The Pharmaceutical Journal
Vol 279 No 7479 p597-598
24 November 2007

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European Symposium on Clinical Pharmacy

Chronic kidney disease redefined

Kidney Disease Improvement of Global Outcomes (KDIGO), an international consensus group, has redefined chronic kidney disease (CKD) and this has important implications for drug dosing, according to Vincent Launay-Vacher, nephrology clinical pharmacist at Pitié-Salpêtrière Hospital, Paris.

Renal function can be measured in several ways but many are too expensive or inconvenient for routine use. Serum creatinine (a product of muscle breakdown) has been used as an indicator of renal function in the past because it was assumed that production was constant and there was no renal tubular secretion or absorption.

However, it is now known that both secretion and reabsorption occur. Moreover, a person with poor renal function can have a normal serum creatinine value if creatinine production (muscle turnover) is low. For these reasons it is no longer considered a reliable index of renal function.

Creatinine clearance or the glomerular filtration rate (GFR) are better reflections of renal function. These are difficult to measure but can be estimated using the Cockcroft-Gault or abbreviated “Modification of diet in renal disease” (aMDRD) equations. Mild, moderate and severe decreases in GFR are defined as 60–89ml/min, 30–59ml/min and 15–29ml/min respectively. A GFR of less than 15ml/min is indicative of kidney failure. Dr Launay-Vacher pointed out that this classification differs from the previously accepted scheme.

Clinical pharmacists have a critical role to play in raising awareness of the new definitions and in ensuring that drug doses are adjusted accordingly. More than 80 per cent of antibiotics and 55 per cent of antineoplastic agents require dose adjustment in renal insufficiency, he said.

Cardiovascular disease and renal disease are inextricably linked and factors that worsen the one inevitably worsen the other, Corinne Isnard-Bagnis, a consultant nephrologist at Pitié-Salpêtrière Hospital in Paris, told the audience. One immediate implication of this is that studies with cardiovascular outcomes should include patients with CKD — hitherto these patients have been systematically excluded.

CKD is also a critical risk factor for infectious disease — the second most common cause of death among CKD patients, said Professor Isnard-Bagnis. Approximately 5–10 per cent of patients with HIV have CKD and the prognosis for this group is poor.

A study at Pitié-Salpêtrière Hospital compared antiretroviral drug doses given to 129 patients undergoing dialysis with the recommended doses. The results showed that 57 per cent of doses were incorrectly prescribed, with 19 per cent being too low and 38 per cent too high.

Worryingly, 26 per cent of patients did not receive any of their treatment at the correct dose. Patients receiving highly active anti-retroviral therapy who were prescribed inadequate doses of protease inhibitors had more severe disease and worse two-year survival than other patients.

Professor Isnard-Bagnis suggested that the results could reflect the difficulty of finding the required information. “Even nephrologists do not always know how to adjust doses of ARVs,” she said.

The KDIGO clinical guidelines recommend that patients with HIV and other chronic infectious diseases such as viral hepatitis (strains B and C), tuberculosis and malaria should be screened for CKD at the time of diagnosis but this is not done routinely at present. Dialysis patients should also be vaccinated for influenza, hepatitis B and pneumococcus, she added.

Turning to cancer and CKD, Professor Isnard-Bagnis pointed out that CKD was almost certainly a risk factor for mortality in all types of cancer. According to the Insuffisance Rénale et Médicaments Anticancéreux study, nearly 60 per cent of cancer patients have some degree of renal insufficiency.

Cancer patients should be routinely screened for CKD at first presentation and then again when treatments are started or changed. In addition, kidney-sparing oncological treatments should be used whenever possible. Finally, patients with CKD should be included in clinical trials for cancer treatments, she said.

In conclusion, Professor Isnard-Bagnis said that CKD was common and harmful and greater awareness of monitoring and treatment is needed among both health care professionals and the general public.

