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Tuesday, April 30, 2013

Hypertension: Immune system as a major player


Some interesting observations have been made on how immune system can modulate blood pressure. First, Guzik et al  reported that mice deficient in B and T cells (RAG1-/-) have attenuated blood pressure response to angiotensin II infusion. This group further defined, by adoptive transfer, that T cells mediate the hypertensive response to angiotensin II.  Similarly, Crowley et al  reported a similar reduction in blood pressure to angiotensin II in mice with Severe Combined Immunodeficiency (SCID). Furthermore, he showed SCID mice are able to excrete more sodium in the urine during angiotensin II infusion.These intriguing results could offer a role for anti-inflammatory modulation in the treatment of hypertension in the future.

As you can see the field of hypertension research continues to expand.  I only highlighted a few of the novel studies that are being investigated in the research community.  Other areas of intensive investigation are in the vascular system, adrenal, oxidative stress, cardiovascular and renal to name a few. When all of the exciting research , hopefully new treatments for hypertension will be developed soon.  

Matthew Sparks, MD

Sunday, April 28, 2013

Hypertension: CNS as a major player












A number of investigators have zeroed in on the brain as the culprit organ in hypertension.  I'll highlight a few of them here.  First, Marvar et al,  described how ablating the anteroventral third ventricle (AV3V) mechanically results in complete protecting from angiotensin-induced hypertension in mice. These regions of the brain are part of the circumventricular organs and are located adjacent to the cerebral ventricles and have a poorly formed blood-brain barrier allowing the neurons to communicate with hormones produced systemically such as angiotensin II. Young et al. recently reported an interesting finding that implicated endoplasmic reticulum stress in the brain subfornical organ (another circumventricular organ). Both of these studies are intriguing and underscore the complexity of hypertension and potentially new therapeutics for treatment down the line. This also underscores how the CNS can modulate effector organs, such as the renal nerves, to impact blood pressure.


Matthew Sparks, MD

Friday, April 26, 2013

Hypertension: Skin as a major player












At first thought the skin is an unlikely culprit in hypertension.  However, the skin represents the human body’s largest organ system with an estimated 12-15% of body weight and a surface area of 1-2 square meters making the skin an ideal reservoir for sodium. In 2009 Machnik et al reported an interesting finding in the journal Nature Medicine. This group found that the interstitium of the skin serves a dynamic role in serving as a reservoir to buffer sodium accumulation in intravascular volume and blood pressure. They found that during high-salt feeding, mice accumulated sodium in the subdermal interstitial spaces at hypertonic concentrations. Macrophages sense the hypertonicity leading to expression of tonicity-responsive enhancer binding protein (TonEBP). TonEBP leads to VEGF-C expression which is a potent inducer of lymphatics allowing for a greater reservoir to store sodium. This same group has also reported that tissue sodium content indeed did accumulate in various tissue beds of hypertensive patients using MRI.

Matthew Sparks, MD

Thursday, April 25, 2013

Clinical Case 69: Answers and Summary


WHILE WE HAVE BEEN "NEPHRO-CENTRIC" IN THE ROLE OF THE KIDNEY IN HYPERTENSION, WHAT OTHER ORGANS HAVE EMERGED AS POTENTIAL CONTRIBUTORS IN DEVELOPMENT OF HYPERTENSION


Given the expertise on this topic of Dr Matthew Sparks, here is his thoughts.  Basically, all the above organs are correct and have a role in hypertension. 


Novel concepts in hypertension- beyond the kidney
Hypertension is one of the most common medical disorders.  The pathogenesis of this complex disease process is multifactorial and defining precisely which organ systems are deranged continues to widen.  For many renal physiologists, Dr Arthur Guyton is seen as the patriarch of the kidney-centric view of hypertension.  Guyton articulated his power studies where he argued that the kidney plays a central role in the determination of long-term blood pressure.  Guyton suggested that the control of blood pressure and sodium balance are tightly linked.  His central tenet referred to as the pressure-natriuresis curve was elegantly described in this paper published in Science in 1991. However, over the last several decades we have witnessed how complex blood pressure regulation really is.  It is not surprising that multiple redundant systems are needed to control something as fundamental to human life as blood pressure. In the next 3 posts, I shall discuss recent advances in the understanding of hypertension from a basic science research perspective involving the skin, central nervous system, and the immune system. 

Stay tuned for role of skin, CNS and immune system in HTN in coming days. 

