Dialysis in ESRD

Velma Herwanto

ESRD Treatment Options

Hemodialysis Peritoneal dialysis: less efficient in solute clearance Transplantation
Outcomes are similar preference and quality-of-life consideration

Epidemiology
Mortality rate on dialysis in US: 1820%/ year, 5-year survival rate 3035% Deaths are due mainly to cardiovascular diseases (50%) and infections (15%) Important predictors of death: age >, male, nonblack race, DM, malnutrition, underlying heart disease

Initiation on Maintenance Dialysis

Uremic symptoms: encephalopathy, neuropathy, pericarditis, pleuritis Persistent ECV expansion despite diuretic therapy Bleeding diathesis Hypertension poorly responsive to antihypertensive until one of this is present! medications Persistent metabolic disturbances that are refractory to medical therapy Persistent nausea and vomiting Evidence of malnutrition CrCl or eGFR < 10 mL/min/ 1.73 m2

Do not delay the initiation of dialysis

Relative Indications to Initiate Dialysis

Decreased attentiveness and cognitive tasking Depression Persistent pruritus Restless leg syndrome

hemodialysis

Hemodialysis

Scheme for Hemodialysis

DIALYZER Bundles of capillary Extracorporeal circuit in tube: 1,5-2 m2 dialysis machine Cellulose vs. Blood pump: 250-500 mL/min, synthetic negative hydrostatis pressure Reprocessed and ultrafiltration BLOOD DELIVERY reused
Safety monitor Dialysis access

Dialysis solution delivery system

K+ 0-4 mmol/L Ca2+ 1.25 mmol/L: modification in hypocalcemia Na+ 140 mmol/L lower hypotension, cramping, nausea, vomiting, fatigue, dizziness Water 120 L: reverse osmosis

DIALYSATE

Hemodialysis Membrane

Chronic Dialysis Access

Fistula, graft, or tunneled catheter AV fistula:
Brescia-Cimino fistula: radiocephalic/ brachiocephalic/ brachiobasiclic arterialization of the vein The highest long-term patency rate and lower complication

Synthetic graft: PTFE straight/ looped forearm, straight/ looped upper arm
Smaller-caliber veins/ veins have been damaged

Complication: thrombosis, infection, steal, aneurysms, venous hypertension, seromas, heart failure, and local bleeding

Chronic Dialysis Access

Dual-lumen tunneled catheter
Indication:
To allow maturation of fistulas/ grafts CVC (require HD <1 year) Contraindication to permanent access Refuse permanent access

Chronic Dialysis Access

Dialysis in Series

CVC: Entire systemic compartment is available for urea extraction urea removal would be maximized

Dialysis in Parallel

- 60-70% - 5-15%

AV access: reduce extraction of urea < theoretical clearance urea removal is limited (the capillaries where this blood refills with urea)

Goals of Dialysis
Removing both low- and highmolecular-weight solutes
Efficiency of dialysis blood and dialysate flow and dialyzer characteristics Dialysate 500-800 Adequacy of dialysis: mL/min fractional removal of urea nitrogen and derivations thereof

Heparinize d blood 300-500 mL/min

Relationship Between Qb and Kd

(also Qd and Kd)

Delivery of new blood (high urea concentration) maintain a high rate of diffusion

The effect of increasing dialyzer blood flow (Qb) on total body urea clearance (Ktb) during HD

Movement of Waste Product

Dialytic Clearance of Solute

Diffusion Ultrafiltration

Convective Clearance

Membrane: Flux, Permeability, and Efficiency

Komass transfer coefficient; Asurface area

Dialysis Prescription (KDOQI 2006)

Urea removal normalized for a measure of body size Kt/V K = dialyzer urea clearance data dialysis membrane size, Qb, Qd t = duration of dialysis in minutes modifiable! V = patient's urea space

Adequacy of HD (KDOQI 2006)

Delivering Adequate Dose of Dialysis

Urea Equilibration in HD

Degree of urea removal rate of urea equilibration between IC and the EC Slow equilibrators lower BUN but a slower rate of total urea removal

Organ Reservoirs of Urea

15-20% CO Low ratio of blood flow to urea content sequester up to 80% of the total body urea rebound and dialysis efficiency

HD Increase in... (KDOQI 2006)

Minimally adequate dose

Frequency
Hyperphosphatemia Chronic fluid overload w/ wo refractory hypertension BW 20% less or < than their peer Recent otherwise unexplained and unplanned weight loss Improving QOL and quality of sleep, reducing sleep apnea, and improving sensitivity to EPO

, any body size Smaller patients BW 20% less or < than their peer Recent otherwise unexplained and unplanned weight loss

5 HD Regimens
Duratio Freq. n (x/wee (h/sessi k) on) 3 7 3 5 7 4 1,6 8 8 8 Qb Qd
Clearance of middle and large molecule

Standard 350 350 300 300 300 600 600 1000 1000 1000 Low flow, long time Daily, short time

Clark WR, et al. Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model. J Am Soc Nephrol 1999; 10:60 .

