Renal failure can present as either acute kidney injury (AKI) (previously acute renal failure (ARF)) or chronic kidney disease (CKD). Acute exacerbations with sudden and often reversible deterioration in renal function may occur in patients with chronic renal failure (acute on chronic renal failure).

Acute kidney injury (acute renal failure)

This is a significant deterioration in renal function occurring over hours or days.

• Clinically, there may be no symptoms or signs, but oliguria (urinary output less than 0.5 mL/kg/hour or 400 mL/24 hours) is common.
• Biochemically, acute kidney injury (AKI) is detected by rising plasma urea and 50% rise in serum creatinine concentration.
  There is also a fall in estimated glomerular filtration rate (GFR) of greater than 25% (if the baseline is unknown assume 75 mL/min/1.73 m²) but GFR must be interpreted with caution as formulae rely on a stable creatinine concentration.
• AKI may arise as an isolated problem; more commonly it occurs in the setting of circulatory disturbance, e.g. severe illness, sepsis, trauma, or surgery, or in the context of nephrotoxic drugs.

Because it requires emergency treatment, all patients with newly detected abnormal renal function should be assumed to have AKI until proven otherwise, although the majority will turn out to have chronic kidney disease (CKD).

Chronic renal failure (chronic kidney disease)

Chronic kidney disease (CKD) represents the gradual, substantial, and irreversible reduction in the excretory and homeostatic functions of the kidneys. It is characterised by progressive destruction of renal tissue over a period of at least months to many years, depending on the underlying aetiology. Glomerular filtration rate (GFR) progressively decreases with loss of functioning nephrons.
Kidney function should be assessed by estimated GFR, and CKD is classified on this basis. The GFR should be estimated from serum creatinine using the 4-variable Modification of Diet in Renal Disease (MDRD) equation:¹

Other evidence of chronic kidney damage may include:

• Persistent microalbuminuria
• Persistent proteinuria
• Persistent haematuria (after exclusion of other causes, e.g. urological disease)
• Structural abnormalities of the kidneys demonstrated on ultrasound scanning or other radiological tests, e.g. polycystic kidney disease, reflux nephropathy
• Biopsy-proven chronic glomerulonephritis

Serum creatinine measurement to allow estimation of the glomerular filtration rate

Serum creatinine concentration should be measured at initial assessment and then at least annually in all adult patients with:²

• Previously diagnosed chronic kidney disease (CKD) including:
  • Identified renal pathology (e.g. polycystic kidney, biopsy-proven glomerulonephritis, reflux nephropathy)
  • Persistent proteinuria
  • Haematuria with no urological cause
• Conditions associated with a high risk of silent development of obstructive kidney disease:
  • Bladder voiding dysfunction (outflow obstruction, neurogenic bladder)
  • Urinary diversion surgery
  • Urinary stone disease (more than one episode per year)
• Conditions associated with a high risk of silent development of parenchymal kidney disease:
  • Hypertension, diabetes mellitus, heart failure
  • Atherosclerotic coronary, cerebral, or peripheral vascular disease
• Conditions requiring long-term treatment with potentially nephrotoxic drugs: examples of potentially nephrotoxic drugs include: angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, non-steroidal anti-inflammatory drugs (NSAIDs), lithium, mesalazine, ciclosporin, tacrolimus
• Multisystem diseases that may involve the kidney, e.g. systemic lupus erythematosus (SLE), vasculitis, myeloma, rheumatoid arthritis

Prescribing in renal failure

See separate article Drug Prescribing in Renal Impairment.

Dose modification

• Dose modification should be related to creatinine clearance, and the extent to which a drug is renally excreted.
• This is significant for aminoglycosides, some antibiotics including cephalosporins, lithium, opiates and digoxin.
• Loading doses should not be changed.
• If the patient is on dialysis, dose modification depends on how well it is eliminated by dialysis. Dosing should be timed around dialysis sessions.

Document references

1. Levey AS, Bosch JP, Lewis JB, et al; A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999 Mar 16;130(6):461-70. [abstract]
2. The Renal Association; UK Guidelines for the management of Chronic Kidney Disease. January 2009.

Internet and further reading

• Diagnosis and management of chronic kidney disease, SIGN (June 2008)
• Chronic kidney disease, NICE Clinical Guideline (September 2008); Early identification and management of chronic kidney disease in adults in primary and secondary care
• Chronic kidney disease - not diabetic, Clinical Knowledge Summaries (July 2009)
• Kidney disease: the five stages. Kidney specialist nurse Nicola Thomas talks about the five stages of chronic kidney disease and the treatments for each. A short video from NHS Choices. (February 2008)

Acknowledgements