² Salford Royal NHS Foundation Trust, Salford, UK

Introduction

Chronic kidney disease (CKD) is an irreversible and often progressive condition. Patients with advanced impairment of kidney function will require lifelong renal replacement therapy (RRT) by dialysis or a functioning kidney transplant to maintain survival. Patients may have CKD for a very long period of time and will become very knowledgeable and informed about their illness and the options for management. Over their lifetime many patients experience the full range of treatment options, and whilst transplantation often offers the most benefit, not all patients are suitable for this option. Advanced renal failure requiring RRT is uncommon, with 416 per million population on dialysis and 375 per million population having a functioning kidney transplant (UK Renal Registry). Thus the typical general practice will have a very small number of these patients.

Wider manifestations of CKD

Patients with advanced CKD (stage 4/5) typically have a complex medical ­history, suffering a variety of other coexistent serious chronic conditions. In many cases this results from their CKD being a manifestation of a condition with multiple systemic manifestations. Diabetes is the commonest and increasing cause of CKD. Many patients with advanced kidney disease due to diabetic nephropathy will have several other complications. CKD is a potent risk factor for the development of cardiovascular disease, and is typically ­associated with hypertension, as well as being a complication of conditions such as diabetes and hypertension which are associated with increased cardiovascular disease risk. Thus ischaemic heart disease, heart failure, peripheral and cerebrovascular disease are common in patients with CKD. Patients with diabetes typically suffer the most from severe and complex vascular disease. The increasing prevalence of CKD with age means that many patients will have other chronic conditions also more common in older people. This complexity can reduce therapeutic options and challenge effective management.

Renal replacement therapy

Advanced CKD may eventually progress to the stage where remaining kidney function is not sufficient to keep the patient free of significant symptoms of kidney failure, or eventually to maintain survival. At this point replacement of kidney function by dialysis or transplantation is required. This is typically when kidney function has decreased to a glomerular filtration rate (GFR) of 10 mL/min/1.73 m² or less, although it should be noted that some patients are more symptomatic at a higher estimated GFR (eGFR), which is why patients should be individually assessed at regular intervals. In patients with progressive CKD, discussions and counselling to inform the patient about possible options for RRT, and to prepare for this, will begin well before this point is reached. Some patients, however, may remain free of symptoms or are ­undiagnosed with CKD until presenting acutely (and urgently) with advanced ­disease. These ‘unplanned starts’ or ‘crash landers’ often require prompt ­commencement of dialysis.

Options for the management at this advanced stage of kidney disease (CKD stage 5) include the different forms of dialysis, haemodialysis, peritoneal dialysis and kidney transplantation. Some patients, typically those of older age and with other chronic conditions, who have greater frailty and more limited life expectancy, may opt for a non-dialytic pathway of care. When kidney function falls to the point where dialysis is usually started, those patients who choose not to have dialysis, or are clinically unsuitable for dialysis, will commence a supportive and palliative pathway, widely referred to as conservative management or active supportive care. This decision may arise from a personal choice regarding the balance of the potential adverse impact of therapy on the patient and his or her quality of life, versus the potential extension of duration of life or improvement in symptoms that would be achieved from dialysis, which may be relatively modest in such patients.

For those following a dialytic pathway, a major consideration is the choice between peritoneal and haemodialysis as an initial mode of therapy. The majority of patients may be suitable for either form, and the final decision will be down to the individual patient in combination with education and guidance from the clinical team. Importantly, it should be explained to patients that rather than making a long-term irreversible decision, many patients will change between different dialysis modalities over their lifetimes, either for clinical reasons (including complications of the initial dialysis modality), or through patient choice for personal and lifestyle reasons. This is the idea of integrated care, whereby best use of all available therapies is made during a patient’s lifetime. Kidney transplantation may provide the best outcomes in terms of survival and rehabilitation, but only a proportion of patients with advanced CKD will be suitable to be considered for transplantation. The majority of patients will receive some form of dialysis before they receive a kidney transplant. However, an increasing proportion may undergo a pre-emptive transplant before needing to start dialysis. This is most likely when there is adequate time for transplant workup before potentially needing to start dialysis, and particularly if the patient has a possible living transplant donor.

Supporting the patient at the key decision-making points of the pathway may be formalised as ‘shared decision making’, and it benefits from the increasing availability of tools such as patient decision aids.

Features of advanced CKD and general aspects of management

Features and complications of CKD arise from a combination of loss of excretory function which leads to accumulation of ‘uraemic toxins’; loss of homeostatic regulation including fluid balance, blood pressure and acid–base regulation; and loss of endocrine effects of the kidney including reduced ­production of erythropoietin and vitamin D metabolism. Dialysis only partly corrects the abnormalities of stage 5 CKD. Clearances of small solutes by standard dialysis techniques are only equivalent to a small percentage of normal kidney function. Other abnormalities such as homeostatic regulation and endocrine function are only replaced partially or not at all by dialysis. Managing abnormalities of renal failure in patients on dialysis also includes important contributions from nutritional management and drug therapy.