Major Components of Dialysis Prescription

Choose a biocompatible membrane Prescribe a Kt/V 1.3 or a URR 70% Ensure that the delivered dose = the amount prescribed Delivered dose < prescribed:
Exclude etiology Increase Qb 400 mL/min Increase Qd 800 mL/min Use a high-efficiency dialyzer Increase treatment time

Choose dialysate composition: sodium, potassium, bicarbonate, calcium Adjust UF rate to achieve patients dry weight

Advantage and Disadvantage in Individualizing Various Components of Hemodialysate

Complications During HD
Complicati on Fever Hypotensio n Differential Diagnosis Bacteremia, water-borne pyrogens, overheated dialysate Excessive UF, cardiac arrhythmia, air embolus, pericardial tamponade; hemorrhage (GI, intracranial, retroperitoneal); anaphylactoid reaction Inadequate removal of chloramine from dialysate, failure of dialysis concentrate delivery system Incomplete removal of aluminum from dialysate water, prescription of aluminum antacids Excessive urea clearance (first treatment), failure of dialysis concentrate delivery system

Hemolysis

Dementia Seizure

Complication During HD
Hypotension ( in systolic BP 20 mm Hg or in MAP 10 mm Hg associated with symptoms), particularly among diabetic. risk in:
Excessive ultrafiltration with inadequate compensatory vascular filling Impaired vasoactive or autonomic responses Osmolar shifts Overzealous use of antihypertensive agents Reduced cardiac reserve High output cardiac failure: shunting through the dialysis access Vasodilatory and cardiodepressive effects of acetate

Management of Hypotension
Discontinuing UF 100250 mL of isotonic saline or 10 mL of 23% saturated hypertonic saline Salt-poor albumin Sequential UF followed by dialysis Midodrine Cooling of the dialysate Avoid heavy meals during dialysis Prevention: careful evaluation of the dry weight and by UF modeling (>fluid is removed at the beginning)

Complication During HD
Muscle cramp:
Excessively aggressive volume removal (> dry weight) Use of low-sodiumcontaining dialysate

Management:
volume removal UF profiling Higher concentrations of sodium in the dialysate or sodium modeling

Sodium Modelling
Intracellular movement of water +UF of water hypotension

Complication During HD
Anaphylactoid reaction to dialyzer
Type A: IgE-mediated hypersensitivity reaction to ethylene oxide within the first few minutes steroids or epinephrine Type B: nonspecific chest and back pain, from complement activation and cytokine release several minutes, resolve over time

Dialysis Disequilibrium Syndrome

Central nervous system disorder in dialysis patients Pathophysiology: cerebral edema
Reverse osmotic shift Fall in cerebral intracellular pH

At risk: new HD patients (with >> BUN), severe metabolic acidosis, older age, pediatric, presence of CNS disease Headache, nausea, disorientation, restlessness, blurred vision, asterixis, muscle cramps, anorexia, dizziness More severe: confusion, seizures, coma, death

DDS: Treatment and Prevention

Qb, consider stop the dialysis session Hypertonic mannitol or 23% saline Prevention: slow urea removal
Initial HD: 2 hours, Qb 150-250 mL/min, small surface area dialyzer, concurrent blood and dialysate flow 3-4 days 50 mL/min (up to 300-400 mL/min), duration 30 minute Marked fluid overload: UF followed by a short period of HD PD Prophylactic phenytoin and/ or mannitol

Peritoneal Dialysis

Normal Anatomy
Peritoneal contains 100 ml fluid Adult can tolerate > 2 L fluid without pain or alteration to the respiratory function : peritoneal cavity is closed : peritoneal cavity is continuous with the Fallopian tubes PD fluid become blood-stained during a menstrual period

