Initial Approach 2/5/2016. Case 1. Case 2. ? Volume Overload = Ultrafiltration Failure

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1 Case 1 Shweta Bansal, MBBS, MD Assistant Professor of Medicine Director, Home Dialysis Program University of Texas Health Science Center at San Antonio San Antonio, TX, USA 35 y/m with ESRD sec to FSGS On PD x 18 months, No episodes of peritonitis PET:.65 CCPD prescription 2 lt x 4 exchanges over 9 hours, Last fill: 2 lt Mostly uses 1.5% and 2.5% dextrose bags Presents to clinic for monthly visit Mild fatigue and dyspnea on exertion x 3 weeks BP: 15/9 mmhg, Weight: 158 lb, O2sat: 96% on RA No JVD, Chest: bilaterally clear Heart: normal S1 & S2, no r/m/g, 1+ bilateral pedal edema Abd: soft, non tender, no localized swelling or hernia, Cath: intact Case 2 6 y/m with ESRD sec to Diabetes Mellitus CAD, PVD and treated basal cell cancer On PD x 4 years 3 episodes of peritonitis treated successfully PET:.65 CCPD prescription 2 Lx 4 exchanges over 9 hours Last fill: 2 L followed by a 2 lt mid day exchange Mostly uses 1.5% and 2.5% dextrose bags, lately more of 4.25% Presents to clinic for monthly visit Mild fatigue and dyspnea on exertion x 3 weeks BP: 15/9 mmhg, Weight: 178 lb, O2sat: 96% on RA No JVD, Chest: bilaterally clear Heart: normal sounds and no r/m/g, 1+ bilateral pedal edema Abd: soft, non tender, no localized swelling or hernia, Cath: intact A1C: 7.5, Kt/V: 2.5 (no renal component x 2 years)? Volume Overload = Ultrafiltration Failure Clinical Failure to maintain volume homeostasis despite fluid restriction and use of at least 3 hypertonic (2.5 or 4.25%) exchanges per day. Technical The International Society for Peritoneal Dialysis defines UFF as less than 4 ml UF after 4 hour dwell with 2L of 4.25% dialysate. (<2 cc with 2.5% dextrose) Case 1 7 ml Case 2 25 ml Increased Intake Volume/Fluid Overload Decreased Residual Renal function Decreased Output Outflow Problem UF Failure Membrane Related Initial Approach History Increased salt and fluid intake Change in dietary habits Change in jobs or daily activities Residual renal function (RRF) Urine volume Frequency Duration of symptoms Bowel movement pattern Positional dialysate flow 1

2 Initial Approach contd. Examination Localized or diffuse swelling Catheter Review the home records Body weights UF volume with each exchange Review the renal component of total Kt/V Protection of RRF Avoid nephrotoxins Avoid hypotensive episodes RAAS blockade but not very definitive Bio compatible PD fluids may like to add more info. Lu, PK. Ann Intern Med 23; 139: Increased Intake Volume/Fluid Overload Decreased Residual Renal function Quick fill and drain with 2 L dialysate to directly observe the nature and rate of inand out flow Decreased Output Outflow Problem UF Failure Membrane Related Catheter Obstruction and Malposition External Constipation Constipation Constipation Migration: catheter follows memory Omental wrap Adhesion Kink Internal Fibrin Blood Clots Evaluation and Management Routine use of laxatives softener or mild stimulants e.g. senna Lactulose or bowel prep TPA for fibrin/clot in cath Flat plate radiograph CT Peritoneogram/IR Surgical revision Repositioning Replacement Dialysis Leak Incidence: 5% of PD patients. The dialysis fluid traverse from intraabdominal cavity to extra abdominal area. Around catheter site from tear in peritoneum into hernia sac Hydrothorax Risk factors Uremia, obesity, anemia, protein loss Diagnosis: intraperitoneal contrast injection followed by X ray or CT. Treatment: Rest and surgery if recurrence. 2

3 Structure of Peritoneal Membrane Peritoneal Membrane Distributed Model Three Pore Model Aroeira LS et al. J Am Soc Nephrol 18:24, 27 Fusshoeller A. Pediatr Nephrol 23:19, 28 Pore Matrix Model Flessner M. Contrib Nephrol 163:7, 29 Standard Peritoneal Equilibration Test (2.5% Dextrose) UF Failure D/Do GLUCOSE Low L Ave H Ave High Drain Volume D/P CREATININE D/Pcr >.8 Large effective surface area Good solute transport but poor UF 1. Type I UFF related to changes in membrane over time 2. Peritonitis: transient but if recurrent and prolonged episodes type I UFF 3. Inherent high transport D/Pcr Low osmotic conductance to glucose (Type II UFF) 2. Increased lymphatic reabsorption (Type IV UFF) D/Pcr <.5 Low efffective surface area (Type III UFF) 1. Simple sclerosis 2. Adhesions 3. EPS Twardowski et al. Perit Dial Bull 7: 138, 1987 Type I UFF: Histopathological Changes At start of PD After 6 Yrs of PD Etiology and Pathogenesis Aroeira et al. J Am Soc Nephrol 18:24, 27 Bioincompatible fluids Fusshoeller A. Pediatr Nephrol 23:19, 28 3

