PRESENTED BY
ISAAC TEITELBAUM

Presentation Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Isaac Teitelbaum

Peritoneal dialysis (PD) has come a long way since its introduction as a form of renal replacement therapy nearly four decades ago. There are a number of parameters that are taken into consideration when aiming to provide an optimum PD treatment nowadays, including achieving an adequate acid-base balance, blood pressure and volume homeostasis, middle molecule and small solute clearance, nutritional status, preservation of residual renal function and keeping the risk of inflammation, mineral bone disease and cardiovascular events to a minimum. When considering these goals, it is necessary to have in mind certain unconventional relationships between these parameters and mortality in PD patients.

PD parameters

Metabolic acidosis is common among end-stage renal failure patients. A recent study showed that a low serum bicarbonate level represents an independent risk factor for mortality in PD patients, interpreting this relationship by enhanced inflammation and more rapid loss of residual renal function which are associated with metabolic acidosis [1]. This finding warrants further research to elucidate whether bicarbonate supplementation would reduce this risk.

Unlike in the general population, in PD patients low systolic blood pressure increases the risk of all-cause and cardiovascular mortality, thus calling for caution when treating hypertension in these patients [2]. Furthermore, it brings up the question of whether an active treatment to increase blood pressure would result in improved survival of PD patients.

Some years ago, a prospective study has challenged the role of traditional measures of PD adequacy, i.e. urea and creatinine removal, as predictors of mortality in PD patients, concluding that the factors associated with survival were sodium and fluid removal [3]. This result was later supported by a finding that N-terminal pro-brain natriuretic peptide is an independent risk predictor of cardiovascular congestion, mortality and adverse cardiovascular outcome in chronic PD patients [4]. Furthermore, the yet unpublished results from dr Pecoits-Filho et al. corroborate that PD patients with prescribed diuretics have lower hazard ratios for mortality as compared to those not taking diuretics, thus emphasizing the importance of fluid removal to achieve better outcomes. Whether this means that patients with residual renal function should be routinely prescribed diuretics and is it appropriate to increase daily glucose exposure to maintain euvolemia remains debatable. To further complicate things, it is possible that the relationship between volume overload and mortality is not that unambiguous and that the additional effect of inflammation should not be underestimated [5, 6]. This brings up other questions related to the best way of monitoring and treating inflammation in PD patients, as well as whether the absence of inflammation should be introduced as a marker of PD adequacy.

In contrast to hemodialysis patients, PD patients are more prone to hypokalemia, which is an independent risk factor for mortality in this population [7]. Hypokalemia is also associated with an increased risk of Enterobacteriaceae peritonitis and poor nutritional status [8]. Still, when present, hyperkalemia is also associated with both all-cause and infection-related mortality in PD patients [9], thus suggesting that both decreased and elevated potassium levels has a negative impact on patient survival.

Sodium disorders are also common among PD patients and may be associated with adverse outcomes, possibly due to cerebral edema, impaired cardiac conduction due to inhibition of calcium channel circuits and higher susceptibility to infectious complications [10, 11].  Nevertheless, it is yet to be determined whether there is indeed a higher frequency of peritonitis in hyponatremic patients and whether the correction of dysnatremia would improve longevity in this population.

Both uncorrected and albumin-corrected serum calcium levels show a typical U-shaped mortality curve in chronic PD patients, while serum phosphorus ≥6.4 mg/dl and magnesium <1.68mg/dL are also associated with increased risk of death [12, 13]. Yet again, questions remain whether interventions to correct these minerals would reduce mortality risk.

PD prescription update

The presently used 2006 guidelines from the International Society of Peritoneal Dialysis (ISPD) have focused on small solute removal and total Kt/V to guide PD prescription [14]. However, it is currently believed that dialysis adequacy should be interpreted clinically and focuses on patients’ overall well-being, rather than by just targeting solute and fluid removal. With this aim, the ISPD convened a group of experts in the autumn of 2017 to discuss further steps in devising optimum PD prescription. The discussion focused on the evident changes of PD population, with more and more older and multi-morbid patients; the trend of increased use of PD in lower and middle income countries; the importance of small solute and fluid removal, but also the need for patient-centered recommendations; and the lack of high quality evidence from randomized controlled trials to guide updated recommendations.

The first decision by the prescribing group was to not use the term “adequacy”, as merely adequate dialysis should not be considered sufficient anymore. The updated recommendations will therefore be titled “Prescribing high quality, goal-directed peritoneal dialysis”, suggesting shared decision-making between the patient and care team to establish realistic care goals to maximize quality of life for the patient, minimize their symptoms, and allow the patients to meet his/her own life goals, while allowing  the physician to provide individualized, high-quality clinical care. This particularly means taking into consideration patients’ own ranking of outcomes important to them, none of which relate to the small solute removal [15, 16].

