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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