Strategies to Prevent Peritoneal Dialysis Failure

Strategies to Prevent Peritoneal Dialysis Failure Constantinos J. Stefanidis, MD, PhD P & A Kyriakou Children s Hospital, Athens, Greece

Technique failure Drop-out Transfer to HD Technique failure rate is defined as the proportion of dialysis patients switching from one modality to another. Peritoneal dialysis (PD) Hemodialysis (HD)

Peritoneal dialysis (PD) in children: outcome 7,039 patients After three years of PD: Continue PD Death 10 % 5 % 25 % Transfer to hemodialysis (HD) 60 % Transplantation Νοrth American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2011

Peritoneal dialysis (PD) termination in children ~10% ~25% ~20% Benchmarking Νοrth American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2011

Peritoneal dialysis (PD) termination in children Νοrth American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2011

Peritoneal dialysis (PD) termination in children ~50% ~70% ~25% Νοrth American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2011

Peritoneal dialysis (PD) termination in children ~95% ~90% ~80% Benchmarking Νοrth American Pediatric Renal Transplant Cooperative Study (NAPRTCS) 2011

Peritoneal dialysis (PD) termination in children 1,697 patients started RRT between 2009-2011 Probability of receiving a transplant within 4 years after initiating RRT: 77% for <5 year olds: 69% ESPN/ERA EDTA Registry database. Chesney N et al. Pediatr Nephrol 2014

Peritoneal dialysis (PD) in children ESPN/ERA EDTA Registry database. Chesney N et al. Pediatr Nephrol 2014

International Pediatric Peritoneal Dialysis Network Global registry active in 33 countries Information for 1900 children around the globe United States 10% Turkey 19% 12 European countries 31% Canada 59% Chile, Argentina, 80% - 90% China, Singapore, Nicaragua, Uruguay, 100% Schaefer F et al. Perit Dial Int. 2012

PD technique survival and GNI GNI: per-capita gross national income ~95% ~85% https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3524840/ Schaefer F et al. Perit Dial Int. 2012

International Pediatric Peritoneal Dialysis Network D.Borzych-Duzalka et al. 2016 Registered Network users: 222 centers in 53 countries Registry participants: 116 centers in 41 countries

Participants 2,453 PD patients (824 incident patients) from 105 pediatric nephrology centers enrolled in the IPPN registry between 2007 and 2015 13% of patients had 452 PD access revisions over 3134 patient-years 23% of the incident patients had a PD access revision over 1066 patient-years 43% within the first 3 months D.Borzych-Duzalka et al. Clin J Am Soc Nephrol2016

D.Borzych-Duzalka et al. Clin J Am Soc Nephrol2016 PD access revisions The need for PD access revision was associated with a higher risk of PD failure or death (hazard ratio [HR], 1.35) The need for access revision due to mechanical dysfunction doubled the risk of technique failure compared with infectious causes (HR, 1.95)

PD access survival by time of revision D.Borzych-Duzalka et al. Clin J Am Soc Nephrol2016

PD access survival by age D.Borzych-Duzalka et al. Clin J Am Soc Nephrol2016

Risk Factors for Access Revision D.Borzych-Duzalka et al. 2016 Odds ratio P Age at first observation 0.93 < 0.001 GNI per capita 1.1 0.01 Presence of any ostomy 1.3 0.01 Swan neck tunnel with curled intaperitoneal portion 1.42 0.02 Two cuff catheter 0.89 ns Exit site pointing upward vs. downward/lateral 0.97 ns Early (<7d) vs. delayed catheter use 0.88 ns

Reasons for Access Revision by Catheter Type D.Borzych-Duzalka et al. 2016 Tenckhoff straight Tenckhoff curled/straight tunnel Tenckhoff curled/swan neck tunnel Other p N (%) 100 (24%) 47 (11%) 247 (58%) 30 (7%) Leak (n=29) 10 (35%) 3 (10%) 12 (41%) 4 (14%) 0.043 Dysfunction (n=270) 59 (22%) 25 (9%) 172 (64%) 14 (5%) <0.001 Peritonitis (n=71) 15 (21%) 11 (15%) 39 (55%) 6 (9%) <0.001 Exit site infection (n=54) 16 (30%) 8 (15%) 24 (44%) 6 (11%) 0.018

Conclusions D.Borzych-Duzalka et al. 2016 Access failure occurs in almost 15% of pediatric PD patients with the highest frequency in the first treatment year Early (< 3 mo) access failure is associated with poor technique survival Access failure risk factors include young age, coexisting stomies, presence of swan-neck tunel with curled intraperitoneal portion

Preventive strategies of PD technique failure Before starting PD During PD period

Establishing a Peritoneal Dialysis Program Location in a Pediatric Hospital with Hemodialysis and Intensive Care Units

Establishing a Peritoneal Dialysis Program One program per million child population

Establishing a Peritoneal Dialysis Program One program per million child population Age Group Total ~ 74 000 0000 0-15 years ~ 20 000 000 (26%) 20 PD programs

