Evaluation of Salivary Indoxyl Sulfate with Proteinuria for Predicting Graft Deterioration in Kidney Transplant Recipients

Abstract

Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a transplanted kidney is limited, the risk of the loss/deterioration of graft function (DoGF) should be estimated to apply the preventive treatment. The collection of saliva and urine is more convenient than collecting blood and can be performed at home. The study aimed to verify whether non-invasive biomarkers, determined in saliva and urine, may be useful in the prediction of DoGF in kidney transplant recipients (KTRs) (n = 92). Salivary and serum toxins (p-cresol sulfate, pCS; indoxyl sulfate, IS) concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary proteins, hemoglobin, and glucose were measured using a semi-quantitative strip test. Salivary IS (odds ratio (OR) = 1.19), and proteinuria (OR = 3.69) were demonstrated as independent factors for the prediction of DoGF. Satisfactory discriminatory power (area under the receiver operating characteristic curve (AUC) = 0.71 ± 0.07) and calibration of the model were obtained. The model showed that categories of the increasing probability of the risk of DoGF are associated with the decreased risk of graft survival. The non-invasive diagnostic biomarkers are a useful screening tool to identify high-risk patients for DoGF.

Salivary and serum periostin in kidney transplant recipients

“…For example, Indoxy Sulphate (IS) (a type of uremic toxin) in saliva was used to predict rejection in KT patients. In this study, as in our results, biomarkers were significant in saliva and insignificant in serum [ 24 ]. Also, a strong correlation was found between the levels of toxins (p_Cresol sulfate and IS) in serum and saliva, and in this study, a significant correlation was reported between the toxic levels of saliva and GFR [ 25 ].…”

“…Its ease of collection, painlessness, ease of storage, and non-invasiveness, all of which can lead to the replacement of blood with this bio-fluid [ 26 ]. In KT patients, collecting saliva or urine at home is more possible than taking blood [ 24 , 27 ]. Saliva can facilitate biochemical and toxicological diagnosis in children and adults [ 27 ].…”

Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

“…-Age (years): 68 [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77] (median, range), 71 [65][66][67][68][69][70][71][72][73][74][75][76][77][78], and 67 [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]. p < 0.001.…”

Fecal Microbiota Transplantation in Reducing Uremic Toxins Accumulation in Kidney Disease: Current Understanding and Future Perspectives

“…Microbiota-derived metabolites may have a negative impact on the outcomes of graft survival and function, since high levels of PCS and IS can cause the production of pro-fibrotic molecules and inflammatory cytokines from renal tubular cells, resulting in increased tubulointerstitial fibrosis, cellular injury, and nephrotoxicity [ 58 , 119 ]. Korytowska et al in 2021 demonstrated that salivary IS can be employed as a non-invasive diagnostic marker in order to recognize the loss/deterioration of the graft function (DoGF) more than a year following kidney transplantation [ 120 ]. The study was carried out on 92 kidney transplant recipients and, although it presents some limitations to the proposed model, this study assessed the role of IS as a potential predictor of DoGF and as a useful marker to prevent graft failure, and therefore, extending the survival and the functioning of the transplanted kidney [ 120 ].…”

“…Korytowska et al in 2021 demonstrated that salivary IS can be employed as a non-invasive diagnostic marker in order to recognize the loss/deterioration of the graft function (DoGF) more than a year following kidney transplantation [ 120 ]. The study was carried out on 92 kidney transplant recipients and, although it presents some limitations to the proposed model, this study assessed the role of IS as a potential predictor of DoGF and as a useful marker to prevent graft failure, and therefore, extending the survival and the functioning of the transplanted kidney [ 120 ]. Nevertheless, in the case of some uremic toxins, different and contrasting results, with respect to those previously described, have been reported.…”