Gastrointestinal and nutritional abnormalities

An extensive list of symptoms and complications may occur in patients with kidney failure, though symptoms may be mild or non-existent until advanced renal failure occurs. Gastrointestinal and nutritional abnormalities are important features. Loss of appetite due to uraemic toxicity, weight loss and nausea can lead to nutritional depletion, and these are often important triggers for commencing dialysis.

Nutritional management, with regular assessment and support by a renal dietitian, is an important part of the basic care of patients on dialysis (see Chapter 9). Malnutrition and wasting are common and associated with reduced patient survival. The pathogenesis is complex, with a variety of contributory factors. Intake of protein and calories is often suboptimal due to reduced appetite. This arises from a multitude of factors including the effects of metabolites retained in renal failure on appetite, effect of multiple medications and delayed gastric emptying. In addition, multifactorial psychosocial factors result in a high incidence of anxiety and depression in this population, which are further compounded by lack of employment and financial insecurity. Dietetic management includes assessment of the adequacy of dietary intake and advice regarding alteration of diet to meet targets for nutritional intake and the use of supplements where required. Other factors leading to wasting, including catabolic processes due to uraemia and inflammation, are not reversible by increasing dietary intake. Specialist dietetic input also includes assessment and advice regarding the intake of potassium, phosphate, sodium, water and micronutrients. Complex relationships between these components of diet require expert dietetic management to avoid changes aimed at one abnormality having unintended adverse consequences (e.g. potassium or phosphate restriction leading to inadequate intake of other nutrients such as protein).

Fluid balance management

Earlier stages of CKD may result in reduced urinary concentrating ability with polyuria and sometimes a tendency to fluid depletion. When renal disease becomes more advanced a tendency to fluid retention is the norm. Fluid excess may manifest with features which are clinically indistinguishable from cardiac failure, with ankle swelling, elevated jugular venous pressure, pulmonary venous congestion or pulmonary oedema. However, the treatment of an acute presentation with standard heart failure therapy may be ineffective. Importantly fluid excess may also manifest as hypertension, even in the absence of other obvious features of fluid excess. Chronic volume overload is believed to be an important contributor to the development of cardiac dysfunction – both through the effects of hypertension and as a direct effect of volume overload. The presence of left ventricular hypertrophy or impaired function is an important adverse risk factor for reduced survival in dialysis patients.

Fluid balance management is an essential aspect of RRT. Hydration depends on a balance between fluid intake and removal. Residual kidney function and urine volume progressively decline after starting dialysis, with patients often eventually becoming anuric. Excess fluid is removed by dialysis and residual urine output, where present, may be enhanced by large doses of loop diuretics (which increase urine volume but not clearances). Patients will also have an individualised restriction of fluid intake, which may often be as low as 1000 mL/day when there is little residual kidney function. It is essential that fluid restriction is accompanied by sodium restriction, because high salt intake will result in excess thirst and difficulty in complying with fluid restriction. As hypertension may partly result from fluid status, managing elevated blood pressure will typically involve assessment by the supervising team and consideration of whether alterations of fluid management are needed in the first instance, rather than simply starting or increasing anti­hypertensive therapy.

Anaemia

Anaemia arises principally from reduced production of the hormone erythropoietin by the kidney. Other contributing factors include functional iron ­deficiency, which presents as normal iron stores determined by serum ferritin, but elevated percentage of hypochromic red blood cells on a full blood count. Management includes optimising iron status followed by treatment with an erythropoiesis-stimulating agent (ESA) or derived analogues. Iron may be administered orally but is often poorly absorbed, and side effects such as ­constipation may be a particular problem in patients on peritoneal dialysis. Alternatively iron is often administered intravenously, and a range of preparations are available with differing administration schedules which are well tolerated. Correction of severe anaemia by ESAs results in marked improvement in patient wellbeing. The reduced requirement for blood transfusion has a number of major benefits, including avoiding sensitisation against possible transplant donor antigens. Recent evidence suggests that complete correction of anaemia by erythropoietin rather than partial correction does not confer any benefits and may even be detrimental, particularly in those with underlying cardiovascular disease. Thus guidelines for anaemia management state target haemoglobin ranges which are less than the normal population range, and suggest that adjustment on an individual basis may be appropriate. The major hazards of ESA therapy include the development of accelerated hypertension and encephalopathy if patients are not appropriately monitored or if the rise in haemoglobin is too rapid (administration is contraindicated where blood pressure is uncontrolled). There is also an increased risk of haemodial­ysis vascular access thrombosis.

