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OS214 20051208 Grp4b Dialysis

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Outline:

I. Objectives

II. Criteria for Dialysis

III. Types of Dialysis: Hemodialysis and Peritoneal Dialysis

IV. Physiologic Principles a. Diffusion

b. Ultrafiltration

c. Urea Kinetic Modeling V. Indications for Dialysis VI. Complications of Dialysis

VII. Hemodialysis vs Peritoneal Dialysis Objectives

• Know the physiologic principles underlying the process of dialysis

• Know the indications for the initiation of dialysis

• Discuss the impact of dialysis on survival and quality of life in patients with renal failure • Discuss and differentiate between the various

modes of dialysis

• Be familiar with the complications of dialysis. • Discuss the socioeconomic implications of

dialysis therapy Criteria for Dialysis

1. Hyperkalemia

2. Unresponsive to conservative measures 3. Extracellular volume expansion

4. Acidosis refractory to medical therapy 5. Bleeding diathesis

6. Creatinine clearance of 10 mL/min per 1.73 m2 Physiologic Principles

• Diffusion • Ultrafiltration

• Urea Kinetic Modeling Diagram of Dialysis:

HEMODIALYSIS vs PERITONEAL DIALYSIS HEMODIALYSIS

• favored in pts ( > 80kg) with no residual renal function bec. of larger volume of distribution Components

1. Dialyzer- plastic device with the facility to perfuse blood and dialysate compartments at very high flow rates

-dialysis membranes maybe composed of cellulose, substituted cellulose,

cellulosynthetic, and synthetic; the latter

being more widely used due to greater biocompatibility

-reuse of dialyzer reduces complement activation

2. Composition and delivery of dialysate- buffer is usually bicarbonate

3. Blood delivery system- composed of: a.) Dialysis machine- blood

pump, dialysis solution delivery system

b.) Dialysis access-fistula, graft or catheter through which blood is obtained for hemodialysis

-complications include thrombosis due to intimal hyperplasia, which results to stenosis 2 to 3cm proximal to the venous anastomosis Diffusion

• Random molecular motion, involving a semipermeable membrane

• Concentration gradient and collision frequency

• Molecular weight, speed, and size • Membrane resistance

• Membrane itself

• The “unstirred” fluid layer •

• Countercurrent flow

• Prevents concentration equilibrium Principle:

-mainly due to solute diffusion down a concentration gradient

-rate affected by:

* magnitude of the concentration gradient * membrane surface area

* mass transfer coefficient of the membrane

-a function of porosity and thickness of membrane, size of solute molecule, conditions of flow on the two sides of the membrane

-maybe due to ultrafiltration, as in the movement of toxic substances such as the urea ( small molecule, 60 Da)

-countercurrent flow prevents the concentration equilibrium

• The Clearance Concept:

ESRD Na 134 mEq/L K 5.9 mEq/L Ca 8 mg/dL HCO3 16 mEq/L Crea 10 mg/dL BUN 75 mg/dL Dialysis Solution Na 134 mEq/L K 0 mEq/L Ca 10 mg/dL HCO3 34 mEq/L Crea 0 mg/dL BUN 0 mg/dL

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• The (hypothetical) volume of blood that is being “cleared” of a waste product per minute

Ex. Creatinine clearance means the volume of blood being cleared of creatinine, and not the volume of creatinine cleared

-Blood water clearance (no need to memorize) Just use blood clearance X 0.894 (shortcut) • Clearance:

• Inlet BUN = 100 mg/dL • Outlet BUN = 25 mg/dL • = 75% reduction

• If BFR (blood flow rate) = 200 mL/min, then 150 mL (200 x 0.75) of blood is being cleared of urea per minute • But urea is only in the plasma

component. The fraction of blood that is plasma = 1 - hematocrit

• If Hct = 0.30, then plasma = 0.70, and • plasma flow rate = 140 mL/min

(200 x 0.70)

• RBC flow rate = 60 mL/min (200 x 0.30)

• Water flow rate:

• Plasma = 140 x 0.93 • RBC = 60 x 0.80 • Blood water clearance:

• Just use Blood clearance x 0.894 (shortcut).

