Overview

Chronic kidney disease (CKD) is defined as a reduction in kidney function, structural damage, or both for more than 3 months with associated health implications. CKD can lead to fluid and electrolyte imbalance, and protein and/or blood leakage into the urine, causing proteinuria and haematuria.

Epidemiology

  • The prevalence of CKD increases significantly with age
  • Incidence is highest in those aged >60 years

Causes

Presentation

  • CKD is often asymptomatic, and it is often detected on routine blood tests. As kidney function decreases, symptoms may emerge including:
  • Uraemia – accumulation of urea due to failure of renal clearance:
    • Reduced appetite
    • Nausea with or without vomiting
    • Pruritus
    • Restless legs
    • If severe, patients may have seizures or coma
    • See Uraemia for more information
  • Reduced urine output – may lead to fluid overload which may present with:
    • Peripheral oedema
    • Weight gain
    • Orthopnoea
    • Pulmonary oedema
  • Anaemia – due to reduced anaemia of chronic disease (AOCD) secondary to erythropoietin (EPO) deficiency:
  • Foamy urine – due to proteinuria
  • Dark urine – due to haematuria

Differential Diagnoses

Acute kidney injury

  • May be difficult to differentiate if no baseline kidney function tests are available. Features favouring CKD include:
  • Anaemia – due to AOCD
  • Hypocalcaemia – due to reduced activation of vitamin D, which takes place in the kidneys
  • Hyperphosphataemia – CKD can lead to decreased phosphate excretion
  • Small kidneys on ultrasound – this may not always be seen:
    • E.g. in polycystic kidney disease, a cause of CKD, the kidneys may be enlarged

Acutely unwell patients or hypovolaemia make CKD less likely and AKI more likely.

Chronic kidney disease

  • Symptoms present more acutely (e.g. acute worsening of hypertension and development of periorbital and peripheral oedema)
  • Blood tests may show hypoalbuminaemia and hyperlipidaemia
  • Serological tests may be positive (e.g. anti-neutrophil cytoplasmic antibodies, ANCA)

Investigations

The most important initial investigations include:

  • Urea and electrolytes (U&Es) and calcium – may identify initial abnormalities:
    • Urea is not a reliable marker of renal function as it varies with diet and hydration
  • Creatinine – important for the estimated glomerular filtration rate
    • May be falsely low/high (e.g. falsely elevated in those with high muscle mass)
    • It may remain normal despite losing over 50% of renal function.
    • Serum sodium may be normal or low
    • Serum potassium may be elevated
    • Serum calcium may be low, normal, or high
  • Estimated glomerular filtration rate (eGFR) – assesses kidney function:
    • Since creatinine is not reliable on its own, eGFR may be used, which is a formula based on serum creatinine, age, gender, and ethnicity
    • Patients should avoid eating meat for at least 12 hours before collecting creatinine measurements
  • Urinary albumin:creatinine ratio (ACR) – to assess proteinuria:
    • This test avoids the need to collect urine over 24 hours to quantify proteinuria
    • Ideally should be performed with an early morning sample for a more accurate result
      • <3 mg/mmol – no proteinuria, no action needed
      • 3-70 mg/mmol – clinically significant proteinuria, repeat within 3 months
      • ≥70 mg/mol – significant proteinuria
    • Urine dipsticks are not recommended unless they can measure small amounts of albumin and report the result as an ACR. If the dipstick shows unexplained proteinuria, offer testing for CKD using eGFR and ACR
  • Urine dipstick – to check for haematuria:
    • ≥1+ blood: arrange mid-stream urine (MSU) sample to rule out a urinary tract infection (UTI)
    • Isolated persistent haematuria (2/3 dipsticks show ≥1+ blood and no decrease in eGFR and proteinuria): rule out urological malignancy

Referral

Patients should be referred to a nephrologist if any of the following apply:

  • ACR ≥70 mg/mmol unless known to be caused by diabetes and appropriately managed
  • ACR ≥30 mg/mmol with persistent haematuria after ruling out a UTI
  • Consider a referral if ACR 3-29 mg/mmol and there is persistent haematuria and other risk factors such as a falling eGFR or cardiovascular disease
  • A sustained decrease in eGFR of ≥25% or ≥15 mL/min/1.73 m2 within 12 months
  • Suspected genetic or rare causes of CKD
  • Hypertension that does not respond to at least 4 antihypertensives
  • Suspected renal artery stenosis

Diagnosis and Classification

Diagnosis

Diagnose CKD if eGFR is persistently <60 mL/min/1.73 m2 and/or proteinuria (ACR >3 mg/mmol) is present for at least 3 months.

