Ana Paula Bernardo. CHP Hospital de Santo António ICBAS/ Universidade do Porto

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1 Ana Paula Bernardo CHP Hospital de Santo António ICBAS/ Universidade do Porto

Clinical relevance of hyperphosphatemia Phosphate handling in dialysis patients Phosphate kinetics in PD peritoneal phosphate clearance Phosphate clearance

2 Clinical relevance of hyperphosphatemia Phosphate handling in dialysis patients Phosphate kinetics in PD peritoneal phosphate clearance Phosphate clearance according to peritoneal membrane transport characteristics and modality: Recent studies Our data The impact of various cycling regimens on phosphate removal Recent studies

3 Hyperphosphatemia is a common clinical finding in patients with chronic kidney disease stage 5D. It has been associated with several hemodynamic disturbances, including ventricular hypertrophy and sistolic disfunction.

4 N= 66 ESRD patients. Hyperphosphatemia was associated with increased BP, increased cardiac work and high arterial tensile stress.

5 Phosphate may directly stimulate vascular smooth muscle cells to undergo phenotypic changes that predispose to calcification.

6 It has emerged as an important factor in cardiovascular mortality both in patients on hemodialysis (HD) or peritoneal dialysis (PD)

7 Cohort study. n = HD patients. Determine associations among disorders of mineral metabolism, mortality and morbidity in HD patients. Hyperphosphatemia was associated with an increased RR of death.

N= 17.236 HD patients Major outcomes: all cause mortality, cardiovascular mortality.

8 N= HD patients Major outcomes: all cause mortality, cardiovascular mortality. Mortality was strongly associated with altered mineral metabolism laboratory values, namely hyperphosphatemia.

Evaluate the relation between plasma concentrations outside the K/DOQI targets for bone metabolism and the risk of cardiovascular morbidity and

9 Evaluate the relation between plasma concentrations outside the K/DOQI targets for bone metabolism and the risk of cardiovascular morbidity and mortality in 586 PD and 1043 HD patients. Cardiovascular mortality risk is increased in PD and HD patients with elevated plasma Ph and CaxPh concentration.

10 Restriction of phosphorus in the diet. Use of phosphate-binding agents. Preservation of residual renal function. Dialysis (hemodialysis and peritoneal dialysis).

11 Peritoneal membrane Ion transport is more complex than small solute transport such as urea or creatinine. Ph is negatively charged, capillaries and interstitium also negatively charged. 96 Da molecular weight. Molecular radius is 2.8 Å. Hydrophilic characteristics (aqueous cover increase effective molecular weight) % protein bound. 5% complexes with other ions. Mainly intracellular (slow intra-extra cellular solute transfer rate; not freely diffusible as urea) Depends on osmotic, chemical and electrical gradients and also trans-membranous active phosphate transporters.

13 24 PD patients with follow up for 7 months. Reported reduction of the Renal Clearance of phosphorus over time. Decrease from 63% to 49% at 7 months. In the short term the decline in Renal Clearance may be offset by an increase in Peritoneal Clearance.

14 In anuric patients increased peritoneal clearances were not enough to compensate for the absence of RRF. 252 PD patients, 29% of patients with RRF versus 44% of anuric patients had hyperphosphatemia >5.5 mg/dl.

16 The correlation between D/P phosphate and D/P creatinine is linear. 2,4,5,6 For a defined dwell time, dialysate tonicity and volume, peritoneal phosphate clearance is expected to vary according to membrane transport characteristic. Fast transporters have better peritoneal phosphate clearance than slow transporters. 2,4,5 2. Bernardo et al. Clin J Am Soc Nephrol Sedlacek et al. Am J Kidney Dis 2000: Badve et al. Clin J Am Soc Nephrol 2008: Schmitt et al. Perit Dial Int 2009:

17 n= 56 PD patients evaluated, 51 patients with PET results. Phosphorus levels were measured in 24-h dialysate and urine collections in order to calculate phosphorus clearances.

18 Patients categorized according to D/P Cr (4h PET) as high or low transporters. Fast transporters had higher phosphate and creatinine clearances than slow transporters.

