ACE inhibitor use may be linked to kidney failure

Behind the Headlines

Thursday November 7 2013

ACE inhibitors are medicines mainly used in the treatment of hypertension and heart failure

ACE inhibitors help reduce blood pressure and improve blood flow

"Blood pressure drugs…could raise the risk of potentially deadly kidney problems," the Daily Mail warns. Researchers have looked at whether there is an association between the prescribing patterns for these drugs and hospital admissions for kidney problems.

They were specifically interested in the relationship between two widely used antihypertensive drugs (ACE inhibitors and angiotensin-II receptor antagonists) and hospital admissions for kidney failure.

Kidney failure (now known as acute kidney injury, or AKI) is when the kidneys suddenly lose the ability to filter waste products from the blood and balance fluids in the body. It leads to a range of serious and potentially fatal symptoms.

The study found that in the four years up to 2010, English hospitals saw a 52% increase in admissions for AKI. During the same period there was a 16% increase in prescriptions for ACE inhibitors and related drugs. They estimate that up to 15% of these increased admissions – one in seven cases – could be as a result of increased prescriptions for these drugs.

The study does not show that the admissions were because of the number of these prescriptions, and only shows an association. The study also contained no information about individual patients and why they were taking the drugs. Some of the conditions these drugs are prescribed for are themselves a risk factor for AKI.

Patients prescribed these drugs should not stop taking them unless advised to do so by their doctor. Left untreated, high blood pressure could trigger a heart attack or stroke.

  

Benefits and risks of medication

There is no such thing as a guaranteed 100% safe drug. Even some of the safest drugs on the market, such as paracetamol, have a very rare chance of triggering a serious allergic reaction.

 

But it's important not to lose sight of the benefits that drugs can bring. ACE inhibitors may carry a small (and as yet unproven) risk of causing AKI, but they have probably saved thousands of people from having a heart attack or stroke.

 

Read more about medicines using the NHS Choices Medicines A-Z.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge, the Institute of Public Health in Cambridge, Cambridge University Hospitals NHS Foundation Trust, and the North Bristol NHS Trust.

It was part-funded by the Cambridge Biomedical Research Centre and the British Heart Foundation, and was published in the peer-reviewed journal PLoS ONE. PloS ONE is an open access journal, so the study is free to read online or download.

The study was covered reasonably well by the Daily Mail and The Daily Telegraph. While the headlines were a little alarmist, the actual reporting was appropriate and responsible.

The Mail included comments from independent experts and advice that patients should not stop taking the drugs, and The Daily Telegraph reported that the link was not proven.

 

What kind of research was this?

This was an observational ecological study looking at whether hospital admission rates for acute kidney injury (AKI) are associated with an increase in the prescribing rates of two drugs called ACE inhibitors (ACE-Is) and angiotensin-II receptor antagonists (ARAs).

This type of study looks for associations between the occurrence of disease and exposure to known or suspected causes. But the unit of observation was at the level of a GP practice rather than the individual patient. This lack of individual detail could have failed to account for a number of other factors.

The authors point out that AKI is associated with the risk of death and leads to prolonged hospital stays and a possible decline in long-term kidney function. Although concerns have been raised in the past about links between AKI and the use of ACE inhibitors and ARAs in some patients, the size of the problem is unknown.

These are the second most commonly prescribed drugs by GPs in England, accounting for 6% of all prescriptions, and are used for a number of conditions, including high blood pressure, chronic kidney disease and heart failure.

 

What did the research involve?

The researchers compared admission rates to English hospitals for AKI with prescribing rates for ACE inhibitors and ARAs during the period 2007-8 to 2010-11.

The researchers used an NHS database to obtain the number of ACE inhibitor and ARA prescriptions from all general practices in England during the study period. They controlled for differences in age and sex demographics of general practice populations in their prescribing rates.

They obtained the number of patients admitted to hospital with AKI using a national database. For the main analysis, the international code classifying AKI (N17 in the ICD-10 system) needed to be present as the primary diagnosis for any episode within seven days of the date of admission.

