Peritoneal dialysis Jana Fialová Martina Peiskerová Klinika nefrologie

Peritoneal dialysis Jana Fialová Martina Peiskerová Klinika nefrologie 1. LF a VFN Praha 10/2007

Modalities of renal replacement therapy Interchangeable, depends on residual renal. Ramesh Khanna & Karl D. Nolph function

Peritoneal dialysis - outline • • • Principles of PD PD solutions PD catheter Indication / contraindication of PD PD schemes : CAPD, CCPD Assessement of PD adequacy, ultrafiltration • Assessement of peritoneal function • Complications • Perspectives – new dialysis solutions

Peritoneal dialysis – introduction • method of RRT for 100. 000 patients worldwide • complementary to hemodialysis Principles: • peritoneum (capillary endothelium, matrix, mesothelium) = semipermeable dialysis membrane through which fluid and solute move from blood to dialysis solution via diffusion and convection • effective peritoneal surface area = perfused capillaries closed to peritoneum (↓ in peritonitis) • ultrafiltration (movement of water) enabled by osmotic gradient generated by glucose or glucose polymers (isodextrin)

Principles of peritoneal dialysis

Scheme of peritoneal solute transport by diffusion through the pores of capillary wall

Model of transport - 3 sorts of pores Ramesh Khanna & Karl D. Nolph

Composition of standard peritoneal dialysis solution Na 132 mmol/l Ca 1, 25 mmol/l Mg 0, 5 mmol/l Cl 100 mmol/l lactate 35 mmol/l glukose 1, 36 -4, 25 g/dl osmolarity 347 -486 p. H 5, 2 ev. lactate/bicarbonate GDP (degradation products of glucose) Ramesh Khanna & Karl D. Nolph

Urea concentration in dialysate, rate of dialysate equalization of solute concentration depends on molecular size of solute

Concentration of Creatinin in dialysate equilibrium of concentrations between dialysate and blood is slower than for urea

Peritoneal catheter • implanted via laparoscopy, punction or laparotomy (total anesthesy) • PD is started 3 weeks following the impantation of catheter

Types of peritoneal catheters

Why to start with PD ? 1. better maintenance of residual renal function

Why to start with PD ? • clinical outcomes comparable to HD, no difference in 2 year and 5 year mortality vs. HD (study NECOSAD) • saves vascular access • preferred for children (APD) • modality choice is a lifestyle issue

Indication / Contraindications of PD 80% of patients have no contra-indication to any of the dialysis methods and may choose according to their life style between HD a PD Absolute contra-indications of PD: 1. peritoneal fibrosis and adhesions following intraabdominal operations 2. inflammatory gut diseases Ramesh Khanna & Karl D. Nolph

Relative contraindications of PD • pleuro-peritoneal leakage • hernias • significant loin pain • big polycystic kidneys diverticulosis • colostomy • obesity • blindness * • severe deformant arthritis • psychosis • significant decrease of lung functions

CAPD – continual ambulatory peritoneal dialysis • manual exchanges

NIPD – night intermitent peritoneal dialysis (cycler)

CCPD – continual cyclic PD

Assessement of PD adequacy PET (peritoneal equilibrium test) 1 • determines quick or slow passage of toxins from the blood into the dialysis fluid • ‘high-fast transporters’ v. s. ‘low-slow transporters’ • helps to decide about the PD scheme (dwell duration and intervals, CAPD vs. CCPD) • performed in hospital, takes 5 hours • involves doing a CAPD exchange using a 2. 27% G, samples of PD fluid and blood are taken at set times

PET (peritoneal equilibration test) 2 Transporter High Waste removal Fast Water removal Poor Average OK OK Slow Good Best type of PD Frequent exchanges, short dwells – APD CAPD or APD CAPD, 5 exchanges daily + 1 exchange at night

Interpretation of peritonal equilibration test ? ?

Results of baseline PET Ramesh Khanna & Karl D. Nolph

Choice of PD scheme depends of BSA and type of transport

Assessement of peritoneal function 1. PET- peritoneal equilibration test (type of transport and ultrafiltration after 4 hours) 2. weekly clearance of creatinine and urea 3. daily UF 4. dicrease of Na in dialysis fluid after 60 minutes using 3, 8% G (test of aquaporines)

Ratio D/P for Na, upper curve – 1, 27% glucose, lower curve - 3, 86% G (initial drop due to transcellular UF of water through aquaporins)

Ultrafiltration during PD Depends on: - type of transporter – low transporters have better UF - concentration and type of osmotic agent in PD fluid: 1. Fluids with glucosis (1, 27%, 2, 5% a 3, 8% ), higher concentration – higher osmotic pressure and UF 2. Fluid with icodextrin (Extraneal) = glucose polymer with a large molecule, resorbs only 10 -20%, offers longtime UF, suitable for long night exchanges, 8 -12 hours) - time between exchanges, using glucose-based fluids, maximal UF obtained after 2 -3 hours, using longer spaces UF dicreases.