Establishing a Peritoneal Dialysis Program Suitable Location in a Pediatric Hospital with Hemodialysis and Intensive Care Units Experienced staff with multidisciplinary team approach

Establishing a Peritoneal Dialysis Program Suitable Location in a Pediatric Hospital with Hemodialysis and Intensive Care Units Experienced staff with multidisciplinary team approach Teaching Plan, Training Manual, Continuing Education, Global Collaboration

Choice of therapy The patient and family should have been actively involved in the choice of therapy This choice has to take into account: the difficulties of vascular access in small children large distances from the tertiary-care center the psychosocial situation GUIDELINES BY AN AD HOC EUROPEAN COMMITTEE FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

Choice of therapy Automated peritoneal dialysis (APD) is generally advocated for children, as APD gives greater freedom during the day for school and social activities. GUIDELINES BY AN AD HOC EUROPEAN COMMITTEE FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

Preventive strategies of PD technique failure Before starting PD During PD period

Main reasons for technique failure Difficulties with peritoneal catheters Serious peritoneal infections Chronic peritoneal changes leading to: - ultrafiltration failure - encapsulating peritoneal sclerosis Declining residual renal function

PD catheter placement 6 tips for problems prevention 1. The placement of a PD catheter requires an experienced surgeon. GUIDELINES BY EPDWG FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

PD access surgeon The issue is not who places the access, but who does it right, every time, to everyone, and everywhere Davidson et al 2007

PD catheter placement 6 tips for problems prevention 1. The placement of a PD catheter requires an experienced surgeon. 2. All catheters in children are placed under general anesthetic. GUIDELINES BY EPDWG FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

PD catheter placement 3. Double-cuffed catheters are preferred: pediatric size in patients 3 10 kg adult catheter in patients > 10 kg GUIDELINES BY EPDWG FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

PD catheter placement 4. The exit site should avoid the belt line and be above the diaper line in infants. 5. A cephalosporin antibiotic should be given IV at the time of catheter implantation. GUIDELINES BY EPDWG FOR ELECTIVE CHRONIC PD IN PEDIATRIC PATIENTS Watson AR et al.perit Dial Int 2001

IRPCPD study: 503 PD catheters Rinaldi S et al Italian Registry of Pediatric Chronic Peritoneal Dialysis, Perit Dial Int 2004

IRPCPD study: 503 PD catheters 6. Paramedian insertion of a PD catheter should be the standard for pediatric PD Rinaldi S et al Italian Registry of Pediatric Chronic Peritoneal Dialysis, Perit Dial Int 2004

PD catheter External Segment Exit site > 4 cm 2 nd cuff subcutaneous tissue Tunneled Segment rectus muscle Intra-Peritoneal Segment Distance from umbilicus to the pubic symphysis + 2cm

PD catheter Exit site

PD catheters Straight catheter Coil catheter Cuffs mechanical anchors not microbiologic barriers

PD catheters Preformed intercuff bend (swan neck) coiled-tip catheter

IRPCPD study: 503 PD catheters Orientation of the exit site: upward 13% lateral 24% downward 46% arcuate configuration No difference in exit site or tunnel infections between the groups Rinaldi S et al Italian Registry of Pediatric Chronic Peritoneal Dialysis, Perit Dial Int 2004

Risk Factors for Access Revision D.Borzych-Duzalka et al. 2016 Odds ratio P Swan neck tunnel with curled intaperitoneal portion 1.42 0.02 Two cuff catheter 0.89 ns Exit site pointing upward vs. downward/lateral 0.97 ns Early (<7d) vs. delayed catheter use 0.88 ns

Main reasons for technique failure Difficulties with peritoneal catheters Serious peritoneal infections Declining residual renal function Chronic peritoneal changes leading to: - ultrafiltration failure - encapsulating peritoneal sclerosis

Νοrth American Pediatric Renal Transplant Cooperative Study

Peritonitis Incidence 1 episode per x months / only within study period

Peritonitis rate NAPRTCS Νοrth American Pediatric Renal Transplant Cooperative Study

Peritonitis rate Continuous monitoring of the rate of peritonitis and other complications Benchmarking

Prevention and management of peritonitis Peritoneal Dialysis International, Vol. 32, pp. S32-S86, 2012 http://www.pdiconnect.com/content/32/supplement_2/s32.full.pdf

ISPD definition of EPS* - Symptoms suggestive of bowel obstruction mild complaints of abdominal pain and/or anorexia severe pain, vomiting and weight loss - Evidence of encapsulation of the bowel documented by: surgery or imaging (CT or ultrasound) *EPS: Encapsulating peritoneal sclerosis Kawaguchi Y et al Perit Dial Int. 2000

Surgical findings Honda K et al Perit Dial Int. 2005

Ascites Thickened peritoneum Calcifications Bowel loops are drawn into the centre of the abdominal cavity Vlijm A et al.ndt Plus 2011

