Peritoneal Dialysis Ultrafiltration Management in Peritoneal Dialysis Peritoneal

Peritoneal Dialysis Ultrafiltration Management in Peritoneal Dialysis

Peritoneal Dialysis Overview • Fluid Management in Peritoneal Dialysis • Kinetics of Peritoneal Ultrafiltration • Icodextrin: Chemistry & Pharmacokinetic Profile • Icodextrin Efficacy Profile: Ultrafiltration • Icodextrin Efficacy Profile: Other Clinical Benefits • Icodextrin: Prescribing Considerations

Peritoneal Dialysis Rationale = Maximise Fluid Balance v. Primary function of renal replacement therapy v. PD represents optimal approach to this therapeutic goal v. Persistently high prevalence of hypertension and CV mortality among ESRD population underscores untapped potential of PD Mujais, et al. Perit. Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Effective Fluid Management Established Clinical Benefits v. Controls blood pressure v. Lowers cardiovascular risk - LVH - CHF - Stroke v. Preserves GFR v. Prevents uremia-like symptoms v. Avoids acceleration of malnutrition, inflammation and atherosclerosis syndrome

Peritoneal Dialysis Fluid Balance A Clinical Challenge v. Maintaining edema-free state v. Dynamic nature of target weight v. Reliance on clinical judgment and indicators of volume status v. Individualized approach to fluid removal Mujais, et al. Perit. Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Optimizing Fluid Management • Symptomatic fluid retention noted in 25% of PD patients 1: • Lower extremity edema 98. 6% • Pleural effusions 76. 1% • Pulmonary congestion 80. 3% • Similar clinical observations in Japan, 2 the Netherlands, 3 and Sweden 4 1 Tzamaloukas, et al. J Am Soc Nephrol. 1995; 6: 198 -206. 2 Kawaguchi, et al. Kidney Int. 1997; 52: S 105 -S 107. 3 Ho-dac-Pannekeet, et al. Perit Dial Int. 1997; 17: 144 -150. 4 Heimbürger, et al. Perit Dial Int. 1999; 19: S 83 -S 90.

Peritoneal Dialysis Current PD Status High Prevalence of Elevated BP Frankenfield, et al. Kidney Int. 1999; 55: 1998 -2010. Cocchi, et al. Nephrol Dial Transplant. 1999; 14: 1536 -1540.

Peritoneal Dialysis Volume Reduction & BP Control 47 hypertensive CAPD patients Na restriction 20 normotensive 27 hypertensive 3 normotensive with enalapril Na restriction & UF 17 normotensive* 7 hypertensive 4 normotensive with enalapril 3 hypertensive *37 normotensives in total achieved with volume control alone Gunal, et al. Am J Kidney Dis. 2001; 37: 588 -593.

Peritoneal Dialysis Fluid Overload An Underappreciated Cause of CV Mortality • The majority of dialysis patients die of cardiac causes; 36% present with CHF 1, 2 • Hypervolemia and hypertension remain important underlying causes 3 Causes of Death in Dialysis Patients 1 20% 7% 4% 16% 6% 1 USRDS 1997 Annual Report Data. 2 Stack, et al. Am J Kidney Dis. 2001; 38: 992 -1000. 3 Lamiere, et al. Perit Dial Int. 2000; 21: 206 -211. Cardiac Other known Infection Unknown Cerebrovascular Malignancy

Peritoneal Dialysis Fluid Overload vs UF Failure An Important Distinction • Fluid overload is a common clinical syndrome with multiple causes • It is the inability to maintain target weight and oedema free state • UF failure is a pathophysiologic characterisation of one of the causes of the clinical syndrome • Distinction between syndrome and cause determines the intervention to be taken Mujais, et al. Perit. Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Causes of Fluid Overload in PD • • • Excessive salt & water intake Loss of residual renal urine volume Cardiac disease Non compliance with PD prescription Insufficient use of hypertonic exchanges Dialysate leak Catheter malfunction Hyperglycaemia UF failure

Peritoneal Dialysis Current UF Management Hampered by Complexity Dietary counseling v Compliance issues v May complicate management Limiting renal excretion 1 v Gradual decline to anuria v Failure to respond to diuretics Peritoneal Ultrafiltration (UF) v Challenge of the long dwell Medcalf, et al. Kidney Int. 2001; 59: 1128 -1133.