19 Few studies have addressed the importance of PD modality concerning dialytic phosphate clearance, and they show conflicting results. Gallar et al 7 studied phosphate clearances in 33 CAPD and 37 CCPD patients. They concluded that weekly peritoneal phosphate clearance in CCPD patients (51 ± 21L) was higher than in the CAPD patients (41 ± 14 L, p<0.005). Sedlacek et al 4 showed slightly better peritoneal phosphate clearances in 20 CAPD patients (5.6 ± 1.3 ml/min) as compared with 36 CCPD patients (4.8 ± 1.7 ml/min, p=ns). Badve and colleagues 5 showed that peritoneal phosphate clearance is better with CAPD as compared with CCPD, after adjusting for membrane status. 4. Sedlacek et al. Am J Kidney Dis 2000: Badve et al. Clin J Am Soc Nephrol 2008: Gallar et al. Nefrologia, 2000:

20 N=129 prevalent PD patients, divided according to membrane transport status and PD modality (CAPD or CCPD). When examined by PD modality alone, there was no significant difference in peritoneal phosphate clearance between patients treated with CAPD or CCPD.

21 Multivariate analysis confirmed that both membrane transport category and PD modality are independently associated with peritoneal phosphate clearance.

264 patients were included and evaluated 12 months after starting PD.

23 Cross-sectional and retrospective study conducted at La Paz University Hospital Home Dialysis Unit. 264 patients were included and evaluated 12 months after starting PD. Patients were classified according to PET results concerning both phosphate and creatinine transport status.

24 D/P Cr is not a sufficiently accurate measure to classify patients for peritoneal membrane phosphate transport status.

25 Concerning peritoneal membrane transport status, patients were classified according to D/P Ph at a 4-h, 3.86% glucose PET. Patients with fast-transport membranes had higher solute clearances than the remaining categories.

26 Patients treated with APD had higher peritoneal urea Kt/V than patients with CAPD, but there was no difference in peritoneal creatinine clearance or in peritoneal phosphate clearance between the 2 modalities.

27 In the slow-average and slow categories, treatment with CAPD was associated with significantly higher phosphate clearance than with APD. Treatment with CAPD is associated with an increase in Ph clearance of 13.6% among slow-average and 38.4% among slow transporters, compared with APD.

28 N = 77 PD patients Cross-sectional study conducted at CHP - Peritoneal Dialysis Unit Slow transporters had higher peritoneal phosphate clearances in CAPD regimens Botelho C., Rodrigues A. et al (in press)

29 27 % Clearance L /night 19 % N= 10 prevalent PD patients, H or HA and Ph > 5.5 mg/dl Int J Artif Organs Dec;28(12):

30 N=35 children on APD. Dialytic 24-h Ph clearance was independently predicted by: - Total fluid turn-over - Number of cycles - D/P Ph - Dwell time - Ultrafiltration Perit Dial Int 29(4): , 2009

31 Automated PD prescription parameters and its relationship with hyperphosphatemia Hyperphosphatemic Normophosphatemic p Value D/P creatinine 0.59 [ ] 0.69[ ] 0.53 Number of PD cycles 5 [5-5] 6 [5-7] 0,019 Treatment time (hours) 7.5[ ] 7. 8[ 8-8.5] 0,004 Dwell time (minutes) 60 [50-60] 44 [39-53] 0,18 N=31 patients on APD. Hyperphosphatemia was associated with shorter time of nocturnal APD treatment and lower number of cycles. Botelho C., Rodrigues A. et al (in press)

32 Hyperphosphatemia is common among dialysis patients and impacts dialysis outcomes. In PD patients, phosphate control is known to deteriorate as residual renal function declines. Once residual renal function is lost, the peritoneal membrane phosphate transport status plays an important role in the management of hyperphosphatemia by PD. Peritoneal phosphate clearance is more closely related with peritoneal creatinine clearance than with peritoneal urea clearance. However D/P Cr is not sufficiently accurate to classify patients for peritoneal membrane phosphorus transport status.

33 Patients with slow-average/slow transport status have significantly lower values of peritoneal small solute clearances than the patients in the fast/fast-average transport category. Previous studies that made direct comparisons of phosphate clearance between CAPD and APD have shown conflicting results (no adjustment for peritoneal membrane transport category). In hyperphosphatemic, particularly anuric patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate Ph control on APD (specially slow and slow-average transporters).

Objectives. Peritoneal Dialysis vs. Hemodialysis 02/27/2018. Peritoneal Dialysis Prescription and Adequacy Monitoring

Objectives. Peritoneal Dialysis vs. Hemodialysis 02/27/2018. Peritoneal Dialysis Prescription and Adequacy Monitoring Peritoneal Dialysis Prescription and Adequacy Monitoring Christine B. Sethna, MD, EdM Division Director, Pediatric Nephrology Cohen Children s Medical Center Associate Professor Hofstra Northwell School