The guidelines will leave more freedom to PD prescribers to conform to local country resources and patients’ wishes. They will also advocate regular assessments of patients’ quality of life, along with standard clinical evaluations, which include the fluid and nutritional status and small solute removal. The use of incremental PD prescription shall be encouraged in patients with residual kidney function and special consideration should be given to the possibility of reducing dialysis prescription in the elderly and frail patients in whom such an approach might minimize the burden of the treatment. Children, on the other hand, should have the same high-quality PD treatment as adults.

Finally, it is important to acknowledge that not all symptoms can be controlled and solved by dialysis and that some of them, and particularly medication adherence, nutritional and psychological status, may require additional efforts to deal with.

References

1. Chang TI, Oh HJ, Kang EW, et al.. A low serum bicarbonate concentration as a risk factor for mortality in peritoneal dialysis patients.. PLoS One. 2013;8(12):e82912. DOI: 10.1371/journal.pone.0082912

2. Goldfarb-Rumyantzev AS, Baird BC, Leypoldt JK, Cheung AK. The association between BP and mortality in patients on chronic peritoneal dialysis. . Nephrol Dial Transplant. 2005 Aug;20(8):1693-701. . DOI: https://doi.org/10.1093/ndt/gfh856

3. Ateş K, Nergizoğlu G, Keven K, et al.. Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. . Kidney Int. 2001;60(2):767-76. DOI: https://doi.org/10.1046/j.1523-1755.2001.060002767.x

4. Wang AY, Lam CW, Yu CM, et al. . N-terminal pro-brain natriuretic peptide: an independent risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic peritoneal dialysis patients. . J Am Soc Nephrol. 2007;18(1):321-330. DOI: https://doi.org/10.1681/ASN.2005121299

5. Chung SH, Heimbürger O, Stenvinkel P, Wang T, Lindholm B.. Influence of peritoneal transport rate, inflammation, and fluid removal on nutritional status and clinical outcome in prevalent peritoneal dialysis patients. . Perit Dial Int. 2003;23(2):174-183.

6. Wang AY, Woo J, Lam CW, et al.. Is a single time point C-reactive protein predictive of outcome in peritoneal dialysis patients? . J Am Soc Nephrol. 2003;14(7):1871-1879. DOI: https://doi.org/10.1097/01.ASN.0000070071.57901.B3

7. Szeto CC, Chow KM, Kwan BC, et al. . Hypokalemia in Chinese peritoneal dialysis patients: prevalence and prognostic implication. . Am J Kidney Dis. 2005;46(1):128-135.

8. Chuang YW, Shu KH, Yu TM, Cheng CH, Chen CH. . Hypokalaemia: an independent risk factor of Enterobacteriaceae peritonitis in CAPD patients.. Nephrol Dial Transplant. 2009;24(5):1603-1608.. DOI: 10.1093/ndt/gfn709

9. Torlén K, Kalantar-Zadeh K, Molnar MZ, Vashistha T, Mehrotra R. Serum potassium and cause-specific mortality in a large peritoneal dialysis cohort.. Clin J Am Soc Nephrol. 2012;7(8):1272-1284. DOI: 10.2215/CJN.00960112

10. Ravel VA, Streja E, Mehrotra R, et al. . Serum sodium and mortality in a national peritoneal dialysis cohort.. Nephrol Dial Transplant. 2017;32(7):1224-1233. DOI: 10.1093/ndt/gfw254

11. Mandai S, Kuwahara M, Kasagi Y, et al.. Lower serum sodium level predicts higher risk of infection-related hospitalization in maintenance hemodialysis patients: an observational cohort study. . BMC Nephrol. 2013;14:276. DOI: 10.1186/1471-2369-14-276

12. Rivara MB, Ravel V, Kalantar-Zadeh K, et al. . Uncorrected and Albumin-Corrected Calcium, Phosphorus, and Mortality in Patients Undergoing Maintenance Dialysis.. J Am Soc Nephrol. 2015;26(7):1671-1681. DOI: 10.1681/ASN.2014050472

13. Cai K, Luo Q, Dai Z, et al. . Hypomagnesemia Is Associated with Increased Mortality among Peritoneal Dialysis Patients. . PLoS One. 2016;11(3):e0152488.. DOI: 10.1371/journal.pone.0152488

14. Lo WK, Bargman JM, Burkart J,et al. . Guideline on targets for solute and fluid removal in adult patients on chronic peritoneal dialysis. . Perit Dial Int. 2006;26(5):520-522.

15. Manera KE, Johnson DW, Craig JC et al. . Patient and Caregiver Priorities for Outcomes in Peritoneal Dialysis: Multinational Nominal Group Technique Study. Clin J Am Soc Nephrol. 2019;14(1):74-83. DOI: 10.2215/CJN.05380518

16. Teitelbaum I. . Peritoneal dialysis adequacy and outcomes: what really matters? . Oral presentation at 56th ERA-EDTA congress, Budapest, Hungary, June 15, 2019. https://www.enp-era-edta.org/material/21890/webcast-external?searchTerm=teitelbaum

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