FRCA Notes

Chronic Kidney Disease

The curriculum asks for knowledge of 'the principles of the anaesthetic management of patients with renal failure for non-transplant surgery, including care of shunt'.

The topic was an SAQ in 2019 (71% pass rate) although examiner feedback was rather vague.

Resources

  • Chronic kidney disease is an abnormality of kidney structure or function that lasts more than 3 months
  • CKD is common, with an estimated UK prevalence of CKD stages 3-5 of between 4.3 - 8.5%
  • Its prevalence and contribution to mortality is increasing
  • This is attributable to increasing prevalence of modifiable risk factors such as HTN, DM and smoking
  • Other, non-modifiable risk factors include ethnicity such as Asian, African and Afro-Caribbean ethnicities

  • CKD only becomes evident when fewer than 40% of nephrons are functioning
  • Tests contributing to diagnosis include:
    • Electrolyte abnormalities due to tubular disorders
    • Proteinuria: albumin to creatinine ratio (ACR) > 3 mg/mmol
    • Haematuria of renal origin
    • Histological or radiological abnormalities in structure e.g. in PKD, reflux nephropathy
    • Abnormal function with resultant raised creatinine and/or cystatin C (eGFR <60ml/min/1.73m2 on two consecutive occasions 90 days apart)

Classification

  • GFR is the internationally accepted measure to express renal function
  • However, it is not routinely measured as it is a complex procedure requiring exogeneous markers (e.g. inulin)

  • More commonly, eGFR is used
    • It uses serum creatinine (or cystatin), age and gender to mathematically derive an eGFR
    • The CKD-EPI equation (2021) is now recommended for calculating eGFR, as it is more accurate than the MDRD or Cockroft-Gault equations
    • Correction for ethnicity is no longer recommended by NICE

  • CKD can be classified according to GFR and degree of albuminuria:
Description Glomerular grade GFR (ml/min/1.73m2) Albuminuria grade Urinary albumin conc.
Normal G1 ≥90 A1 <30mg/g
Mild G2 60-89 - -
Mild/mod. G3a 45-59 A2 30-300mg/g
Mod/severe G3b 30-44 - -
Severe G4 15-29 A3 >300mg/g
Kidney failure G5 <15 - -


  • Diabetes mellitus is the commonest cause
Class Examples
Associated with comorbidities Diabetes mellitus (25%)
Hypertension (8%)
(Reno-)Vascular disease (5%)
Intrinsic renal disease Glomerulonephritis (14%)
Pyelonephritis (7%)
Following AKI
Interstitial nephritis
Nephropathies
Genetic PKD (8%)
Fabry disease
Alport syndrome
Metabolic Hypercalcaemia
Hyperparathyroidism (nephrocalcinosis)
Oxalosis
Autoimmune disease Amyloidosis
Scleroderma
SLE
Goodpasture's syndrome
IgA vasculitis
Neoplastic Renal tumours
Myeloma
Drugs/toxins NSAIDs
Calcineurin inhibitors
Chemotherapy
Lead toxicity
Other HUS
Gout
Obstructive uropathies


Respiratory

  • Prone to pulmonary oedema and pleural effusions, necessitating cautious fluid balance
  • Can lead to:
    • Decreased pulmonary compliance
    • Increased V/Q mismatch
    • Reduced FRC
  • Overall leads to a relative restrictive pulmonary defect

Cardiovascular

  • Hypertension is very common, either as the primary cause or consequence of CKD

  • Accelerated atherosclerosis and ischaemic heart disease
    • Impaired endothelial function due to reactive oxygen species generated by RAAS activation
    • Low grade inflammation
    • Dyslipidaemia with changes in lipoprotein metabolism increasing accumulation of intermediate-density lipoproteins
    • There is a 10 - 20x increased cardiovascular mortality in uraemic patients

  • Increased risk of major cardiac complications; MI, heart failure, stroke
    • Increased circulating inflammatory mediators
    • Hypercoagulability
    • Arterial calcification
    • Endothelial dysfunction
    • LV dysfunction from chronic volume- or pressure-overload

  • Pericarditis (uraemic)
  • Increased peripheral vascular disease
  • Fistulas may complication venous and arterial access
  • Calciphylaxis; an accumulation of calcium in small blood vessels, presence of which positively correlates with vascular calcification and valvular heart disease

  • Patients therefore often require statins, diietary sodium restriction and diuretics to manage fluid overload, and tight blood pressure control perioperatively is required

Neurological

  • Polyneuropathy esp. if DM is underlying aetiology
  • Autonomic neuropathy
  • Myopathy
  • Dialysis disequilibrium
    • Transient encephalopathy precipitated by rapid dialysis, or missed dialysis sessions
    • Perhaps due to relatively rapid plasma urea clearance vs. CSF urea clearance

