Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Silvio Borrelli,Alessandro Carbone,Claudia Elefante,Luca De Nicola,Luigi Pennino,Carlo Garofalo,Tiziana Rappa,Roberto Minutolo,Ilaria De Gregorio,Lucio Polese

doi:10.3390/ijms222312804

Silvio Borrelli, Alessandro Carbone + Show 8 more

Open Access

https://doi.org/10.3390/ijms222312804

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Abstract

Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.

Highlights

The kidneys play a pivotal role in the body’s sodium balance [1]; kidney failure is a well-known condition coupled with a remarkable sodium overload, which by inducing expansion of the extracellular volume (ECV), causes blood pressure (BP)elevation, left ventricular hypertrophy, and heart failure [2,3]
The sodium concentration in standard peritoneal dialysis (PD) solutions (132/134 mmol/L) is slightly different from blood concentration, lowering sodium in the dialysate has been proposed as a potential strategy to increase the sodium gradient between blood and dialysate and improve sodium removal; no benefit associated with the use of low-sodium
In a small, nonrandomized study, Davies et al compared the effects on sodium removal and UF found with using uncompensated ultralow sodium (102 mmol/L) vs. compensated low sodium solutions (115 mmol/L); the authors reported that improvements in BP, thirst, and fluid status were only achieved when increasing the diffusive component of sodium removal whilst maintaining ultrafiltration by glucose-compensated solutions [36]

Summary

Introduction

The kidneys play a pivotal role in the body’s sodium balance [1]; kidney failure is a well-known condition coupled with a remarkable sodium overload, which by inducing expansion of the extracellular volume (ECV), causes blood pressure (BP). Restoring the sodium body balance in end-stage kidney disease (ESKD) patients represents a cornerstone of dialytic treatment, but remains challenging [5]. This narrative review provides an update on the novel pathophysiological model of sodium toxicity in patients with chronic renal failure, and, in particular, in ESKD patients and looks at possible future strategies to improve sodium removal by PD

Extrarenal Mechanisms for Sodium Body Balance and Hypertension

Volume-Independent Sodium Toxicity in End-Stage Kidney Disease

Alternative Strategies to Remove Sodium by Peritoneal Dialysis

Findings

Conclusions