Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) refers to abnormal kidney function and/or structure present for longer than 3 months. It is a relatively common condition that usual coexists with several prevalent conditions. CKD is usually asymptomatic until advanced stages, so can progress unrecognised for many years.

Epidemiology

The global prevalence of CKD in adults is approximately 9%. The commonest causes are hypertension and diabetes mellitus.

Diagnosis

As most patients are asymptomatic, diagnosis relies on lab evidence of kidney damage. This can include:

• Presence of haematuria and/or proteinuria
• Reduction in glomerular filtration rate (GFR)

Staging

CKD can be staged according to glomerular filtration rate (GFR). This can be estimated using a variety of equations; a formula recommended by the UK National Institute for Health and Clinical Excellence (NICE) guidelines is the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which estimates GFR using the following factors:

• Age
• Sex
• Serum creatinine
• Race

Causes

The commonest causes of CKD are diabetes and hypertension and together account for more than half of all CKD cases worldwide.  

1. Diabetes mellitus
2. Hypertension
3. Glomerulonephritis
4. Genetic:
   • Polycystic kidney disease
   • Abort’s syndrome
5. Systemic diseases e.g. systemic lupus erythematosus, vasculitis
6. Repeated urinary infections
7. Urinary obstruction e.g. kidney stones, benign prostatic hypertrophy, congenital malformations
8. Idiopathic

Clinical features

Most patients are asymptomatic until GFR is less than 30 mL/min. Clinical features result from deranged homeostatic and endocrine functions and can include:

• Uraemia:
  • Nausea or vomiting
  • Reduced appetite
  • Fatigue
  • Weakness
  • Pruritus, orange skin
  • Restless leg syndrome
  • Pericarditis
• Normochromic, normocytic anaemia (secondary to low erythropoietin production)
• Acidosis
• Oliguria
• Electrolyte changes:
  • Hyperkalaemia
  • Hypocalcaemia and vitamin D deficiency (including reduced calcitriol)
• Fluid retention
• Increased infection susceptibility
• Renal osteodystrophy
• Increased risk of cardiovascular disease, including:
  • Myocardial infarction
  • Left ventricular hypertrophy
  • Pericarditis
• Raised prolactin:
  • Males: reduces libido via reduction in testosterone, galactorrhoea
  • Females: Amenorrhoea

Investigations

The aim of investigations in CKD are:

1) Confirm long-standing CKD

2) Identify underlying cause(s)

3) Identity reversible factors

Urine tests

Urine analysis:

• Urinary protein/albumin: use to check and quantify proteinuria. Using urine albumin:creatinine ratios is recommended over protein:creatinine ratios because of its greater sensitivity at low levels of proteinuria. An albumin:creatinine ratio of >3 mg/mmol is consistent with proteinuria.
• Detects haematuria

Blood tests

Routine tests include:

• Urea and electrolytes: check creatinine to estimate GFR and assess for any electrolyte imbalance
• Cystatin C levels: can be used as an alternative to creatinine to estimate GFR in cases where creatinine can be difficult to interpret e.g. bodybuilders, patients with amputations, muscle wasting disorders
• Glucose and HbA1c: check for diabetes mellitus

Consider the following further tests in CKD stages 4 and 5:

• Bone profile (including calcium and phosphate): assess for renal osteodystrophy
• Full blood count: may show normochromic, normocytic anaemia as a result of reduced erythropoietin production
• Liver function tests: check for hypoalbuminaemia

Renal imaging

Renal ultrasound scans can be used to assess renal size and diagnose structural abnormalities, including obstructive pathologies. Kidneys are usually atrophied in CKD (except in polycystic kidney disease, amyloidosis and multiple myeloma). Asymmetry between the 2 kidneys suggests arterial or developmental pathology.

Renal biopsy

Consider renal biopsy if disease is rapidly progressive or if the cause is unclear.

Management

CKD stages 1-3 are generally managed in primary care, while stages 4 and 5 are reviewed by specialists. Management aims to limit progression of CKD (to avoid requirement for dialysis and/or transplantation) and its complications.

Treat underlying cause

1. Optimise glucose control
2. Control blood pressure
3. Stop nephrotoxic drugs
4. Advise on weight loss and smoking cessation
5. Relieve obstruction (if present)

Limiting complications

The following strategies are commonly used in patients with CKD.

1. Blood pressure control:
   1. ACE inhibitors are generally used first-line as they have evidence of reducing proteinuria and CKD progression
   2. Aim blood pressure less than 140/90 mmHg in most CKD patients. Patients with diabetes and/or albumin:creatinine ratio >70 mg/mmol should aim for a blood pressure less than 130/80 mmHg.
2. Reduce cardiovascular risk using:
   1. Statins
   2. Low-dose aspirin
3. Renal bone disease:
   1. Vitamin D deficiency correction: colecalciferol or ergocalciferol. Offer alfacalcidol in CKD stages 4 and 5.
   2. Dietary restriction: reduce phosphate intake

Symptom control

1. Anaemia: iron supplementation if iron deficient. Consider use of recombinant erythropoietin if symptomatic anaemia despite adequate iron stores
2. Acidosis: sodium bicarbonate supplements to counteract acidosis
3. Oedema: loop diuretics to promote diuresis
4. Restless leg syndrome (as a result of raised urea):
   • Clonazepam
   • Gabapentin

Renal replacement therapy (RRT)

Consider renal replacement therapy in advanced cases (CKD stage 5 and/or uraemic), be it as definitive therapy or until a kidney transplant is available. Long-term, this can be done via haemodialysis or peritoneal dialysis. However, RRT is also associated with potential complications, including:

• Raised cardiovascular risk e.g. myocardial infarction, stroke
• Malnutrition
• Renal bone disease
• Infection

Renal transplantation

Used for stage 5 CKD or patients with uraemia. Potential complications of transplantation include:

1. Hyperacute, acute or chronic graft rejection
2. Increased infection risk due to immunosuppression, notably cytomegalovirus
3. Increased risk of cancer, including squamous cell carcinoma of skin
4. Drug toxicity from immunosuppressant agents

Screening for CKD

Screening for kidney disease is done in at-risk patient populations, including those suffering from:

• Diabetes mellitus
• Hypertension
• Structural renal disease e.g. congenital malformation

Complications

Complications of CKD include:

• Cardiovascular disease
• Anaemia
• Renal osteodystrophy
• Accelerated atherosclerosis
• Hyperkalaemia
• Metabolic acidosis
• Uraemia and its associated complications e.g. pericarditis, neurological effects
• Fluid overload and pulmonary oedema
• Endocrine effects:
  • Reduced insulin availability
  • Raised prolactin (galactorrhoea) àlow testosterone (reduced libido), low oestrogen (amenorrhoea)