Principles of Peritoneal Dialysis

Jeremy Levy et al, Oxford Handbook of Dialysis, 2003

Solute and Water Transport Mechanism in PD

Diffusion Solute (e.g. Ur, Cr, K)
Via mid-size pores Most important High concentration (blood) low concentration (dialysate) to the concentration gradient Best for clearance of small molecules In response to a positive transmembrane pressure Less dependent on molecular size

Convection

Solute (e.g. protein, Na)

Ultrafiltratio Water n

Low osmotic concentration (blood) high osmotic concentration (dialysate), via aquaporin-1 Highest at the beginning, ceases when osmolarity has decreased to equal serum osmolarity Reabsorbtion of water if dialysate is allowed to dwell beyond the time past when osmotic equilibrium is reached

Access to Peritoneal Cavity

Peritoneal catheter: silicon rubber with numerous side holes at the distal end Dacron cuffs: promote fibroblast proliferation, granulation, and invasion of the cuff
Seal from bacteria from the skin surface Prevents external leakage of fluid

Types of PD Catheter

PD Solutions
Ideal osmotic agents:
Metabolized easily with non-toxic degradation products Poorly absorbed Inert and non-toxic to the peritoneal membrane Inexpensive Effective osmotic agent at low concentration No metabolic consequences of absorption Must be of nutritional value Not difficult to manufacture Should not inhibit peritoneal defenses

PD Solutions
Glycerol: Glucose Polypeptides Glucose-containing Amino acid polymer (1.1%): (5%): (icodextran (dextrose7.5%): monohydrate 1.5, 2.5, 4.25%): Low High molecular molecular weight weight

PD Solutions
Solutions: 1.5 to 6.0 L Lactate is the preferred buffer, other: acetate, bicarbonate Electrolyte: Na, Ca, Mg, K Additives: heparin, antibiotics, insulin

CAPD 3-5x/ day

CCPD

DAPD

NIPD

Adequacy of PD: K/ DOQI 2006

T Peritoneal

Calculation of Solute Clearance

, 70 kg on CAPD has a drain volume of 10.5 L/day, and D/P urea of 0.95 Kt = 10.5 x 0.95 = 10 L The urea volume of distribution (V) = 42 L (60% of lean body weight in men, 55% in women) Daily Kt/Vurea = 10 42 = 0.24 Weekly Kt/Vurea = 0.24 x 7 = 1.68

Adequacy of PD
Efficiency of solute clearance volume of dialysate (> volumes > solute clearance), physical activity Peritoneal equilibrium test: measures the transfer rates of creatinine and glucose across the peritoneal membrane
Low transporter: fewer exchanges Lowaverage transporter Highaverage transporter High transporters: absorb > glucose, lose efficiency of UF with long daytime dwells, lose > albumin require more frequent, shorter dwell time exchanges

PET: 3-4 weeks after catheter insertion and on complication

High

Using Transport Type to Select PD Regimen

Indication to Repeat Peritoneal Membrane Transport Testing

KDOQI 2006

Unexplained volume overload Decreasing drain volume on: overnight dwell (CAPD) or daytime dwell (APD) Increasing clinical need for hypertonic dialysate dwells to maintain DV Worsening of HTN Change in measured peritoneal solute removal (Kt/Vurea) Unexplained signs/ symptoms of uremia

PD Prescription Target and Measurement (KDOQI 2006)

If a patient is not thriving + no other identifiable cause, consider to increase dialysis dose. Patient with minimal RKF continuous 24 h/day of PD dwell to maximize middle molecule clearance

Fluid Balance
The 2006 NKF-KDOQI guidelines: one should achieve euvolemia and optimal BP control Maintenance of euvolemia: PD drain volume, RKF, blood pressure The 2005 European Best Practices Guidelines: in anuric patients, minimum UF target is 1.0 L/day

Complications During PD
Peritonitis: peritoneal fluid leukocytes 100/mm3 (at least 50% are PMN) pain, cloudy dialysate, fever
Gram-positive cocci, gram-negative rod, fungal, mycobacterial Intraperitoneal/ oral antibiotics Due to hydrophilic gram negative rods (e.g., Pseudomonas sp.) or yeast: require catheter removal

Catheter-associated nonperitonitis infections Weight gain Hypoproteinemia: dietary protein intake Hyperglycemia Hypertriglyceridemia Residual uremia (esp. in patients with no residual kidney function)

Terima Kasih