Chronic kidney disease - clinical review

An in-depth guide to the diagnosis and management of chronic kidney disease (CKD) in primary care.

Coloured gamma scan showing kidney failure in right kidney with low activity (green) in the hilar area (Photo: SPL)
Coloured gamma scan showing kidney failure in right kidney with low activity (green) in the hilar area (Photo: SPL)

Section 1: Epidemiology and aetiology

Chronic kidney disease (CKD) describes persistent abnormal kidney function or structure.

CKD is common, often unrecognised, expensive to treat and associated with an increase in mortality at all ages when the glomerular filtration rate (GFR) is <60ml/min.

In the UK, the prevalence of stage 3-5 CKD is 8.5%; 45,000 adults are on renal replacement therapy (RRT) and 2% of the total NHS budget is spent on these patients. CKD often coexists with other medical conditions.

Strategies aimed at the early identification and prevention of progression of CKD are required. Hypertension and diabetes are responsible for up to two-thirds of cases. CKD also significantly increases the patient’s risk of cardiovascular events, especially when the GFR is <45ml/min.

Patients with diagnosed CKD are more likely to die from cardiovascular disease (CVD) than progress to endstage renal disease, so interventions to minimise cardiovascular risk are essential.

Defining CKD
The definition of CKD has been refined and evolved in the past decade and now follows the Kidney Disease Improving Global Outcomes (KDIGO) guidance, which categorises CKD based on GFR and proteinuria (see table 1). This is an evolution of an earlier five-stage system.

Glomerular filtration rate
Normal GFR is considered to be about 100ml/min/1.73m2, so any given result is approximately the percentage of normal kidney function for that patient.

GFR is estimated using a formula (CKD-EPI) based on age, sex and creatinine. Results should be multiplied by 1.16 for patients from an African or Caribbean background.

GFR falls with age, but the level of normal decline is unclear. However, reductions in GFR caused by renal pathology are very common in older people, so at any stage of CKD, management should not be influenced by age alone.

It is generally agreed that patients over 70 years of age, with a stable GFR >45ml/min/1.73m2 and no other evidence of kidney damage, are unlikely to develop CKD-related complications.

Levels of proteinuria are known to be important indicators of CKD and higher levels indicate higher risk of complications. As a result, the albumin/creatinine ratio (ACR) is an intrinsic part of the classification of CKD (see table 2).

An ACR of 70mg/mmol is equivalent to a protein/creatinine ratio (PCR) of 100mg/mmol and to a 24-hour protein loss of 1,000mg.

Section 2: Making the diagnosis

Early identification and treatment of CKD is vital to reduce the risk of cardiovascular disease and renal function decline. However, CKD is often unrecognised – in the early stages, patients are asymptomatic and in the latter stages, symptoms are non-specific.

It may not be until patients develop oedema and breathlessness with advanced renal impairment that CKD is diagnosed on laboratory testing. It is vital to identify high-risk groups (see boxes 1 and 2) and monitor their renal function at least annually, along with performing urinalysis.

Renal function
The detection of an initial abnormal eGFR (<60ml/min/1.73m2) should prompt a repeat test within two weeks to assess the rate of change in GFR. If the result is stable, a further test is required after 90 days to confirm the CKD diagnosis.

When abnormal renal function is detected, the patient’s history, examination and investigations should be reviewed. It is vital to determine the timescale over which the deterioration has taken place.

Progressive renal disease is a fall in eGFR of >5ml/min/1.73m2 over one year or >15ml/min/1.73m2 over five years.

Ask patients about urinary tract symptoms and review their medications, especially new ones, looking for NSAIDs, ACE inhibitors/ARBs, diuretics, antibiotics and mesalazine. Assess BP, urinalysis and palpate for an enlarged bladder, along with looking for signs of infection, volume depletion and fluid overload.

Dip their urine to look for haematuria and proteinuria. If either are present on urine dipstick, exclude a UTI with a urine culture. Dipstick tests are not usually sensitive enough to detect ACR.

If the ACR is high, the urinary PCR can be used to quantify and monitor the degree of proteinuria; 24-hour urine collections are no longer necessary.

Organise a renal tract ultrasound if the patient has any of:

  • Accelerated progression of CKD
  • Visible or persistent invisible haematuria
  • Symptoms of urinary tract obstruction
  • Family history of polycystic kidney disease and age >20 years
  • eGFR <30ml/min/1.73m2 (GFR category G4 or G5)

Serum cystatin C can be used for a more accurate estimation of GFR, although this is much more expensive and is not available in all areas.

It can be used as a one-off test to confirm or rule out CKD for patients with eGFRcreatinine of 45-59ml/min/1.73m2 and ACR <3mg/mmol and no other marker of kidney disease.

If eGFRcystatinC is >60ml/min/1.73m2, CKD is not present and no further testing is required.