  • Uraemic encephalopathy
  • Seizures (10%)
    • As high as 33% in those with uraemic encephalopathy
    • Due to creatinine metabolites being pro-convulsant (inhibit GABA but stimulate NMDA receptors)
  • Up to 60% have chronic pain issues
  • Approximately 40% are on at least one long-term analgesic and up to 20% are on chronic opioid therapy

Renal

  • Impaired sodium and water excretion means difficult handling large fluid loads
  • Fluid balance is fragile and must be carefully managed
  • Increased hydrostatic pressure leads to generalised & pulmonary oedema
  • Low/no urine output, so caution with drugs with active forms excreted in urine e.g. rocuronium, morphine metabolites

Metabolic/endocrine

  • Hyperkalaemia
    • Loss of nephron function increases renal retention of potassium
    • As GFR declines, remaining nephrons adapt by increasing renal excretion of potassium
    • Once GFR <15ml/min, extra-renal mechanisms for potassium handling become key e.g. increased colonic excretion of potassium
    • Patients are often on a low-potassium diet, and one should avoid drugs likely to cause hyperkalaemia e.g. suxamethonium

  • Altered acid/base balance; typically metabolic acidosis
    • Increased production of non-volatile acids
    • Decreased renal excretion of acids
    • Increased loss of bicarbonate
    • Patients are often on bicarbonate supplements

  • Hyperphosphataemia
    • Due to reduced renal excretion
    • Patients undergo dietary phosphate restriction and take phosphate binding drugs

  • Hypocalcaemia
    • Due to reduced active Vit. D synthesis and hyperphosphataemia
    • Increased PTH levels over time and secondary hyperparathyroidism
    • Bone demineralisation ensues and risk of fractures increases
    • Patients often take vitamin D analogues and calcimimetics e.g. 1ɑ-calcidol

  • Hypermagnesaemia
  • Hyperuricaemia
  • Hypoalbuminaemia

Gastrointestinal

  • Symptoms of CKD such as anorexia, nausea, vomiting or diarrhoea can lead to dehydration
  • Poor nutritional intake leads to impaired wound healing in post-operative period
  • Reduced GI motility due to autonomic neuropathy
  • Increased risk of bleeding due to gastric ulceration

Haematological

  • Anaemia due to reduced EPO production from extraglomerular mesangial cells
    • Patients may take iron supplements or receive erythropoiesis-stimulating agents e.g. erythropoietin, darbepoetin alpha

  • Platelet dysfunction due to:
    • Reduced thrombopoietin production
    • Uraemia
    • Decreased ADP content of platelets
    • Impaired aggregation
    • Increased endogenous NO production
    • Reduced TXA2 levels
    • Defective vWF-GpIIb/IIIa receptor interactions

  • Pro-thrombotic state
    • Increased fibrin formation and fibrin-platelet interactions
    • Decreased fibrinolysis
  • CKD is an independent risk factor for VTE, which increases with worsening GFR or increasing age

  • Haemostasis may be complicated by:
    • Underlying disease state
    • Decreased clearance of drugs affecting clotting

Immunological

  • Increased infection risk

Pharmacokinetics

  • Absorption
    • Delayed gastric emptying due to neuropathy means drug concentrations may be slower to rise
    • Reduced absorption due to:
      • Altered gastric pH (owing to gastric urease converting urea to ammonia)
      • Small bowel oedema due to fluid overload

  • Distribution
    • Increased total body water, and therefore increased VD for hydrophilic drugs
    • However, decreased serum concentrations of drugs as a result
    • Reduced protein binding of acidic drugs, because of hypoalbuminaemia and competition with organic acids
    • Increased protein binding of basic drugs, because of relatively increased ɑ1-acid glycoprotein concentration

  • Metabolism
    • Altered CYP450 isoenzyme kinetics; inhibited CYP2C9 and CYP3A4 but induced CYP2E1

  • Elimination
    • Altered clearance of medications with renal excretion
    • Non-renal clearance of drugs is also reduced

  • Most patients with ESRF will be managed with renal transplant surgery (56%)
  • Other options include
    • Haemodialysis (37%)
    • Peritoneal dialysis (5%)
    • Home haemodialysis (2%)

  • RRT is associated with a 3 - 20x relative risk of death, depending on age, from:
    • Cardiovascular disease (34%)
    • Infeciton (20%)
    • Withdrawal of treatment (14%)

  • Haemodialysis is more efficient and carries lower risk of infection than peritoneal dialysis
  • For peritoneal dialysis patients, must ensure their PD fluid is drained prior to anaesthetic