Clinical pharmacy services for CKD patients

Clinical pharmacists can contribute to the care of patients with chronic kidney disease (CKD) in many ways, said Thierry Romanet, senior nephrology clinical pharmacist at Grenoble Teaching Hospital. He described how a clinical pharmacy service for nephrology outpatients had been built up at Grenoble Teaching Hospital over the past 10 years.

The main elements of the service are clinical trials, pharmaceutical care of transplant patients and a pharmacist-led anaemia management service. The anaemia service has developed progressively over the past few years.

Initially, the nephrology clinical pharmacist was involved in an educational programme for patients undertaking self-injection of erythropoietin. The pharmacists worked with patients on a one-to-one basis explaining the treatment and providing training in injection technique.

Each session took about 45 minutes and patients were expected to administer their first injection during the session. A 12-week prospective study of 10 new patients in 2003 showed that the programme was effective.

At the end of the study all were still self-injecting, overall compliance had risen to more than 90 per cent (compared with 50 per cent beforehand) and the target haemoglobin level (greater than 11g/dl) had been achieved for eight of the 10 patients. More than 200 patients have now been through this programme, said Dr Romanet.

Recently Dr Romanet has been working closely with nephrologists to establish a fully fledged, pharmacist-led anaemia management service in the nephrology department. The overall aim is to ensure that clinical practice guidelines are followed and that treatment is appropriately monitored. The service runs on two mornings each week alongside the nephrology consultant sessions.

Outpatients with CKD in stages 2–4 (mild, moderate or severe renal insufficiency) who require de novo therapy with an erythropoiesis stimulating agent (ESA) are referred by nephrologists. The pharmacist is responsible for ESA dose adjustment, prescribing of iron and vitamins, ordering of appropriate laboratory tests and blood pressure monitoring.

So far, 22 patients have been managed in this way and it has taken three or four consultations (at monthly intervals) to achieve the target haemoglobin levels, said Dr Romanet. It is hoped that this service could become the model for a broader service dealing with all the pharmaceutical care needs of CKD patients, he added.

Community pharmacists continue cancer care

About 50 per cent of pharmaceutical care issues identified in patients receiving chemotherapy require follow-up in the community in order to provide the best quality of care, according to Julie Fisher, senior oncology pharmacist, Edinburgh Cancer Centre, Western General Hospital.

In a session devoted to the integrated roles of hospital and community pharmacists, Ms Fisher described how a referral form had been developed that contained a “patient medication profile” comprising a list of the pharmaceutical care issues (PCIs) and suggested actions for the community pharmacist.

Over the past decade, increasing numbers of cancer patients have received treatment at day-case chemotherapy clinics. New chemotherapy regimens have been designed specifically for day-case administration, such as carboplatin and gemcitabine for the treatment of non-small cell lung cancer.

Moreover, the increasing use of ambulatory pumps means that, for example, a seven-day course of 5-fluorouracil for colorectal cancer can be delivered at home.

In addition, the availability of oral chemotherapy has increased. However, misunderstandings and miscommunications can also occur, said Ms Fisher. There have been several incidents in which three-day courses of dexamethasone (for post-chemotherapy nausea and vomiting) have been mistakenly continued by the patients’ GPs, resulting in inappropriate steroid treatment for several weeks.

Both the GP and the community pharmacist need to be aware of the therapeutic plan so that they can participate in monitoring for adverse events, she advised.

A prospective survey in 90 day-case patients receiving chemotherapy showed that the most common PCIs related to supportive therapy (eg, for nausea and vomiting), corticosteroid use and warfarin treatment. Awareness of supportive treatments could allow community pharmacists to identify situations where chemotherapy was poorly tolerated and prompt a referral back to the hospital clinic, said Ms Fisher.

For example, a request for further supplies of loperamide for chemotherapy-induced diarrhoea could indicate poorly tolerated treatment, a referral could be made, and the treatment could be modified, she suggested.

