Key Facts

CKD is a long-term condition characterised by progressive loss of kidney function. Most patients with CKD G1-G3 are asymptomatic and managed in primary care. The primary goals are cardiovascular risk reduction and slowing progression to end-stage kidney disease.

Epidemiology

• Prevalence: approximately 13% of UK adults (many undiagnosed)
• CKD G3-G5 prevalence: 5-7%
• More common with increasing age: >30% of adults aged >75 have eGFR <60
• CKD is more common in people of Black African and South Asian ethnicity

Aetiology

• Diabetic nephropathy: most common cause in developed countries (25-30%)
• Hypertensive nephrosclerosis: 15-25%
• Glomerulonephritis: 10-15%
• Polycystic kidney disease: 5-10% (most common inherited cause)
• Obstructive uropathy: particularly in older men (BPH)
• Other: renovascular disease, reflux nephropathy, interstitial nephritis (NSAIDs, lithium)

Pathophysiology

• Regardless of initial insult, progressive nephron loss leads to glomerular hyperfiltration in remaining nephrons
• Hyperfiltration activates RAAS, promoting further glomerular injury, proteinuria, and fibrosis
• Proteinuria itself is toxic to tubular cells, driving progressive tubulointerstitial fibrosis
• Reduced kidney function leads to impaired electrolyte handling, acid-base disturbance, reduced EPO production (anaemia), and disordered mineral metabolism (CKD-MBD)

Early CKD (G1-G3a)

• Usually asymptomatic
• Detected on routine blood tests or screening in at-risk groups
• May have non-specific fatigue

Moderate CKD (G3b-G4)

• Fatigue, malaise
• Nocturia, polyuria
• Mild oedema
• Pruritus
• Restless legs

Advanced CKD (G5)

• Severe fatigue, lethargy
• Nausea, vomiting, anorexia
• Peripheral oedema
• Uraemic symptoms: pericarditis, encephalopathy, seizures
• Metabolic bone disease: bone pain, fractures
• Anaemia: pallor, breathlessness

Red Flags

• Rapidly declining eGFR (≥25% decline or ≥15 mL/min drop in 12 months)
• Visible haematuria — exclude urological malignancy
• Hyperkalaemia (K+ >6.0 mmol/L) — ECG changes, cardiac risk
• Severe hypertension with CKD — possible renovascular disease
• Nephrotic syndrome (heavy proteinuria, oedema, hypoalbuminaemia)
• Uraemic symptoms — encephalopathy, pericarditis, bleeding

Bedside

• Blood pressure (seated, standardised)
• Urinalysis: dipstick for blood, protein
• BMI, weight

Bloods

• eGFR (CKD-EPI equation): confirm on ≥2 occasions ≥3 months apart
• Urine ACR: early morning sample preferred
• U&Es: creatinine, potassium, sodium, bicarbonate
• Calcium, phosphate, PTH: from CKD G4 onwards (CKD-MBD screening)
• Vitamin D: 25-OH vitamin D level
• FBC: anaemia of CKD (normocytic normochromic; check from G3b)
• HbA1c: diabetes screening/monitoring
• Lipid profile: cardiovascular risk assessment

Imaging

• Renal ultrasound: recommended in new CKD diagnosis (assess size, symmetry, obstruction)
• Doppler USS: if renovascular disease suspected

Special Tests

• Renal biopsy: if cause uncertain, especially with significant proteinuria, haematuria, or rapid decline
• Immunology: ANA, ANCA, anti-GBM, complement (if glomerulonephritis suspected)
• Serum and urine electrophoresis: if myeloma suspected

Non-pharmacological

• Dietary advice: low-salt diet (<6g/day); moderate protein intake in advanced CKD; potassium restriction if hyperkalaemia
• Smoking cessation
• Weight management and exercise
• Avoid nephrotoxic drugs (NSAIDs, gentamicin, iodinated contrast where possible)
• Annual influenza vaccination; pneumococcal vaccination
• Sick day rules: temporarily stop ACEi/ARB, metformin, NSAIDs, diuretics during acute illness

Pharmacological

Blood pressure control:

• Target <140/90 mmHg (general); <130/80 mmHg if ACR ≥70 mg/mmol or diabetes with ACR ≥30
• ACE inhibitor first-line if ACR ≥30 mg/mmol or diabetes: ramipril 1.25-10mg OD
• ARB if ACEi intolerant: losartan 50-100mg OD, candesartan 8-32mg OD
• Monitor K+ and creatinine 1-2 weeks after starting/uptitrating ACEi/ARB

SGLT2 inhibitors:

• Dapagliflozin 10mg OD: for CKD with ACR ≥22.6 mg/mmol (irrespective of diabetes); DAPA-CKD trial showed 39% reduction in composite kidney endpoint
• Can be started down to eGFR 20 mL/min (NICE TA775)

Cardiovascular risk:

• Atorvastatin 20mg OD for primary prevention (NICE CG181)
• Antiplatelet therapy if established CVD

CKD-MBD:

• Phosphate binders (calcium acetate, sevelamer) if phosphate elevated
• Alfacalcidol or calcitriol for secondary hyperparathyroidism (specialist-led)
• Cholecalciferol for vitamin D deficiency

Anaemia:

• Iron replacement (IV iron preferred in CKD G4-5)
• Erythropoiesis-stimulating agents (ESA): specialist-initiated when Hb <100 g/L

Metabolic acidosis:

• Sodium bicarbonate 500mg-1g TDS if serum bicarbonate <22 mmol/L

Surgical

• Renal replacement therapy preparation: arteriovenous fistula creation (ideally 6 months before anticipated dialysis)
• Renal transplant: best option for eligible patients with ESKD
• Dialysis: haemodialysis or peritoneal dialysis

Referral Criteria (NICE NG203)

• eGFR <30 mL/min/1.73m² (G4-G5)
• ACR ≥70 mg/mmol (unless known diabetic, already on optimal treatment)
• Sustained eGFR decline ≥25% or ≥15 mL/min in 12 months
• Uncontrolled hypertension despite ≥4 agents
• Suspected renovascular disease
• Haematuria with proteinuria (possible glomerulonephritis)
• Hyperkalaemia persisting despite management

• CKD G3a: 10-year risk of ESKD <1%; cardiovascular mortality is the leading cause of death
• CKD G3b: 10-year risk of ESKD 1-3%
• CKD G4: 10-year risk of ESKD 20-50%
• CKD G5 on dialysis: 5-year survival approximately 35-40%
• Renal transplant: 5-year graft survival >90% (living donor); >85% (deceased donor)
• Cardiovascular risk: CKD G5 patients have 10-20× higher CV mortality than age-matched general population
• ACEi/ARB + SGLT2i combination reduces progression to ESKD by 35-40% in proteinuric CKD

CKD Staging (NICE NG203)

Albuminuria Categories