Ultrafiltration in different types of PD solutions

Criteria of PD adequacy

Complications of PD 1 Infectious: • exit-site inflammation (flare, suppurative secretion, granulation) • peritonitis (turbid dialysate, abdominal pain, fever) Non-infectious: • hernias • hydrothorax • sclerosing encapsulating peritonitis (rare, life threatening complication, mostly after ≥ 6 years on PD, peritoneum is massively thickened and calcificated, leading to intestinal obstruction)

Complications of PD 2 Non-infectious: • Leakage of dialysate along the peritoneal catheter • Drainage failure of dialysate (dislocation or catheter obstruction by fibrin) • Morphologic changes of peritoneum following longlasting PD (peritoneal fibrisis, mesotelial damage, vasculopathy and neo-angiogenesis) leading to loss of UF capacity – reason for PD cessation in 24% of all patients, and in 51% of patients treated above 6 years.

Causes of UF failure • Large vascular surface of peritoneum (due to neo-angiogenesis, vasodilation), leading to high (fast) type of transport including fast loss of osmotic glucose pressure • Decreased function of aquaporins • High lymfatic absorption

Morphologic changes of peritoneum due to PD (1) Obr. 1 -before starting PD, norm. peritoneum (omentum)

Morphologic changes of peritoneum due to PD (2) Obr. 2 -after 3 years of PD, submesotelial fibrosis and neo-angiogenesis (enlargement of vascular surface of peritoneum)

Peritonitis • Clinical features: cloudy PD effluent, abdominal pain, nausea, vomiting, • Laboratory: leucocytosis, CRP, > 100 wbc/ mm 3, PD fluid culture • Bacteriology: Gram + cocci (incl. S. aureus) in 75%, Gram – (incl. Pseudomonas) in 25%, culture negative, mycobacterial (1%), fungal (3%), allergic (Icodextrin) • Complications: relapses, antibiotic treatment failure, acute and chronic UF failure • Treatment for. 14 -21 days : Gram + cocci: Vankomycin / cephalosporin, Gram -: aminoglycoside / cephalosporin III. Generation (+ antimycotics, metronidazole) • Goal: < peritonitis / 18 months

From PD gudelines (ISPD) • biocompatible PD solutions - normal p. H, low concentration of glucose • insertion of PD catheter – 10 days-6 weeks before RRT • urea / creatinine clearance measured every 6 months • PET: 6 weeks after commencing treatment + annually • avoid routine use of high glucose concentrations )use of icodextrin, aminoacids instead) • preserve residual diuresis, obtain UF above 750 ml/day • peritonitis and exit-site infection rates, regular revision of technique • invasive procedures cover by ATB prophylaxis • topical ATB administration if needed (S. aureus, Ps. aeruginosa) • beware central obesity

Perspectives - New dialysis solutions protect peritoneal membrane Physioneal 1 • • GDPs and AGEs Lactate Physiologic p. H and p. CO 2 Membrane and immune cell function Extraneal 2 • Isosmolar to plasma • No glucose exposure • GDPs and AGEs • Membrane and immune cell function Nutrineal 2 • No glucose exposure • No GDPs or AGEs • Membrane and immune cell function 1 Skoufos, et al. Kidney Int. 2003; 64(suppl 88): S 94 -S 99. 2 Vardhan, et al. Kidney Int. 2003; 64(suppl 88): S 114 -S 123.

Clinical advantages of new dialysis solutions Physioneal Infusion pain Peritonitis Glycemic control Appetite Patient acceptance No UF Extraneal Glucose load Glycemic control UF, control of fluid status Dyslipidemia Quality of life Time on PD Nutrineal Glucose load Glycemic control Protein intake, nutritional status Pecoits-Filho, et al. Kidney Int. 2003; 64(suppl 88): S 100 -S 104. Vardhan, et al. Kidney Int. 2003; 64(suppl 88): S 114 -S 123.

Absorbtion of glucose from peritoneal solutions 1. Solutions containing glucose (green) lead to significant glucose absorbtion 2. Solutions based on another osmotic agent (blue, violet) do not lead to glucose absorbtion, so decrease total daily glucose load). Glucose absorbed = 159 g/day 1 2. 5 L Physioneal 1. 36% 2. 5 L Physioneal 3. 86% Glucose absorbed = 50 g/day 2 2. 5 L Physioneal 1. 36% 2. 5 L Nutrineal 2. 5 L Physioneal 1. 36% 2. 5 L Extraneal