Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease

Ponticelli, Claudio; Podestà, Manuel Alfredo; Moroni, Gabriella

doi:10.1016/j.kint.2020.05.056

Cited by 109 publications

(75 citation statements)

References 150 publications

(152 reference statements)

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“…Hyperuricemia results in the accumulation of uric acid crystals in collecting ducts, thickening of arteriolar walls, and subsequent hypoxia and tubulointerstitial fibrosis. Additionally, hyperuricemia boosts local chemokine expression and inflammatory process in renal tissues (17) . Furthermore, urine PCR was markedly higher in group 2.…”

Section: Discussionmentioning

confidence: 99%

Association between Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios with Chronic Allograft Nephropathy

Abdelhamid

2021

The Egyptian Journal of Hospital Medicine

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Background: In several diseases, both neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are reliable indicators of chronic inflammation. Endothelial dysfunction is widely distributed in renal transplant patients and is caused by inflammation and can lead to the malfunction of the graft. Objective: To detect the correlations of NLR and PLR with chronic allograft nephropathy (CAN) in recipients of kidney transplants and determine the cutoff values for the prediction of CAN. Patients and Methods: 68 kidney transplant recipients shared in the study between January 2017 and December 2019. They were two groups. Group 1 (44 subjects) had estimated glomerular filtration rate (eGFR) ≥ 60 ml/m/1.73 m 2 and group 2 (24 subjects) had eGFR less than 60 ml/m/1.73 m 2 . Results: The two groups had similar age and sex distributions. eGFR was shown to be adversely linked to NLR and PLR. The optimal cutoff level of NLR for predicting chronic allograft nephropathy was ≥1.58 and the optimal cutoff level of PLR was ≥109.13. Conclusion: Significant correlations were detected between kidney function tests and each of NLR and PLR. PLR is a more sensitive inflammatory marker to predict chronic allograft nephropathy than NLR with a sensitivity of 83.33 % versus 66.67 %.

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Section: Discussionmentioning

confidence: 99%

Association between Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios with Chronic Allograft Nephropathy

Abdelhamid

2021

The Egyptian Journal of Hospital Medicine

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“…High urate levels have also been linked to blood pressure [ 26 ]. Growing evidence indicates that asymptomatic hyperuricemia is involved in the development of hypertension via activation of the renin–angiotensin system and inhibition of nitric oxide synthesis, which promotes endothelial dysfunction, proliferation of vascular smooth muscle cells, and sodium reabsorption [ 27 , 28 ]. Deposition of urate crystals (extracellular uric acid) in the urinary lumen and in the endothelium of arteries can cause inflammation and pro-inflammatory responses, respectively [ 28 ].…”

Section: The Double Face Of Uratementioning

confidence: 99%

“…A pilot study monitoring blood pressure of adolescents with stage 1 primary hypertension and borderline hyperuricemia demonstrated that blood pressure decreased upon administration of allopurinol, a conventional antihyperuricemic medication [ 29 ]. The study, however, had limitations as detailed in the article, and a more recent review that acknowledges serum urate level as an independent risk factor for hypertension urges further studies to explore if a reduction of serum urate could be beneficial in preventing or treating hypertension [ 27 , 30 ].…”

Section: The Double Face Of Uratementioning

confidence: 99%

Modulation of Urate Transport by Drugs

2021

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Background: Serum urate (SU) levels in primates are extraordinarily high among mammals. Urate is a Janus-faced molecule that acts physiologically as a protective antioxidant but provokes inflammation and gout when it precipitates at high concentrations. Transporters play crucial roles in urate disposition, and drugs that interact with urate transporters either by intention or by accident may modulate SU levels. We examined whether in vitro transporter interaction studies may clarify and predict such effects. Methods: Transporter interaction profiles of clinically proven urate-lowering (uricosuric) and hyperuricemic drugs were compiled from the literature, and the predictive value of in vitro-derived cut-offs like Cmax/IC50 on the in vivo outcome (clinically relevant decrease or increase of SU) was assessed. Results: Interaction with the major reabsorptive urate transporter URAT1 appears to be dominant over interactions with secretory transporters in determining the net effect of a drug on SU levels. In vitro inhibition interpreted using the recommended cut-offs is useful at predicting the clinical outcome. Conclusions: In vitro safety assessments regarding urate transport should be done early in drug development to identify candidates at risk of causing major imbalances. Attention should be paid both to the inhibition of secretory transporters and inhibition or trans-stimulation of reabsorptive transporters, especially URAT1.

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“…Metabolic disorders of the circulatory system are typically characterized by the presence of abnormally increased or decreased metabolites in the circulating blood, which can cause many clinical diseases (e.g., hyperglycemia [17], hyperlipidemia [18], hypercholesterolemia [19,20], and hyperuricemia [21]). It is particularly interesting that patients with hyperproteinemia generally display metabolic changes (e.g., abnormal blood glucose and blood lipid levels) [4,5], and there is a significant change in the proportion of circulating blood cells [8,22].…”

Section: Introductionmentioning

confidence: 99%

Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in Bombyx mori

Wang

et al. 2021

Biology

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Metabolic disorders of the circulatory system of animals (e.g., hyperglycemia and hyperlipidemia) can significantly affect immune function; however, since there is currently no reliable animal model for hyperproteinemia, its effects on immunity remain unclear. In this study, we established an animal model for hyperproteinemia in an invertebrate silkworm model, with a controllable plasma protein concentration (PPC) and no primary disease effects. We evaluated the influence of hyperproteinemia on innate immunity. The results showed that high PPC enhanced hemolymph phagocytosis via inducing a rapid increase in granulocytes. Moreover, while oenocytoids increased, the plasmacytes quickly dwindled. High PPC inhibited hemolymph melanization due to decreased phenoloxidase (PO) activity in the hemolymph via inhibiting the expression of the prophenoloxidase-encoding genes, PPO1 and PPO2. High PPC upregulated the gene expression of antimicrobial peptides via differential activation of the Toll and Imd signaling pathways associated with NF-κB signaling, followed by an induction of inconsistent antibacterial activity towards Gram-positive and Gram-negative bacteria in an animal model of high PPC. Therefore, high PPC has multiple significant effects on the innate immune function of the silkworm circulatory system.

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Hyperuricemia as a trigger of immune response in hypertension and chronic kidney disease

Cited by 109 publications

References 150 publications

Association between Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios with Chronic Allograft Nephropathy

Association between Neutrophil-To-Lymphocyte and Platelet-To-Lymphocyte Ratios with Chronic Allograft Nephropathy

Modulation of Urate Transport by Drugs

Influence of Hyperproteinemia on Insect Innate Immune Function of the Circulatory System in Bombyx mori

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