Chronic renal failure

Introduction

• ESRF = Irreversible loss of renal function resulting in accumulation of toxins and loss of internal homeostasis
• New cases
  • 50% are over 65yo
  • Major causes are diabetes and hypertension
• 70% of cases receive dialysis (92% haemodialysis)
• 30% have renal transplants (opposite in children)
• 5-year survival is 35% (mostly cardiac deaths)

Pathophysiology of uraemia

• Uraemia = Contamination of blood with urine
• Azotaemia = Build-up of nitrogen in the blood
• Excretory failure
  • Uraemic toxins include urea, cyanate, guanidine, polyamines and beta-2 microglobulin
  • Dialysis removes all of these but does NOT completely reverse uraemic organ damage

Pathophysiology of uraemia

• Biosynthetic failure
  • Loss of 1,25-(OH)2 Vitamin D and erythropoietin
  • 85% of EPO is produced in kidneys
  • Decreased GI calcium absorption results in secondary hyperparathyroidism and renal bone disease
• Regulatory failure
  • Uraemic state leads to excess free oxygen radicals, which react with carbohydrates, lipids and amino acids to produce advanced glycation end-products, which cause amyloidosis and atherosclerosis and ARE NOT cleared by dialysis (hence progressive nature of amyloidosis and atherosclerosis in ESRD)

Clinical features of uraemia

• Correlation does exist between eGFR <8-10 and clinical uraemia
• Serum urea and creatinine DO NOT correlate with clinical uraemia
• Decision to initiate long-term dialysis is dependent upon the severity of symptoms NOT numbers

Clinical features of uraemia

• Neurological
  • Uraemic encephalopathy: Cognitive defects, memory loss, reduced attention, slurred speech, reversal of sleep-wake cycle, asterixis, seizure, coma. Improves with dialysis.
  • Dialysis dementia: Progressive neurological decline without improvement with dialysis
    • 4% of HD patients. 2-4 year survival is 24%. Usually after at least 2 years of dialysis
  • Subdural haematoma: 10x more common than general population
    • Often bilateral without focal neurology. Consider in HD patients with ALOC
  • Peripheral neuropathy: Singultus (hiccups), restless legs syndrome, sensorimotor neuropathy, autonomic neuropathy
    • Responds poorly to dialysis but reverses with renal transplant
  • Stroke occurs in 6% of HD patients, 52% of which are ICH

Clinical features of uraemia

• Cardiovascular
  • Coronary artery disease
    • Mortality 10-30x general population
    • CAD in 40% of dialysis patients; LV hypertrophy in 70% and CCF in 40%
    • Levels of CK-MB, TnI and TnT are not significantly elevated if receiving regular dialysis and are specific markers of myocardial ischaemia in these patients
  • Hypertension: Essential, glomerulonephritis, renal artery stenosis, fluid overload

Clinical features of uraemia

• Cardiovascular continued…
  • Heart failure: Fluid overload, uraemic cardiomyopathy, high-output AV fistula
    • Uraemic cardiomyopathy is a diagnosis of exclusion but may due to digitalis-like toxin accumulation. Dialysis rarely improves this.
    • In APO, frusemide may be effective even with minimal urine output. IV frusemide 60-100mg promotes pulmonary vasodilatation, improving oxygenation
    • Can also induce diarrhoea with sorbitol
    • Can remove 150mL of blood via phlebotomy as life-saving measure (colect in transfusion bags for auto-transfusion during dialysis)
    • HD is the ultimate treatment

Clinical features of uraemia

• Cardiovascular continued…
  • Pericarditis: Uraemic, dialysis-related, pericardial tamponade
    • Pericarditis occurs in 30% of dialysis patients and carries 8% mortality rate
    • Uraemic pericarditis makes up 75% of cases. Causes loud pericardial friction rub and inflammatory cells do not penetrate the myocardium, hence do not see usual ECG changes. If it does show typical pericarditis changes, suspect infection
    • Dialysis-related pericarditis
      • Mostly during catabolic state (trauma, sepsis) or inadequate dialysis
      • Suffer more constitutional symptoms (e.g. fever) and often suffer recurrent pericardial effusions +- haemorrhage
    • Management of pericarditis is intensive dialysis +- anterior pericardiotomy if refractory

Clinical features of uraemia

• Cardiovascular continued…
  • Tamponade
    • Main concern in any patient with pericarditis and must be considered in differential of critically ill ESRD patient
    • Rarely have Beck’s triad and instead present with ALOC, hypotension or SOB
    • Early signs
      • Increased interdialytic weight
      • Increased oedema
      • Intradialytic hypotension
      • Increased heart size on CXR

