Hemodialysis: an overview

Principle of hemodialysis

  • Diffusion
  • Ultrafiltration
  • Convection
  • Adsorption

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Adsorption is the adherence of molecules to the dialyzer membrane. This is clinically relevant in the removal of cytokines.

  • The difference between the mass acquired in the dialysate and the mass removed from the body is called mass balance error and usually
    reflects the solute binding to the dialyzer membrane.

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Basic components of hemodialysis machine

A more sophisticated version

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Assessing solute removal

  • Extraction ratio
  • Clearance

Extraction ratio

  • (Cin – Cout)/Cin; Cin is concentration of solute in the blood entering the dialyzer, Cout is the concentration of solute exiting the dialyzer
  • Dependent on blood flow and dialyzer flow rate (slower = more time for ultrafiltration), the dialyzer membrane  (porosity) and intrinsic properties of the molecule eg size.

Clearance

  • Volume (of plasma, serum, blood, or the entire body) from which all the solute was removed during a specific period; hence, the units are volume/time.
  • For urea, we often evaluate dialysis dose by total-body clearance,
    which is the K in Kt/V (“Dimensionless” ratio);  t refers to the duration of the clearance period, and the V, to the volume of
    distribution of the substance (for urea, V = total-body
    water).
  • A ratio of 1 = a volume of blood equal to the distribution volume of urea has been completely cleared of urea.
  • When a solute’s concentration gradient is from blood cells to plasma water (eg, potassium), the amount removed during dialysis
    may exceed the amount in plasma water (i.e Kt/V >1)
  • in HD, clearance is determined from what was removed from the blood, whereas in peritoneal dialysis (PD), clearance is
    determined by what is acquired in the dialysate (i.e volume of the dialysate)

Blood clearance in HD = Cin-Cout/Cin (Extraction ratio) X Qb (blood flow rate)

  • Qb = clearance when extration ratio = 1 (all solute in the blood entering the plasma has been cleared).
  • If the dialysate is saturated with solute, no gradient exists so clearance = Qd (Clearance can never exceed Qd)
    – Important in PD when the dialysate is limited.
  • Saturation in PD = Concentration of dialysate / Concentration of plasma
    Saturation in HD = Qd/Qb (also called flow fraction)
    – When FF <0.4, clearance of plasma urea is >90%

Mechanism of solute transport and removal by HD

In tissues

  • Urea is extensively distributed in all tissues.  During h/d, sharp decrease in blood urea level is re-equilibrated by urea which is recruited from the tissues (in minutes-hours).
  • This is called urea rebound in which the level increases after h/d.
  • Blood levels immediately after dialysis do not perfectly reflect urea levels in all tissues.

In dialyzer

  • Solute transport within the dialyzer is a function of blood flow distribution, blood membrane interactions, membrane characteristics, and dialysate flow distribution.

Practical issues

  • Minimum spKt/V = 1.2 (3 times of HD/week)
  • Types of dialyzer membrane:

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  • Choice is based on cost and idiosyncracies.
    – Use of ethylene oxide (ETO) for sterilization of dialyzer and polyacrylonitrile membranes (PAN) membranes, especially  in patients on ACE-inhibitors can cause anaphylactic reactions.
  • High flux vs low flux:
    – The HEMO and Membrane Permeability Outcomes (MPO) studies could not prove a clear benefit of high versus low-flux dialyzers, but a subgroup analysis of the HEMO Study showed a statistically significant decrease in all-cause mortality in the high-flux arm
    with dialysis vintage longer than 3.7 years.
    – It may take years of end-stage renal disease for conditions attributed to middle-sized molecules to emerge.
    – Because the cost is hardly different, the only reason to use low-flux dialyzers would be when water purity is suspect.
  • Assessing inadequate urea clearance:
    – Blood flow from access (Qb too less)
    – Dialysis time (too fast = not much time for ultrafiltration)

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  • Anticoagulation: weight based UFH is most commonly used. Recurrent exposure risks bleeding and heparin-induced thrombocytopenia. Alternatives include low-molecular-weight heparins, direct thrombin inhibitors.

