Abstract
PurposeIndoxyl sulfate (IS) is one of the most potent uremic toxins involved in chronic kidney disease (CKD) progression, induction of inflammation, oxidative stress, and cardiovascular diseases occurrence. It is proved that hypertension is a common CVD complication and a major death risk factor as well as contributes for decline in a renal function. The aim of our study was to investigate how implementing of antihypertensive therapy impact IS concentrations and the associations between IS and markers of renal function, inflammation and oxidative stress.MethodsStudy was conducted on 50 patients diagnosed with CKD and hypertension, divided into three groups: without hypotensive therapy (CKD-NONE), hypotensive monotherapy (CKD-MONO), and hypotensive polypharmacotherapy (CKD-POLI), and 18 healthy volunteers. The markers of inflammation [interleukin-6, tumor necrosis factor-alpha (TNF-α), high-sensitive C-reactive protein (hs-CRP), neopterin, ferritin], oxidative status [superoxide dismutase (Cu/Zn-SOD), antibodies against oxidized low-density lipoprotein (oxLDL-abs)], and selectins were determinate using immunoenzymatic methods. IS levels were assayed using high-performance liquid chromatography and other parameters were analysed using routine laboratory techniques. Then cross-sectional analysis was performed.ResultsElevated levels of IS, indicators of kidney function, markers of inflammation and blood pressure values were observed in each CKD subgroups. There was no effect of antihypertensive therapy on IS levels between studied groups, as well as there was no clear relationship between IS and blood pressure values in each studied group. The positive associations between IS and Cu/Zn SOD, neopterin, hs-CRP, creatinine and neutrophils/lymphocytes ratio were observed in CKD-NONE and CKD-POLI subgroups. Additionally, in CKD-POLI group IS positively correlated with TNF-α, ferritin and neutrophils. In CKD-MONO group, IS was positively related to oxLDL-abs, neopterin, E-selectin and creatinine, whereas it was inversely associated with hs-CRP.ConclusionsOur study showed for the first time that the antihypertensive therapy has no impact on IS levels in CKD patients with hypertension. However, the introduction of the antihypertensive therapy modified the dependencies between IS and the studied markers of kidney function, inflammation, oxidative stress and hematological parameters that are crucial for mortality and morbidity amongst the CKD patients with hypertension.
Highlights
Inflammation as an essential part of chronic kidney disease (CKD) has been recognized in the late 1990s, when it was linked to nearly 20 times higher mortality in CKD resulting from cardiovascular disease and an exceptionally high mortality rate overall [1]
Mean albumin values were statistically decreased in each of uremic groups compared to controls, whereas only CKD-TOTAL and CKD-POLI group presented lowered concentrations of total protein compared to controls, achieving p < 0.05
None of the complete blood count test parameters was significantly changed amongst the CKD subgroups, result of multiple comparison test in case of PLT count was on the edge of significance (p = 0.066)
Summary
Inflammation as an essential part of chronic kidney disease (CKD) has been recognized in the late 1990s, when it was linked to nearly 20 times higher mortality in CKD resulting from cardiovascular disease and an exceptionally high mortality rate overall [1]. The variety of factors contribute to chronic inflammatory status during renal diseases including. International Urology and Nephrology (2019) 51:491–502 increased production and decreased the clearance of proinflammatory cytokines, reactive oxygen species (ROS), chronic and recurrent infections, including those related to dialysis access, and intestinal dysbiosis [2]. Inflammation in CKD accelerates the progression of deterioration in excretory kidney function resulting in the accumulation of uremic toxins [5]. Uremic toxins are endogenous products of metabolism and are accumulated in the body fluids during the progression of CKD due to inadequate renal clearance. There is a growing number of clinical studies that supports the idea that IS is a crucial factor which contributes to CVD in the CKD, and can be considered as the main link between these diseases [7, 8]. IS seems to play modulatory roles in some cellular pathways in hypertensive rats [10, 11]
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