Key Facts

CKD is a major public health burden with significant cardiovascular implications. Cardiovascular disease is the leading cause of death in CKD patients, not progression to end-stage renal disease. Early detection and management of risk factors are essential.

Epidemiology

• Affects ~7% of UK adults; prevalence increases with age (30-40% in over 75s)
• ~3 million people in the UK; majority undiagnosed
• Approximately 65,000 patients on renal replacement therapy (dialysis or transplant) in the UK
• CKD disproportionately affects South Asian and African-Caribbean populations
• Costs the NHS an estimated £1.45 billion per year

Aetiology

• Diabetes mellitus: 30% (most common cause of ESRD in the UK)
• Hypertension: 25%
• Glomerulonephritis: 15%
• Polycystic kidney disease (ADPKD): 5-10%
• Renovascular disease: 5%
• Chronic pyelonephritis/reflux nephropathy: 5%
• Drugs: NSAIDs, lithium, calcineurin inhibitors
• Unknown/idiopathic: 10-20%

Pathophysiology

• Progressive nephron loss → compensatory hyperfiltration in remaining nephrons
• Hyperfiltration causes glomerular hypertension and further injury (vicious cycle)
• Proteinuria is both a marker and mediator of progressive renal damage
• RAAS activation drives fibrosis and progressive scarring
• Complications develop progressively: anaemia (reduced EPO), mineral bone disease (reduced 1α-hydroxylation, phosphate retention), acidosis, hyperkalaemia
• Cardiovascular risk driven by hypertension, dyslipidaemia, chronic inflammation, vascular calcification

Early CKD (Stages G1-G3a)

• Usually asymptomatic – detected on screening bloods
• Nocturia (loss of concentrating ability)
• Foamy urine (proteinuria)

Advanced CKD (Stages G3b-G4)

• Fatigue and lethargy (anaemia)
• Peripheral oedema and fluid retention
• Hypertension
• Pruritus
• Anorexia and weight loss
• Restless legs

End-Stage Renal Disease (Stage G5)

• Uraemic symptoms: nausea, vomiting, metallic taste, hiccoughs
• Uraemic encephalopathy: confusion, drowsiness, asterixis, seizures
• Pericarditis: chest pain, friction rub
• Peripheral neuropathy: glove-and-stocking sensory loss
• Skin changes: sallow complexion, uraemic frost, pruritus

Red Flags

• Rapid decline in eGFR (>5 mL/min/year) → accelerated investigation
• Haematuria with proteinuria → consider glomerulonephritis
• Uncontrolled hyperkalaemia → urgent intervention
• Uraemic pericarditis or encephalopathy → urgent dialysis

Bedside

• Urinalysis: dipstick for blood/protein
• Blood pressure: ideally ambulatory/home monitoring
• BMI and cardiovascular risk assessment

Bloods

• eGFR (CKD-EPI equation): defines stage; repeat at 3 months to confirm chronicity
• Urine albumin:creatinine ratio (ACR): early morning sample; A1 (<3), A2 (3-30), A3 (>30 mg/mmol)
• Calcium, phosphate, PTH: CKD-mineral bone disease assessment from stage G3b
• FBC: normocytic normochromic anaemia (reduced EPO)
• Iron studies: ferritin and transferrin saturation (iron deficiency common)
• Bicarbonate: metabolic acidosis
• Lipid profile: cardiovascular risk
• HbA1c: diabetic control

Imaging

• Renal ultrasound: assess kidney size (small = chronic, large = ADPKD/amyloid/diabetic nephropathy), cortical thickness, obstruction
• MR angiography: if renovascular disease suspected

Special Tests

• Renal biopsy: if unexplained CKD with active sediment, nephrotic-range proteinuria, or rapidly declining eGFR
• Immunology screen: ANA, ANCA, complement, immunoglobulins if GN suspected
• Serum and urine electrophoresis: if myeloma suspected
• Genetic testing: ADPKD, Alport syndrome

Non-pharmacological

• Lifestyle modification: smoking cessation, weight management, regular exercise
• Dietary advice: reduce sodium intake (<6g/day), potassium restriction in advanced CKD, phosphate restriction, adequate protein intake (0.8-1.0 g/kg/day in G4-G5)
• Fluid management: generally unrestricted unless oliguric/fluid overloaded
• Education: sick day rules – stop ACEi/ARB/NSAIDs/metformin/diuretics during acute illness

Pharmacological

Blood pressure control:

• ACE inhibitor (ramipril 1.25-10mg OD) or ARB (losartan 25-100mg OD): first-line, especially with proteinuria
• Target: <140/90 mmHg (or <130/80 if ACR ≥70 or diabetic with ACR ≥3)
• Monitor creatinine and K+ 1-2 weeks after starting/dose change (accept up to 25% rise in creatinine)

SGLT2 inhibitors:

• Dapagliflozin 10mg OD: recommended if ACR ≥22.6 mg/mmol (DAPA-CKD trial – 39% reduction in composite renal endpoint)
• Can be initiated down to eGFR 15 mL/min

Anaemia:

• IV iron first (ferric carboxymaltose 500-1000mg) if ferritin <200 or TSAT <20%
• ESAs (epoetin alfa, darbepoetin alfa): if Hb <100 g/L despite iron repletion; target Hb 100-120 g/L

CKD-Mineral Bone Disease:

• Phosphate binders: calcium acetate, sevelamer, lanthanum if phosphate elevated
• Alfacalcidol 0.25-1mcg OD or calcitriol: if PTH elevated despite phosphate control
• Cinacalcet: for secondary/tertiary hyperparathyroidism not controlled with above

Other:

• Sodium bicarbonate 500mg-1g TDS: if serum bicarbonate <22 mmol/L
• Statin therapy: atorvastatin 20mg for cardiovascular risk reduction
• Erythropoietin: as above for anaemia management

Referral Criteria (NICE NG203)

• eGFR <30 mL/min (G4-G5)
• ACR ≥70 mg/mmol (unless known diabetic already optimised)
• eGFR decline >5 mL/min/year or >10 mL/min within 5 years
• Uncontrolled hypertension despite 4+ agents
• Suspected renal artery stenosis
• Haematuria with proteinuria after urological causes excluded
• Plan for renal replacement therapy (eGFR <20)

• CKD G3a: minimal progression risk with good management; 10-year ESRD risk <5%
• CKD G4: 20-30% progress to ESRD within 5 years
• CKD G5: requires renal replacement therapy (median life expectancy on dialysis ~5-10 years)
• Cardiovascular mortality: 5-10× higher than age-matched general population
• Death from cardiovascular disease is more common than progression to ESRD in most CKD stages
• Transplant recipients have a 10-year graft survival of approximately 60-70%
• SGLT2 inhibitors reduce progression to ESRD by ~40% (DAPA-CKD, EMPA-KIDNEY trials)

CKD Staging (NICE NG203)

Albuminuria Staging

Landmark Trials in CKD