Clinical features of uraemia

• Haematological
  • Anaemia
    • Reduced red cell survival, loss in dialysis, frequent phlebotomy
    • Reduced EPO
  • Bleeding diathesis
    • Reduced platelet function, abnormal platelet-vessel wall interaction, altered vWF, anaemia, abnormal NO production
    • Increased risk of SDH, subcapsular liver haematomas and introcular bleeding
    • Desmopressin improves bleeding time in 1 hour, cryoprecipitate 4hrs, conjugated oestrogens in 6hrs and erythropoietin over weeks
  • Immunodeficiency
    • Reduced leukocyte chemotaxis and phagocytosis due to anaemia, malnutrition, zinc/selenium/vitamin deficiency
    • Dialysis therapy does not improve immune function

Clinical features of uraemia

• Gastrointestinal
  • Anorexia, metallic taste, nausea, vomiting – often indication for HD
  • GI bleeding: More common due to bleeding dyscrasias and angiodysplasias
  • Diveritulosis/itis likely due to chronic constipation due to phosphate binders
  • Ascites

Clinical features of uraemia

• Renal bone disease
  • Once CaxPhos product is >4mmol2/L2 get metastatic calcification with increased mortality
    • Pseudogout, skin and finger necrosis, cardiac/pulmonary calcifications
    • Treat: Low-calcium dialysate and phosphate-binding gels
  • Hyperparathyroidism (osteitis fibrosa cystica)
    • Calciphylaxis and Vitamin D 3 deficiency results in depressed iCa and stimulation of PTH release (Secondary hyperPTH)
    • High bone turnover results, with bone pain, muscle weakness and susceptibility to fracture
    • Diagnosed by high PTH and ALP

Clinical features of uraemia

• Renal bone disease
  • Vitamin D3 deficiency and aluminium intoxication (Osteomalacia)
    • Aluminium in dialysate diluent and phosphate binding gels leads to intoxication, weakened bones, bone pain and muscle weakness
    • Get low-normal ALP and low PTH + elevated serum aluminium (desferrioxamine effective Rx)
  • Beta-2 microglobulin amyloidosis
    • Seen in dialysis patients >50yo on HD for >10 years
    • Advanced glycation end-products lead to amyloid deposition in GI tract, bones and joints
    • Complications include GI perforation, bone cysts, pathological fractures, arthropathies, carpal tunnel and rotator cuff tears

Haemodialysis

• Complications of vascular access
  • Ideally use native vein or artery, otherwise, interposing vascular graft of autologous vein, polytetrafluoroethylene, or bovine carotid artery is used
  • Grafts have shorter functional life expectancies and more complications
  • Tunneled, cuffed catheters (Hickmann) can be placed in right IJV alternatively
  • Access complications causes the most inpatient stays of any HD complication
    • Most commonly poor flow (<300mL/min) and infection
  • Thrombosis and stenosis
    • Common cause for poor flow 
    • Presents with loss of bruit/thrill over access site
    • Not a true emergency and can be managed within 24 hours with angiographic clot removal or angioplasty or direct injection of thrombolysis

Haemodialysis

• Complications
  • Vascular access infections
    • 2-5% of fistulas and 10% of grafts in their lifetime
    • Often present septic without overt signs of infection at fistula/graft site
    • Dialysis catheters: Within 6 months of use, 48% of patients suffer bacteraemia with 5-10% of these suffering a serious adverse outcome (endocarditis, death, osteomyelitis, septic arthritis, epidural abscess)
    • Mostly S.aureus
    • Usually trial IV antibiotics to try and save catheter in first instance as opposed to immediate removal
    • If catheter blood sample has 4x high colony count than peripheral BC, suggests catheter as source
    • Vancomycin is drug of choice 15mg/kg with 5-7 day half-life in dialysis patients
    • Gentamicin can be added if gram-negative suspected (100mg IV stat then after each HD session)

Haemodialysis

• Complications
  • Vascular access haemorrhage
    • Rare but can occur due to aneurysms, anastamotic rupture or over-anticoagulation
    • Manual pressure for 5-10 minutes then observe 1-2 hours
    • Consult vascular surgery if this fails
  • Vascular insufficiency distal to access
    • 1% of all patients suffer ’steal syndrome’
    • Presents with exercise-pain, non-healing ulcers, cool pulseless digits
  • High-output cardiac failure
    • Occurs if >20% of CO diverted through access
    • Branham sign = Drop in HR with temporary occlusion
    • Requires surgical banding

