Data for Medicines Optimisation and Best Practice: Case Example - Polypharmacy and Its Influence on Nephrotoxicity and Renal (Kidney) Impairment

I have recently been working on a poster presentation in collaboration with a research scientist, for Cardiff University's Data-Driven Systems Medicine event.  This event brought together individuals from academia, technology companies and the pharmaceutical industry to discuss the use of data science techniques, such as machine learning in the journey towards personalised health and care.  

The poster presentation is titled "Data for Medicines Optimisation and Best Practice", with sub-sections looking at "Data Insights Into Medicines Use in Care and Nursing Homes" and a case example "Polypharmacy and its Influence of Nephrotoxicity and Renal Impairment".  This blog takes a closer look at this example.  Finally, it explores NICE guidance, and how individuals working in care can help reduce the risk of adverse outcomes due to renal impairment in the individuals they care for.

What is the Issue?
Around 70% of total health and care expenditure in England is attributed to patients with Long-Term Conditions. An estimated 15 million patients in England have at least one Long-Term Condition with the prevalence of cancers, Chronic Kidney Disease (CKD) and Diabetes quickly rising. This consequently has an impact on the individuals health, lives and healthcare services. About 2-million adults in England have been diagnosed with moderate to severe CKD. Much of the monitoring of these patients occurs in mild-moderate disease by GPs in primary care, with only the final stages of disease managed in secondary care.

CKD is as an irreversible Long-Term Condition where reduced renal function is evident; and damaged kidneys cannot filter blood effectively as they normally would. It is staged from 1 (kidney damage with normal function) to 5 (kidney failure).  This differs from Acute Kidney Injury (AKI), which is a rapid decline in kidney function that is often reversible if it is managed promptly.  This can occur for many reasons, including as a result of 'nephrotoxic' medicines (medicines that can damage the kidneys in the long-term). 

Kidney disease is a major public health concern.  There is considerable overlap between CKD, diabetes and cardiovascular disease and the risk of developing CKD increases with age.  Meanwhile it costs the UK £1.02 billion to prevent Acute Kidney Injury (AKI) and there is a higher risk of dying from AKI than from a Heart Attack, Breast Cancer, Heart Failure and Diabetes. There is also a risk of CKD developing or worsening as a result of AKI.  There are several risk factors that interact with kidney disease. According to the UK Renal Registry 18th Annual Report, Diabetic kidney disease remains the single most common cause of kidney failure (26.9%). By 90 days, around 2/3 of patients were on Haemodialysis, 1/5 on Peritoneal Dialysis, 1/10 had a functioning kidney transplant and 1/20 had died or stopped treatment.

What is Polypharmacy and how does this influence Nephrotoxicity?
The use of multiple medicines, commonly referred to as polypharmacy is typical in the older population with multi-morbidity (multiple medical conditions), as one or more medicines may be used to treat each condition. While in many instances the use of multiple medicines or polypharmacy may be clinically appropriate, it is important to identify individuals with inappropriate polypharmacy, which may place individuals at increased risk of adverse events and poor health outcomes.  Adverse events include kidney damage for individuals taking nephrotoxic medicines, while other risks of polypharmacy include falls, adverse drug reactions, increased length of stay in hospital re-admission to hospital soon after discharge and sadly even death in some cases.  Individuals with AKI and CKD are at greater risk of the adverse effects of certain medicines that are cleared from the body by the kidneys.

Polypharmacy on the Care Home Population
Individuals living in care and nursing homes, especially older individuals, require special care and consideration from prescribers. This is reflected in Medicines for Older People, a component document of the National Service Framework for Older People, which describes how to maximise the benefits of medicines and how to avoid excessive, inappropriate, or inadequate medicines use by individuals living in care and nursing homes.  With respect to age, the most important effect is reduced renal clearance.  This makes these individuals more susceptible to kidney damage as a result of nephrotoxic medicines.  Furthermore, the absorption, distribution, metabolism and excretion of drugs can be affected by renal insufficiency to varying degrees and acute illness can lead to rapid reduction in the ability of the kidneys to clear medicines from the body, especially if accompanied by dehydration. This means the dose of the medicine that an individual has been taking may become toxic in these circumstances.

