Topic Discussion: LIK and glomerular diseases

Lymphomatous infiltration of the kidney(LIK) is not an uncommon finding in many liquid malignancies. Majority of cases present with AKI or sonogram findings suggestive of this entity.  Some cases have been described of this entity presenting as a glomerular disease. One study of 18 patients, 10 had glomerular pathology associated with LIK.(most of them had leukemias and lymphomas)

The classic were immune complex mediated:- MPGN, Membranous
Others had paraprotein related AL Amyloidosis, LCDD
Two had MCD and one had crescentic pauci immune GN.
Clearly, this association of LIK and glomerular diseases is important and one to keep cause and association in mind.

Topic Discussion: Plain water intake and CKD

A recent article published in the Am J of Nephrology raises an interesting question- does drinking more plain water benefit CKD or renal disease? This was a study of analysis of the NHANES database.
Over 3000 patients reviewed and 13% had CKD and 18% had cardiovascular disease.
CKD turned out to be the highest amongst the lowest plain water drinkers( <2 liters/day) and lowest in the highest water drinkers( >4.5L/day).

The authors suggest a protective effect of plain water intake.  Unclear what the mechanism of this might be.  Two years ago, the Australians had shown a similar finding. In their study, they showed that increased fluid intake was protective for CKD. Increased urine volume might be protective for progression of CKD.  Even the lay press in NYTimes took notice of these findings and had a blog post on this very topic.

What is the mechanism for this? Any thoughts, could this be ADH related? or flow related?

CLINICAL CASE 72: ANSWERS AND SUMMARY

Which one of these are causes of distal renal tubular acidosis? ( click all that apply)

All of the above causes have been associated with distal RTA. The most common is Sjogren's syndrome and one to always consider with dRTA.  Chemotherapy agents and other rheumatic diseases are known causes as well.

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

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

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

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