Matthew Sparks, MD

Friday, April 19, 2013

CONSULT ROUNDS: TINU

Tubular interstitial disease and Uvietis (TINU) 
Some interesting facts:

1. First described in 1975
2. Usually seen in young females more than males
3. Usually uvietis occurs 2-3 months prior to the renal disease but can be as late as a year after renal disease.
4. Elevated ESR and b2 microglobulin levels might be the only lab clue
5. Sarcoidosis and Sjorgren's syndrome have to be ruled out
6. There is some indication that this might fit into the big category of IgG4 related diseases
7. Not uncommon to see proximal tubular dysfunction.
8. Treatment is steroids for 3-6 months.

Monday, April 15, 2013

International Update on Glomerular Diseases: A conference

We are hosting an international conference on glomerular diseases(ISN and NKF endorsed) as part of our division with exceptional speakers. All interested in learning about the conference and to register, can see the entire brochure online at the listed website of NSLIJ CME. Online registration is offered.

An International Update on Glomerular Diseases
Saturday, April 27, 2013
North Shore University Hospital
Rust Auditorium
300 Community Drive
Manhasset, NY 11030


Program of the Day | April 27, 2013 • 7:30 am - 4:00 pm
7:30 am Registration, Continental Breakfast and Exhibitors
8:00 am Welcome and Introduction to Glomerular Diseases
Kenar D. Jhaveri, MD and
Steven Fishbane, MD
8:15 am Minimal Change Disease and FSGS: An Update
Daniel Cattran, MD
8:45 am Clinical Approach to Membranous Nephropathy
Claudio Ponticelli, MD
9:45 am MPGN: The New Classification and Emergence of C3 Nephropathy
Naveed Masani, MD
10:15 am BREAK AND EXHIBITORS
10:30 am HIV Associated Glomerular Diseases
Pravin C. Singhal, MD
11:00 am Treatment of ANCA Associated Vasculitis
Fernando Fervenza, MD, PhD
11:30 am Cancer and Glomerular Diseases
Hitesh H. Shah, MD
12:00 pm LUNCH
1:00 pm Lupus Nephritis: Lessons Learned From Clinical Trials
Richard Furie, MD
1:30 pm Paraproteins and Glomerular Disease
Kenar D. Jhaveri, MD
2:00 pm New Diagnostic Tests and Therapies of IgA Nephropathy
Gerald Appel, MD
2:30 pm Pathology-Based Case Discussion
Glen Markowitz, MD and Panel
4:00 pm Closing Remarks and Adjourn
Kenar D. Jhaveri, MD and Steven Fishbane, MD

Wednesday, April 10, 2013

FSGS: A novel finding


FSGS has been the most researched glomerular disease from a basic science perspective. A recent urge in studying micro RNAs has led to some interesting new findings re glomerular diseases. A recent Nature paper discuses microRNA-miR-193a as a potentially inducing FSGS with extensive podocyte foot process effacement. This was elegantly done using transgenic mice of this expression of miRNA.

There has been data on wilm's tumor protein(WT-1) being central in podocyte integrity. It allows for differentiation of podocyte and classically this has been studied most in collapsing variant of FSGS where the podocytes are presumed to be dedifferentiated and loose that WT-1 marker. miR-193a inhibits the expression (WT1). Decreased expression levels of WT1 lead to downregulation of its target genes podocalyxin and nephrin leading to podocyte damage. The current study compared individuals with FSGS and normal kidneys and this expression of micro RNA. 



Check out the full study at Nature.

Tuesday, April 9, 2013

MGRS: We need to think a new way!

Many times we have come across monoclonal deposition in the kidney of Ig and there is no bone marrow or blood findings to suggest malignancy.  Lately, there has been findings of association of many such instances with glomerular diseases:

1. MGUS with MPGN
2. New findings of proliferative GN with monoclonal deposits( but no real bone marrow findings)
3. Immunotactoid GN and its's perhaps relationship with CLL and monoclonality
4. Fibrillary GN and similar findings ( less often than immunotactoid GN)
5. LCDD but no BM findings fully suggestive of >10% plasma cells to make a Myeloma diagnosis.

Clearly, there is monoclonal gammopathy of RENAL significance(MGRS) in all above states and perhaps we need to re look at a group of these disease states more carefully. Unfortunately, no studies exist to tell us how to treat them. Do we treat them as denovo renal diseases or treat the underlying plasma cell or B cell clone?

Some recent articles are worth a read to perhaps start some thought provoking discussions re these associations.