• Factors affecting blood water urea clearance: • Blood flow rate

• Dialysis solution flow rate • Dialyzer efficiency (KoA)

• when BFR & DFR are ∞

WWhat about protein-bound substances?

• Cannot pass through the membrane unless “freed” from the protein

• Charcoal – used in a special type of dialyzer to adsorb these substances (ex. Removal of certain poisons), but not for routine maintenance hemodialysis

Ultrafiltration

• Hydrostatic pressure

• Transmembrane pressure (TMP mmHg)

• Ultrafiltration coefficient (KUf mL/hr/mmHg gradient)

• Osmotic force

• Membrane acting as a sieve

• Smaller solutes pass through by solvent drag

• Larger solutes held back

• Patients advised to gain only around 1 kg per day (mostly water) between HD sessions • Target dry weight

The Dialyzer Membrane • High Efficiency:

• = High KoA • High Flux:

• = High Kuf

PERITONEAL DIALYSIS

• favored in younger pts. bec. of better manual dexterity and greater visual acuity

• preferred the independence and flexibility of home-based treatment

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• infusion of 1 to3 L of dextrose containing solution into peritoneal cavity

DIFFUSION

• Peritoneal membrane

• Fluid film over endothelium • Capillary endothelium • Interstitium

• Mesothelium

• Fluid film over peritoneal membrane • Pores

• Large ( >20 nm: protein)

• Small (4-6 nm: urea, crea, Na, K) • Ultra (<0.8 nm: water)

ULTRAFILTRATION

• Instead of TMP, use an osmotic agent • Glucose 1.5%

• Glucose 2.5% • Glucose 4.25% • Icodextrin

UREA KINETIC MODELING as a way to measure dialysis dose

• Why urea?

• Ideally, we should quantify the removal of specific toxic solute concentrations by dialysis.

• However, knowledge of the molecular basis of uremia is still very incomplete. • In the low molecular weight range,

urea (MW 60)

• Has been extensively studied as a marker solute

• Has been shown to demonstrate correlation between level of transport attained and clinical endpoints. • Used to measure the amount of low molecular

weight dialyzer clearance prescribed and delivered.

• Urea reduction ratio (URR)

• = PreHD BUN – Post-HD BUN / PreHD BUN

• = 100 – 25 / 100 = 0.75 • Kt/V (dimensionless: L/hr x hr x L-1

• K = dialyzer blood water clearance (L per hour)

• t = dialysis session (hours)

• V = volume of distribution (of urea) (L)

K/DOQI Hemodialysis Guideline 4

• The dialysis care team should deliver a Kt/V of at least 1.2 (single-pool, variable volume) for both adult and pediatric hemdialysis patients.

• For those using the URR, the delivered dose should be equivalent to a Kt/V of 1.2, ie, an average URR of 65%. However, URR can vary substantially as a function of fluid removal.

K/DOQI Peritoneal Dialysis Guideline 15 & 16

For CAPD, the delivered PD dose should be a total Kt/Vurea of at least 2.0 per week and a total creatinine clearance (CCr) of at least 60 L/wk/1.73 m2 for high and high-average transporters, and 50 L/wk/1.73 m2 in low and low-average transporters.

For NIPD, the weekly delivered PD dose should be a total Kt/Vurea of at least 2.2 and a weekly total creatinine clearance of at least 66 L/1.73 m2. • For CCPD, the weekly delivered PD

dose should be a total Kt/Vurea of at least 2.1 and a weekly total creatinine clearance of at least 63 L/1.73 m2. INDICATIONS: Acute Renal Failure

• Uremia symptoms:

• Nausea, vomiting, anorexia, gastritis with hemorrhage, ileus, colitis +/- hemorrhage • Altered mental status

● Lethargy, somnolence, malaise, stupor, coma, delirium • Uremic encephalopathy ● Asterixis, tremor, multifocal myoclonus, seizures • Pericarditis

• Bleeding diathesis due to thrombocytopathy

• Refractory, progressive fluid overload • Uncontrollable hyperkalemia

• Severe metabolic acidosis • Steadily worsening renal function INDICATIONS: ESRD

