Chronic kidney disease

The management of chronic kidney disease is now part of the core work of the practice nurse. A clear understanding of the condition directly affects the quality and effectiveness of the care we give

Chronic kidney disease (CKD) is a gradual impairment in kidney function. It can progress, over time, to end stage renal disease, although with careful management and treatment of underlying causes, this can be slowed or even reversed. CKD affects all functions of the kidney; late consequences include anaemia, vitamin D deficiency and phosphate deficiency. It is also associated with an increased risk of cardiovascular disease.¹

Early CKD is asymptomatic. It is therefore essential that we identify patients who could be at risk, and test them. There is clear evidence that treatment can prevent or slow both the progression of CKD and the associated risk of cardiovascular disease. It’s also clear that early diagnosis and intervention produces the most dramatic benefits.1–3 The earlier our intervention, the greater the impact.

HOW COMMON IS CKD?

This is difficult to answer accurately since prevalence varies with the population being tested. The risk of developing CKD increases with age, since renal function declines with age. A 2010 study suggested the overall prevalence of stage 3-5 CKD was 5.9%, but in elderly patients it is much higher.⁴ As our population ages, and with increasing rates of obesity, hypertension and diabetes, prevalence will continue to rise.

DEFINITION

CKD is defined by the presence of markers of renal disease present in urine, blood or on ultrasound – with or without impaired glomerular filtration rate (GFR) – for at least 3 months. The level of kidney function is assessed using a combination of the estimated GFR (eGFR) and the urine albumin:creatinine ratio (ACR). The Kidney Disease: Improving Global Outcomes (KDIGO) guideline has defined the stages and prognosis of CKD in detail,5 (Table 1), and produced evidence-based guidelines on the aspects of care most likely to improve patient outcomes.

FUNCTION OF THE KIDNEYS

The kidney has multiple functions, all of which can be affected by CKD:

• Removal of waste products, including drugs and toxins
• Regulation of fluid balance
• Regulation of salt balance, particularly sodium, potassium, phosphate and acidity
• Participation in the feedback loop of hormones that regulate blood pressure
• Production of vitamin D for bone strength
• Production of erythropoietin, which stimulates red blood cell production.

CAUSES OF RENAL IMPAIRMENT

Age is one of the main contributors to CKD, and age related reduction in renal function adds significantly to the effects of other conditions.⁴

Damage to the kidneys may result from conditions that directly affect the nephron or the tissues around it (renal causes), conditions which reduce blood flow into the system (prerenal causes), and conditions that prevent drainage out of it (postrenal causes).

Chronic vascular conditions

CKD is most often associated with diabetes and hypertension, but also with obesity and cardiovascular disease. In the developed world, diabetes and hypertension are the main causes of CKD and, between them, account for two thirds of cases.^1,4

Renal blood flow is reduced, and the glomerulus may become leaky, allowing protein molecules and/or blood cells to escape into the urine.

Renal inflammation

Glomerulonephritis, a group of diseases causing inflammation of the nephron, is the third most common cause of CKD. It can be a primary kidney disease, or secondary to bacterial, viral or parasitic pathogens, drugs or systemic disorders such as systemic lupus erythematosus (SLE) and diabetes.

Recurrent infections, interstitial nephritis and some inherited conditions such as polycystic kidney disease may directly damage renal tissue.

Obstructive conditions

Chronic outflow obstruction e.g. from renal stones or prostatic hypertrophy, through backpressure and repeated, retrograde infection can result in impaired renal function.

Toxins and metabolites

As filters the kidneys are vulnerable to toxins, whose effects may build up over time e.g. non-steroidal anti-inflammatory drugs (NSAIDs). Many drugs have the potential to harm the kidneys.

Metabolic abnormalities, such as hypercalcaemia, and metabolites arising from neoplastic conditions can also directly damage the kidney.

Acute kidney injury (AKI)

Acute injury, e.g. due to toxins, hypovolaemia and trauma, also has the potential to become chronic if it, or the conditions leading to it, are not reversed.

Congenital or inherited renal abnormalities

Conditions such as polycystic kidney disease may lead directly to CKD.

ASSESSING AND MONITORING RENAL FUNCTION: GFR, eGFR and ACR

Kidney function is assessed using both a measure of the kidneys’ ability to filter the blood, and a measure of glomerular leakiness:1

• ACR (urine albumin-creatinine ratio): a measure of the degree to which large molecules like protein and blood cells are getting through to the urine
• GFR (glomerular filtration rate): a measure of the volume of blood being filtered each minute, corrected for the size of the patient
• eGFR (estimated GFR): We can’t ‘measure’ GFR directly, but we can calculate an estimated GFR (eGFR), using the serum creatinine corrected for the patient’s age. eGFR is accurate enough to assess change over time in most patients.

Creatinine is a product of muscle metabolism and is excreted unchanged by the kidneys. If filtration in the kidney is deficient, creatinine blood levels rise.