Blood vs dialysate

Sodium

  • Modern hemodialysis machine removes sodium via convection. As a result, more complications arise eg thirst, hypovolemia, hypotension, dialysis dysequilibrium syndrome.
  • To solve this problem, dialysate sodium concentration is increased by either fixing dialysate sodium at a higher concentration for the entire HD session or systematically varying the dialysate sodium concentration over the course of the HD session, a process called sodium modeling.
    – Other means include periodic infusion of D5W, Normal saline but this may lead to intradialytic accumulation of sodium –> intradialytic weight gain and hypertension

Potassium

  • Post-dialysis hypokalemia
    – If liver and skeleta muscles are atrophied, there will be a loss of intracellular potassium storage –> post dialysis hypokalemia
    – If acidosis is corrected too rapidly (acidosis causes potassium efflux and hyperkalemia). Absorption of dialysate potassium leads to insulin release to try to decrease K+ removal.
  • Th dialysate potassium must not be too low to avoid excessive loss of K+
    – The “rule of 7s” is a basic approach that states that the patient’s potassium level plus dialysate potassium concentration should equal
    approximately 7

Bicarbonate

  • Hemodialysis corrects acidosis by removing acids and adding bicarbonate.
  • Managing chronic metabolic acidosis too aggressively may result in acute metabolic alkalosis. A lower base concentration should be used in patients susceptible to alkalosis, such as individuals with poor
    protein intake, small muscle mass, or persistent vomiting.
  • The National Kidney Foundation’s KDOQI (Kidney Disease Outcomes Quality Initiative) guidelines recommend a midweek predialysis plasma bicarbonate level of 22 mEq/L. Lower mortality risk has been
    observed in patients with predialysis serum bicarbonate levels of 18-23 mEq/L.
  • Bicarbonate buffered dialysate is most commonly used.
  • A lower pre-dialysis serum HCO3 can be corrected by increasing the dialysate concentration; a high pre-dialysis serum HCO3 reflects decreased protein intake and cannot be simply corrected by decreasing the dialysate concentration
    – Protein eaten will be broken down into amino acids, which are buffered by bicarbonate.

Calcium

  • Calcium ion is important for contracting both vascular smooth muscle and cardiac myocytes, which affects BP. Lower dialysate calcium concentrations may cause intradialytic hypotension,
    acute arrhythmias, and sudden cardiac death
  • Acidosis leads to increas in ionized plasma calcium. Rapid correction of acidosis can therefore lead to post-dialysis hypocalcemia.
  • Alkalosis leads to decrease in ionized plasma calcium. Therefore, use of dialysate bicarbonate can induce alkalosis post-dialysis can lead to hypocalcemia.

Complications from h/d

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Hypotension

  • Most common acute complication.
  • Due to multiple mechanisms
    – Thermal transfer from the warmed dialysate to plasma
    – HD is catabolic event that generates heat and stimulates vasodilation
    – patients have autonomic dysfunction therefore poor cardiac compensatory system
    – rate of intravascular volume removal exceeds its rate
    of refilling (ultrafiltratin >1.5 L/hr
    – Movement of water from extracellular to intracellular compartments due to reduction in plasma osmolality post-dialysis.
    – Antihypertensive use before dialysis (should be d/c and continued after dialysis !)
  • Hypotension can occur when the patient’s weight is at or less than the “estimated dry weight,”the weight below which the patient develops symptomatic hypotension; therefore patient’s weight post-dialysis is important !
  • Management
    – Reduce ultrafiltration rate by increasing dialysis time (allow time for body to restore its fluid equilibrium); UFR >10 ml/hr/kg is associated with CV mortality (http://www.medscape.com/viewarticle/738631_2)
    – Antihypertensives should not be given within 4 hours before h/d.
    – Cooled dialysate to 35 celcius will reduces frequency of hypotension.
    – Midodrine maybe used in autonomic dysfunction

** Calculation of UFR

  • Eg patient weight = 70 kg, dialysis for 4 hours and 2L of fluid is removed = 2000 mL/4hr/70 kg = 7.14 ml/hour/kg
  • Compare to 4L being removed = 14.2 ml/hour/kg (t00 much!)

Cramps

  • Maybe related to volume although cause is unknown. Cramps have been found to be more often when UF rate is high and dialysate has low sodium content
  • Treatment includes reducing UF rate and increasing dialysis time.
  • For patients without diabetes, D50W is useful as hyperosmolality when the glucose is metabolized helps to draw water into extracellular compartment and therefore supporting the circulation.