  • See the separate page on renal replacement therapy on intensive care

Perioperative management of the patient with chronic kidney disease


  • Patients with CKD have an increased rate (13x) of major surgery vs. baseline population

History and examination

  • Aetiology of CKD
  • Severity of renal impairment (clinical, biochemical)
  • Fluid status and dry weight
  • Normal urine production
  • RRT: modality, last session, volume of fluid removal
  • Drug history, esp. immunosuppressants and long-term steroid therapies
  • Presence of AV fistula

Investigations

  • Bloods
    • FBC
    • U&E
    • Clotting, esp. if coagulopathy suspected or high risk peri-operative bleeding, although normal results don't preclude thrombopathy

  • 12-lead ECG
  • CXR if evidence of fluid overload
  • TTE if known cardiac impairment

Optimisation

  • Continue disease-specific treatments where possible; ACE-I remain controversial and no consensus as to whether continuation or cessation is more harmful
  • Close liaison with Renal team re: peri-operative dialysis to optimise timings with respect to surgery
  • Up-to-date electrolytes ± potassium on day of surgery

Monitoring and access

  • AAGBI, must ensure NIBP cuff on non-fistual arm
  • Lower threshold for invasive monitoring, especially if co-existent cardiovascular disease or prolonged surgery
  • Carefully wrap fistulae to avoid pressure injury

  • May need central venous access
    • Poor peripheral access
    • To protect potential fistula sites
    • Need for vasopressors
    • Goal-directed fluid therapy

  • Urine output monitoring to assess end-organ perfusion and fluid balance

Induction

  • In general, drugs with shorter half-lives or those non-dependent on renal elimination should be used
  • Gastroparesis may necessitate RSI
    • Rocuronium with sugammadex reversal; the rocuronium-sugammadex complex is relatively stable and can be cleared by dialysis

Maintenance

  • Metabolism of volatile anaesthetics by the hepatic CYP450 system causes production of inorganic fluoride ions
    • These cause vasopressin-resistant high-output renal insufficiency
    • Methoxyflurane is particularly troublesome in this respect
    • However, studies have demonstrated that neither peak fluoride concentration nor duration of systemic fluoride exposure correlated with anaesthetic nephrotoxicity

  • Compound A, a haloalkane sevoflurane by-product, is nephrotoxic in rats
  • However, concentrations of Compound A produced in clinical practice are insufficient to induce nephrotoxicity

  • Intra-operative NMBA is ideally with (cis)-atracurium, owing to non-renal dependent metabolic pathways
    • Rocuronium is 33% renally excreted and its clearance is reduced by 40% in CKD
    • Vecuronium is 30% renally excreted: longer duration of action
    • Pancuronium has reduced clearance and prolonged half-life and is best avoided
    • Cis-cis isomer of mivacurium may accumulate in CKD and cause longer block
    • Suxamethonium should be avoided due to risk of exacerbating pre-existing hyperkalaemia

Regional anaesthesia

  • May be used as an adjunct to GA or as the primary anaesthetic technique, benefitting for reduced need for opioids

  • Neuraxial blockade is not contra-indicated, but have to bear in mind:
    • Hypotension may cause or exacerbate existing renal impairment
    • Judicious use of fluids to avoid overload; use vasopressors preferentially
    • Patients may be coagulopathic

  • Patients may require dialysis post-operatively and plans should be made a priori for this to occur
  • Patients may require an extended period of recovery and oxygen supplementation due to prolonged effects of anaesthetic drugs and consequent drowsiness

Opioids

  • Are not directly nephrotoxic
  • Do have an anti-diuretic effect, so may cause urinary retention

  • Morphine-6-glucuronide is responsible for the analgesic, sedative and respiratory depressant effects of morphine
  • It is renally eliminated; its normal half-life is 2hrs but increases to 27hrs in patients with CKD

  • Oxycodone
    • Both oxycodone and its metabolites accumulate in CKD
    • Elimination half-life is prolonged from 2.3hrs to 3.9hrs
    • May necessitate dose reduction and/or longer dosing interval

  • Fentanyl
    • 7% is excreted unchanged in the urine therefore reduced clearance in CKD

  • Alfentanil
    • Reduced protein binding in CKD
    • Greater amount of free drug present

  • Tramadol
    • 30% excreted unchanged in urine
    • May be epileptogenic in CKD due to lowered seizure threshold in context of already pro-seizure state

  • Codeine and dihydrocodeine
    • Prolonged elimination half-lives; use with caution

NSAIDs

  • Generally avoided due to potential for nephrotoxicity from reduced renal blood flow, reduced GFR and interstitial nephritis
  • Increase risk of major vascular events and bleeding in patients already at risk
  • May impair potassium excretion, exacerbating hyperkalaemia