4 Treatment of Type I UFF: Peritoneal Resting Look at the paper for Details Before After P value MTC urea 25.7 ± ±6.2 <.5 Effect of Peritoneal Resting on UF is Sustained for at Least One Year Look at paper concern if UFF was present more than 6 mont then may not be helpful MTC creat 16.7 ± ±4.1 <.5 UF (ml) ± ± <.1 MTC= mass transfer cofficient De Alvaro et al. Adv in Perit Dial 9:56, 1993 De Alvaro et al. Adv in Perit Dial 9:56, 1993 Icodextrin: Treatment and Prevention Glucose polymer High MW (16Kd), isoosmolar Non absorbable Maintains oncotic gradient longer Reduces Glucose toxicity GDP exposure AGE exposure Hyperosmolar stress Icodextrin is Not Associated with Longitudinal Change in Membrane Function Icodextrin ( ) No Icodextrin ( ) Cooker et al. Kid Int Suppl 81:S34, 22 Davies SJ et al. Kid Int 67:169, 25 Epithelial to Mesenchymal Transition: The Role of RAAS The peritoneal mesothelial RAAS is up regulated by: Glucose Low ph Peritonitis Peritoneal mesothelial cells Local renin angiotensin aldosterone system contributes to interstitial fibrosis Increases TGF β Increases fibronectin Increases VEGF Nessim S et al. Kid Int 78:23, 21 RAAS Blockers Improve Membrane Small Solute Permeability 24 hr D/P creatinine Years of Follow up Control p =.5 ACEI/ ARB Kolesnyk I et al. Nephrol Dial Transpl 24:272, 29 4

5 Neutral ph, Low GDP, Bicarbonate PD Solutions Conventional glucose based PD fluid High concentration glucose degradation products (GDPs) Secondary to heat sterilization Buffered by lactate at low ph 5 6 Role of amino acid Bioincompatible Soln to decrease exposure t The glucose 2 bag system more neutral ph Low ph compartment contains glucose Reduces GDPs during sterilization Bicarbonate or lactate/bicarbonate compartment Avoids calcium precipitation Neutral ph, low GDP solution (Balance ) or conventional (stay.safe ) Nutrneal if not directly good Reduced glucose exposure Johnson et al. Nephrol DialTransp(212) 27: 4445 Inherent High Transporter 1% of original PD patients have this profile. Fluid overload due to loss of residual renal function. Treatment CAPD CCPD Decrease dwell time Increase # of exchanges Icodextrin Peritonitis Associated UFF Acute episode Increase in D/Pcreat Decrease in UF Mediators TNF α, NO, IL 6, Prostacycline Transient and reversible. Recurrent and prolonged episodes lead to type I UFF. Prompt recognition and treatment Low threshold to replace catheter Type I Ultrafiltration Failure Due to changes in the peritoneal membrane over time. Angiogenesis: Increase in effective peritoneal surface area Dissipation of osmotic gradient faster Submesothelial fibrosis Failure to transmit the osmotic gradient Unfortunately, slowly increasing hyperpermeability is a typical feature of chronic PD. D/P Creat =.5.8 Type II UFF: Decreased Transcellular Water Transport Sodium meq/l Dwell time (min) 2.5% D 4.25% D Due to AQP 1 malfunction 1. Increase with vintage 2. No change in number 3. Glycation or NO mediated Heimburger et al. Kid Int 38: 495, 199 Goffin et al. Am J Kid Dis 33:383,

6 In Vivo Effects of AQP 1 Agonist: AqF26 D/P Creat =.5.8 Type IV UFF: Lympha c Absorp on Cumulative transport (ml) Absorption Transcapillary UF Net UF Lymphangiogenesis VEGF and TGF β mediated Diagnosis of exclusion Time (min) No response to ico Bethanechol chloride Cholinergic properties contraction of subdiaphragmatic lymphatic stomata 2% improved UF after 4 hr dwell Yool et al. J Am Soc Nephrol 24:145, 213 Mactier et al. JCI 8:1311, 1987 Baranowska Daca et al. Adv Perit Dial 11:69,1995 D/P Creat <.5 Type III UFF: Low Effective Surface Area Due to fibrosis/ sclerosis, adhesions, compartmentalization Simple Sclerosis Recurrent and severe peritonitis, intra abdominal catastrophy and surgery lead to adhesion Decrease in dialysate flow and effective surface area Contrast injection or peritoneal scintigraphy Adhesion lysis Sometimes due to the most extreme complication of PD EPS (encapsulating peritoneal sclerosis) EPS: a clinical syndrome characterized by bowel obstruction (intermittent, recurrent, or persistent) caused by a wide range of adhesions of a diffusely hypertrophied peritoneum Suspected clinically when PD patients with peritoneal deterioration complain of GI symptoms of insidious nature. Peritoneal biopsy CT Scan Loculated ascites Adherent bowel loops Bowel luminal narrowing Calcification Thickening of peritoneal membrane. The PET Decrease in both solute transport and ultrafiltration. Kawaguchi Y et al. Perit Dial Int 2:Suppl 4; 3, 2 Encapsulating Peritoneal Sclerosis Factors Implicated in the Pathogenesis of EPS Duration of PD Prior peritonitis High transport status Withdrawal of PD Bioincompatibility (glucose, hypertonicity, low ph) Acetate based dialysate Plasticizers Chlorhexidine Church and Junor NEJM 347: 737, 22 6

7 Stop PD Continue intermittent peritoneal lavage? Nutritional support (TPN) Surgery enterolysis Immunosuppression (case reports and series) Corticosteroids Azathioprine Mycophenolate mofetil Sirolimus/ Everolimus Tamoxifen Treatment of EPS Dutch EPS Registry Tamoxifen No Tamoxifen P<.4 Summary Not all the volume overload are UF failure Dietary intake Residual renal function Catheter malfunction Careful review of the is very crucial. Treatment records History Examination Real UFF can be managed with change in the prescription, icodextrin and PD rest. Time is the key for management of PD related infection to avoid UFF in future. Korte MR et al. Nephrol Dial Transpl 26:691, 211 7