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21 Growth van Stralen KJ, et al., Kidney Int, 2014

22 Blood Pressure Management van Stralen KJ, et al., Kidney Int, 2014

23 Sodium Losses on PD Infants might need higher UF rate per BSA as compared to adults to achieve adequate nutrition. Ultrasmall pores (Water-exclusive transcellular AQP1 channels) Small pores UF UF + Na + In such cases, UF-related convective solute transport is considerable. Large pores Macromolecules Schmitt CP and Fischbach M. Int J Nephrol 2011

24 Salt-losing Nephropathies Tubular Immaturity (Renal Dysplasia) Tubular Damage (Congenital or Acquired) (Chronic Interstitial Nephritis) (Renal Cystic Diseases)

25 PD-Induced Hypotension Pathophysiology Sodium depletion Decreased extracellular osmolality Intracellular osmotic fluid loss Hyponatremic hypovolemia Failure of blood flow autoregulatory mechanisms Excessive UF Antihypertensive medications Fever Vomiting Diarrhea Complications (i.e. AION) Exaggerated nocturnal BP dipping

26 Anterior Ischemic Optic Neuropathy Source: Nat Clin Prat Oncol 2006 (Nature Publishing Group)

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28 PD During Infancy and Peritonitis Months Between Infection Vidal (>28 d) IPPN (>28 d) Vidal (<28 d) IPPN (<28 d) Ledermann Jander N=64 N=251 N=20 N=90 N=20 N=33

29 NAPRTCS and Peritonitis N of episodes Annualized Rate Expected Months between infections Years of FU Rate 95% CI Months 95% CI Total ( ) 20.1 ( ) Age at initiation 0-30 days ( ) 16.4 ( ) days ( ) 16.7 ( ) 1 - <2 years ( ) 15.8 ( ) 2 - <6 years ( ) 19.4 ( ) 6 - <13 years ( ) 20.7 ( ) > 3 years ( ) 22.5 ( ) NAPRTCS, 2016

30 SCOPE and Peritonitis 1.5 Annualized Rate Initial Hospital Stay Initial Year n=94 SCOPE, 2015

31 Parent Perspectives on Caring for a Child with Chronic Kidney Disease Tong A, et al., Child: care, health and development, 2009

32 Patient Survival on PD Neu AM, et al., Perit Dial Int, 2012

33 Comorbidities in Neonates Any Comorbidity Yes 81/111 (73%) Type of comorbid conditions Developmental delay 22/110 (20%) Cardiovascular disorder 17/92 (18%) Pulmonary disorder 11/92 (12%) Neurological disorder 22/92 (24%) Liver disease 18/76 (24%) van Stralen KJ, et al., Kidney Int, 2014

34 Infant Dialysis and Survival 34 Hijazi R. et al., J Pediatr, 2009

35 Infant Survival on HD (<1 month) (1-12 months) Pollack S, et al., Pediatr Nephrol, 2016

36 Patient Outcome Patients (%) Transplant Change modality Died Died < 1 yr < 28 d Vidal E, et al. Nephrol Dial Transplant, 2011

37 264 patients 32 countries (ESPN/ERA-EDTA, IPPN, ANZDATA, Japanese RRT Registries) 100% started RRT within the 1st month of life (53.4% started RRT in the 1st week of life) van Stralen KJ, et al., Kidney Int, 2014

38 Patient Characteristics Main causes of renal failure CAKUT 55% Cystic kidneys 13% Tubular necrosis 11% First RRT modality PD 91.7% HD 8.0% Tx 0.4% Birth weight: 2869 g [ ] Serum creatinine at start 3.9 mg/dl [ ] egfr at start 5.5 ml/min per 1.73 [ ] Residual renal output 87.5 ml/day[0-350] van Stralen KJ, et al., Kidney Int, 2014

39 Treatment Changes van Stralen KJ, et al., Kidney Int, 2014

40 Patient Survival van Stralen KJ, et al., Kidney Int, 2014

41 Patient Survival Main causes of death: Infection 16 (36%) Cardiac arrest 4 Hemorrhage 2 Withdrawal 1 Lung hypoplasia/pulmonary edema 4 Unknown/missing 18 No significant differences in the risk of death regarding: Week of RRT initiation Initial treatment modality Gender Primary renal disease Birth weight Registries and Countries Concomitant neurological disorders increased the risk of death fivefold (HR 5.2, 95%CI ; p=0.003). van Stralen KJ, et al., Kidney Int, 2014

42 241 neonatal patients Initiated PD from (n=143) and (n=98) Median age at RRT initiation: 11.0 and 8.5 days, respectively Most frequent diagnoses: obstructive uropathy (18.2 and 21.4%) and renal dysplasia (39.2 and 28.6%) Carey WA, et al., Pediatrics, 2015

43 Survival During Initial Course of Peritoneal Dialysis P = 0.002

44 Overall Survival P = 0.003

45 Multivariate Cox Regression Model for Overall Survival Baseline Factor Comparison group Reference group Hazard ratio 95% CI p-value Era of dialysis initiation to Age 0-31 days 1-12 months to Sex Female Male to Race (overall p=0.8076) Black Hispanic Other White to to to Primary Disease status (overall p=0.0006) A/hypo/dysplastic Congenital nephrotic Polycystic disease Other/Unknown Obstructive Uropathy to to to to <

46 Patient Mortality Age/Era group Cause of Death <=31Days <=31Days Days Days N N N N CAUSE Infection, viral Infection, bacterial Infection, not specified Cancer/malignancy Cardiopulmonary Hemorrhage Recurrence Dialysis-related complications Other, specify Unknown/Missing All

47 Termination Characteristics Peritoneal Dialysis Status <=31Days <=31Days Days Days Total Dialysis status (%) N=143 N=98 N=205 N=182 N=628 On initial course at follow-up Terminated dialysis mode Reason for Termination (%) N=131 N=74 N=190 N=131 N=526 Death reported in non-terminated patient Patient transplanted * ** 54.6 Change of modality Death (as reason for termination) Native kidney function returned Other/Unknown * P = < 0.001, ** P = 0.036

48 Graft Survival * * p = 0.05

49 Survival Following CPD Initiation By Initiation Era and Age <1 month n= month n=1149 P = Years from Dialysis Initiation Sanderson K, et al., ASN, 2015

50 Summary The provision of chronic dialysis to neonates and the achievement of targeted outcomes remains one of the most significant challenges in pediatric dialysis care. The availability of a pediatric trained multidisciplinary team and a dedicated family is mandatory if the best possible outcomes are to be accomplished. Whereas mortality data have improved over time, additional efforts are required to decrease associated morbidity and further improve patient survival.