1. FREQUENT HEMODIALYSIS AND OUTCOME Dr. Sandeep G Huilgol MBBS., DNB (Internal Medicine)., MMedSci(Nephrology)
2. PURPOSE OF THE STUDY• Despite the increasing efforts in adequate dialysis in the mortality of patients still remains high according to US and UK registries. (24-30 % mortality)• The causes of high mortality of patients still remain elusive.• Adequacy of hemodialysis is being measured on the basis of urea reduction ratio which has improved over the years in various centers throughout the world.• But as mortality has not improved much, various other factors were thought of like beta-2 microglobulin, blood pressure variability and Phosphorus etc.
3. • To concentrate the efforts on the adequacy of dialysis based on these factors various observational studies as well some RCTs were conducted by increasing the dialysis duration and frequency, and to better understand the kinetics of their removal.• Any Indian study of frequent dialysis is not known.
4. GOALS OF HEMODIALYSIS AND ITS KINETICS• The primary goal of hemodialysis is to restore the intracellular and extracellular fluid environment that is characteristic of normal kidney function.• This is accomplished by the movement of solutes such as urea from the blood into the dialysate.• Solute concentration and molecular weight are the primary determinants of diffusion rates.
5. • Small molecules such as urea diffuse quickly• Larger molecules such as – phosphate, – β (Beta) 2 microglobulin, and – albumin (because it is retained in the vascular compartment as it is not permeable through the endothelial surface)are compartmentalized and thus diffuse much more slowly.
6. Taken from : Hemodialysis, Jonathan Himmelfarb et al. N Engl J Med 2010;363:1833-45
7. Panel A• Low-molecular-weight solutes such as urea are readily dialyzed.• The efficiency of total urea removal declines over the course of treatment because of decreasing plasma urea concentrations.• After dialysis, there is a rebound in urea levels.
8. Panel B and C• For compartmentalized solutes, such as phosphate, the plasma space is rapidly cleared (Panel B)• Whereas most phosphate in cells and bone remains there.• After dialysis, there is much rapid rebound in the plasma phosphate concentration because of equilibration of the body compartments;• Thus, overall removal is inefficient.• Longer dialysis time provides more effective clearance or the dialysis process should be more frequent.
9. • Dialysis of Beta-2 microglobulin is also limited because of compartmentalization.• Similar is the case with protein bound substances because protein binding limits the free-solute concentration, which is the driving force for diffusion (Panel C).• Similar to panel B frequent dialysis might help in the complete removal.
10. EFFECTS OF INCREASING THE DOSE OF HEMODIALYSIS• Well powered trials done earlier NCDS and HEMO did not show any improvement in the all cause mortality or outcome with increased dose of hemodialysis.• Hence novel approach was necessary.
11. FREQUENT HEMODIALYSIS• Frequent Hemodialysis is based on the concept that middle molecules which are compartmentalized can be removed by increasing the frequency of dialysis.• Various observational studies have been done and recent Frequent Hemodialysis Network trial (RCT) published recently.• Most have shown good outcome although long-term follow up is not available.
12. • A majority of such studies have shown reductions in blood pressure levels and in the need for antihypertensive medications, with various effects on regression of left ventricular hypertrophy.• Health-related quality-of-life measures appear to improve with frequent dialysis treatments.• Results for measures of anemia control and calcium phosphate metabolism show a mixed response
13. RATIONALE OF FREQUENT HEMODIALYSIS• Blood solute concentrations and water/sodium retention rise or fall irregularly in conventional thrice weekly Hemodialysis, with peak values being recorded before each HD session (particularly before the first HD session of the week) and low values at the end.
14. • This non physiological condition can be potentially associated with: (as described by Locatelli et al).• Peak concentration toxicity e.g. hyperkalaemia peaks and/or pulmonary oedema can be lethal.• Disequilibrium syndrome: due to sudden removal of urea and sodium, manifesting mainly as headache and post-dialysis fatigue.• Intra-HD hypotensive episodes: due to abrupt blood volume reduction.• Triggering of cardiac arrhythmias due to rapid electrolyte blood concentration changes (particularly regarding potassium).
15. Various studies can be quoted showing benefits of frequent hemodialysis.
16. CONCLUSION• Frequent Hemodialysis can be considered as a very useful procedure which can replace the conventional dialysis frequency to improve outcome but is not feasible economically and organizationally,• Hence an alternative like dialysis every alternate day can be followed to improve hemodynamic and electrolyte stability which would mean just one dialysis procedure extra fortnightly which is feasible.• Such a study has not been done so far.