3/21/2017. Solute Clearance and Adequacy Targets in Peritoneal Dialysis. Peritoneal Membrane. Peritoneal Membrane

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1 3/21/2017 Solute Clearance and Adequacy Targets in Peritoneal Dialysis Steven Guest MD Director, Medical Consulting Services Baxter Healthcare Corporation Deerfield, IL, USA Peritoneal Membrane Image courtesy of Steven Guest MD 2 Peritoneal Membrane Visceral Peritoneum Parietal Membrane Image courtesy of Steven Guest MD 3 1

2 After Evisceration Rubin J, et al. The importance of the abdominal viscera to peritoneal transport during peritoneal dialysis in the dog. Am J Med Sci 1986;292: Peritoneal Capillaries 5 Image courtesy of Steven Guest MD Peritoneal Endothelium as a Filter 6 Image courtesy of Steven Guest MD 2

3 Three Pore Model 7 Image courtesy of Steven Guest MD Diffusion Image courtesy of Steven Guest MD 8 Dialysate/Plasma Diffusion Dialysate Blood Peritoneal Membrane Image courtesy of Steven Guest MD creatinine 9 3

4 Dialysate/Plasma Diffusion Dialysate Blood D = 7mg/dL P = 8mg/dL Equilibration ratio = D/P = 7/8 = ~ 0.9 creatinine Image courtesy of Steven Guest MD 10 Diffusion Curves Popovich RP, Moncrief JW, Nolph KD, et al. Continuous ambulatory peritoneal dialysis. Ann Intern Med 1978;88: Convection Image courtesy of Steven Guest MD 12 4

5 Peritoneal Equilibration Test Twardowski Z, Nolph KO, Khanna R, et al. Perit Dial Bull. 1987;7: Peritoneal Equilibration Test 14 Adapted from: Twardowski Z, Nolph KO, Khanna R, et al. Peritoneal equilibration test. Perit Dial Bull. 1987;7: PET Distribution in N. America 33% 37% 15% 15% Low Low-Avg High-Avg High Mujais S, et al. Kidney Int. Volume 62: s81, S17-S22,

6 Peritoneal Equilibration Test 16 Adapted from: Guest S. Peritoneal permeability tests. In: Guest S, ed. Handbook of Peritoneal Dialysis. 2 nd ed San Bernardino, CA; Dwell Time and Consequence Transport Solute Clearance UF Prescription High Short dwell High A CAPD/CCPD Low A CAPD/CCPD Low Long dwell *Always try to maximize instilled volumes 17 National Cooperative Dialysis Study (NCDS) Time Long v short BUN Higher (100 mg/dl) Lower (50 mg/dl) 151 patients No difference in Mortality Greater hospitalization and medical issues in high BUN Lowrie EG, et al. N Engl J Med 1981;305:

7 Gotch and Sargent Kidney Int 1985;28:526. Peak Concentration Hypothesis 1989 Perit Dial Int 1989;9:257. Peak Concentration Hypothesis Perit Dial Int 1989;9:257. 7

8 CANUSA Study (1996) CANUSA study: Demographics Prospective, observational study: centers in Canada and USA. Follow-up period: 24 months. 680 incident CAPD patients, 78 at the end of study: Mean age 54.3 years. Mean weight 67.8 kgs. Median dialysate flow: 8 liters/day. Mean residual creatinine clearance: 3.8 ml/min. 30% diabetics, ~ 25% cardiovascular disease (CVD). Churchill et al: JASN, CANUSA Trial Theoretical constructs suggest that the target Weekly Kt/V should be 2.0 to

9 K/DOQI Recommendations 1997 CAPD Kt/V = 2.0 CCPD Kt/V = 2.1 NIPD Kt/V = 2.2 CAPD Cr Cl 60 L/wk CCPD Cr Cl 63 L/wk NIPD Cr Cl 66 L/wk PET categories 20 different targets Reanalysis of CANUSA Study CANUSA study: Clearances Weekly Kt/V Months peritoneal Kt/V renal Kt/V Churchill et al: JASN,

10 CANUSA study: Clearances Weekly Kt/V peritoneal Kt/V renal Kt/V Months Churchill et al: JASN, Residual Kidney Function and Risk of Death 29 Bargman JM, et al. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol 2001;12: ADEMEX Study pts J Am Soc Nephrol 13: ,

