Chronic Kidney Disease

Presence of structural or functional kidney impairments for >90 days (3 months), irrespective of clinical diagnosis.

Background and Epidemiology

• Around 8.5-15% of the population is estimated to have ≥ stage 3 CKD
• Most causes are irreversible and many patients’ renal disease will progress
• CKD is a major risk for cardiovascular disease and events, hospitalisation and carries significant mortality (56% higher than the general population) and morbidity

Aetiology/Risk Factors

• Multiple factors can increase the risk of renal disease.
  • Congenital/Inherited disease
    • Polycystic kidney disease; Medullary cystic disease; Tuberous sclerosis; Congenital obstructive uropathy/malformations
  • Glomerular disease
    • Primary Glomerulonephritides
    • Secondary glomerular disease e.g. due to SLE; polyangitis; Wegener’s granulomatosis; amyloidosis; diabetic glomerular sclerosis; accelerated hypertension; HUS;
  • Vascular disease
    • Hypertension (hypertensive nephrosclerosis); renovascular disease; small and medium sized vessel vasculitis
  • Tubulointerstitial disease
    • Tubulointerstitial nephritis (most commonly due to drugs e.g. NSAIDs); Reflux nephropathy; tuberculosis; Schistosomiasis; Multiple myeloma; Renal Papillary Necrosis
  • Urinary tract obstruction
    • Calculi; prostatic disease; pelvic tumours; retroperitoneal fibrosis
• Smoking, age, previous cardiovascular disease, obesity, low socioeconomic status and chronic use of NSAIDs (including aspirin- not uncommon) are also risk factors

Classification

• Based on patient eGFR (ml/min/1.73m²)
  1. Stage 1: GFR≥90- i.e. normal or increased GFR with other evidence of kidney damage*
  2. Stage 2: GFR 60-89- slight decrease in GFR with other evidence of kidney damage
  3. Stage 3- Moderate decrease in GFR with or without other evidence of kidney damage
     1. GFR 45-59
     2. GFR 30-44
  4. Stage 4- GFR 15-29- Severe decrease in GFR with or without other evidence of kidney damage
  5. Stage 5- GFR <15- Established renal failure

Clinical Features/Complications

• Most patients are asymptomatic and most diagnoses are incidental after routine blood tests or blood tests for another cause.  Once a patient is symptomatic of CKD (i.e. not symptoms of aetiological factors), this usually indicates more severe (stage 4/5) disease
  • NB Patients may present with symptoms/signs of underlying conditions
• Nocturia is a common first symptom.  Other symptoms include
  • Renal anaemia (lack of erythropoietin and abnormal iron metabolism)- tiredness, breathlessness
  • Generalised pruritus
  • Bruising
  • Anorexia, weight loss, nausea/vomiting
  • In severe disease, patients can experience hiccups and deep breathing (Kussmaul’s respiration); muscle twitching, fits, drowsiness, coma
• Other signs include
  • raised JVP
  • brown discolouration of the nails
• Other complications include
  • Raised susceptibility to infections (immunosuppression)
  • Increased risk of metabolic bone disease due to lack of conversion of inactive precursors of vitamin D to its active metabolite
    • Leads to reduced absorption of calcium and hypocalcaemia.  This raises PTH secretion and induces calcium resorption from bone.
  • Phosphate levels also initially drop due to increased FGF23 in response to reduced GFR
    • In severe disease, this mechanism fails and phosphate levels rise (hyperphosphataemia)

Investigations

• Assess renal function
  • eGFR is used routinely (other GFR measurements e.g. isotopic GFR (gold-standard is rarely performed)
    • Remember to correct for ethnicity (multiply by 1.21 for African-Caribbean patients)
    • Be cautious in patients with extremes of muscle mass (patients with large muscle bulk, eGFR tends to be under-estimated and vice versa)
    • When interpreting changes in eGFR, remember that eGFR will vary with creatinine (±5% creatinine)
  • Whilst eGFR is best practice, if creatinine levels rise by 20%, this may indicate renal dysfunction
• Test for proteinuria
  • Albumin:creatinine ratio is preferred for diagnostic purposes (higher sensitivity than PCR) (>30mg/mmol abnormal; >70mg/mmol is diagnostic of kidney disease)
    • PCR can be used for follow-up
• Urinalysis (only for haematuria)
  • See haematuria (i.e. investigate for UTI/malignancy in the first instance)
• Other tests include
  • U&Es- identify hyperuricaemia; hyperkalaemia; hypocalcaemia; hypophosphataemia
  • PTH and vit D
  • FBC and Iron studies- identify anaemia but treat potential other causes before managing as renal anaemia
  • Lipids and Glucose/HbA1c- for management of CVD risk factors- treat aggressively
  • If there are urinary symptoms e.g. nocturia, LUTS etc, kidney USS
  • If hyperkalaemic, urgent ECG (see also AKI)
• NB Also investigate appropriately for underlying causes of CKD e.g. antibody tests

Management

• Renoprotection: 
  • Reduced/Control Blood Pressure
    • Aim to keep systolic BP <140mmHg  and diastolic BP <90mmHg (<130/80mmHg in diabetics or in patients with an ACR of >70mg/mmol)
    • Try and aim for BP above 120mmHg
  • Reduce/Control Proteinuria
    • Aim for as low as possible (<0.3mg/day)
  • Treatments
    • ACE inhibitor first line (increasing to maximum dose)
      • regardless of blood pressure
    • Angiotensin-II receptor antagonists can be used if intolerant to ACE inhibitors (also can be added to ACE inhibitor if there are still problems)
    • Add diuretic and/or calcium channel blocker if required
• Reduce cardiovascular risk
  • Statins, low dose aspirin (for patients with stage I, II, III disease)
• For patients with bone disease/low vit D levels
  • Measure calcium, phosphate and PTH in stage IV and V disease
  • Offer bisphosphonates if indicated (at risk) for prevention of osteoporosis in patients with stage I, II, III disease
  • If vit D required
    • Offer cholecalciferol or ergocalciferol for stage I, II, III CKD
    • 1-alpha-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol for stage IV or V
• Lifestyle advice
  • Weight
  • Smoking
  • Low salt diet

NB Management of underlying causes is important.  Likewise, manage acute complications e.g hyperkalaemia.

Referral to specialist

• Refer patients with stage IV-V disease; high ACR (unless known to be diabetic cause); rapidly declining GFR (>5ml/min in 1 year or 10 in 5 years); refractory hypertension; suspected rare/genetic cause; suspected renal artery stenosis
• Refer to urology and manage appropriately if outflow obstruction is suspected

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