Those with significantly more muscle than average have naturally higher creatinine levels – which can make their eGFR look worse than it is. Those with very low muscle mass, including the very elderly, will have lower creatinine levels – which may make their kidney function look better than it really is.

SYMPTOMS AND SIGNS

CKD is usually discovered by chance following a routine blood or urine test. Specific symptoms usually develop only in severe CKD. They include anorexia, nausea, vomiting, fatigue, weakness, pruritus, lethargy, peripheral oedema, dyspnoea, insomnia, muscle cramps, pulmonary oedema, nocturia, polyuria and headache. Sexual dysfunction is common, although hiccups, pericarditis, coma and seizures are only seen in very severe CKD.

Although there are generally no signs of CKD until the condition is advanced, there may be signs of underlying causes, e.g. SLE, diabetes, hypertension. Other possible signs include increased skin pigmentation, pallor, postural hypotension, peripheral oedema, left ventricular hypertrophy, peripheral vascular disease, pleural effusions, peripheral neuropathy and restless legs syndrome.

SCREENING AND DIAGNOSIS

Patients who are at increased risk of developing CKD should be offered screening tests.¹ This should include assessment of the eGFR and urine ACR. Offer people testing for CKD if they have any of the following risk factors:

• Acute kidney injury
• Cardiovascular disease
• Diabetes
• Structural renal tract disease, recurrent renal calculi or prostatic hypertrophy
• Multisystem diseases with potential kidney involvement, e.g. SLE
• Family history of end-stage kidney disease
• Haematuria.

ASSESSMENT OF THE NEW PATIENT

When a new patient presents we need to assess both where they are on the spectrum of CKD, and also how fast they are changing. When raised creatinine or lowered eGFR is found on testing you should immediately:1

• Review all previous measurements of creatinine and eGFR to assess the rate of deterioration. At least three assessments of eGFR should be made over not less than 90 days, to evaluate the rate of change. If you have only one low reading assess the second in two weeks to rule out swift deterioration.
• Check the urine. Haematuria and proteinuria suggest glomerulonephritis, which can progress rapidly. Seek advice.
• Assess blood pressure and look for signs of sepsis, heart failure, atrial fibrillation, hypovolaemia, palpable bladder.
• Review all medication including OTC drugs; particularly consider recent additions that can affect kidney function, e.g. diuretics, ACE inhibitors, NSAIDs, or any drug capable of causing interstitial nephritis, such as penicillins, cephalosporins, mesalazine. Consider drugs that may be more toxic in renal failure, e.g. digoxin. (See Activity 1)
• Repeat serum creatinine measurement within five days to exclude rapid progression.
• Check haemoglobin, electrolytes, calcium, folate and B12 if these have not already been recorded.
• Check criteria for referral (See Activity 2)
• Ensure entry into your chronic disease management register.

MANAGEMENT

The aims of management are the prevention of disease progression and the associated risks through:

• Management of underlying causes
• Assessment and reduction of cardiovascular risk
• Blood pressure control
• Nutrition, exercise and lifestyle
• Smoking cessation
• Bone health
• Fluid and salt balance
• Management of late symptoms.

Cardiovascular risk management

Patients should have an annual cardiovascular risk assessment including lipid profile, BMI, exercise, alcohol and smoking habits, as well as a review of interventions to reduce cardiovascular risk.¹

Medications to consider include:

• Statins, which lower death and major cardiovascular events by 20% in people with CKD.1,2,6 Offer atorvastatin 20 mg initially.
• Folic acid and B vitamin supplements should be offered unless B12 levels, and serum and red cell folate are in the normal range.
• Antiplatelet drugs are, overall, beneficial for the secondary prevention of CVD, but be aware of the increased risk of bleeding.¹ The choice of drug varies with the patients age, CKD stage, and other risk factors.

Blood pressure control1

Aim to keep the blood pressure below 140/90 mm Hg in patients with CKD.

In those who also have diabetes, and in people with an ACR of 70 mg/mmol or more, aim to keep the blood pressure below 130/80 mm Hg.

An angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) should be used (if not otherwise contraindicated) in those with:

• Diabetes and an ACR of 3 mg/mmol or more
• Hypertension and an ACR of 30 mg/mmol or more
• An ACR of 70 mg/mmol or more.

Otherwise, follow normal NICE hypertension guidelines.⁷

Measure serum potassium concentrations and eGFR before starting ACE inhibitors. Repeat these measurements between one and two weeks after starting the drugs and after each dose increase.

Nutrition8

All patients with stage 4-5 CKD should have body weight and BMI recorded regularly, and should receive dietary advice to restrict sodium intake to 8

Some dietary restriction of sodium and potassium is appropriate, although this needs a flexible approach to avoid making patients’ lives miserable. The risk of hyperkalaemia may be reduced by avoiding specific foods rich in potassium such as some fruits, chocolate and coffee.