11 ADEMEX-TIME COURSE OF pkt/v urea VALUES Paniagua R et al. J Am Soc Nephrol 13: , ADEMEX: Survival (Primary Outcome) Sub-group analyses, based upon age, diabetic status, serum albumin and urine output, showed no effect of peritoneal clearances on outcomes. Paniagua, J Am Soc Nephrol, 2002 Hong Kong Trial Cumulative Patient Survival Lo et al. Kidney Int 64: ,

12 Hong Kong Trial Cumulative Patient Survival 320 CAPD patients recruited from 5/96 to 7/99 Usual initial prescription three 2L exchanges/day Randomized to one of three groups based on different total Kt/V urea targets: Group A Kt/V urea Group B Kt/V urea Group C Kt/V urea > 2.0 Lo et al. Kidney Int 64: , 2003 Hong Kong Trial Cumulative Patient Survival Lo et al. Kidney Int 64: , 2003 Hong Kong Trial Cumulative Patient Survival Lo et al. Kidney Int 64: ,

13 Adequacy targets Prior PD adequacy targets: CAPD Kt/V 2.0 CCPD Kt/V 2.1 NIPD Kt/V 2.2 Updated adequacy targets established a minimal total Kt/V of 1.7 Creatinine target dropped the minimal delivered dose of total small solute clearance should be a total clearance (peritoneal and renal) Kt/V urea of at least 1.7 Residual Kidney Function What intrinsic GFR correlates to a Kt/V of 1.7? Guest S, et al. Intermittent peritoneal dialysis: urea kinetic modeling and implications of residual kidney failure. Perit Dial Int 2012;32: Residual Kidney Function What intrinsic GFR correlates to a Kt/V of 1.7? Guest S, et al. Intermittent peritoneal dialysis: urea kinetic modeling and implications of residual kidney failure. Perit Dial Int 2012;32:

14 Empiric PD Prescription Image courtesy of Baxter Healthcare Corporation NKF-KDOQI Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis 2006;48 (Suppl 1):S91-S158 High Transporter Adapted from Twardowski ZJ, Nolph KO, Khanna R et al. Peritoneal Equilibration Test. Peritoneal Dialysis Bulletin. 1987;7:

15 Low Transporter Adapted from Twardowski ZJ, Nolph KO, Khanna R et al. Peritoneal Equilibration Test. Peritoneal Dialysis Bulletin. 1987;7: Appropriate Dwell Times Adapted from Twardowski ZJ, Nolph KO, Khanna R et al. Peritoneal Equilibration Test. Peritoneal Dialysis Bulletin. 1987;7: Longitudinal Membrane Changes Devuyst O, Margetts P, Topley N. The pathophysiology of the peritoneal membrane. J Am Soc Nephrol 2010;21:

16 Changes in Transport Properties with Time Adapted from Davies SJ, Bryan J, Phillips L, et al. Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis. Nephrol Dial Transplant 1996;11: Glucose Exposure and Transport Characteristics Davies SJ, Phillips L, Naish PF, Russell GI. Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis. J Am Soc Nephrol 2001;12: PET Category and Vascularity Adapted from Twardowski ZJ, Nolph KO, Khanna R et al. Peritoneal Equilibration Test. Peritoneal Dialysis Bulletin. 1987;7:

17 3/21/2017 Dwell Time and Consequence Transport Solute Clearance UF Prescription High Short dwell High A CAPD/CCPD Low A CAPD/CCPD Low Long dwell *Always try to maximize instilled volumes 49 Appropriate Dwell Times Adapted from Twardowski ZJ, Nolph KO, Khanna R et al. Peritoneal Equilibration Test. Peritoneal Dialysis Bulletin. 1987;7: Fill Volumes Image courtesy of Steven Guest MD 51 17

18 Prescription Adjustment Assuming Kt/V targets not achieved or to proactively increase delivered dose of PD. Adapted from Blake P, et al. Recommended clinical practices for maximizing peritoneal dialysis clearance. Perit Dial Int. 1996;16: Fill Volumes 53 Maintaining Adequacy of PD Preserve residual kidney function Dietary interventions to reduce sodium intake Attempt to employ a low glucose regimen Empiric prescription PET for membrane type should adjustments be necessary Prudent use of dialysate volume in lower transporters Total weekly Kt/V of 1.7 Euvolemia NKF-KDOQI Clinical practice guidelines for peritoneal dialysis adequacy. Am J Kidney Dis 2006;48 (Suppl 1):S91-S158 18

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