“Adequacy in PD prescription What, How, When? Wim Van Biesen

Overview What is “adequacy”? How to measure adequacy? How much is enough?:impact of adequacy How to improve adequacy?

Aims of dialysis Remove uremic toxins Remove salt and water ( blood-pressure, fluid control) Avoid toxic side effects (glucose, hyperlipidemia; obesitas) At the lowest cost and inconvenience for patient and society (decrease incompliance, increase quality of life, decrease cost)

THREE PHYSICO-CHEMICAL TYPES OF TOXINS The small water soluble compounds (prototype urea): < 500D The protein-bound compounds (prototype p-cresol) The larger “middle molecules” (prototype ß2-microglobulin): > 500D Some of these exceed 12,000 D (prototype leptin)

Quantified measurement of adequacy Biochemical parameters Urea:* influenced by protein intake, hydration *low urea correlated with high mortality(Degoulet et al, Nephron, 31-103-110, 1982) Creatinine: * influenced by nutritional status, muscle mass * inverse correlation Screa-mortality (Lowrie et al, AJKD, 15, 458-482,1990) Conclusion: “Static” biochemical markers are no good markers of adequacy

Quantified measurement of adequacy Urea kinetic modelling: 1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution.

Quantified measurement of adequacy Urea kinetic modelling: 1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution. Total urinary volume * urinary urea concentration plasma urea concentration * V Kt/V renal= Total DRAINED dialysate volume * dialysate urea concentration plasma urea concentration * V Kt/Vper =

BCM – Body Composition Monitor… quantifies individual overhydration determines urea distribution volume V for dialysis dose assessment provides a basis for nutritional assessment measures non-invasively, fast and easy

Removal of Uraemic Toxins CAPD vs high volume APD Eloot et al, PDI, 2014

Quantified measurement of adequacy Urea kinetic modelling: 1) Kt/V: sum of the peritonal clearance of urea and the residual renal urea clearance, multiplied by 24 hours and divided by the volume of distribution. Total urinary volume * urinary urea concentration plasma urea concentration * V Kt/V renal= Total DRAINED dialysate volume * dialysate urea concentration plasma urea concentration * V Kt/Vper =

PET test.

Quantified measurement of adequacy Ratio’s of D/P for creatinine and urea

Phosphate clearance in CAPDvs CCPD Liters dialysate Phosphate clearance ml/min Sedlacek et al, AJKD 2000, 36, 1020-1024

P-cresol and Beta 2 microglobulin clearance in CAPDvs CCPD Evenepoel et al, KI, 2006

A PD dwell Dwell time IP volume Drain fill Time

More (shorter) exchanges: steeper transperitoneal transport rate more « no exchange time » due to in and outflow Inefficient use of fluid volume Take care for « larger » molecules: Kt/V urea and creatinine clearance tell different stories Less (longer) dwells at the end, slower transperitoneal transport rate risk of lower drained volume

Efficient use of solution in APD. BSA 1.71 - 2.0m² RRF = 0 mL CrCl/L/Wk/1.73m² Blake et al, PDI, 16, 1996.

Efficient use of solution in APD. BSA 1.71 - 2.0m² RRF = 0 mL CrCl/L/Wk/1.73m² Blake et al, PDI, 16, 1996.

Demetriou et al, KI 2006

APD and adequacy Demetriou et al, KI 2006

Impact of normal vs high volume APD Demetriou et al, KI 2006

More is not always better!

Survival

Peritoneal Kt/V péritoneale and survival Rumpsfeld et al, PDI, 2009

Peritoneal Kt/V péritoneale and survival If you push too far, you get into trouble… Rumpsfeld et al, PDI, 2009

ADEMEX: Causes of dropout %

AGE’s and GDP Pyrraline (pmol/mgprotein) in fluid Zeier et al, Kidney Int, 63, 298-305

Effect of dwell number on compliance p=NS Blake et al, AJKD, 35, 3, 506-514, 2000

Impact of volume on intraperitoneal pressure Peritonitis free survival Dejardin et al, NDT, 2007

Impact of intra abdominal pressure Figure 2. Impact of intra abdominal pressure Gastrointestinal microcirculation and cardiopulmonary function during experimentally increased intra-abdominal pressure *. Olofsson, Pia; Berg, Soren; MD, PhD; Ahn, Henrik; MD, PhD; Brudin, Lars; MD, PhD; Vikstrom, Tore; MD, PhD; Johansson, Kenth; MD, PhD Critical Care Medicine. 37(1):230-239, January 2009. DOI: 10.1097/CCM.0b013e318192ff51 Figure 2. Microcirculatory organ blood flow (mean +/- sem). Micorcirculatory flow (% of baseline) measured by laser Doppler flowmeter at each pressure level (mm Hg). The blood flow is reduced progressively with increased intra-abdominal pressure. This reduction is less pronounced in small bowel mucosa. x = statistically significant difference (p o = statistically significant difference (p < 0.05) compared with the previous value. 2

Adequate dialysis Remove uremic toxins Remove salt and water ( blood-pressure, fluid control)

I am preserving my residual renal function

Icodextrin and residual renal function GFR ml/min P=0.001 Konings et al, KI, 2003

Icodextrin and residual renal function Change in daily diuresis Davies et al, JASN 2003

Aims of dialysis Remove uremic toxins Remove salt and water ( blood-pressure, fluid control) Avoid toxic side effects (glucose, hyperlipidemia; obesitas)

Body Composition PD vs HD: the EuroBCM trial Van Biesen et al, NDT, 2013

Body Composition PD vs HD: the EuroBCM trial Van Biesen et al, NDT, 2013

Relation inflammation, nutrition, fluid overload Albumin [g/L] <35.0 35.0-40.0 >40.0 N Mean ± SD BMI [kg/m2] 314 25.0±4.6 333 26.3±4.9 302 26.5±4.8 LTI [kg/m2] 311 13.1±3.1 329 13.5±3.2 300 14.2±3.5 FTI [kg/m2] 310 7.8±3.8 8.9±4.2 7.7±4.0 FO [L] 2.9±2.6 1.6±2.1 1.0±1.7 CRP [mg/L] 267 13.7±24.1 276 10.0±21.0 257 5.8±10.4 Verger, ISPD, 2014

Relation inflammation, nutrition, fluid overload Verger, ISPD, 2014