Risk Factors - Peritonitis Etiology of peritonitis in EPS patients : 35% Staphylococcus aureus 11% Fungal infections 2% Pseudomonas Brown M et al Clin J Am Soc Nephrol, 2009

Risk Factors Peritonitis: EPDWG Study Annualized peritonitis rate EPS patients No EPS patients 1.9 (0.9 3.1) 0.72 (0.3 1.2) P = 0.02 European Pediatric Dialysis Working Ggroup study. Shroff R. et al. Nephrol Dial Transplant 2013

Advanced chronic kidney disease Prolonged exposure to PD solutions Mesothelial dysfunction Simple peritoneal sclerosis

Advanced chronic kidney disease Prolonged exposure to PD solutions Mesothelial dysfunction Alterations in the fibrinolytic cascade Simple peritoneal sclerosis Increased fibrin Severe peritonitis Peritoneal adhesions Discontinuation of PD Genetic predisposition Encapsulating peritoneal sclerosis

Staging of EPS Stages Asymptomatic Clinical symptoms Ultrafiltration failure Ascites Nakamoto H, et al. Perit Dial Int, 2005

Staging of EPS Stages Asymptomatic Inflammatory Clinical symptoms Ultrafiltration failure Ascites Loss of appetite Diarrhea Weight loss Fever Deterioration of anemia Blood-stained ascites Increased CRP Nakamoto H, et al. Perit Dial Int, 2005

Staging of EPS Stages Asymptomatic Clinical symptoms Ultrafiltration failure Ascites Inflammatory Progressive or encapsulating Loss of appetite Diarrhea Weight loss Fever Deterioration of anemia Blood-stained ascites Increased CRP Disappearance of the signs of inflammation Gastrointestinal obstruction Abdominal complaints Abdominal mass Ascites Nakamoto H, et al. Perit Dial Int, 2005

Possible fibrogenic effects of PD fluid Low ph and lactate buffer High concentration of glucose Glucose degradation products (GDPs) Advanced glycation end-products (AGEs)

Incidence of EPS in different registries Habib SM et al. Neth J Med, 2011

What patients are at risk for EPS? Patients on long-term (>5 years) PD, who develop ultrafiltration failure.

Should there be an expiration date for PD?

Incidence rates of EPS - duration of PD The Scottish Renal Registry has folllowed a cohort of adult PD patients from the start of PD for a total of 8 years Brown M et al Clin J Am Soc Nephrol, 2009

Prevention of EPS No evidence-based data supports a benefit of preemptively transferring long-term PD patients to HD PD may itself play a protective role against the development of EPS. Scotish EPS Registry: 74 % of EPS cases were diagnosed after PD had been stopped

Multidisciplinary approach 55 centres Study period: 2007-2012 1338 patients received PD for an average of 40 months 14 patients developed EPS Nakayama M et al. Perit Dial Int 2014

Next-PD study Nakayama M et al. Perit Dial Int 2014

Next-PD study 1338 patients Nakayama M et al. Perit Dial Int 2014

Number of EPS /all CPD patients Country Authors 3/35 (1 post-tx*) France Niaudet P et al. 1987 11 /687 Japanese Registry Hoshii S et al. 2000 2 /109 Japan Araki Y et al. 2000 2 /104 Turkey Ekim M et al. 2005 1 Germany von Schnakenburg et al. 2005 1 Singapore Tan FL et al. 2008 1 US Garces-Inigo et al. 2008 1 US Marsenic et al. 2009 1 (post-tx) Netherlands Tan R et al. 2012 1 (post-tx) Portugal da Silva N et al. 2012 14/712 (3 post-tx) Italian Registry Vidal E et al. 2013 22/1472 (2 post-tx) EPDWG report Shroff R et al. 2013 Total Nr: 60 Stefanidis CJ, Shroff R. Pediatr Nephrol 2013

EPS Data from the three studies 87 pediatric nephrology centres 2871 children received PD 47 children developed EPS Prevalence of 1.6% ~7 cases per 1000 patient-years on PD 11 patients died

Prevention of EPS Minimize the use of high-glucose PD solutions Use Biocompatible PD solutions Preserve residual renal function Children on long term PD, with ultrafiltration failure, should discontinue PD

Residual renal function

Residual renal function Urine output was monitored in 401 pediatric patients in the global IPPN registry who commenced PD with significant residual renal function. The risk factors of developing oligoanuria (under 100 ml/m 2 /day) were analyzed.

Residual renal function Dialysis prescription resulting in high ultrafiltration rate was a risk factors for rapid progression to oligoanuria. An increased duration of urine output associated with the use of biocompatible PD fluids was detected.

Take home messages Appropriate development of a PD center Adequate training in PD technique Prevention policies of technique failure Continuous surveillance and adherence to PD recommendations

Multiprofessional team

Benchmarking Continuous monitoring and comparing with the standards of the rate of technique failure, peritonitis and other complications Benchmarking

35 years of challenges Today Early 80 s