Haemodialysis

• Complications during HD
  • Hypotension
    • Occurs during 20-30% of treatments
    • Usually due to overzealous ultrafiltration due to low approximation of dry weight
    • Consider diastolic dysfunction, sepsis, ischaemia, hypoxia, arrhythmias and early cardiac tamponade as differentials
    • If early in session: Pre-existing hypovolaemia
    • Mid-session: Blood tubing or haemodialyser filter leaks
    • Late-session: Excessive ultrafiltration, pericardial or cardiac disease
    • On arrival to ED: Assess for volume status, cardiac function, pericardial disease, infection and GI bleeding

Haemodialysis

• Dialysis disequilbrium
  • Clinical syndrome at end of dialysis session with nausea, vomiting, hypertension, seizure, coma and death
  • Must distinguish from SDH, stroke, hypertensive crisis, hypoxia, hypotension and seizures
  • Seen in first dialysis sessions or during hypercatabolic states (Trauma/sepsis) when large amounts of solute are cleared and subsequent cerebral oedema from osmolar imbalance
  • Treatment is stopping dialysis and delivering IV mannitol

Haemodialysis

• Air embolism
  • If sitting up, get cerebral venous embolism via retrograde transport up jugular
  • If supine, get pulmonary embolism
  • If right-to-left shunt exists, can suffer coronary or cerebral arterial embolism
  • Treatmnent: Clamp venous blood line and place patient supine, 100% O2 delivered and consider percutaneous aspiration from RV, IV steroids, full heparinisation and hyperbaric O2 therapy
• Electrolyte disturbances
  • Hard water syndrome: Dialysate with high Ca and/or Mg levels leading to nausea, vomiting, headaches, burning skin, muscle weakness, lethargy and hypertension
• Hypoglycaemia
  • Seen in diabetic and non-diabetic patients. Consider drugs, malnutrition and sepsis

Peritoneal dialysis

• Complications
  • Peritonitis
    • Most common complication
    • 1 episode every 15-18 months on average
    • Mortality rates 2.5-12.5%
    • Presents with fever, abdominal pain, rebound tenderness and cloudy effluent
    • Cell counts in PD peritonitis are usually:
      • >100 leukocytes/mm3
      • >50% neutrophils
      • Gram-stain positive in 10-40% of culture-proven peritonitis
    • Organisms: S. epidermidis (40%), S. aureus (10%), Streptococcus (15-20%), gram negative (15-20%), anaerobes (5%) and fungi (5%)

Peritoneal dialysis

• Complications
  • Peritonitis continued…
    • Nystatin 500 000 IU PO QID
    • Heparin 500IU/litre to bags containing fibrin or clots
    • Known MRSA: Vanc 30mg/kg up to 2g in one bag stat + Gent 0.6mg/kg up to 50mg in one bag daily
    • No MRSA: Cefazolin 15mg/kg in one bag daily + Gent
    • Usually treated for 7 days post-negative culture, usually for total 10 days
  • Infections around PD catheter
    • Pain, erythema, swelling, discharge
    • Usually S. aureus or Pseudomonas
    • Cephalexin or ciprofloxacin advised
  • Abdominal wall hernias
    • Occur in 10-15% of patients and pericatheter hernias have high risk of incarceration so need surgical repair

Peritoneal dialysis

• Weight gain
  • May be sign of ischaemia or pericardial effusion
  • Alternatively may be sign of ultrafiltration failure (late sign of peritonitis)

Troponin

• Majority of patients have detectable baseline level above 99th centile of hsTn
  • Likely chronic myocardial injury and underlying structural heart disease vs. coronary disease
  • Unclear if decreased renal clearance or increased cardiac release is the predominant factor
  • Stably increased levels confer increased long-term CV outcomes and poor survival in asymptomatic CKD patients
• Twice as likely to actually have an AMI
• Need to use rise or fall over 3-6 hours to define AMI (vs. single value above 99th centile)
  • >20% change is probably acceptable cut-off
• Results are similar with TnI or TnT (QHealth uses hsTnI)
• Dialysis
  • Levels of both TnI and TnT can rise (haemoconcentration/cardiac release) or fall (clearance) with studies showing contradictory results

Colchicine and Cardiovascular Risk

• Colchicine 0.5mg once daily reduces risk of recurrent combined myocardial infarction, fatal MI (COLCOT study)
• Use in chronic coronary artery disease reduces risk of composite endpoint from 9.6% to 6.8% with no significant increase in adverse events (NEJM Nidorf et al. 2020)

Last Updated on November 18, 2020 by Andrew Crofton