Peritoneal Dialysis The Long Dwell in PD APD Long dwell Cycles 1 to 4 CAPD Long dwell Nighttime Manual exchange Daytime v. APD and CAPD both have long dwells v. In APD, even high-dose nighttime exchanges involve long dwells of 8 -12 hours

Peritoneal Dialysis Value of the Long Dwell Toxin removal v Small solutes fluid flow-dependent v Middle and large MW toxins time-dependent v Continuously wet abdomen required for therapy success Lifestyle v Logistic burden and compliance v Realistic therapy imperative

Peritoneal Dialysis ISPD Ad Hoc Committee UF Management in PD “The most frequently ignored principles in PD that lead to UF difficulties are the need to avoid long dwells [with glucose] in high transporters and balancing glucose concentration and dwell time. ” —Peritoneal Dialysis International, 2000 Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis 4. 25% Dextrose Long Dwell Limitations • Rapid glucose absorption and loss of UF potential and small solute clearance • Negative net UF • Fluid overload • Systemic metabolic effects and obesity • Local biocompatibility issues and impact on peritoneal membrane structure and function

Peritoneal Dialysis Assessing Volume Status Proactive Monitoring and Evaluation v. Achieving and maintaining target weight (goal: normal BP, with euvolemia) v. Review of dietary compliance/guidelines v. Monitoring residual renal function v. Evaluating solute clearance v. Awareness of peritoneal function Mujais, et al. Perit. Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Redefining what is a “dry weight” Minimal definition v Oedema-free body weight Maximal definition v Weight below which further fluid removal results in signs and symptoms of hypovolemia Clinical definition v Between minimal and maximal definitions with resolution of volume-dependent derangements in homeostasis (explained – please make notes on this!) Mujais, et al. Perit. Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis ISPD* Guidelines Optimal Fluid Management in PD v. Routine standardized monitoring and awareness of PET† status v. Dietary counseling of appropriate salt and water intake v. Protection of RRF‡ v. Loop diuretics if RRF present v. Patient education for enhanced compliance v. Preservation of peritoneal membrane function v. Hyperglycemia control *International Society for Peritoneal Dialysis; †Peritoneal equilibration test; ‡Residual renal function. Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Definition of UF Failure • Drain volume <2400 ml after 4 hour dwell with 2 L 4. 25% glucose • 4. 25% is preferred to 2. 5% PET because the greater osmotic challenge of a 4. 25% dwell is more likely to be discriminating in the assessment of UF

Peritoneal Dialysis UFF Classification Type I Ø High transport status Ø Rapid loss of glucose osmotic gradient Ø Commonest; increases with time Type II Ø Low transport status Ø Loss of peritoneal surface area Ø Not common Type III Ø High lymphatic flow rate Ø By exclusion of other types only Ø Prevalence unknown Type IV Ø Aquaporin dysfunction Ø Rare Overall, UFF occurs in <3% of patients in Year 1, In 9. 5% by 3 years and in 30% by 6 years

Peritoneal Dialysis UFFailure UF structured diagnostic to managing a patient AAStructured Diagnosticapproach Approach RRF* REVERSIBLE CAUSES Appropriate Rx Dwell time Dialysate tonicity *Residual renal function Dietary indiscretion, compliance Deficient education Complex regimen Burn-out PERITONEUM Mechanical causes Low transport Leaks Low-average or high-average transport Obstructions High transport Entrapment Malposition Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis UF Failure Evaluating the Clinical Syndrome Initial Evaluation for Reversible Causes Evaluation of Peritoneal Membrane Function UF Response Small Solute Transport Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis UF Failure Identifying Reversible Causes Clinical Syndrome Initial Evaluation for Reversible Causes Dietary Non-Compliance Appropriate Prescription Mechanical Problems Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis UF Failure Assessing UF Response Clinical Syndrome Initial Evaluation for Reversible Causes Evaluation of Peritoneal Membrane Function UF Response Drain Volume <2400 m. L / 4 hr Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21. Drain Volume >2400 m. L / 4 hr

