Chronic Kidney Disease

Chronic kidney disease (CKD) describes a chronic reduction in kidney function sustained over three months. It tends to be permanent and progressive.

Causes

Kidney function naturally declines with age. Factors that can speed up the decline and cause CKD include:

• Diabetes
• Hypertension
• Medications (e.g., NSAIDs or lithium)
• Glomerulonephritis
• Polycystic kidney disease

Presentation

Most patients with CKD are asymptomatic. Signs and symptoms as the renal function worsens may be non-specific:

• Fatigue
• Pallor (due to anaemia)
• Foamy urine (proteinuria)
• Nausea 
• Loss of appetite
• Pruritus (itching) 
• Oedema 
• Hypertension
• Peripheral neuropathy

Investigations

The estimated glomerular filtration rate (eGFR) is based on the serum creatinine, age and gender. It estimates the glomerular filtration rate (the rate at which fluid is filtered from the blood into Bowman’s capsule).

Proteinuria (protein in the urine) is quantified with a urine albumin:creatinine ratio (ACR).

Haematuria (blood in the urine) can be assessed with a urine dipstick or microscopy. Microscopic haematuria is when blood is identified on testing but not visible on inspection. Macroscopic haematuria refers to visible blood in the urine. Haematuria can indicate infection, malignancy (e.g., bladder cancer), glomerulonephritis or kidney stones.

Renal ultrasound helps identify obstructions (e.g., kidney stones or tumours) and polycystic kidney disease.

Other investigations are necessary to identify risk factors, including:

• Blood pressure (for hypertension)
• HbA1c (for diabetes)
• Lipid profile (for hypercholesterolaemia)

Classification

A diagnosis can be made when there are consistent results over three months of either:

• Estimated glomerular filtration rate (eGFR) is sustained below 60 mL/min/1.73 m²
• Urine albumin:creatinine ratio (ACR) is sustained above 3 mg/mmol

The G score is based on the eGFR. The A score is based on the albumin:creatinine ratio.

Accelerated progression is a sustained decline in the eGFR within one year of either 25% or 15 mL/min/1.73 m².

Complications

• Anaemia
• Renal bone disease
• Cardiovascular disease
• Peripheral neuropathy
• End-stage kidney disease
• Dialysis-related complications

Management

The Kidney Failure Risk Equation can be used to estimate the 5-year risk of kidney failure requiring dialysis.

The NICE clinical knowledge summaries (May 2023) suggest referral to a renal specialist when:

• eGFR less than 30 mL/min/1.73 m²
• Urine ACR more than 70 mg/mmol
• Accelerated progression (a decrease in eGFR of 25% or 15 mL/min/1.73 m² within 12 months)
• 5-year risk of requiring dialysis over 5%
• Uncontrolled hypertension despite four or more antihypertensives

Treating the underlying cause involves:

• Optimising diabetic control
• Optimising hypertension control
• Reducing or avoiding nephrotoxic drugs (where appropriate)
• Treating glomerulonephritis (where this is the cause)

The blood pressure target is less than 130/80 in patients under 80 with CKD and an ACR above 70 mg/mmol.

Medications that help slow the disease progression are:

• ACE inhibitors (or angiotensin II receptor blockers)
• SGLT-2 inhibitors (specifically dapagliflozin)

Reducing the risk of complications involves:

• Exercise, maintain a healthy weight and avoid smoking
• Atorvastatin 20mg for primary prevention of cardiovascular disease (in all patients with CKD)

Management of complications involves:

• Oral sodium bicarbonate to treat metabolic acidosis
• Iron and erythropoietin to treat anaemia
• Vitamin D, low phosphate diet and phosphate binders to treat renal bone disease

Management of end-stage renal disease involves:

• Special dietary advice
• Dialysis
• Renal transplant

ACE Inhibitors

ACE inhibitors are offered to all patients with:

• Diabetes plus a urine ACR above 3 mg/mmol
• Hypertension plus a urine ACR above 30 mg/mmol
• All patients with a urine ACR above 70 mg/mmol

The serum potassium needs close monitoring, as both CKD and ACE inhibitors can cause hyperkalaemia.

SGLT-2 Inhibitors

Dapagliflozin is the SGLT-2 inhibitor licensed for CKD. It is offered to patients with:

• Diabetes plus a urine ACR above 30 mg/mmol

Dapagliflozin is considered for patients with:

• Diabetes plus a urine ACR or 3-30 mg/mmol
• Non-diabetics with an ACR of 22.6 mg/mmol or above

Anaemia in Chronic Kidney Disease

Healthy kidneys produce erythropoietin, a hormone that stimulates the production of red blood cells. CKD results in lower erythropoietin and a drop in red blood cell production. It causes a normocytic (normal sized) normochromic (normal colour) anaemia. 

Anaemia may be treated with erythropoiesis-stimulating agents, such as recombinant human erythropoietin. Blood transfusions can sensitise the immune system (allosensitization), increasing the risk of future transplant rejection.

Iron deficiency is treated before using erythropoietin. Intravenous iron is usually given, particularly in dialysis patients.

Renal Bone Disease

Renal bone disease is also known as chronic kidney disease-mineral and bone disorder (CKD-MBD). It involves:

• High serum phosphate
• Low vitamin D activity
• Low serum calcium

Reduced phosphate excretion by diseased kidneys results in high serum phosphate. 

Healthy kidneys metabolise vitamin D into its active form. Active vitamin D is essential in calcium absorption in the intestines and reabsorption in the kidneys. It is also responsible for regulating bone turnover and promoting bone reabsorption to increase the serum calcium level. Chronic kidney disease leads to less vitamin D activity and low serum calcium.

The parathyroid glands react to the low serum calcium and high serum phosphate by excreting more parathyroid hormone, causing secondary hyperparathyroidism. Parathyroid hormone stimulates osteoclast activity, increasing calcium absorption from bone.

Osteomalacia occurs due to increased turnover of bones without adequate calcium supply.

Osteosclerosis occurs when the osteoblasts respond by increasing their activity to match the osteoclasts, creating new tissue in the bone. Due to the low calcium level, this new bone is not properly mineralised.

Rugger jersey spine is a characteristic finding on a spinal x-ray. This involves sclerosis of both ends of each vertebral body (denser white) and osteomalacia in the centre of the vertebral body (less white). The name refers to the stripes found on a rugby shirt.

Management of renal bone disease involves a combination of:

• Low phosphate diet
• Phosphate binders
• Active forms of vitamin D (alfacalcidol and calcitriol)
• Ensuring adequate calcium intake

Osteoporosis can exist alongside renal bone disease and may be treated with bisphosphonates.

Last updated September 2023