JOURNAL CLUB: AASK TRIAL 2010

A recent journal club presentation by Dr.Kellie Calderon

AASK  about Hypertension- JOURNAL CLUB

View more presentations from Nephrology, NSLIJ.

TOPIC DISCUSSION: An uncommon consult:-OHSS!

Here is a case: someone with elevated serum creatinine, hyponatermia, marked edema and hypoalbuminemia --> 6 weeks into pregancy induce by in vitro fertilization.

We will pause here to recognize British researcher Robert Edwards who was just awarded the 2010 Nobel Prize in Medicine...

Ovarian Hyperstimulation Syndrome(OHSS) typically presents as volume overload and elevated serum creatinine early in the course of IVF. Hormonal therapy (appropriately) stimulates the ovaries, but occasionaly "hyper"-stimulated ovaries enlarge, become cycstic and large fluid shifts can occur in a capillary-leak like syndrome. It is believed that Vascular Endothelial Growth Factor plays a role by increasing sensitivity to nitric oxide and promoting neoangiogenesis.

Cases range from mild to life-threatening and are graded in severity from 1-3. Mild cases are treated with observation and discontinuation of hormonal therapy, whereas severe cases can have marked electrolyte disorders (hyponatremia, hyperkalemia), severe ascites, pericarial/pleural effusions and thromboembolic phenomenon from hemoconcentration.

IN THE NEWS- Nephrology Workfore

The latest issues of ASN Kidney News talks about a very important issue being the nephrology workforce.
Given the rise in population and the aging nephrologists, along with decline in medical residents applying for nephrology, there is going to be a big shortage of Nephrologists in the coming few years!

What can be done to help decrease this burden that we might all be faced with?
The article mentions some good ideas and wanted to add a few more:-
Lobbying for more support for our fellowship programs
Perhaps having more fellowships
Getting medical students interested and residents interested in nephrology early on
Innovative tools of passing down nephrology knowledge will attract more applicants
Removing the "fear" of renal medicine that many residents and medical students carry.
ASN and NKF doing more medical and resident oriented talks

What we need to do as a community is to "package" and "sell" Nephrology as a FUN, CHALLENGING and EXCITING field to our students and residents. It is !!! and we just have to do a better job with promoting our field!

http://www.asn-online.org/publications/kidneynews/archives/2010/oct/KN_oct2010.pdf

Basic concepts in Immunology

Concept 1
Think of Innate immune system as "non antigen presenting mediated". it can get activated without antigen presentation. Cells that are major players: NK cell and Macrophage
Adaptive immune system is " antigen presentation mediated". Needs that extra help.
Cells that play role here:- B cells, T cells, DC

Concept 2
Think of the immune system as : Effector system and Regulatory system
Effector systems play a role in causing inflammation and damage and " doing their job" best!!! CD4+T, CD8+T cells, NK cells, B effector cells are all major players
Regulators are the "policemen". They are the Tregs and Bregs. They are out there trying to shut out fires and inflammation and try to "tone down" the reaction.  Having more police around makes for a more robust and more "Controlled" immune system

Concept 3
The adaptive immune response has two arms
Afferent arm:-Antigen presentation
Efferent arm:- T cell activation

Concept 4
Two types of destruction:- cell mediated via Cd4 and Cd8 cells- granzyme and perforin and killing the cell
or antibody mediated via B cell-- leading to complement activation killing

Role Playing exercise in Transplant Education

We did another session of role playing with the fellows and transplant medicine
Each fellow was assigned a "cell" that is an active playing in Immunology. Then they were asked to describe themselves in Homeostasis and then a state of Immunosuppression. A nice discussion and arguments ensued and a live display of the immune reaction was done.  The teaching of basic immunology for transplantation was mediated via this teaching method.
The cells the fellows' role played were: NK cell, macrophage, CD4+ T cell, CD8+T cell, DC, B effector cell, T Reg cell, B reg Cell.

TOPIC DISCUSSION

A recent quiz page in Kidney International Oct 2010 issue talks about a very interesting case of someone with hypophosphatemia and hyperphosphaturia, with normal calcium and Vitamin D levels.
A nice table shows the breakdown of someone with hypophosphetemia and loss of Phos via urine

If there is hypercalcemia along with it:- think of primary parathyroidism and post transplant parathyroid disease or pthrp production or hypocalciuric hypercalcemia.

If there is normocalcemia along with it:- only acquired disease is oncogenic osteomalacia. genetic causes are FGF23 mutation or PHEX mutation.  Usually all of them are associated with elevated FGF23 levels.
If the FGF23 are low think HHRH

If there is hypocalcemia think Barter's, Fanconi syndrome or other RTAs.

It is interesting that people are now measuring FGF23 levels to help dilenate different disorders of calcium and phosphate.  Take a look at this case in KI.

http://www.ncbi.nlm.nih.gov/pubmed/20877382

CLINICAL CASE 26 , ANSWER and SUMMARY

Which Statement regarding " Milk Alkali Syndrome" is False? The "true" Milk Alkali syndrome incidence declined in the 1980s due to the advent of H2 blockers	0 (0%)
Currently, the cases of this entity are more accurately termed Calcium Alkali syndrome	1 (5%)
It is NOT a common cause of hospital admissions for hypercalcemia	5 (29%)
It classically presents with hypercalcemia, hypophosphatemia, metabolic alkalosis and acute renal injury	4 (23%)
Levels of 1,25 hydroxy vitamin D are usually low in majority of these cases, but not all.	2 (11%)
It affects post menopausal women and pregnant women the most	5 (29%)

Lets take it one by one.  In the early 1900s, due to excessive milk intake and Sippy method - there were many cases of Milk Alkali syndrome. It did decline in 1980s due to the advent of H2 Blockers and also the decrease intake of Milk in general.  There are now cases started in 1990s in large part seen in post menopausal women due to increase intake of Calcium and Vitamin D medications and the new term for this entity might be " Calcium Alkali syndrome".  It is the 3rd most common cause of hospital admissions for hypercalcemia in the US, following hyperparathyrodisim and malignancy induced hypercalcemia.
It classically presents with Increased ca, low phos and met alk and acute kidney injury.  "Tums" might be most common culprit.  The earlier cases of "Milk-Alkali" syndrome usually presented with hypercalcemia and hyperphosphatemia due to MILK ingestion.  Levels of 1,25 Vitamin D in patients with this syndrome are usually low due to suppression but there can be few cases of normal to inappropriately high as well( due to possible prior exposure to Vitamin D supplements).

In summary, its a disorder that we have to keep in our differential if the incidence is too high. The correct answer hence is 3 as it is a common cause of hospital admissions, perhaps not diagnosed right away!

take a look at a recent JASN reference
http://www.ncbi.nlm.nih.gov/pubmed/20413609