1. Hemodialysis: History and Current Perspective Nadeem A Siddiqui MD Dallas Nephrology Associates

2. Hemodialysis:History and Current Perspective History of Dialysis History of Dialysis Principles of Hemodialysis Principles of Hemodialysis Practice of Hemodialysis Practice of Hemodialysis Complications of Hemodialysis Complications of Hemodialysis

3. Dialysis Process by which the solute composition of a solution “A” is altered by exposing it to a second solution “B” through a semi- permeable membrane Process by which the solute composition of a solution “A” is altered by exposing it to a second solution “B” through a semi- permeable membrane

5. Necessary pre-requisites for Hemodialysis 1) Semi-permeable membrane 1) Semi-permeable membrane 2) Anticoagulation 2) Anticoagulation 3) Knowing what to remove and how much of it 3) Knowing what to remove and how much of it

6. 1773: Nurepuel isolates Urea by boiling urine in a pan 1773: Nurepuel isolates Urea by boiling urine in a pan

7. 1828: Wohler synthesizes Urea and describes its molecular structure 1828: Wohler synthesizes Urea and describes its molecular structure

8. Thomas Graham (1805-1869)

9. 1850 Glasgow, Scotland: 1850 Glasgow, Scotland: Thomas Graham ‘s experiment to demonstrate diffusion across a semi- permeable membrane (Pergamon paper) Thomas Graham ‘s experiment to demonstrate diffusion across a semi- permeable membrane (Pergamon paper)

12. Dialysis Membranes 1750:Advances in the dovelopment of smokeless gunpowder led to the synthesis of a strong Nitrocellulose called “collodion”. It was a combination of Nitric acid and cotton 1750:Advances in the dovelopment of smokeless gunpowder led to the synthesis of a strong Nitrocellulose called “collodion”. It was a combination of Nitric acid and cotton Addition of Camphor to this substance led to the synthesis of stable and strong “plastics” Addition of Camphor to this substance led to the synthesis of stable and strong “plastics” 1957:Helmut Staldiger polymerized “Cellulose” 1957:Helmut Staldiger polymerized “Cellulose”

14. 1913:The First Hemodialysis Experiment

15. 1937: William Thalhimer successfully lowers BUN by performing Hemodialysis in anephric dogs 1937: William Thalhimer successfully lowers BUN by performing Hemodialysis in anephric dogs

16. 1926:The First Human Experiment George Haas used a collodion tube arrangement to successfully dialyze human subjects George Haas used a collodion tube arrangement to successfully dialyze human subjects Allergic reactions to impurities in Hirudin led him to abandon his experiments Allergic reactions to impurities in Hirudin led him to abandon his experiments

17. 1937:Nils Alwall used the Alwall Kidney to perform the first ever hemodialysis treatment at the university of Lund, Sweden 1937:Nils Alwall used the Alwall Kidney to perform the first ever hemodialysis treatment at the university of Lund, Sweden

19. “ If I have seen farther it is because I have stood on the shoulders of Giants” Sir Isaac Newton Sir Isaac Newton

20. Hemodialysis:History and Current Perspective History of Dialysis History of Dialysis Principles of Hemodialysis Principles of Hemodialysis

21. Mechanisms of Solute transfer Diffusion Diffusion Convection Convection

22. Diffusive Clearance A result of random molecular motion A result of random molecular motion Influenced by concentration gradient of the solute and its Molecular weight as well as by the membrane permeability to the solute Influenced by concentration gradient of the solute and its Molecular weight as well as by the membrane permeability to the solute

23. Convective Clearance Water molecules passing through a SPM carry with them the solutes in their original concentration. This is called the “solvent drag phenomenon” Water molecules passing through a SPM carry with them the solutes in their original concentration. This is called the “solvent drag phenomenon” Water can be made to move across a SPM by the application of either a hydrostatic or an osmotic gradient Water can be made to move across a SPM by the application of either a hydrostatic or an osmotic gradient

26. Hemodialysis:History and Current Perspective History of Dialysis History of Dialysis Principles of Hemodialysis Principles of Hemodialysis Practice of Hemodialysis Practice of Hemodialysis

27. The Hemodialysis circuit

28. Dialysis Membranes MembraneHydr.Perm.ExamplesBiocomp. Regen. cellulose Low flux cuprophanePoor Modif.Cellulose Low/High Flux Cell.acetate Cell di-acet. Interm. Synthetic High/Low flux PAN,PS,PA,PC,PMMCGood

29. Dialysis Solution ComponentConcentrationmmol/L Na140 K2 Ca 1.25 (5 mg/dl) Mg 0.5 (1.2 mg/dl) Acetate3.0 Chloride108 Bicarbonate35 Glucose 5.6 (100 mg/dl)

30. Water Purification

33. Water Treatment System for Hemodialysis

34. Vascular Access

43. Indications for initiating Hemodialysis In patients with calculated creatinine clearance <20 ml/min/1.73 m 2 the onset of: In patients with calculated creatinine clearance <20 ml/min/1.73 m 2 the onset of: *Uremic symptoms *Uremic symptoms Nausea/emesis Nausea/emesis Altered sleep pattern Altered sleep pattern *Altered mental status *Altered mental status Coma Coma Stupor Stupor Tremor Tremor Asterixis Asterixis Clonus Clonus Seizures Seizures

44. Indications for Hemodialysis *Pericarditis or Tamponade (urgent indication) *Uremic platelet dysfunction (urgent indication) *Refractory volume overload *Refractory hyperkalemia *Refractory Metabolic acidosis with anuria