In their statistical analysis, the researchers matched the NHS prescribing data to the number of hospital admissions for AKI at the general practice level. The data combined four one-year periods starting on April 1 2007. They used a recognised statistical method to model the number of admissions for AKI occurring in each practice for each of the four years from 2007.

To ensure the robustness of their findings, the researchers performed a number of sensitivity analyses. For example, they examined whether their results could be affected by improvements in the thoroughness of clinical coding for AKI over time, and whether including admissions for unspecified kidney failure, which is coded differently, affected their findings.

 

What were the basic results?

The researchers found that from 2007-8 to 2010-11 in England:

  • AKI admission rates increased from 0.38 to 0.57 per 1,000 patients (51.6% increase)
  • annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 per 1,000 patients to 0.234 (15.8% increase)
  • there was strong evidence that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates
  • the increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1%
  • they predict that 1,636 (95% confidence interval [CI] 1,540-1,780) AKI admissions would have been avoided if prescribing rates for ACE-Is and ARAs had remained at the 2007-8 level – this is equivalent to 14.8% of the total increase in AKI admissions

 

How did the researchers interpret the results?

The researchers say that up to 15% of the increase in AKI admissions in England over a four-year time period is potentially attributable to the increased prescribing of ACE inhibitors and ARAs.

They argue that better understanding of individual risk factors for AKI associated with ACE inhibitors and ARAs is needed to reduce the potential harms associated with these important and commonly prescribed medications.

Their analysis, they say, "throws uncertainty on the balance of benefits and risks associated with use of these drugs".

 

Conclusion

ACE inhibitors and ARAs are recognised as a potential risk factor for AKI in some patients. This particular study has tried to estimate the possible size of the problem, but its findings should be viewed with some caution. As the authors point out:

  • some of the conditions these drugs are prescribed for are themselves a risk factor for AKI
  • changes in hospital coding and better recognition of AKI could explain the rise in admissions
  • an ageing population leads to both increased prescribing of these drugs and an increased risk for AKI
  • increased use of these drugs may be a marker for increased use of other drugs known to cause kidney injury, such as diuretics and non-steroidal anti-inflammatories
  • findings are limited by the lack of information about individual patients

Further research is required on this important topic undertaken at the level of individual patients rather than GP practices.

It is important that you do not stop taking any prescribed medication for high blood pressure, chronic kidney disease or heart failure without first consulting your GP. Doing so could lead to a sudden worsening of your symptoms.

 

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

Kidney failure risk of blood pressure pills taken by 5 million: Tablets linked to sudden renal failure. Daily Mail, November 7 2013

ACE inhibitor drugs linked to kidney damage. The Daily Telegraph, November 6 2013

Links to the science

Tomlinson LA, Abel GA, Chaudhry AN, et al. ACE Inhibitor and Angiotensin Receptor-II Antagonist Prescribing and Hospital Admissions with Acute Kidney Injury: A Longitudinal Ecological Study. PLoS One. Published online November 6 2013

Ratings

How helpful is this page?

Average rating

Based on 5 ratings

All ratings

3  ratings
1  ratings
0  ratings
0  ratings
1  ratings

Add your rating

Hypertension

High blood pressure has no symptoms, but if it's not treated it can damage the kidneys, heart and brain.

Media last reviewed: 03/05/2016

Next review due: 03/05/2018

What is Behind the Headlines?

What is Behind the Headlines?

We give you the facts without the fiction. Professor Sir Muir Gray, founder of Behind the Headlines, explains more...

Follow us on Twitter

Join more than 160,000 who follow @NHSChoices for the latest and best health news and lifestyle advice

Bodybuilding and sports supplements

Supplements are popular for people wanting to lose weight and build muscle, but some are illegal and dangerous

Kidney health

Find out about how to look after your kidneys and whether you need to have them checked

Is your blood pressure too high?

At least 25% of adults have high blood pressure. Get tips on how to keep healthy