CKD can be excluded if eGFR is persistently >60 mL/min/1.73 m2 and/or no proteinuria (ACR <3 mg/mmol) and no markers of kidney damage.

  • These patients should have annual creatinine, eGFR, urinary ACR, and urine dipstick monitoring if they have ongoing risk factors for CKD

Classification

CKD is classified by combining eGFR (G stage), urinary ACR (A stage), and the presence of markers of kidney damage (e.g. proteinuria, haematuria, deranged U&Es, histological abnormalities, or a history of kidney transplantation):

The G and A stages can be combined to give an overall score. For example, a patient with an eGFR of 50 with an ACR of 25 would have G3aA2 CKD.

Management

Overview

The major cause of death in patients with CKD is cardiovascular disease (CVD), therefore management of CKD involves lipid modification, glycaemic, and hypertensive control. Other aspects of management include treating complications, which are discussed below.

Lipid modification

Patients are offered atorvastatin for the primary prevention of CVD

  • If eGFR is ≤30 mL/min/1.73 m2, seek specialist advice before increasing the dose

Hypertension

Hypertension causes CKD and CKD causes hypertension. ACE inhibitors or ARBs are first-line in CKD as they slow progression and are offered if any of the following apply:

  • CKD with diabetes (type 1 or 2) and A2 or above (ACR ≥3 mg/mmol)
  • CKD with hypertension and A3 or above (ACR ≥30 mg/mmol)
  • CKD and ACR >70 mg/mmol, regardless of their blood pressure or risk of CVD – these patients should be referred to nephrology

Other

Immunisation:

  • CKD stage 3, 4, or 5: offer annual influenza vaccination
  • CKD stage 4 or 5: offer 5-yearly pneumococcal vaccine

Monitoring:

  • Patients have their eGFR and ACR monitored annually. How frequently each year depends on the stage of their CKD.

Complications

Anaemia

CKD may cause anaemia once eGFR is between 30-60 mL/min/1.73 m2 (G3a or less). This usually occurs due to reduced EPO secretion. Anaemia is unlikely to be due to CKD if eGFR >60 mL/min/1.73 m2 and other causes should be sought.

If patients have suspected anaemia secondary to CKD:

  • Carry out tests to determine iron status:
    • Measure % of hypochromic red blood cells only if this can be done within 6 hours
    • If unavailable/patient has thalassaemia/trait, measure transferrin saturation + ferritin
  • Optimise iron status:
    • Not having haemodialysis: oral iron
    • Having haemodialysis/oral iron not tolerated/target haemoglobin not reached in 3 months: IV iron
  • Erythropoietic-stimulating agents (ESAs) are given once the iron deficiency is optimised:
    • Examples are erythropoietin and darbepoetin

Mineral and bone disorders

Activation of vitamin D normally happens in the kidneys, however, in CKD this is reduced, leading to low vitamin D. The kidneys also normally excrete phosphate, therefore in CKD, more is retained, leading to hyperphosphataemia.

Low vitamin D leads to reduced calcium absorption and hypocalcaemia. Hyperphosphataemia removes calcium ions from the circulation and deposits them in the insoluble salt calcium phosphate, worsening hypocalcaemia. Hypocalcaemia, low vitamin D, and hyperphosphataemia then cause secondary hyperparathyroidism (HPT).

This generally happens at CKD G3 and can lead to osteomalacia, osteopenia, osteoporosis, and osteosclerosis.

Management of mineral and bone disorders includes:

  • 1st-line: reduce dietary phosphate intake
  • Phosphate binders (e.g. calcium acetate)
  • Vitamin D supplements (e.g. alfacalcidol, calcitriol)

Metabolic acidosis

This may occur as the kidneys are responsible for excreting excess H+. Oral sodium bicarbonate may be considered if eGFR is <30 mL/min/1.73 m2 (G4 or G5) and serum bicarbonate is <20 mmol/L.

End-stage renal disease (ESRD)

People with CKD stages 4-5 may need renal replacement therapy (RRT). This is either haemodialysis or a kidney transplant.

Other complications

Prognosis

  • The most common cause of death in CKD is CVD rather than renal failure
  • The risk of all-cause mortality is increased with CKD

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