45. Indications for Hemodialysis Steadily worsening renal function in a patient with measured 24 hour urinary creatinine clearance<15 ml/min when accompanied by worsening azotemia, poor nutritional status and refractory edema Steadily worsening renal function in a patient with measured 24 hour urinary creatinine clearance<15 ml/min when accompanied by worsening azotemia, poor nutritional status and refractory edema

46. Equations for estimation of renal function Cockcroft and Gault equation Cockcroft and Gault equation MDRD Formula MDRD Formula

47. The Cockcroft-Gault equation Cr Cl =(140-age) x wt/72(serum Cr) Cr Cl =(140-age) x wt/72(serum Cr) Decrease 15% for women Decrease 20% for paraplegia,40% for quadriplegia Increase 12% for AA males

48. The MDRD formula Modification of diet in renal disease study JASN2000 GFR (ml/min/1.73m 2 )= GFR (ml/min/1.73m 2 )= 186 x Pcr -1.154 x age -0.203 x1.212 if black X0.742 if female 186 x Pcr -1.154 x age -0.203 x1.212 if black X0.742 if female The MDRD equation calculates GFR, hence values are lower than those of creatinine clearance by Cockcroft Gault equation.

49. Measurement of nutritional status Physical Exam Physical Exam Skin fold thickness Skin fold thickness Mid arm muscle thickness Mid arm muscle thickness Protein catabolic rate <1* Protein catabolic rate <1* Serum Albumin Serum Albumin Serum Cholesterol Serum Cholesterol Blood Lymphocyte count Blood Lymphocyte count

50. Monitoring Dialysis Adequacy

54. Hemodialysis:History and CURRENT Perspective History of Dialysis History of Dialysis Principles of Hemodialysis Principles of Hemodialysis Practice of Hemodialysis Practice of Hemodialysis Complications of Hemodialysis Complications of Hemodialysis

55. Complications of Hemodialysis 1. Dialysis Reactions 2. Intradialytic Hypotension 3. Neuromuscular complications 4. Dialysis dysequilibrium 5. Hemolysis 6. Intradialytic hypoxemia 7. Postdialysis syndrome 8. Cardiac arrhythmia and sudden death 9. Steal syndrome 10. Dialysis associated hypoxemia 11. Air embolism 12. Metabolic derangements

56. Dialysis Reactions

58. Management of Intradialytic Hypotension 1. Assess dry weight frequently 2. Avoid BP meds before HD 3. Avoid rapid UF 4. Use sequential UF and HD 5. Avoid feeding patients on HD 6. Use Sodium modeling 7. Use HCO 3 based dialysate 8. Keep Hct >33 9. Use non Cellulosic membranes 10. Keep Dialysate temperature<37 degrees Celsius 11. Assess cardiac function, r/o pericardial effusion/tamponade

59. Neuromuscular Complications: Muscle Cramps Etiology: Hypo-osmolality, Carnitine deficiency, Hypomagnesemia, excessive inter-dialytic weight gain Etiology: Hypo-osmolality, Carnitine deficiency, Hypomagnesemia, excessive inter-dialytic weight gain Rx: Dietary counseling, Sodium modeling, Saline or 50% dextrose bolus, ? Prophylactic Quinine sulfate or Oxazepam Rx: Dietary counseling, Sodium modeling, Saline or 50% dextrose bolus, ? Prophylactic Quinine sulfate or Oxazepam

60. Neuromuscular complications Seizures Seizures Restless legs syndrome Restless legs syndrome Headache Headache

61. Dialysis Disequilibrium Syndrome (DDS) Risk factors: Young age, severe and chronic azotemia, Initial dialysis treatment, High flux/ large surface area dialyzer Risk factors: Young age, severe and chronic azotemia, Initial dialysis treatment, High flux/ large surface area dialyzer Symptoms: Headache, nausea, emesis, blurred vision, hypertension, disorientation, muscle twitching Symptoms: Headache, nausea, emesis, blurred vision, hypertension, disorientation, muscle twitching

62. DDS Pathogenesis: Pathogenesis: 1. Reverse urea effect ( rapid reduction of serum urea while CSF urea concentration remains high) 2. Paradoxical CSF acidosis 3. Intracerebral accumulation of idiogenic osmoles in uremia

63. DDS Treatment Treatment 1. Early detection of uremia, early intervention with dialysis 2. First few treatments should aim to achieve modest reduction in serum urea concentration ( 30% or less) 3. Sodium modeling, use of Bicarbonate dialysis, slow QB 4. Prophylactic use of Mannitol is not recommended

64. Intradialytic Hemolysis Uncommon Uncommon From contamination of dialysate with Chloramine or Copper (deionization failure) From contamination of dialysate with Chloramine or Copper (deionization failure) From Methemoglobinemia from nitrate contamination From Methemoglobinemia from nitrate contamination

65. Intradialytic Hypoxemia Arterial p O 2 drops by 5 to 30 mm Hg during Hemodialysis due to central Hypoxemia. Arterial p O 2 drops by 5 to 30 mm Hg during Hemodialysis due to central Hypoxemia. This is a result of a drop in CO 2 that accompanies correction of acidosis on dialysis This is a result of a drop in CO 2 that accompanies correction of acidosis on dialysis V/Q mismatch can occur due to pulmonary sequestration of activated leukocytes V/Q mismatch can occur due to pulmonary sequestration of activated leukocytes Acetate can induce respiratory muscle fatigue Acetate can induce respiratory muscle fatigue

66. Intradialytic Hypoxemia Treatment : Supplemental oxygen during Hemodialysis in susceptible patients Treatment : Supplemental oxygen during Hemodialysis in susceptible patients