Arrhythmias

  • Mainly due to electrolyte imbalance (read above) and patient’s intrinsic heart abnormalities eg LVH and coronary artery disease

Hypoxia

  • Only in acetate buffered dialysate due to low dialysate pCO2 –> net movement of CO2 from blood into dialysate.
  • Low pCO2 in blood –> hypoventilation and hypoxia.
  • In bicarb buffered dialysate pCO2 is high ( nearly 100 mm Hg), which leads to the net transfer of carbon dioxide into the blood, stimulating respiratory drive

Hypoglycemia

  • Insulin half life is prolonged in eGFR <20
  • Uremia causes peripheral insulin resistance. Therefore, h/d (which removes uremia) improves the insulin sensitivity.
  • These 2 factors may lead to hypoglycemia during HD.
  • Management
    – Decrease insulin dose during the day of dialysis
    – Diabetic patients should not be dialyzed against a bath that has
    a glucose concentration , 100 mg/dL

Dialysis dysequilibrium syndrome

  • Reduces plasma osmolality (reduction in plasma solute) after dialysis leads to movement of water into the cells –> cerebral edema
  • Patients at risk: hypernatremia and uremia (pre-dialysis hyperosmolar blood)
  • Main symptoms are headache, nausea & vomiting, confusion, seizure and neurological signs (signs of elevated ICP)
  • Management
    – Prophylactic infusion of Mannitol 20% at 1g/kg is suggested for initial dialysis session.
    – Goal to reduce solute removal rate: reduce the blood flow rate (Qb)

Diets in h/d vs PD

  • Generally for PD, diet is less strict as you will be dialyzed everyday.
  • Main idea is to eat a diet of
    – high protein with adequate calories
    – less sodium, potassium and phosphorus
  • Patients in PD are more prone to hyperglycemia therefore they may eat lesser carbohydrates than the patients in HD.

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  1. Modern HD uses diffusion + convection & ultrafiltration. Diffusion removes small molecules, convection & ultrafiltration removes larger molecules eg cytokines.
  2. Solute removal in HD is assessed by extraction ratio (Cin-Cout/Cin) and clearance (Kt/V). spKt/v is used to evaluate HD adequacy. spKt/V of at least 1.2 is the recommendation (3X dialysis/week).
  3. Clearance of urea can never exceed Qd (=Qd when dialysate is saturated, important in PD in which dialysate is limited). Clearance = Qb when all solutes are cleared (C = Removal fraction X Qb).
  4. Blood urea level measured post-dialysis does not reflect urea level in all tissues as it takes some time for intracellular urea to re-equilibrate with extracellular compartments (urea rebound).
  5. Avoid use of PAN membrane with ACEi or membrane sterilized with ethylene oxide –> anaphylactic reactions
  6. Inadequate clearance of urea (despite 3X HD/week)? Normally the problem is the Qb. Check whether the assess is adequate to deliver a large enough blood flow (>300 mL/min)
  7. Rapid removal of sodium via dialysis may lead to hypotension and dialysis dysequilibrium syndrome. Prolong the dialysis time !
  8. Rapid correction of acidosis may lead to hypokalemia (insulin is stimulated to drive potassium into the cells), hypocalcemia (free ionized calcium is cleared from the blood and predisposes patient to metabolic alkalosis (especially for those with low muscle mass and poor protein intake).
  9. Avoid hypokalemia post-dialysis by using rule of 7s. Dialysate potassium concentration should not be too low !
  10. Try to aim for normal pre-dialysis serum bicarbonate level. Too low or too high isn’t good. A too high serum bicarbonate level cannot be easily corrected by decreasing bicarbonate conc of the dialysate, it is linked to decreased protein intake.
  11. Complications of dialysis: most common are hypotension and cramps. Others include electrolyte imbalance (which causes arrhythmias), hypoglycemia, hypoxia and dialysis dysequilibrium syndrome.
  12. Hypoglycemia in dialysis is due to combined factors of prolonged insulin half life in CKD and improved peripheral sens after dialysis.
  13. Drugs to avoid at dialysis day
    – Antihypertensives
    – Cut the dose of insulin !

Reference:

Thomas A. Golper et al. Hemodialysis: Core Curriculum 2014. Am J Kidney Dis. 2014;63(1):153-163

http://www.ccmtutorials.com/renal/rrt/page2.htm

http://www.hemodoc.info/2012/04/do-you-know-your-ultrafiltration-rate-ufr.html

http://www.rogosin.org/treatment-areas/treatment-dialysis/treatment-dialysis-nutrition-services.php

 

 

 

 

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