A daily energy intake of 30-35 kcal/kg of body weight/day is recommended, depending upon age and physical activity.

Lifestyle1

Patients should try to perform regular moderate exercise and should be advised and assisted to give up smoking.

Mineral and bone disorders1

Advanced CKD and renal failure affect vitamin D metabolism and increase the risk of osteoporosis. The management of these conditions in patients with CKD is a specialist area, and treatment needs to be carefully tailored to the patient. Seek advice.

Hyperphosphataemia1

Hyperphosphataemia occurs because of insufficient filtering by the kidneys, and can lead to the development of hyperparathyroidism. A specialist renal dietitian should give individualised information and advice.

Fluid balance1

Most patients with CKD pass normal volumes of urine. Fluid restriction intake is only required for patients with low urine output end-stage kidney disease. However all patients should avoid binge drinking and be vigilant about replacing extra fluid losses in hot weather and during episodes of diarrhoea or vomiting.

TALKING TO PATIENTS

Patients may think kidney disease means renal dialysis and be understandably anxious. You will need to reassure them and explain that CKD is a widely varying disease. Mild CKD is common and rarely progresses to a more severe form.

You will also need to explain what the test results mean, in ways that are understandable – e.g. the eGFR is roughly equivalent to the percentage ‘performance’ of the kidneys. A normal GFR is over 90, so an eGFR of 50 = 50% of the normal renal function. However, it is still important to stress that kidneys that are working more slowly ARE still working, but that they are less efficient and therefore need more care. Their eGFR will need to be monitored to make sure things aren’t getting worse, and if things do get worse treatment will be intensified and changed.

The link between CKD and an increased cardiovascular risk will need to be explained. Patients will need to understand the importance of tight blood pressure control to limit further damage to the kidneys and reduce their cardiovascular risk. Similarly, patients with diabetes need to understand that really tight glycaemic control will help their kidneys.

Lifestyle advice is also important. Exercise, achieving a healthy weight and stopping smoking will make a really significant contribution to improving the prognosis and, apart from working with you, these are the most important things they can do to help themselves.

The importance of medication reviews, to ensure that doses are appropriate, will also need to be explained. Patients will also need to be warned to avoid nephrotoxic drugs, including NSAIDS, and to always ask the pharmacist for advice before taking OTC medications.

CKD impairs immunity. Patients should be immunised against pneumococcus and influenza as they are at increased risk.

PROGNOSIS1–5

Early diagnosis, regular monitoring and early treatment can prevent development and slow disease progression, reduce complications and the risk of cardiovascular disease, and improve survival and quality of life.^1,2 CKD progresses to end-stage kidney disease in a small but significant percentage of people.

Moderate-to-severe CKD is also associated with an increased risk of other adverse outcomes such as AKI, falls, frailty and mortality. As kidney dysfunction progresses, some co-existing conditions become more common and increase in severity.

People with CKD are at increased risk of progression to end-stage kidney disease if they have either of the following:

• A sustained decrease in eGFR of 25% or more over 12 months, or
• A sustained decrease in eGFR of 15 ml/minute/1.73 m2 or more over 12 months.

CONCLUSION

The mainstay of the prevention of CKD is early diagnosis and good control of the main potential causes: diabetes, hypertension and urinary tract obstruction, together with general measures to improve lifestyle in the areas of smoking, diet and physical exercise.

However, once the condition is established there is still a great deal that we can offer. The mainstay of all good treatment is good, informed communication with patients, continuity of care and a shared approach to management that keeps patients fully engaged with their own care.

REFERENCES

1. NICE. Chronic Kidney Disease in Adults, assessment and management. 2014 CG182 (updated Jan 2015): https://www.nice.org.uk/guidance/cg18

2. NICE. Nice Pathways, Chronic kidney disease https://pathways.nice.org.uk/pathways/chronic-kidney-disease

3. The Renal Association. Information and Resources http://www.renal.org/information-resources/the-uk-eckd-guide/ckd-stages#sthash.CVGHd9i7.dpbs

4. Jameson K, Jick S, Hagberg KW et al. Prevalence and management of chronic kidney disease in primary care patients in the UK. International Journal of Clinical Practice 2014; 68(9):1110-21 http://www.ncbi.nlm.nih.gov/pubmed/24852335

5. Kidney Disease: Improving Global Outcomes. Clinical practice guideline for the evaluation and management of chronic kidney disease. 2012. Kidney International 2013; 3(1) Suppl: 1-150 http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf

6. Palmer SC, Navaneethan SD, Craig JC, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2014 May 31;5:CD007784. doi: 10.1002/14651858.CD007784.pub2.

7. NICE. Hypertension in adults: diagnosis and management. NICE 2011, CG 127 https://www.nice.org.uk/guidance/cg127

8. Wright M, Jones C. Nutrition in Chronic Kidney Disease. The Renal Association, 2010 http://www.renal.org/guidelines/modules/nutrition-in-ckd#sthash.CUICrpmi.dpbs