Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications

Abstract BACKGROUND Hypertension (HTN) is associated with target organ damage such as cardiac, vascular, and kidney injury. Several studies have investigated circulating microRNAs (miRNAs) as biomarkers of cardiovascular disease, but few have examined them as biomarker of target organ damage in HTN. We aimed to identify circulating miRNAs that could serve as biomarkers of HTN-induced target organ damage using an unbiased approach. METHODS AND RESULTS Fifteen normotensive subjects, 16 patients with HTN, 15 with HTN associated with other features of the metabolic syndrome (MetS), and 16 with HTN or chronic kidney disease (CKD) were studied. Circulating RNA extracted from platelet-poor plasma was used for small RNA sequencing. Differentially expressed (DE) genes were identified with a threshold of false discovery rate <0.1. DE miRNAs were identified uniquely associated with HTN, MetS, or CKD. However, only 2 downregulated DE miRNAs (let-7g-5p and miR-191-5p) could be validated by reverse transcription-quantitative PCR. Let-7g-5p was associated with large vessel stiffening, miR-191-5p with MetS, and both miRNAs with estimated glomerular filtration rate (eGFR) and neutrophil and lymphocyte fraction or number and neutrophil-to-lymphocyte ratio. Using the whole population, stepwise multiple linear regression generated a model showing that let-7g-5p, miR-191-5p, and urinary albumin/creatinine ratio predicted eGFR with an adjusted R2 of 0.46 (P = 8.5e−7). CONCLUSIONS We identified decreased circulating let-7g-5p and miR-191-5p as independent biomarkers of CKD among patients with HTN, which could have pathophysiological and therapeutic implications.

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Therapeutic implications of shared mechanisms in non-alcoholic fatty liver disease and chronic kidney disease

Journal of Nephrology ◽

10.1007/s40620-020-00751-y ◽

2020 ◽

Author(s):

Mehmet Kanbay ◽

Mustafa C. Bulbul ◽

Sidar Copur ◽

Baris Afsar ◽

Alan A. Sag ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Liver Disease ◽

Kidney Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Therapeutic Implications ◽

Alcoholic Fatty Liver Disease

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Malformative Reno-Urinary Pathology in Patients with HIV Infection-Clinical and Therapeutic Implications

ARS Medica Tomitana ◽

10.2478/arsm-2020-0006 ◽

2020 ◽

Vol 26 (1) ◽

pp. 24-30

Author(s):

Sotila Gianina Gabriela ◽

Dumea Elena ◽

Cernat Roxana ◽

Dumitru Magdalena Irina ◽

Rugina Sorin

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Hiv Infection ◽

Renal Dysfunction ◽

Horseshoe Kidney ◽

Renal Stones ◽

Hiv Positive ◽

Therapeutic Implications ◽

Wide Range ◽

Tract Infections

Abstract Chronic kidney disease is an important comorbidity of HIV infection causing real problems in the evolution and medical healthcare of HIV-positive patients. In recent years, a significant number of HIV-positive patients develop renal dysfunction, several mechanisms being incriminated: direct effect of the virus, toxic effect secondary to of antiretroviral medication, secondary to associated comorbidities, given that life expectancy has increased significantly in the last decade, thanks to the use of antiretroviral therapies. There are few studies in the literature to evaluate malformative renourinary pathology in patients with HIV infection. We present the case of a patient with HIV infection, horseshoe kidney, chronic kidney disease and incomplete Fanconi syndrome, secondary to the administration of tenofovir fumarate, a nucleoside reverse transcriptase inhibitor. Malformations, abnormalities or dysmorphysms of the renal tract should be considered in the HIV-positive patient with secondary renal dysfunction because they take a wide range of forms, are underdiagnosed and predispose to multiple complications, with varying degrees of severity, such as urinary tract infections, renal stones or progression of chronic kidney disease. Tenofovir fumarate and atazanavir must be avoided in patients with HIV infection and chronic renal dysfunction.

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Small Intestinal Phosphate Absorption: Novel Therapeutic Implications

American Journal of Nephrology ◽

10.1159/000518110 ◽

2021 ◽

pp. 1-9

Author(s):

Jerry Yee ◽

David Rosenbaum ◽

Jeffrey W. Jacobs ◽

Stuart M. Sprague

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Paracellular Pathway ◽

Phosphate Binders ◽

Phosphate Absorption ◽

Therapeutic Implications ◽

Sodium Hydrogen ◽

Sodium Hydrogen Exchanger ◽

Dietary Phosphate ◽

Intestinal Phosphate Absorption

Background: Chronic kidney disease (CKD) affects approximately 15% of adults in the USA. As CKD progresses, urinary phosphate excretion decreases and results in phosphate retention and, eventually, hyperphosphatemia. As hyperphosphatemia is associated with numerous adverse outcomes, including increased cardiovascular mortality, reduction in phosphorus concentrations is a guideline-recommended, established clinical practice. Dietary phosphate restriction, dialysis, and phosphate binders are currently the only options for phosphate management. However, many patients with hyperphosphatemia have phosphorus concentrations >5.5 mg/dL, despite treatment. Summary: This review presents recent advances in the understanding of intestinal phosphate absorption and therapeutic implications. Dietary phosphate is absorbed in the intestine through two distinct pathways, paracellular absorption and transcellular transport. Recent evidence indicates that the paracellular route accounts for 65–80% of total phosphate absorbed. Thus, the paracellular pathway is the dominant mechanism of phosphate absorption. Tenapanor is a first-in-class, non-phosphate binder that inhibits the sodium-hydrogen exchanger 3 or solute carrier family 9 member 3 (SLC9A3) encoded by the SLC9A3 gene, and blocks paracellular phosphate absorption. Key Messages: Targeted inhibition of sodium-hydrogen exchanger 3 effectively reduces paracellular permeability of phosphate. Novel therapies that target the paracellular pathway may improve phosphate control in chronic kidney disease.

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