Avsnitt
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Episode Overview:
Donald Kohan, PhD is an Emeritus Professor at the University of Utah Health with expertise in endothelin receptors, sodium transporters, and the renin-angiotensin-aldosterone system in chronic kidney disease.
In this episode, Professor Kohan provides an overview of the endothelin system and how it relates to the pathophysiology of chronic kidney disease and IgA nephropathy specifically.
Key Quotes:
“Endothelin 1 is a really unusual molecule. It's highly stable because it has 2 interchain disulfide bonds that resist degradation. It's extremely potent having about 10 fold higher potency than any other known vasoactive factor.”“Angiotensin and ET-1 cause their effects through different pathways.”“Angiotensin stimulates transient calcium release, which causes more short-term contraction and other effects. While endothelin 1 stimulates more sustained calcium release, which then elicits longer lasting pathophysiologic effects.”Key Takeaways:
(04:41) Endothelin-1 acts via ETA receptors to cause vasoconstriction, fibrosis, cell proliferation and other effects that promote chronic kidney disease(06:15) The endothelin and renin-angiotensin systems interact, forming a vicious cycle that worsens kidney injury (12:19) In IgA nephropathy models, combined ETA + angiotensin receptor blockade with sparsentan reduced proteinuria and kidney injury more than angiotensin blockade alone -
Overview:
In this episode of the Rare Kidney Disease Show, Professor Jonathan Barratt discusses the need to take a long-term approach when managing IgA nephropathy patients. He presents data from the UK National Registry of Rare Kidney Diseases (RaDaR). During this recording you will hear Professor Barratt discussing the continued risk of progression to end stage renal disease even in patients with proteinuria of less than 1g/day, the current threshold of high risk as per KDIGO guidelines. The data from the UK has been reinforced by recent database studies and these will also be discussed by Professor Barratt.
Key Quotes:
"If you have IgA Nephropathy and you're diagnosed as a child, half of those children have developed kidney failure at 20 years.""We need to be thinking, what is it like for that patient in front of us being 50 or 60, not necessarily what's going to happen in the next five or ten years.""If we don't think the longer term, we're going to under-treat and not serve our patients well."Key Takeaways:
IgA nephropathy patients often have decades of life ahead of them, so physicians should focus on minimizing lifetime risk of kidney failure rather than short-term outcomes (00:02:11)RaDaR data shows high rates of kidney failure among IgA nephropathy patients in the UK, even those diagnosed and treated as children (00:04:05)Per the RaDaR publication, an eGFR decline of <1 ml/min per 1.73 m2 per year must be the target if patients are to avoid kidney failure (00:06:48)In the UK, 1 in 4 IgA nephropathy patients with 0.5-1 g/day proteinuria reach ESRD within 10 years (00:08:23)Recent US database searches confirm high rates of CKD progression and kidney failure in IgA nephropathy patients, even those with lower proteinuria levels (00:13:20) -
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Overview:
“IgAN progresses more often than we thought and progresses even in patients with low levels of proteinuria.” “We continue to strive for greater improvements.”“Approaching IgAN with targeted therapies can affect different aspects of IgAN pathogenesis.”
In this episode of the Rare Kidney Disease Show, Dr. Rovin, Professor of Internal Medicine and Pathology at Ohio State University and chair of the RKD Scientific Network and Podcast, discusses advances in the management of IgAN through a patient case study.Key Takeaways:
Understanding the Underlying IgAN pathophysiology: Highlight the 4-Hit Hypothesis and the intricate disease mechanism (4:27)IgAN Case Study Introduction (6:57)Treatment Initiation (8:26)Management of Progression: Question the outcomes of initial intervention for this patient (9:50)Foundational Therapy: Optimization for improved outcomes (10:24)Maintenance Options: Explore available therapies to sustain treatment effectiveness (11:05)Postulated Algorithm: Discover an algorithm for inflammation management and proteinuria reduction (11:49)Closing Remarks: Gain insight into future episodes (14:10)
