD and proteinuria (ACR >70mg/mmol) <130/80 mmHg

Managing fluid retention can be difficult and may need to be shared between nephrologists and GPs. There appears to be some ongoing reluctance or lack of confidence amongst GPs to initiate or appropriately increase diuretics, because of concerns about their potential adverse effect on the kidneys, but patients with advanced CKD actually often need higher doses of diuretics than other patients to benefit.

Spironolactone should be used with particular caution because it can cause significant hyperkalaemia. Recent trials have suggested significant benefits from cardioselective beta-blockers (such as bisoprolol) in CKD patients.

Lipid management

A meta-analysis of 50 trials2,3 of more than 30,000 patients showed that statins reduced fatal and non-fatal cardiovascular events by about 20%, irrespective of stage of CKD. There is less evidence of benefit in patients on dialysis, but no evidence of harm, and treatment is usually recommended.

General calculation tools regarding lipid management are largely not useful for patients with established CKD. Therefore NICE advises1,4 that all patients with eGFR less than 60 ml/min/1.73 m² and/or who have albuminuria (A2 or A3) should receive at least atorvastatin 20 mg daily for primary or secondary prevention and aim for a reduction by 40% of non-HDL cholesterol. If this is not achieved, the dose should be increased, provided the eGFR remains greater than 30ml/min/1.73m2.

 Important! For lipid management, patients with eGFR less than 60 ml/min/1.73 m² and/or who have albuminuria (A2 or A3) should receive at least atorvastatin 20 mg daily.

Summary

Patients with CKD are at significantly higher risk of cardiovascular complications and death. Actively managing their CVD risks is in large part within the scope of primary care and can markedly reduce such complications.

As CKD is usually a result of other chronic disease with multisystemic implications, the management can be complex and often needs input from various teams and, at later stages, specialists. However, any increase of confidence and experience in primary care to detect and manage mild and moderate cases effectively frees up many precious and expensive secondary care resources, which can then be used more readily for the patients with the greatest need.

It is important to engage patients actively in the decision and treatment process, if at all possible, because lifestyle adjustments and ongoing compliance with regard to multiple long-term medical treatments are essential aspects of managing CKD.

  • Dr Neil Iosson is a GP in West Sussex

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References

  1. National Institute for Health and Care Excellence. Chronic kidney disease in adults: assessment and management (CG182). NICE, 2014.
  2. Tan KS, Johnson DW. Managing the cardiovascular complications of chronic kidney disease. Aust Prescr 2008; 31: 154-8.
  3. Strippoli GF, Navaneethan SD, Johnson DW et al. Effects of statins in patients with chronic kidney disease: meta-analysis and meta-regression of randomised controlled trials. BMJ 2008; 336: 645-51.
  4. National Institute for Health and Care Excellence. Cardiovascular disease: risk assessment and reduction, including lipid modification (CG181). NICE, 2014.

Further reading

Jardine AG, McLaughlin K. Cardiovascular complications of renal disease. Heart (2001); 86: 459-66. doi:10.1136/heart.86.4.459

National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management (CG127). NICE, 2011.

Herzog CA, Asinger RW, Berger AK et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney International 2011 Meeting Report p1-15.

Holt S, Goldsmith D. Renal Association Guidelines: Cardiovascular Disease in CKD. (2010)1

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