Peritoneal Dialysis UF Failure Peritoneal Membrane Function UF Response Drain Volume <2400 m. L/4 hr Small Solute Profile Low Transport D/P Cr <0. 5 High-Avg or Low-Avg 0. 81> D/P Cr >0. 5 Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21. High Transport D/P Cr >0. 81

Peritoneal Dialysis UF Failure Low Drain, Low Transport Drain Volume <2400 m. L/4 hr Small Solute Profile Low Transport D/P Cr <0. 5 § § Disruption of peritoneal space, adhesions, etc. Peritoneography Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis UF Failure Low Drain, High-Avg or Low-Avg Transport Drain Volume <2400 m. L/4 hr Small Solute Profile High-Avg or Low-Avg Transport 0. 5< D/P Cr <0. 81 § § § Mechanical problems Tissue absorption Aquaporin deficiency Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis UF Failure Low Drain, High Transport Drain Volume <2400 m. L/4 hr Small Solute Profile High Transport D/P Cr >0. 81 § § § Inherently high transport Recent peritonitis High transport of long-term PD Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Therapeutic Approaches Universal Measures Low Drain, High Transport – CAPD – Icodextrin for long dwells Low Drain, High-Avg or Low-Avg Transport – Icodextrin for long dwells – Dextrose for short dwells Low Drain, Low Transport – High-dose loop diuretics with RRF – Adjunctive HD or transfer to HD Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Guidelines for improving UF CAPD v v v Avoidance of long dwells with low glucose concentrations Use of nighttime exchange devices Tailoring prescriptions to transport profiles determined by PET APD v v Avoidance of long dwells with low glucose concentrations Use of short day dwells even when no additional exchanges needed for clearance

Peritoneal Dialysis Volume Control Algorithm

Peritoneal Dialysis Volume Control Algorithm

Peritoneal Dialysis Volume Control Algorithm

Peritoneal Dialysis Volume Control Algorithm

Peritoneal Dialysis Volume Control Algorithm

Peritoneal Dialysis High transport & outcome High transporters: Efficient membranes for small solute clearance but may have difficulty with ultrafiltration, especially during the long dwell Impact on outcomes in PD % Surviving 100 90 High Average Low 80 70 60 0 6 12 18 Time in Months 1 Davis et al. KI 1999 Vol 54 p 2207 – 2217 2 Churchill et al JASN 1998 - Vol 9 1285 - 1292 24 Recent studies (Davis 1 and Churchill 2) have shown that high transporters had a worse prognosis probably due to a more difficult fluid balance management

Peritoneal Dialysis Therapeutic approaches Inherent high transporters • APD & icodextrin for the long dwell is the recommended therapeutic approach Recent peritonitis • “Several studies have indicated that UF during an episode of peritonitis can be satisfactorily achieved with the use of icodextrin” High transport during long term PD • For patients with a net UF less than 400 m. L/4 hours and a high transport profile of small solute clearance, APD and icodextrin for the long dwell are the recommended therapeutic approaches Mujais, et al. Perit Dial Int. 2000; 20(suppl 4): S 5 -S 21.

Peritoneal Dialysis Summary: 12 Strategies to improve Volume Management in PD 1. Start PD earlier 2. Protect residual renal function 3. Use high-dose loop diuretics o maintain urine output 4. Educate patients regarding salt and water intake and regarding significance of oedema, weight gain, etc 5. Appropriate use of hypertonic solutions 6. Awareness of PET status

Peritoneal Dialysis Summary: 12 Strategies to improve Volume Management in PD 7. Consider APD in high and high average transporters 8. Night exchange device in CAPD if night –t im dwell is reabsorbed 9. Short day dwells on APD – long enough to give good clearance and short enough to give good UF 10. Icodextrin for long dwells in CAPD & APD 11. Frequent reassessment of the patient’s target weight 12. Anti-hypertensives only when volume removal has failed to reduce BP.

Peritoneal Dialysis Case Study