Oxycodone is predominantly metabolised in the liver, but does have 10 per cent of its metabolites excreted by the kidney and can therefore cause toxicity from accumulation. However, it can be used safely in most patients with impaired renal function. Modified-release preparations should be avoided.4 Buprenorphine and fentanyl have largely inactive metabolites which are excreted via the kidneys in normal renal function, but offer a good first-line choice for moderate to severe pain.3,6 An analgesic ladder for use in ESRF is outlined in Box 6.

Fluid overload
Large doses of loop diuretics may be required to treat salt and water overload in patients with advanced renal failure. Doses of 40-120mg of furosemide may be effective, but a dose of 250mg daily is more likely to be effective. The maximum recommended daily dose is 2g in divided doses.


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Fluid restriction to one litre per day or less can be helpful, but in practice, is diffficult for the patient to tolerate. Identifying an ideal body weight, with daily weighing at home and adjustments to fluid intake and diuretics to maintain it, can be useful in managing renal failure with coexistent heart failure.

Renal bone disease
Renal bone disease can be a complicated problem; Figure 2 shows a flowchart for managing this. If patients develop a low serum calcium level, they should be treated with oral calcium replacement, such as chewable calcium carbonate or calcium carbonate. Consider chewable calcium carbonate with vitamin D3 if the patient also requires vitamin D replacement. If the calcium level is very low or the patient has symptoms of hypocalcaemia, IV calcium may be required. Elevation of phosphate levels may be encountered; Box 7 outlines strategies for dealing with this.

Modest elevations of parathyroid hormone (PTH) frequently settle when calcium and phosphate levels are corrected by diet and/or phosphate binders. If PTH rises to two or three times the upper limit of normal, 1,25-hydroxyvitamin D (alfacalcidol) can be used. The starting dose is 0.25 microgram per day, titrated as required. In severe uncontrolled hyperparathyroidism, calcimimetics can be considered under specialist supervision. Oversuppression of PTH can cause adynamic bone disease, which increases the risk of fractures.

Restless legs, dry mouth
Restless legs and muscle cramps often trouble patients and mild symptoms can be controlled using quinine sulphate 200mg daily. Moderate symptoms may be controlled with clonazepam 0.5mg at night and more severe symptoms may respond to gabapentin 100-300mg at night. In the end-of-life situation, if symptoms are severe, midazolam can be administered by syringe driver.

A dry mouth is a common consequence of fluid restriction and medication, but is aggravated by the anticholinergic effects of ESRF. Symptomatic measures, such as sucking ice cubes, sipping fluids, chewing gum, and using artificial saliva, may help. In severe cases or the end-of-life phase, it may help to consider lifting any fluid restriction. Acidosis can be determined by measuring serum bicarbonate and corrected in most cases with oral sodium bicarbonate tablets 500mg-3g in divided doses. The aim is to maintain the serum bicarbonate level above 22mmol/L. If hypokalaemia or fluid retention are problematic, potassium citrate, with careful monitoring of serum potassium, may be used.

If there is hyperkalaemia, correction of acidosis will often return potassium levels to normal in patients who have a daily urine output >800ml. Producing an increase in urine output using loop diuretics in patients retaining fluid is a valuable adjunctive therapy for hyperkalaemia. Exceptions to this occur in renal tubular acidosis, a situation common in diabetes.

Avoidance of dietary potassium can help, in addition to other measures. Severe hyperkalaemia (>7mmol/L) is life-threatening; IV therapy with insulin and dextrose or bicarbonate may be appropriate in these patients. The source of the excess potassium must be identified. For example, it may be related to blood transfusion or anaesthesia. Ion-exchange resins (calcium resonium 15g once or twice daily) administered with laxatives may control potassium in the non-acute situation, but they are poorly tolerated by patients. Particular caution is needed in patients with hyperparathyroidism or hypercalcaemia.

Depression and anxiety
Depression has been found in 25-30% per cent of patients with ESRF, while higher numbers can have depressive symptoms, without having depressive disorder. Many renal centres have counsellors attached to their service, who can provide tailored advice on psychological therapies for patients having maximal conservative management.

Drug therapies can be used, although doses may need to be lowered. In addition, these patients are usually elderly, with comorbid disease, and this should be taken into account when deciding appropriate doses. Most renal centres have specialist renal pharmacists who can be contacted for advice.

Dr. Joanna Peasegood is a specialist registrar in nephrology and Dr. Aine Burns is consultant nephrologist at the Royal Free Hospital, London. Competing interests: None declared

References
1. Murtagh FE, Addington-Hall JM, Edmonds PM et al. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. J Palliat Med 2007;10:1266-76.
2. Macdougall I. Intravenous administration of iron in epoetin-treated haemodialysis patients – which drugs, which regimen? Nephrol Dial Transplant 2000;15:1743-5.
3. Game DS, Brown EA. Maximal conservative management. Medicine 2007;35:470-2.
4. Burns A, Williams B, Johnston S. What can patients and their families who choose not to dialyse expect? Renal Association Annual Conference Abstract Book, 2002.
5. National Kidney Foundation/Kidney Disease Outcomes guidelines. KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for Anaemia in Chronic Kidney Disease: 2007 Update of Haemoglobin Target. Available from (accessed 5 February 2009).
6. Western H, Fieldhouse F. Guidelines for palliative prescribing in renal failure. (accessed 12 February 2009).
7. Joint Specialty Committee on Renal Medicine of the Royal College of Physicians and the Renal Association, and the Royal College of General Practitioners. Chronic kidney disease in adults: UK guidelines for identification, management and referral. Royal College of Physicians, London, 2006.

1. Murtagh FE, Addington-Hall JM, Edmonds PM et al. Symptoms in advanced renal disease: a cross-sectional survey of symptom prevalence in stage 5 chronic kidney disease managed without dialysis. 2007;10:1266-76.2. Macdougall I. Intravenous administration of iron in epoetin-treated haemodialysis patients – which drugs, which regimen? 2000;15:1743-5.3. Game DS, Brown EA. Maximal conservative management. 2007;35:470-2.4. Burns A, Williams B, Johnston S. What can patients and their families who choose not to dialyse expect? , 2002.5. National Kidney Foundation/Kidney Disease Outcomes guidelines. : 2007 Update of Haemoglobin Target. Available from (accessed 5 February 2009).6. Western H, Fieldhouse F. . (accessed 12 February 2009).7. Joint Specialty Committee on Renal Medicine of the Royal College of Physicians and the Renal Association, and the Royal College of General Practitioners. Royal College of Physicians, London, 2006.

Originally published in the March 2009 edition of MIMS Oncology & Palliative Care.