Bone mineral metabolism

Abnormalities of bone mineral metabolism are highly prevalent in CKD. Elevated serum phosphate results from reduced renal excretion of phosphate taken in from dietary sources. Reduced metabolism (1-alpha-hydroxylation) of vitamin D results in reduced vitamin D activity. The effects of this include a reduction in serum calcium concentrations and secondary hyperparathyroidism. Management of hyperphosphataemia includes dietary restriction and the use of medication taken at meal times, in order to bind dietary phosphate in the gastrointestinal tract and prevent its absorption. Phosphate binders include calcium compounds such as calcium carbonate or acetate, and non-calcium binders such as the organic polymer sevelamer, and lanthanum ­carbonate. Phosphate is also removed from the body by dialysis.

Active analogues of vitamin D such as alfacalcidol and calcitriol are used to treat hypocalcaemia and secondary hyperparathyroidism. Tertiary hyperparathyroidism may develop, where parathyroid hormone (PTH) secretion is inappropriately high, despite the development of hypercalcaemia, and this is treated by suppression of parathyroid hormone activity by the calcimimetic drug cinacalcet, or definitive surgical parathyroidectomy in patients fit for the surgery. Skeletal symptoms may result from hyperparathyroid bone ­disease or an osteomalacia picture, and some patients may develop adynamic bone disease (often from therapeutic over-suppression of PTH secretion). Other clinical features include itching, which may be associated with hyperphosphataemia and may have a significant effect on quality of life in dialysis patients. An important change of emphasis in managing these abnormalities has resulted from the increasing evidence of disturbed bone mineral metabolism and vascular calcification and the relationship of accelerated ­cardiovascular disease.

Life expectancy in CKD

Life expectancy is significantly reduced in patients with advanced CKD. The data show the median remaining life expectancy for dialysis patients to be 20 years for patients in the 25–29-year-old age group, and 4 years for those aged over 75 years (UK Renal Registry 2010). The major cause of increased mortality is accelerated cardiovascular disease, with a range of underlying risk factors. Traditional cardiovascular risk factors remain important. Hypertension is common, of long duration and often severe. Control of hypercholesterolaemia improves cardiovascular outcomes in non-dialysis CKD patients with lesser degrees of renal impairment. The evidence in dialysis patients is less conclusive. The pathophysiology of cardiovascular disease in CKD differs from the population without renal disease, with predominant features including medial vascular calcification and left ventricular hypertrophy and dysfunction, rather than the typical arterial atheroma seen in non-renal patients. Specific risk factors in renal failure may include the effects of volume overload, vascular calcification, anaemia, an inflammatory state and increased oxidative stress, which are common in advanced CKD.

Management of drug therapy

Management of medication in patients with advanced CKD is complex because of the effects of renal disease and dialysis on drug pharmaco­kinetics, and the potential for interactions with the often extensive lists of prescribed medications (see Chapter 8). Many drugs require dose reduction or cannot be used in patients with advanced renal failure or on dialysis, because of the risk of accumulation and toxicity resulting from reduced renal excretion. Commonly used drugs where there is a need for marked dose reduction and a risk of serious toxicity include digoxin and antivirals such as aciclovir. Many antimicrobials also require dose reduction. It is essential when prescribing any drug for these patients to be aware of recommendations for prescribing regimes in renal disease. Metformin should be used with caution in renal impairment and is contraindicated in the presence of a GFR less than 30 mL/min/1.73 m² because of the risk of life-threatening lactic acidosis. Nephrotoxic drugs should still be avoided in dialysis patients who have residual kidney function.

The wider multidisciplinary team

Management of patients with stage 5 CKD in secondary care involves an extensive multidisciplinary team, including doctors, specialist nurses, pharmacists, dietitians, psychologists and social workers. Close links exist with a range of other secondary care specialties including radiology, vascular surgery, general and transplant surgery, diabetes and cardiology. When these patients present to other specialties or primary care, early liaison with the renal team may be needed to facilitate investigation (for instance limitations on the use of radiological contrast or to interpret blood results) and management. This includes situations where illness may relate to CKD or its treatment such as dialysis- or transplant-related sepsis, fluid overload and hypertension or electrolyte abnormalities, or where advice regarding drug therapy may be required. Discussion with the specialist team is also required where hospital admission is necessary, either for planning provision of dialysis during the patient’s illness or admission, or for advice regarding care of a kidney transplant.

Urea and creatinine

Serum urea and creatinine levels remain markedly elevated in dialysis patients compared with patients with normal kidney function. Values are strongly influenced by dietary protein intake or muscle mass respectively and are not a useful measure of the efficacy of dialysis, which is determined by measurements of clearance by the dialysis procedure. Relatively lower serum urea and creatinine values are actually associated with worse outcomes on dialysis, often reflecting poor nutrition or wasting rather than more efficient dialysis.

Haemodialysis

Related posts:

Acute Kidney Injury in Hospitalised Patients General Considerations Related to Treatment Modalities Optimising Nutrition in People with Chronic Kidney Disease Supportive and Palliative Care for Patients with Advanced Kidney Disease Medication Management and Chronic Kidney Disease A Practical Approach to Chronic Kidney Disease in Primary Care

Stay updated, free articles. Join our Telegram channel

Join