The performance of the NHS is driven by quality and patient outcomes. The increase in provision of care home staff will assist in supporting the NHS to drive quality improvements, according to NHS Outcomes Framework. Care home managers have an invaluable role in ensuring that correct medications reach the correct patient, who must be provided with the necessary information on how to use the treatment effectively. The core roles of medicines management involve delivery of personalised care for patients with chronic conditions, access to reliable healthcare advice and treatment, and being a local health and well-being hub.  Approximately, 7% of all admissions to UK hospitals arise from the adverse effects of prescription medicines. This includes inappropriate medication-taking by patients.  About half of individuals do not, in fact, adhere to their prescribed regimen, and wastage from unused prescribed medicines is estimated to cost almost £100 million every year in the UK.

What do studies highlight on this issue?
A 2009 retrospective cohort study of 396 stage 4 (severe) CKD patients in Scotland and Northern Ireland found that 89 individuals commenced Renal Replacement Therapy while 20 chose conservative care.  Sadly, most individuals with severe CKD died before being offered Renal Replacement Therapy.  The cost per patient of conservative care provided by a renal department has been estimated at £397 per month (£4,764 per year). However, expert opinion suggests that not all conservative care patients are likely to receive such resource-intensive care. In the early stages of conservative care, resource use may be like that of a stage 3–4 CKD patient, with care (and expenditure) increasing over time with disease progression.

What have we found by looking at data from Invatech Health's ATLAS eMAR system?
Approximately 3/10 of individuals were prescribed at least one nephrotoxic medicine. The most common type of nephrotoxic medicine prescribed was diuretics, followed by ACE inhibitors (e.g. ramipril, used for high blood pressure) and NSAIDs (e.g. ibuprofen). Meanwhile 2/3 of individuals were prescribed either a nephrotoxic medicine or a medicine that requires the dose to be adjusted in individuals with poor kidney function. This emphasises the need for the medicines of individuals with CKD to be reviewed regularly, to ensure they are taking the appropriate dose for their level of kidney function.

How can you help reduce the risk of adverse outcomes due to renal impairment in individuals you care for?
Look out for individuals on multiple medicines e.g. 10 or more, and get this reviewed.  A 'triple whammy' of NSAIDs (e.g. ibuprofen), ACE inhibitors (e.g. ramipril) and diuretics (e.g. furosemide) is considered particularly risky for kidney injury. The risk of AKI can also be reduced by ensuring individuals are well-hydrated.  If this is not possible, for example due to diarrhoea or vomiting, then discuss this promptly with a doctor, as they may need to temporarily hold some of their medicines or have their kidney function checked.  This is particularly important for individuals who already have known kidney disease.

Certain medical conditions such as diabetes, high blood pressure, heart disease and prostate disease increase an individuals risk of CKD.  If you suspect an individual may be at high risk, then discuss this with their GP, who can check the health of their kidneys using urine and blood tests.  It is worth noting that NICE recommends that individuals avoid eating meat for 12 hours prior to the most commonly used blood test for kidney function (creatinine).

Some Important Recommendations
For individuals with known CKD, make sure 
their kidney function and medicine use is regularly reviewed with their GP or specialist. Encourage the individual to be involved in management decisions, particularly in the later stages.  In most cases, CKD is a result of an underlying condition such as diabetes or high blood pressure, and it is important that these are also monitored and managed as best as possible to help reduce the risk of progression.  Encourage them to exercise to the best of their ability, maintain a healthy weight and stop smoking if they do so. Medicine doses, diet and fluid intake often needs to be adjusted, so discuss this with their doctor at their review and create an individualised plan for this.

Want to find out more?
Take a look at the NICE guidance for AKI and CKD.

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