Palliative and end-of-life care in advanced renal failure

Advanced chronic kidney disease

Pain. Pain in renal failure is often related to renal bone disease and poorly addressed due to anxiety about prescribing and poor recognition.

Codeine and morphine should be avoided in renal failure. If taken regularly, their toxic metabolites, which are renally excreted, accumulate and can quickly cause over-opiation. Clinical trial evidence on the use of strong opioids in renal failure is limited, but in clinical practice oxycodone is better tolerated than morphine and may be used for patients with GFRs of 50–20 ml/min. The metabolites of oxycodone also accumulate and, as GFR falls, lower doses of oxycodone and a longer dose interval may be needed.

When GFR falls below 20 ml/min, buprenorphine and fentanyl preparations should be used. Buprenorphine and fentanyl preparations are better tolerated in severe renal impairment because their metabolites are largely inactive and excreted by the liver. When patients have stable analgesic requirements, transdermal buprenorphine patches may be used for those requiring small to moderate doses, or fentanyl patches if a higher dose is required. Either fentanyl or alfentanil can be used in a syringe driver if more dose flexibilty is needed when GFR is less than 20 ml/min and at the end of life.¹³

Theoretically, methadone shows little accumulation but has wide interpatient variation and a narrow therapeutic index. It should not be used without specialist advice.¹⁴

Non-steroidal anti-inflammatory drugs (NSAIDs) alter glomerular haemodynamics and, as such, are nephrotoxic. They should be used with caution in patients with severe renal impairment, but may be appropriate when the benefits outweigh the burdens such as in the last few days of life. There is no strong evidence that one NSAID has significant ‘renal advantages’ over any other.

Neuropathic pain. Amitriptyline should be titrated from low doses such as 10 mg once daily. No dose adjustment is required.

Gabapentin and pregabalin require significant dose adjustments. The maximum dose of gabapentin with a GFR of less than 30 ml/min is 300 mg daily. If the GFR is below 20 ml/min, very small doses of gabapentin such as 50 mg od are often effective.

Nausea. Patients with renal failure frequently have a chemical cause for nausea and vomiting. Haloperidol, ondansetron and granesitron are therefore the most effective anti-emetics. Levomepromazine is also useful as an antiemetic and sedative in the terminal stages. Haloperidol and levomepromazine have increased sedative effects in renal failure so doses should be reduced, particularly when GFR is less than 10 ml/min, and titrated accordingly. If a prokinetic antiemetic is required, metoclopramide is well tolerated but the dose needs to be reduced when GFR is below 20 ml/min.

Pruritus. Renal osteodystrophy results in low calcium and high phosphate levels, the latter inducing itch. This can be treated by preparations which bind dietary phosphate in the gut. Renal patients tend to have dry, and therefore itchy, skin which can be relieved by regular use of a simple moisturiser such as aqueous cream.

Uraemia can also cause itching, usually when GFR is below 10 ml/min. Antihistamines are not particularly helpful for uraemic itch. There is some evidence that ondansetron, a 5-hydroxytryptamine-3 receptor antagonist, may help both nausea and itch in these patients and that low-dose gabapentin may relieve uraemic itch.¹⁵

Renal replacement therapy

Patients on dialysis who require palliative care should, on the whole, be treated in the same way as patients with severely impaired GFR not on dialysis. In peritoneal dialysis, clearance rates of drugs are constant and the timing of doses not important. On haemodialysis, patients will be receiving intermittent treatment but only rarely do drug administration times need adjusting. Dialysis clears non-protein-bound water-soluble drugs of low molecular weight, so usually only intravenous antibiotics need to be adjusted occasionally. The agents described above can be used at any time during the ‘dialysis cycle’.

No dialysis

A further choice is now offered: no dialysis. Patients making this choice are reviewed by a palliative medicine consultant within the renal clinic, and therefore still receive regular medical, nursing and dietetic review, and management of their anaemia to minimise fatigue. However, a greater emphasis is placed on symptom control and social support with a dedicated social worker. These patients tend to be elderly with multiple comorbidities, but as many as one in six patients in our service snow choose this treatment option. There is evidence that patients over 75 years with multiple comorbidities, particularly ischaemic heart disease, may not increase their longevity as a result of receiving dialysis.¹⁶

Renal function is monitored regularly, so that this can be optimised and used as a prognostic marker. Phosphate and calcium levels and vitamin D metabolism are also monitored and treated with diet and medication. Uraemic symptoms are assessed and palliated.

Patients who choose to be treated conservatively may continue to live with very low GFRs for some time, but approximately 75% will die within the year.¹⁷ Patients opting for conservative treatment tend to die when their GFR reaches approximately 5 ml/min.

Patients who withdraw from established dialysis have a mean survival of 8–11 days.¹⁸ Advance care planning should therefore ideally start before dialysis is withdrawn.