Protection of Residual Renal Function and Nutritional Treatment: First Step Strategy for Reduction of Uremic Toxins in End-Stage Kidney Disease Patients.

Adamasco Cupisti,Claudia D’Alessandro,Domenico Giannese,Piergiorgio Bolasco,Alice Sabatino,Enrico Fiaccadori

doi:10.3390/toxins13040289

Adamasco Cupisti, Claudia D’Alessandro + Show 4 more

Open Access

https://doi.org/10.3390/toxins13040289

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Abstract

The retention of uremic toxins and their pathological effects occurs in the advanced phases of chronic kidney disease (CKD), mainly in stage 5, when the implementation of conventional thrice-weekly hemodialysis is the prevalent and life-saving treatment. However, the start of hemodialysis is associated with both an acceleration of the loss of residual kidney function (RKF) and the shift to an increased intake of proteins, which are precursors of uremic toxins. In this phase, hemodialysis treatment is the only way to remove toxins from the body, but it can be largely inefficient in the case of high molecular weight and/or protein-bound molecules. Instead, even very low levels of RKF are crucial for uremic toxins excretion, which in most cases are protein-derived waste products generated by the intestinal microbiota. Protection of RKF can be obtained even in patients with end-stage kidney disease (ESKD) by a gradual and soft shift to kidney replacement therapy (KRT), for example by combining a once-a-week hemodialysis program with a low or very low-protein diet on the extra-dialysis days. This approach could represent a tailored strategy aimed at limiting the retention of both inorganic and organic toxins. In this paper, we discuss the combination of upstream (i.e., reduced production) and downstream (i.e., increased removal) strategies to reduce the concentration of uremic toxins in patients with ESKD during the transition phase from pure conservative management to full hemodialysis treatment.

Highlights

In end-stage kidney disease (ESKD), progressive retention of molecules which are normally excreted into urine occurs, causing impairment of several biological functions
Lowering uremic toxins is a substantial part of ESKD treatment
Uremic toxins production is increased in chronic kidney disease (CKD)/ESKD, mainly because of the increased protein fermentation by proteolytic bacteria, prevalent in the dysbiotic gut of CKD/ESKD patients

Summary

Introduction

In end-stage kidney disease (ESKD), progressive retention of molecules which are normally excreted into urine occurs, causing impairment of several biological functions. Some evidence exists that bacterial generation rates in the gut do not change in the different CKD stages and this makes the loss of RKF the major role for the increased protein-bound uremic toxins levels, such as IS and PCS [30]. Another important gut microbiota-derived uremic toxin is trimethylamineN-oxide (TMAO), derived from l-carnitine and phosphatidylcholine, being associated with increased mortality and cardiovascular morbidity [31]. It accumulates in the blood of patients on hemodialysis, but differently from IS and PCS, TMAO does not circulate bound to albumin; it is more removable by dialysis, though at a lower efficiency than urea [32]

Protection of Residual Kidney Function

Nutritional Treatment

Once-Weekly Hemodialysis Plus Low-Protein Diet

Findings

Conclusions