Peritoneal dialysisJana FialovMartina Peiskerov Klinika nefrologie 1. LF a VFN Praha10/2007

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

Peritoneal dialysis - outlinePrinciples of PDPD solutionsPD catheterIndication / contraindication of PDPD schemes : CAPD, CCPDAssessement of PD adequacy, ultrafiltrationAssessement of peritoneal functionComplications Perspectives new dialysis solutions

Peritoneal dialysis introduction method of RRT for 100.000 patients worldwidecomplementary to hemodialysisPrinciples: peritoneum (capillary endothelium, matrix, mesothelium) = semipermeable dialysis membrane through which fluid and solute move from blood to dialysis solution via diffusion and convectioneffective 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

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

Ramesh Khanna & Karl D. Nolph Na 132 mmol/lCa 1,25mmol/lMg 0,5 mmol/lCl 100 mmol/llactate 35 mmol/l ev. lactate/bicarbonateglukose 1,36-4,25 g/dlosmolarity 347-486pH5,2GDP (degradation products of glucose)Composition of standard peritoneal dialysis solution

Urea concentration in dialysate, rate of 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

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

Relative contraindications of PD pleuro-peritoneal leakage herniassignificant loin painbig polycystic kidneys

severe deformant arthritis psychosissignificant decrease of lung functions

* diverticulosis colostomy obesity blindness

CAPD continual ambulatory peritoneal dialysis

manual exchanges

NIPD night intermitent peritoneal dialysis (cycler)

CCPD continual cyclic PD

Assessement of PD adequacyPET (peritoneal equilibrium test) 1determines quick or slow passage of toxins from the blood into the dialysis fluidhigh-fast transporters v.s. low-slow transportershelps to decide about the PD scheme (dwell duration and intervals, CAPD vs. CCPD) performed in hospital, takes 5 hoursinvolves 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

Interpretation of peritonal equilibration test ??

Ramesh Khanna & Karl D. Nolph Results of baseline PET

Choice of PD scheme depends of BSA and type of transport

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

Assessement of peritoneal function

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)

Depends on:- type of transporter low transporters have better UF- concentration and type of osmotic agent in PD fluid:Fluids with glucosis (1,27%, 2,5% a 3,8% ), higher concentration higher osmotic pressure and UFFluid 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 during PD

Ultrafiltration in different types of PD solutions

Criteria of PD adequacy

Infectious:exit-site inflammation (flare, suppurative secretion, granulation)peritonitis (turbid dialysate, abdominal pain, fever)Non-infectious:herniashydrothoraxsclerosing 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 1

Non-infectious:Leakage of dialysate along the peritoneal catheter Drainage failure of dialysate (dislocation or catheter obstruction by fibrin)Morphologic changes of peritoneum following long-lasting 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.

Complications of PD 2

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 aquaporinsHigh lymfatic absorption Causes of UF failure

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, > 100wbc/ mm3, PD fluid cultureBacteriology: 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 failureTreatment 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 pH, low concentration of glucoseinsertion of PD catheter 10 days-6 weeks before RRTurea / creatinine clearance measured every 6 monthsPET: 6 weeks after commencing treatment + annuallyavoid routine use of high glucose concentrations )use of icodextrin, aminoacids instead)preserve residual diuresis, obtain UF above 750 ml/dayperitonitis and exit-site infection rates, regular revision of techniqueinvasive procedures cover by ATB prophylaxistopical ATB administration if needed (S.aureus, Ps. aeruginosa)beware central obesity

Perspectives - New dialysis solutions protect peritoneal membrane GDPs and AGEs LactatePhysiologic pH and pCO2 Membrane and immune cell functionPhysioneal11Skoufos, et al. Kidney Int. 2003;64(suppl 88):S94-S99.2Vardhan, et al. Kidney Int. 2003;64(suppl 88):S114-S123. Nutrineal2No glucose exposureNo GDPs or AGEs Membrane and immune cell function

Isosmolar to plasmaNo glucose exposure GDPs and AGEs Membrane and immune cell functionExtraneal2

Physioneal Infusion pain Peritonitis Glycemic control Appetite Patient acceptanceNo UFClinical advantages of new dialysis solutions Extraneal Glucose load Glycemic control UF, control of fluid status Dyslipidemia Quality of life Time on PDPecoits-Filho, et al. Kidney Int. 2003;64(suppl 88):S100-S104.Vardhan, et al. Kidney Int. 2003;64(suppl 88):S114-S123. Nutrineal Glucose load Glycemic control Protein intake, nutritional status

Absorbtion of glucose from peritoneal solutions Solutions containing glucose (green) lead to significant glucose absorbtion Solutions based on another osmotic agent (blue, violet) do not lead to glucose absorbtion, so decrease total daily glucose load). 12

NzevAutorPracovitDatum zpracovn pednkyCategory: Peritoneal Membrane Preservation This slide shows the beneficial effects of the newer PD solutions containing alternate buffers and osmotic agents.All three solutions reduce levels of GDPs and AGEs. With Physioneal, it is because glucose is sterilized at a very low pH. With Extraneal and Nutrineal, it is because there is no glucose in either solution.Additional benefits of Physioneal : Physiologic pH and pCO2, reduced lactate levels.Additional benefit of Extraneal: Same osmolarity as plasma.As a result of its unique properties, each solution has been shown to improve membrane and peritoneal immune cell function.

Skoufos L, Topley N, Cooker L, et al. The in vitro biocompatibility performance of a 25 mmol/L bicarbonate/10 mmol/L lactate-buffered peritoneal dialysis fluid. Kidney Int. 2003;64(suppl 88):S94-S99.Vardhan A, Zweers MM, Gokal R, Krediet RT. A solutions portfolio approach in peritoneal dialysis. Kidney Int. 2003;64(suppl 88):S114-S123.

Category: Peritoneal Membrane Preservation This slide shows the beneficial effects of the newer PD solutions containing alternate buffers and osmotic agents.All three solutions reduce levels of GDPs and AGEs. With Physioneal, it is because glucose is sterilized at a very low pH. With Extraneal and Nutrineal, it is because there is no glucose in either solution.Additional benefits of Physioneal : Physiologic pH and pCO2, reduced lactate levels.Additional benefit of Extraneal: Same osmolarity as plasma.As a result of its unique properties, each solution has been shown to improve membrane and peritoneal immune cell function.

Skoufos L, Topley N, Cooker L, et al. The in vitro biocompatibility performance of a 25 mmol/L bicarbonate/10 mmol/L lactate-buffered peritoneal dialysis fluid. Kidney Int. 2003;64(suppl 88):S94-S99.Vardhan A, Zweers MM, Gokal R, Krediet RT. A solutions portfolio approach in peritoneal dialysis. Kidney Int. 2003;64(suppl 88):S114-S123.

This slide summarizes the clinical benefits of Physioneal, Extraneal, and Nutrineal as described in the articles by Pecoits-Filho, et al (S100) and Vardhan, et al (S114).Pecoits-Filho R, Tranaeus A, Lindholm B. Clinical trial experiences with Physioneal. Kidney Int. 2003;64(suppl 88):S100-S104.Vardhan A, Zweers MM, Gokal R, Krediet RT. A solutions portfolio approach in peritoneal dialysis. Kidney Int. 2003;64(suppl 88):S114-S123.