Section 3: Managing the condition

At all stages of CKD, regular clinical and laboratory assessment must take place to reduce the risk of progression and to manage cardiovascular risk (see figure 1).

The three established risk factors for CKD progression and CVD are hypertension, diabetes and proteinuria. South Asian patients with diabetes and African-Caribbeans with hypertension are more likely to develop progressive renal disease and should be treated aggressively.

For most CKD patients, the BP target is 140/90mmHg, but for patients with diabetes or those with ACR >70mg/mmol (or PCR >100mg/mmol), the target is 130/80mmHg.

NICE guidelines (CG127) for anti­hypertensives should be followed, taking into account the advice given below for proteinuria.

Patients aged under 55 years are started on an ACE inhibitor/ARB first line. Measure creatinine and eGFR before therapy and seven to 10 days after starting.

A small rise in creatinine (<30%) or fall in eGFR (<25%) is normal, owing to the reduction in filtration pressure in the glomerulus. If the eGFR has deteriorated by >25%, look for other causes, such as other medications or volume depletion, and only stop or reduce the ACE inhibitor/ARB as a last resort.

The ACE inhibitor/ARB should also be withdrawn if the patient’s potassium rises above 6mmol/L and other drugs known to promote hyperkalaemia have been stopped.

If hyperkalaemia is a persistent problem, advice about following a low-potassium diet is helpful.

Older or African-Caribbean patients should be given a calcium-channel blocker or thiazide diuretic. For uncontrolled BP, alpha- and beta-blockers can be added.

Diabetes management should be in accordance with NICE guidance NG17 (type 1) and CG87 (type 2).

A low-cost ACE inhibitor or ARB should be offered to patients with CKD and:

  • Diabetes and ACR A2 or A3
  • Hypertension and ACR A3
  • ACR of >70mg/mmol irrespective of cause

CVD risk
Based on NICE guidance (CG181), Qrisk2 should not be used for patients with CKD G3-5 or albuminuria, because they are already at significant risk of CVD, and these patients should be offered atorvastatin 20mg as primary prevention (increased if necessary and safe).

NICE recommends apixaban is preferable to warfarin for patients with eGFR 30-50ml/min/1.73m2 who have AF and risk factors for stroke. Anti­coagulation for patients who have CKD G4 and G5 should only be commenced following specialist advice.

Medication and lifestyle
Nephrotoxic drugs should be reviewed. Appropriate dose adjustments for all drugs should be made for the level of renal function.

General lifestyle advice should be given to all patients on smoking, weight loss, exercise, and salt and alcohol intake, which have an impact on renal progression and cardiovascular risk.

The use of antiplatelet and cholesterol-lowering agents should be used in concordance with the standard recommendations for primary and secondary prevention of CVD.

Anaemia and bone disease
The prevalence of anaemia increases as GFR declines, especially from stage G3b onwards, owing to the failure of the kidneys to produce erythropoietin.

NICE guidance NG8 suggests that patients with CKD G3b, G4 and G5 and Hb ≤11g/dL are referred for IV iron and subcutaneous erythropoietin-stimulating agents when other causes of anaemia have been excluded.

However, oral iron can be used to maintain ferritin levels >200 microgram/L.

Alterations in calcium and phosphate homeostasis affect bone turnover and mineralisation, along with progressive vascular and soft tissue calcification. Clinically significant changes are not generally apparent until stage G4 CKD.

Calcium, phosphate, parathyroid hormone and vitamin D monitoring is not routinely necessary for CKD G1-G3. It is necessary in CKD G4 and G5, but these patients will usually be under the supervision of a nephrologist.

Hyperphosphataemia can be controlled with a low-phosphate diet, otherwise binders may be required with meals.

If vitamin D supplementation is required in patients with stage 4-5 CKD, 1-alpha hydroxylated preparations are used.

For advanced CKD, the multidisciplinary team plan for RRT and try to manage CKD complications.

Frequency of monitoring
NICE advises tailoring monitoring to the patient, their wishes, the speed of progression of disease and the severity of CKD. For those in G1, G2 and G3aA1-A2, annual monitoring is adequate. G3aA3, G3b and G4A1-A2 require twice-yearly monitoring, and G4A3 and beyond, more frequent monitoring, but these patients are likely to be under the supervision of a nephrologist. Monitoring should be more frequent if there are changes to medication, comorbidities or intercurrent illness.

Referral to nephrology
Consider the patient as a whole and their preferences when discussing referral.

Normally, refer if the patient has CKD and any of:

  • GFR category G4 or G5
  • ACR >70mg/mmol (unless known to be due to diabetes and already treated)
  • ACR >30mg/mmol (ACR A3) with haematuria
  • Sustained decrease of 15ml/min/1.73m2 in one year or a decrease in GFR of >25% and a change in CKD category
  • Hypertension despite four antihypertensive drugs
  • A known or suspected rare or genetic cause of CKD
  • Suspected renal artery stenosis

Seeking specialist advice by email, telephone or letter may avoid the need for a hospital appointment.

