By Jeffrey Perl MD SM FRCP (C)
Division of Nephrology St. Michael’s Hospital
perlj@smh.ca

Adequate sodium and water removal continues to remain an important therapeutic endpoint among patients on PD and may be limiting the long-term success of PD therapy1. Low sodium PD solutions represent an attractive option to increase peritoneal sodium removal. Conventional PD solutions have a dialysate sodium concentration of between 130-135 mmol/L. Therefore, the majority of peritoneal sodium removal occurs by convective clearance across the peritoneal membrane.   By reducing the concentration of sodium in the PD solution, one may be able to obtain further sodium removal by creating a greater sodium gradient between the blood and dialysate leading to greater diffusive removal of sodium.

Though these solutions have been evaluated before, Rutkowski et al should be commended on their rigorous prospective clinical trial which has provided some important findings regarding the role of low sodium PD solutions.2 In this study, 108 hypertensive CAPD patients were randomized to either 6-months of standard sodium concentration PD solutions (Na-134 mmol/L) vs. low sodium concentration PD solutions (Na-125 mmol/L) among all exchanges. Though the primary end-point was to demonstrate non-inferiority in the achieved weekly total Kt/Vurea between the groups, arguably perhaps more important and interesting were the secondary outcomes of BP control, safety and tolerability.  Though non-inferiority could not be demonstrated in the primary outcome (Kt/Vurea, 2.53+/-0.89, low sodium group) vs. (Kt/Vurea  2.97+/-1.58), the low sodium group had an approximately 1.2 g greater peritoneal sodium removal per day at week 12 , and significant improvements in BP control over the course of the study with less antihypertensive therapy by study end and a difference in systolic and diastolic BPs at week 12 of 8.6 mm Hg and 4.6 mm Hg.

An initial greater decline in residual kidney function was seen in the low sodium group that was not different at the study’s end. The safety profile in both groups was similar with the exception of mild/moderate hyponatremia which was greater in the low sodium group.

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The present findings suggest that the use of low sodium PD solutions are safe and may lead to improvements in blood pressure control and maintenance of euvolemia. Study in CAPD patients alone and those with significant residual kidney function represents a limitation worth noting. In the majority of developed countries, APD represents the predominant therapy3, and furthermore, sodium removal may be more challenged in APD relative to CAPD owing largely to the impact of sodium sieving and potentially greater thirst.  Therefore, the results would have been that much more relevant (and perhaps magnified) if an APD population was included. Given that anuric patients struggle the most with adequate sodium removal, inclusion of a cohort of anuric PD patients would have similarly shed important findings and removed the confounding ‘’noise’’ residual kidney function played in this study. Further concerning is the dropout of approximately 20% of the cohort for various reasons from randomization to study end.  Lastly, the transient decline in residual kidney function may have been the result of extracellular fluid volume contraction among the low-sodium solution patients due to excessive sodium removal as has been seen before with aggressive sodium removal4.  Inclusion of bioelectrical impedance analyses measures may have been able to shed important insights in this regard.

In my opinion, are low sodium PD solutions ready for primetime?  Given the increasingly smaller role Kt/Vurea is playing in the evaluation of well-being among patients on PD I am least excited about the study’s primary outcome. In my PD patient population, I am most concerned about reducing future cardiovascular risk. I would welcome further prospective studies among both incident and prevalent PD patients and the inclusion of APD patients assessing the impact of these solutions on the potential reduction of future cardiovascular events.  Daring to dream though, as reality sets in, I would look back down to earth and those studies conducted by our frequent hemodialysis colleagues5, 6. In this regard, to change practice, I would settle on a larger, more generalizable study that would assess the impact of these solutions on an important cardiovascular surrogate outcome such as positive changes in left ventricular geometry while recapitulating the safety profile of these solutions initially demonstrated.

References:

  1. Ates K, Nergizoglu G, Keven K, Sen A, Kutlay S, Erturk S, Duman N, Karatan O, Ertug AE: Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. Kidney Int, 60: 767-776, 2001
  2. Rutkowski B, Tam P, van der Sande FM, Vychytil A, Schwenger V, Himmele R, Gauly A, Low Sodium Balance Study G: Low-Sodium Versus Standard-Sodium Peritoneal Dialysis Solution in Hypertensive Patients: A Randomized Controlled Trial. Am J Kidney Dis, 67: 753-761, 2016
  3. Jain AK, Blake P, Cordy P, Garg AX: Global Trends in Rates of Peritoneal Dialysis. J Am Soc Nephrol, 2012
  4. Gunal AI, Duman S, Ozkahya M, Toz H, Asci G, Akcicek F, Basci A: Strict volume control normalizes hypertension in peritoneal dialysis patients. Am J Kidney Dis, 37: 588-593, 2001
  5. Rocco MV, Lockridge RS, Jr., Beck GJ, Eggers PW, Gassman JJ, Greene T, Larive B, Chan CT, Chertow GM, Copland M, Hoy CD, Lindsay RM, Levin NW, Ornt DB, Pierratos A, Pipkin MF, Rajagopalan S, Stokes JB, Unruh ML, Star RA, Kliger AS, Kliger A, Eggers P, Briggs J, Hostetter T, Narva A, Star R, Augustine B, Mohr P, Beck G, Fu Z, Gassman J, Daugirdas J, Hunsicker L, Li M, Mackrell J, Wiggins K, Sherer S, Weiss B, Sanz J, Dellagrottaglie S, Kariisa M, Tran T, West J, Unruh M, Keene R, Schlarb J, Chan C, McGrath-Chong M, Frome R, Higgins H, Ke S, Mandaci O, Owens C, Snell C, Eknoyan G, Appel L, Cheung A, Derse A, Kramer C, Geller N, Grimm R, Henderson L, Prichard S, Roecker E, Rocco M, Miller B, Riley J, Schuessler R, Lockridge R, Pipkin M, Peterson C, Hoy C, Fensterer A, Steigerwald D, Stokes J, Somers D, Hilkin A, Lilli K, Wallace W, Franzwa B, Waterman E, Levin A, Sioson L, Cabezon E, Kwan S, Roger D, Lindsay R, Suri R, Champagne J, Bullas R, Garg A, Mazzorato A, Spanner E, Burkart J, Moossavi S, Mauck V, Kaufman T, Chan W, Regozo K, Kwok S: The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial. Kidney Int, 2011
  6. Culleton BF, Walsh M, Klarenbach SW, Mortis G, Scott-Douglas N, Quinn RR, Tonelli M, Donnelly S, Friedrich MG, Kumar A, Mahallati H, Hemmelgarn BR, Manns BJ: Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial. JAMA, 298: 1291-1299, 2007

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