Highlighting Levels of Indoxyl Sulphate among Critically Ill Patients with Acute Nephrotoxicity; Correlations Between Indoxyl Sulphate Levels and Patients’ Characteristics

Abstract

Background: Many animal studies suggested that the uremic toxin indoxyl sulphate can add to renal damage following induced nephrotoxicity and this effect has not been proved in patients with such complication. Methods: This is a prospective, case-control, and an observational study conducted on 74 critically ill patients with acute nephrotoxicity. It was designed to measure serum levels of indoxyl sulphate on the day of enrollment and over the course of their illness using high performance liquid chromatography (HPLC-UV) and to test the correlation between these levels and patient's demographics, clinical characteristics, physiological variables, and their outcomes. Results: Critically ill patients with acute nephrotoxicity had significantly higher total (tIS) and free (fIS) indoxyl sulphate than healthy controls and significantly lower than patients with end-stage renal disease (ESRD). Although, no correlation was found between tIS or fIS and mortality, among survivors, tIS, fIS, creatinine and eGFR were independently associated with no renal recovery. Conclusions: Serum indoxyl sulphate levels were elevated in critically ill patients with acute nephrotoxicity. There is an association between high levels of indoxyl sulphate and no renal-recovery outcome among survivors of acute nephrotoxicity. Early removal of indoxyl sulphate from patients' blood may improve their outcomes.

The Role of Gut-Derived, Protein-Bound Uremic Toxins in the Cardiovascular Complications of Acute Kidney Injury

“…The relative heterogeneity concerning sample size, population background, clinical setting, the timing of measurements, and severity of AKI may limit the interpretation of the data. The kinetics of IS accumulation appear to follow those of serum creatinine [ 103 ], and two studies showed that IS levels increase with the severity of AKI [ 104 , 105 ], the highest observed among patients presenting with severe AKI and those who needed renal replacement therapy support. Except for one study reporting a particularly high level [ 71 ], the observed level of total IS remained relatively low compared to that in CKD [ 106 ], ranging from 0.64 to 3.33 µg/mL.…”

“…On the other hand, systemic inflammation and fluid accumulation, resulting in a decrease in serum albumin levels, may also reduce the measured total serum level of IS, particularly in septic AKI. Two studies analysed the correlation between IS levels and recovery from AKI [ 104 , 105 ], and one study reported an independent association between total IS levels at AKI diagnosis and 90-day mortality [ 107 ]. In addition, the complications of AKI patients may depend on the elimination time course of PBUTs, reflecting the AKI recovery rate independently from renal replacement therapy.…”

“… * estimated according to Figure 3 in reference [ 105 ]. aHR: adjusted hazard ratio, IAA: indol-3-acetic acid, IS: indoxyl sulfate, PCS: para-cresyl sulfate, tIS: total IS, fIS: free IS.…”