The association between clearance of protein-bound uraemic toxins in PD patients and patient-focused outcomes

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The association between clearance of protein-bound uraemic toxins in PD patients and patient-focused outcomes

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Co-author 1

Aruni Malaweera aruni.malaweera@monash.edu Eastern Health Nephrology Melbourne Australia *

Co-author 2

Louis Huang louis.huang@monash.edu Eastern Health Nephrology Melbourne Australia -

Co-author 3

Lawrence McMahon lawrence.mcmahon@monash.edu Eastern Health Nephrology Melbourne Australia -

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Introduction

PBT clearances in haemodialysis (HD) and peritoneal dialysis (PD) are 10-fold lower than that of urea and creatinine due to strong, non-covalent binding to albumin. This might explain why PBTs are associated with poorer patient outcomes and symptom burden. Various PD prescriptions have shown no improvement in PD clearance of PBTs. Recent studies in HD show improved clearance of PBTs with the use of furosemide but is untested in PD patients

Methods

This was a cross-sectional study of 30 PD patients to determine the associations between the clearance of protein-bound uraemic toxins, p-cresyl sulfate (PCS) and indoxyl sulfate (IS), with patient-focused outcomes using the IPOS-renal and EQ-5D-5L questionnaires to determine symptom burden and quality of life, respectively. Physical capacity was determined using the timed up-and-go (TUG) test and hand-grip strength (HGS). We also assessed the association of PD prescription (dialysate volume and type of PD) and furosemide use on PD and urine clearance of PBTs.

Results

The median PD clearance of PCS was 27-fold lower than creatinine, and 32-fold lower than urea (p<0.0001 for both). IS was not cleared on PD. The urine clearance of PBTs were better than PD, but still up to 12-foldlower than clearance of creatinine and urea. Higher urine output was associated with better PBT clearance (p<0.05). Type of PD (CAPD vs. APD) or PD volume did not affect PD clearance of PBTs. Unsurprisingly, PBT clearances in PD and urine were not associated with patient-focused outcomes including uraemic symptoms, quality of life or physical capacity. PD-related PCS clearance was approximately 20% of the total clearance of PCS [0.19 (0.03-0.45)], but the higher PD PCS clearance group did not have improved patient-focused outcomes. Furosemide was prescribed in 12 out of 30 patients; however, neither its use nor the dose affected PBT clearances, either from dialysate or urine.

Conclusion

Neither dialysis, residual kidney function or furosemide contribute meaningfully to PBT clearance in PD compared with small water-soluble molecules. PD-related PCS clearance is approximately 20% of the total clearance of PCS, whereas IS does not appear to be cleared on PD. PBT clearances were not associated with patient-focused outcomes. Larger studies are needed to corroborate these findings and to investigate other therapeutic interventions to improve PD clearance of PBTs.

Kewords