Matrix metalloproteinases in nephrotic syndrome; a vital but obscure field of research

Context: Matrix metalloproteinases (MMPs) are involved in the remodelling of the glomerular basement membrane (GBM) by tightly regulating the metabolism of extracellular matrix (ECM) of the GBM. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed, EBSCO, Scopus and Web of Science have been searched. Results: Gelatinases (MMP-2 and MMP-9) are mainly found involved in the remodelling of GBM and therefore this review focuses on these two MMPs and their action in nephrotic syndrome (NS), which is a protein losing enteropathy occurring due to the loss of integrity of GBM. In addition to the blood corpuscles, glomerular epithelial cells and mesangium are also expressing MMPs, and various cytokines and growth factors are involved in addition to tissue inhibitors of metalloproteinases (TIMPs) in regulating the metabolism of ECM via MMPs. While examining the results of MMP activity and expression in NS, except diabetic nephropathy (DN), membranoproliferative glomerulonephritis (MPGN) and hereditary NS where there was a clear down-regulation of MMP, all the other types of NS showed conflicting results. Both suppression and induction of MMPs are finally leading to GBM thickening, loss of integrity and proteinuria. Enhanced MMP activity leads to increase in matrix turnover and accumulation of ECM remnants and apoptotic cells leading to fibrosis. On the other hand, diminished expression of MMPs prevents the normal ECM turnover and matrix accumulation. The review compiled the mechanisms of action of both downregulation and upregulation of MMPs. Conclusions: Imbalance of ECM metabolism due to varied expression levels and activities of MMPs in different types of primary NS might contribute to the progression of nephropathies. Further studies are required to identify the potential and usage of MMPs as a diagnostic/prognostic/ therapeutic tool

Role of oxidant-antioxidant enzymes in managing the cardiovascular risks in nephrotic syndrome patients

Increased reactive oxygen species (ROS) in nephrotic syndrome (NS) are involved in the oxidation of membrane proteins, lipoproteins and several receptor molecules ultimately leading to their functional deficit. It is involved in the pathogenesis of dyslipidemia in NS and also increases the oxidation of LDL (oxLDL), which is an important risk factor in thrombus generation and atherosclerosis. Myeloperoxidase (MPO) is an early predictor of myocardial infarction and adverse cardiac events in patients with chest pain. MPO can also foresee the recurrent acute coronary syndrome (ACS) and myocardial infarction in patients. ‘MPO oxidized LDL’ also induces ROS production, lipid accumulation and reduces the antioxidant response in macrophages, however in an augmented way by using different pathways and might be more atherogenic. Paraoxonase 1 (PON1) prevents the oxidative modification of serum lipoproteins, which is one of the crucial steps in the initiation of atherogenesis. PON1 also contributes to the anti-atherogenic effect of HDL-c. Adult NS patients have increased lipid hydroxide levels and significantly decreased PON1 activity and total sulfhydryl levels when compared to healthy controls. While the increased risk of cardiovascular disease in NS patients is well documented, the exact etiology still remains controversial. This prevents the development of a specific treatment modality for the same. MPO as well as PON1 were found as important markers for the management of cardiovascular risk in NS patients. Estimation of these enzymes can therefore be performed in routine clinical practice as prognostic markers, owing to its ease of estimation and cost effectiveness

Antioxidant Activity and Lipid Peroxidation in Preeclampsia

Epidemiologic studies demonstrate a relation between preeclampsia and an increased risk of future maternal coronary heart disease. The pathophysiology of the underlying mechanism is unknown. Disorders of lipoprotein metabolism may contribute to endothelial dysfunction. Oxidative stress and decreased antioxidant defense enhances free radical-mediated membrane lipid peroxidation and possibly vascular endothelial damage. The aim of this study was to elucidate the possible relation between lipidemic status, lipid peroxidation and albumin with total antioxidant activity (AOA) that may contribute to atherogenicity in preeclamptic women. Methods: Twenty-five women with preeclampsia and 25 normal pregnant women who were matched for maternal and gestational age were selected for the study. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), atherogenic index (AI), malondialdehyde (MDA), a marker of lipid peroxidation, AOA and albumin levels were measured. Results: MDA, TC and AI were significantly elevated (p < 0.001), and HDL-C, AOA and albumin levels were significantly decreased (p < 0.001) in preeclamptic patients compared to the control group. Conclusion: We conclude that hypercholesterolemia leads to excessive lipid peroxidation. Coexistent diminution in antioxidant activity leads to an imbalance between prooxidants and antioxidants, resulting in oxidative stress. Oxidative stress and elevated AI may contribute to atherogenicity in preeclampsia

Screening of school children for blood lead levels and attempts to reduce them by nonpharmacological means in a coastal city of India

Context : Lead is a major health hazard, especially in children. Impact of lead poisoning on our society is not known. Effectiveness of environmental interventions in reducing blood lead levels is not exactly known, though the Center for Disease Control and Prevention strongly advocates use of such means. Aims: We aimed at screening school children for blood lead levels (BLLs) and reducing the BLLs of children with preliminary BLL> 20 µg/dL by environmental intervention and intensive education. Materials and Methods: To assess the extent of lead poisoning, a screening of 106 children was done, which showed that children belonging to a particular government primary school had higher BLLs. A second screening program of 87 children conducted in that school showed that only 19% had BLL < 10 µg/dL; whereas 44% had BLL between 10 and 20 µg/dL, and 37% had BLL> 20 µg/dL. Thirty-eight children having BLL> 20 µg/dL were selected from the two screening programs. After removing all potential sources of lead from their environment and educating them about the ways to prevent exposure to lead, follow-up of their BLLs was carried out at an interval of 6 months for a period of 1 year. Statistical Analysis: Values of the different follow-up studies were compared using repeated-measure ANOVA. Results : Our results showed that there was a significant (P < 0.0001) reduction in the BLLs in the first and second follow-up studies. Conclusions: The study is a proof of the concept that a decline in the BLLs can be achieved by intense education and avoiding the potential environmental sources of lead

A scoping review identifies multiple emerging knowledge synthesis methods, but few studies operationalize the method

Objectives: To systematically identify, define, and classify emerging knowledge synthesis methods through a scoping review. Study Design and Setting: MEDLINE, CINAHL, EMBASE, PsycINFO, the Cochrane Methodology Register, the Cochrane Database of Systematic Reviews, Social Sciences Abstracts, Library and Information Science Abstracts, Philosopher's Index, and Education Resources Information Center were searched to identify articles reporting emerging knowledge synthesis methods across the disciplines of health, education, sociology, and philosophy. Two reviewers independently selected studies and abstracted data for each article. Results: In total, 409 articles reporting on 25 knowledge synthesis methods were included after screening of 17,962 titles and abstracts and 1,010 potentially relevant full-text articles. Most of the included articles were an application of the method (83.9%); only 3.7% were seminal articles that fully described the method (i.e., operationalized the steps). Most of the included articles were published after 2005. The methods were most commonly used across the fields of nursing, health care science and services, and health policy. Conclusion: We found a lack of guidance on how to select a knowledge synthesis method. We propose convening an international group of leaders in the knowledge synthesis field to help clarify emerging approaches to knowledge synthesis.The study was funded by a Canadian Institutes of Health Research (grant number: KST-116633) (CIHR) Knowledge Synthesis grant. A.C.T. holds a CIHR/Drug Safety and Effectiveness Network New Investigator Award in Knowledge Synthesis, and S.E.S. holds a Tier 1 Canada Research Chair in Knowledge Translation