K/DOQI Peritoneal Dialysis Adequacy

Guideline 1:

• when the weekly renal Kt/Vurea falls below 2.0 (equivalent to CrCl 9-14 mL/min/1.73 m2)

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K/DOQI Nutrition Guideline 27:

• If protein-energy malnutrition (PEM) develops or persists despite vigorous attempts to optimize protein and energy intake and there is no apparent cause for malnutrition other than low nutrient intake

Impact of Dialysis on Survival • Prior to 1850

• Applying heat

• Immersing in warm baths • Blood letting

• Administering diaphoretic mixtures with nitric acid in alcohol and antimonial wine

Evolution of Hemodialysis

• 1854, “Osmotic forces” by Thomas Graham • 1924, first clinical dialysis, by George Haas: • Plate dialyzer, blood pump, heparin • 1945, Willem Kolff saves a patient with ARF • Elaboration of dialyzer

• Improvement of sterile dialysis solution • Vascular access

• James Cimino, 1964: arteriovenous fistula

• Belding Scribner and Wayne Quinton: catheter

• 1876, Wegner: saline and glycerine

• 1895, Orlow: Solute concentration in blood versus in peritoneal cavity

• 1923, Ganter: saved a patient for a few days • 1945, Frank, Seligman and Fine: saved an

ARF patient

• 1960's: Henry Tenckhoff's catheter Types of Dialysis • HEMODIALYSIS • Intermittent • Continuous • CVVH • CVVHD • CVVHDF

• Slow Low Efficiency Extended Hemodialysis (SLED) • PERITONEAL DIALYSIS • CAPD • CCPD • NIPD • NTPD

*Continuous Ambulatory Peritoneal Dialysis (CAPD) – Dialysis solution manually infused into the peritoneal cavity during the day and exchanged three to four times daily. Nighttime dwell frequently instilled during bedtime and remains in the

peritoneal cavity through the night.

*Continuous Cyclic Peritoneal dialysis (CCPD) – Exchanges performed in an automated fashion, usually at night; pt is connected to the automated cycler, which performs four to five exchange cycles while the patient sleeps.

*Nocturnal Intermitent Peritoneal dialysis (NIPD) – Dry during day, 10 hours cycling per night.

Complications during Hemodialysis • Common

• Hypotension • Muscle cramps

• Restless legs syndrome • Nausea & vomiting • Headache

• Chest & back pain • Pruritus

• Fever & chills • Uncommon • Dialysis dysequilibrium • Dialyzer reaction • Arrhythmia • Cardiac tamponade • Intracranial bleeding • Seizures • Hemolysis • Air embolism

Long-term Complications of Hemodialysis • Osteomalacia (aluminum?)

• Dialysis-induced beta-2 microglobulin • Myopathy (middle molecules?)

• Accelerated atherosclerosis, vascular calcification

• Hyperpigmentation

• Hepatitis B/C, idiopathic ascites

• Leukopenia, hypocomplementemia, bleeding diathesis

Complications of Peritoneal Dialysis • Catheter • Pain • Bleeding • Leakage • Poor flow • Acute perforation • Peritonitis • Peritonitis • Nutrition

• High glucose, protein loss • Hernia

• Genital edema • Hydrothorax • Back Pain

• Peritoneal fibrosis

Hemodialysis vs Peritoneal Dialysis

• Cost: HD versus PD? (hard to tell the difference)

• Effectiveness: close to similar • Prognosis: worse if with diabetes

Hemo – 40% survival in 5 years Peritoneal – 70% survival in 2 years • Note:

• Antihypertensives

• Erythropoietin, iron supplements • Calcium supplements, phosphate

binders • Comorbidities:

• Cardiovascular: CVD

• Gastrointestinal: malnutrition, ulcer, dysmotility

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• Genitourinary: impotence, infertility

• Musculoskeletal: osteodystrophy

• Insomnia, depression, anger, suicide, etc.

• Nervous system: neuropathy, dementia, encephalopathy Why don’t pts live on Dialysis?

*Dialysis does not replace ALL the functions of the kidneys especially those with long-term significance such as erythropoietin production and Vitamin D3 synthesis.

References

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