Always arrange eGFR monitoring while the patient is waiting to be seen by specialists. Consider organising a renal tract ultrasound.

Features of post-renal obstruction or malignancy should also be referred to urologists.

Acute kidney injury
Patients who have had acute kidney injury (AKI) are at higher risk of developing CKD and should be monitored regularly for CKD for two or three years afterwards, even if the eGFR returns to baseline.

Patients with CKD are much more vulnerable to AKI – discussing sick day rules about hydration, holding off antihypertensives and NSAIDs when patients are unwell can help to prevent AKI developing.

Patient education
Informing patients of their diagnosis and providing tailored education and support can improve compliance with medication and reduce complications.

Section 4: Prognosis

The nephrologist’s role in managing patients with CKD includes identifying those who may require RRT, providing additional input into managing difficult complications of CKD (for example, uncontrolled hypertension despite four maximal-dose antihypertensives), giving advice on rare or genetic causes of CKD, and providing specialist tests, such as renal magnetic resonance angiography for suspected renal artery stenosis.

All appropriate patients with rapidly declining GFR (>15ml/min over one year or a 25% reduction and change in CKD category) and CKD G4 and G5 should be referred.

Adults over 50 years of age who have persistent microscopic haematuria should undergo prompt investigations for malignancy by a urologist, under the two-week rule if appropriate.

If these investigations are negative, patients with persistent microscopic haematuria but <0.5g/day proteinuria should be followed up in primary care with annual urinalysis, PCR, eGFR and BP assessments (unless they reach other criteria for referral). The rationale is that they are in a good prognostic group, but are at risk of progressive renal disease.

The patient’s wishes and any comorbidities should be taken into account. A number of patients with CKD G5 opt for conservative management instead of RRT and are supported symptomatically.

Once a referral has been made and a management plan jointly agreed, routine follow-up can take place in primary care until specific criteria are reached, at which point the patient is referred back for further specialist input.

Section 5: Case study

A 60-year-old male was registered as a new patient at the GP practice. His medical history included hypertension, type 2 diabetes for the past 11 years and an MI at the age of 55 years. Previously he had been told that he had protein in his urine. He was a smoker and had a BMI of 32. He was not taking NSAIDs.

Clinical examination revealed a BP of 155/90mmHg; he was euvolaemic and had a peripheral neuropathy. Urinalysis showed 3+ protein and 1+ blood.

Investigations revealed eGFR 28ml/min/1.73m2, when last year it had been 38ml/min/1.73m2.

At that time, metformin was discontinued and an ACE inhibitor continued at the same dose.

The urine culture was sterile, ACR was 70mg/mmol and PCR was 100mg/mmol (equivalent to 1g/24 hours of proteinuria).

The results of the patient’s remaining blood tests demonstrated Hb 104g/L, MCV 90, albumin 38g/L, HbA1c 76mmol/mol, normal bone profile and protein electrophoresis.

The patient had evidence of both microvascular and macrovascular disease. His GFR had deteriorated by 10ml/min (26%) over the past year from G3b to G4, which may be related to the above complications, although alternative diagnoses should be considered. He also had microscopic haematuria. He was CKD stage G4A3.

He was referred for smoking cessation counselling and given advice on weight reduction. His antihypertensive medications were increased.

An ultrasound was arranged and he was referred to a nephrologist in view of the rapid decline in renal function, and a urologist to investigate the haematuria, given his age and smoking history.

The ultrasound revealed a large prostate and mild bilateral hydronephrosis, which the urologists treated by transurethral prostatectomy. Urothelial malignancy was excluded.

The nephrologists worked in conjunction with his GP to optimise his BP and reduce the proteinuria, as well as giving him IV iron. Over the next year, the renal function stabilised.

Section 6: Evidence base


Key text

  • Steddon S, Ashman N, Chesser A et al. Oxford Handbook of Nephrology and Hypertension. Oxford, Oxford University Press, 2006

Based on the Oxford Textbook of Clinical Nephrology, this more concise book provides clear information and practical advice on the day-to-day management of patients with CKD and other aspects of renal disease.


This website provides information on the latest advances in renal disease and clinical guidelines for all aspects of renal care.

  • Dr Neil Iosson is a locum GP in Sussex; Dr Victoria Ingham is consultant in nephrology at Brighton and Sussex University Hospital NHS Trust and Dr Marlies Ostermann is consultant in nephrology and critical care, Guy’s & St Thomas’ NHS Foundation Trust, London

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This is an updated version of an article that was first published March 2011.

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