Another important task is monitoring of warfarin therapy. Many patients receiving chemotherapy have central (intravenous) lines in situ and are prescribed warfarin 1mg daily for thromboprophylaxis. These patients do not routinely require international normalised ratio (INR) monitoring unless they are prescribed other medicines that can interact with the warfarin.

There is a significant drug interaction between warfarin and capecitabine, which is used to treat breast and colorectal cancers. This can increase the INR and in such cases regular monitoring of clotting status is required. Community pharmacists should check that patients taking this combination have regular INR monitoring performed, recommended Ms Fisher.

A referral form that listed PCIs and suggested actions was tested in 20 patients and their nominated community pharmacists. The results showed that 52 PCIs were listed on the forms and the community pharmacists had followed up about half of them. Lack of time was the reason for not following up more.

Patients who should be targeted for the referral service include those prescribed unusual products or unusual doses and those receiving interacting medicines, recommended Ms Fisher.

Observational and intervention studies needed in clinical pharmacy

Both observational and intervention studies are needed in clinical pharmacy, according to Marcel Bouvy, from the SIR Institute for Pharmacy Practice and Policy, Leiden, and Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht University.

Clinical pharmacy research could usefully be categorised under the four domains of Hippocrates, suggested Dr Bouvy. They are diagnosis, aetiology, prognosis and therapy. The general questions that fit under these headings are respectively, “What is it?”, “Where does it come from?”, “How bad is it?” and “What can I do?”.

Although diagnosis is not normally a pharmacist’s responsibility, pharmacists are increasingly undertaking diagnostic tasks such as diabetes screening and, in the UK, chlamydia testing in community pharmacies, said Dr Bouvy.

Clinical risk management also falls under the heading of diagnosis and is commonly undertaken in community pharmacies. Making reference to the Swiss cheese model for medication errors, Dr Bouvy pointed out that the pharmacist is the last person who has the opportunity to intercept an erroneous prescription and prevent an incorrect medicine from reaching the patient.

Research carried out in the Netherlands showed that of 2,572 drug interaction alerts (identified on computerised prescriptions), 72 per cent had already been taken into account by the prescriber but 27 per cent required action by the community pharmacist — usually communication with the patient or relative. A typical example was separating the administration of iron tablets and antibiotics, said Dr Bouvy.

More serious interactions require contact with doctors. For some interactions, such as statins and macrolides or coumarins and cotrimoxazole there is good adherence to recommended prescribing guidelines but for others, such as the interaction between phosphodiesterase inhibitors and nitrates, the guidelines are usually overridden.

A study showing that 6.5 per cent of hospital admissions in the UK that were due to adverse drug reactions fell under the heading of “aetiology”. The drugs most commonly involved in this study were aspirin, diuretics, warfarin and non-steroidal anti-inflammatory drugs. A similar picture emerged from the “hospital admissions related to medication” study published in the Netherlands in 2007, said Dr Bouvy.

Another study that examined represcribing of medicines after they had caused adverse reactions in elderly patients could be classified under the heading of “prognosis”, commented Dr Bouvy. The results showed that the overall represcribing rate was 27 per cent and 22 per cent of medicines responsible for “serious adverse reactions” were prescribed again for the same patients within six months.

Studies of adherence to long-term therapies also fell under this heading. A 10-year study of adherence to antihypertensive therapy had shown that adherence fell by about 40 per cent after the first year and then changed little over the next nine years.

There are many studies concerned with therapy — most commonly the type that show that intervention by a pharmacist improves patient outcomes compared with “usual care”. Meta-analyses of some of these studies had now confirmed these findings, Dr Bouvy pointed out.

In conclusion, he said that research is needed in several domains and the local situation should determine the starting point. For example, in the UK, pharmacists should be involved in intervention studies because observational studies have already shown where the problems are.

In other countries observational studies might be the best starting point to find out where the problems are. “We have to show that clinical pharmacy really improves patient outcomes” he said.