The etiology and pathophysiology of COVID-19 associated acute kidney injury

Hospitalized COVID-19 patients often develop acute kidney injury (AKI), leading to increased mortality. In order to improve patients’ survival rate, it is important to understand the pathophysiology mechanism of AKI. In this brief review, we highlight the most important elements of the etiology and pathophysiology of COVID-19 associated AKI. Acute tubular injury seems to be more frequent than prerenal azotemia in COVID-19 patients and collapsing glomerulopathy is the most encountered form of glomerular disease. Another important role in acute kidney injury seems to play immune cell infiltration, inflammation, endothelial injury and microvascular thrombi. Renin-angiotensin-aldosterone system is also important in the pathophysiology of COVID-19 associated AKI

Immunosupression in IgA Nephropathy

IgA Nephropathy (IgAN) is one of the most frequent types of glomerulonephritis encountered in adults from Western countries and Asia. IgAN is responsible for approximately 40% of end-stage renal disease (ESRD) mediated by glomerular impairment. The majority of adult IgAN patients present a slowly progressive pattern towards ESRD. Current types of treatment are based mainly on supportive care: i.e., life style risk factors, measures that lower blood pressure and reduce proteinuria, weight loss, smoking cessation or glycaemia control. Because IgAN is an immune complex-mediated disease, immunosuppression therapy gains more and more attention as a modality of treatment. Despite the beneficial effects, the value of immunosuppression remains controversial due to high rates of adverse reactions. The aim of this review is to highlight the benefits and limitations of promoting immunosuppression in IgAN with mild to moderate proteinuria despite supportive antiproteinuric therapy up titrated to maximum tolerated doses

Genetic correction of PSA values using sequence variants associated with PSA levels

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research UK C522/A8649 Medical Research Council of England G0500966 ID 75466 National Cancer Research Institute (NCRI), UK Southwest National Health Service Research and Development NCRI National Institute for Health Resear

Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy

Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophy versus death choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy

Magnesium&mdash;A More Important Role in CKD&ndash;MBD than We Thought

Chronic kidney disease (CKD) is associated with different complications, including chronic kidney disease&ndash;mineral and bone disorder (CKD&ndash;MBD), which represents a systemic disorder that involves the presence of different mineral or bone structure abnormalities (i.e., modification of bone turnover, strength, volume, etc.), including even vascular calcification development. Even if, over the years, different pathophysiological theories have been developed to explain the onset and progression of CKD&ndash;MBD, the influence and importance of serum magnesium level on the evolution of CKD have only recently been highlighted. So far, data are inconclusive and conflicting; therefore, further studies are necessary to validate these findings, which could be useful in developing a better, more adequate, and personalized management of CKD patients

Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

Background: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin–angiotensin–aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. Conclusions: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients’ long-term prognosis and their quality of life