Genetic Deletion of the Lipid Raft Protein Caveolin-1 Leads to Worsening Renal Fibrosis (2018)

Type of publication:
Journal article

Author(s):
*Chand S, Hazeldine J, Smith S, Borrows R.

Citation:
Journal of Clinical Nephrology and Renal Care 2018 Jun;4(1):037

Abstract:
Background
Renal disease is a major global public health issue. Renal interstitial fibrosis is the characteristic histopathological finding in all progressive renal disease. Caveolin-1 is the essential structural protein for lipid rafts called caveolae that are ubiquitously distributed among fibroblasts, endothelial and epithelial cells. Caveolin-1 acts as an intracellular signalling pathway chaperone in fibrotic disease. Presently, caveolin-1 expression is associated with more severe renal disease in human and previous murine studies. In non-renal fibrosis, caveolin-1 protects against fibrosis. The purpose of this study was to investigate if caveolin-1 knockout led to an increased fibrotic phenotype using the unilateral ureteric obstruction model of renal fibrosis.
Methods
Using 2 time-points of the unilateral ureteric obstruction model, wild-type and caveolin-1 knockout mouse kidneys were analysed for caveolin-1 expression and markers of fibrosis using histology, Gomori staining, real-time quantified polymerase chain reaction, Western blotting and confocal microscopy.
Results
Confocal microscopy shows caveolin-1 staining mainly in glomerulus, lining of tubules as well as the vasculature. There was increased caveolin-1 expression the longer the unilateral obstruction occurred as well as in the contralateral compensating non-obstructed kidney. Caveolin-1 knockout had less fibrosis at day 3 histologically but more at day 14 as compared to wild-type. There were significantly more F4/80 positive staining cells at day 3 and day 14 in the wild-type injured kidney as compared to the caveolin-1 knockout mouse.
Conclusion
Caveolin-1 knockout leads to a worse fibrosis upon unilateral ureteric obstruction. Caveolin-1 expression manipulation timing remains to be elucidated in reducing renal fibrosis.

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Strategies for investigating the genetics of chronic kidney disease (2018)

Type of publication:
Journal article

Author(s):
*Chand S.

Citation:
Scientific Journal of Genetics and Gene Therapy. 2018 July 4(1): 004-006.

Abstract:
This short review describes the strategies employed for investigating genetic variation in chronic kidney disease as well as highlighting potential shortfalls that should be overcome in future studies.

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Caveolin-1 in renal disease (2018)

Type of publication:
Journal article

Author(s):
*Chand S.

Citation:
Scientific Journal of Genetics and Gene Therapy. 2018 July: 007-014.

Abstract:
Caveolin-1 is the essential structural formation for lipid raft formation. It has been ascribed to several
disease processes in humans due to its ubiquitous distribution. Patients with chronic kidney disease suffer
great morbidity and mortality where manipulation of caveolin-1 could lead to new potential therapeutic
targets in this patient group. This review highlights caveolin-1 structure, signalling and provides examples
of studies of caveolin-1 single nucleotide polymorphism in chronic kidney disease.

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Diagnostic accuracy of point-of-care tests for detecting albuminuria: A systematic review and meta-analysis (2014)

Type of publication:
Journal article

Author(s):
*McTaggart M.P., Newall R.G., Hirst J.A., Bankhead C.R., Lamb E.J., Roberts N.W., Price C.P.

Citation:
Annals of Internal Medicine, April 2014, vol./is. 160/8(550-557), 0003-4819;1539-3704 (15 Apr 2014)

Abstract:
Experts recommend screening for albuminuria in patients at risk for kidney disease. Purpose: To systematically review evidence about the diagnostic accuracy of point-of-care (POC) tests for detecting albuminuria in individuals for whom guidelines recommend such detection. Data Sources: Cochrane Library, EMBASE, Medion database, MEDLINE, and Science Citation Index from 1963 through 5 December 2013; hand searches of other relevant journals; and reference lists. Study Selection: Cross-sectional studies, published in any language, that compared the accuracy of machine-read POC tests of urinary albumin-creatinine ratio with that of laboratory measurement. Data Extraction: Two independent reviewers extracted study data and assessed study quality using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. Data Synthesis: Sixteen studies (n = 3356 patients) that evaluated semiquantitative or quantitative POC tests and used random urine samples collected in primary or secondary ambulatory care settings met inclusion criteria. Pooling results from a bivariate randomeffects model gave sensitivity and specificity estimates of 76% (95% CI, 63% to 86%) and 93% (CI, 84% to 97%), respectively, for the semiquantitative test. Sensitivity and specificity estimates for the quantitative test were 96% (CI, 78% to 99%) and 98% (CI, 93% to 99%), respectively. The negative likelihood ratios for the semiquantitative and quantitative tests were 0.26 (CI, 0.16 to 0.40) and 0.04 (CI, 0.01 to 0.25), respectively. Limitation: Accuracy estimates were based on data from singlesample urine measurement, but guidelines require that diagnosis of albuminuria be based on at least 2 of 3 samples collected in a 6-month period. Conclusion: A negative semiquantitative POC test result does not rule out albuminuria, whereas quantitative POC testing meets required performance standards and can be used to rule out albuminuria.

Link to more details or full-text: Hepatology