Paricalcitol and CNI injury?

The most recent issue of Kidney International talks about an animal model that showed that paricalcitol attenuated cyclosporine induced kidney injury. This is interesting to note.
First, why do we get CNI related toxicity. CNI exposure leads to increased inflammatory response in addition to its beneficial effects and as a result increased TGF-B expression and fibrosis and nephropathy.
Also the renal vasomotor impairment leads to RAAS activation and oxidative stress and nephropathy.
The trial shown in the issue is an excellent start of a set of trials that might follow in animal models and hopefully this will one day make it to clinical world.

Reference
http://www.ncbi.nlm.nih.gov/pubmed/20237458
Image source
http://dailymed.nlm.nih.gov/dailymed/archives/image.cfm?archiveid=1741&type=img&name=zemplar-injection-structure.jpg

Nephrology Crosswords

Check out the next in series of the crosswords in KI

http://www.ncbi.nlm.nih.gov/pubmed/20508666

TOPIC DISCUSSION: Shock wave lithotripsy for kidney stones

Shock wave lithotripsy has been used for many years now for treatment of kidney stones. This might be old news to some people but i learned about this recently that around 2006-2007, there was a big debate about SWL causing DM and HTN.  Results from a retrospective study of 630 patients by researchers at the Mayo Clinic showed a more-than-threefold increased risk of diabetes and a 1.5-fold increased risk of hypertension among patients who underwent SWL 19 years previously compared with a cohort of matched, conservatively treated, nephrolithiasis patients. This was published in the Journal of Urology.
Another study showed the opposite in 2008.
The mechanism of this is unclear, but one possibly is direct toxicity from damage of islet cells from the shock.
The HTN is likely from the scarring and intrinsic kidney damage. 
This is still controversial and under debate in the medical community.

Some good references:

http://www.ncbi.nlm.nih.gov/pubmed/16600747
http://www.ncbi.nlm.nih.gov/pubmed/18387387
http://www.ncbi.nlm.nih.gov/pubmed/18423676

Role Playing in Transplant Teaching

Today at our transplant conference we did something fun.
A month ago, each fellow in training was assigned a transplant drug( MMF, imuran, cyclosporine, prograf, sirolimus, steroids and belatecpt).
In the one hour, each fellow had to play a role of the drug and stay in character. Initial rounds were introduction rounds and then followed debate rounds where major debates between Steroids vs no steroids, CNI vs belatecept, Cyclo vs prograf, sirolimus vs CNI and Imuran vs MMF happened.
It was tons of fun and fellows enjoyed it. Role playing of drugs taught them the strengths, mechanism of actions and their weaknesses.

Hoping to use tools like this to teach nephrology as we more forward; and make it lot of fun!!

Role Playing in Transplant Teaching

Today at our transplant conference we did something fun.
A month ago, each fellow in training was assigned a transplant drug( MMF, imuran, cyclosporine, prograf, sirolimus, steroids and belatecpt).
In the one hour, each fellow had to play a role of the drug and stay in character. Initial rounds were introduction rounds and then followed debate rounds where major debates between Steroids vs no steroids, CNI vs belatecept, Cyclo vs prograf, sirolimus vs CNI and Imuran vs MMF happened.
It was tons of fun and fellows enjoyed it. Role playing of drugs taught them the strengths, mechanism of actions and their weaknesses.

Hoping to use tools like this to teach nephrology as we more forward; and make it lot of fun!!

The SPLEEN in ANTIBODY MEDIATED REJECTION

The recent AJT May 2010 issue has a nice histopathology and immunotyping of the spleen in a case of renal allograft antibody mediated rejection. Splenectomy is done in rare cases to treat ABMR.  What this case illustrates is what they found in the spleen that might have been causing the damage.
The spleen biopsy was abundant with clusters of CD 138+ plasma cells.  This can explain the rapid response that we see once the spleen is removed.  They postulate that the spleen might be a reservoir for converting CD 20+ B cells to antibody secreting CD138+ plasma cells at the time of stress.
The HLA antibody is specific. Is the spleen really producing that specific antibody is unclear.
But this staining showed something novel about the plasma cells.
It has been noted that the kidney biopsy that is rich in plasma cells and ABMR has a worse prognosis.
It might be coming in bursts and splenectomy might help. Anti Plasma cells agents like Bortezomib might also be possible options in a case like this. I think it might worked as well as the splenectomy.

Regardless a nice read!

Image source: http://www.lifespan.org/tmh/services/surgery/mininvasive/images/spleenlarge.jpg

IN THE NEWS ---> FONT TRIAL

Treating FSGS is tough. It has been a long haul in trying to get the best drug to treat it.
Besides steroids, cyclosporine and scattered literature on cellcept, there is no other magic drug to treat resistant FSGS. Antifibrotic agents are the ones being studied in this study that is still ongoing called the FONT study.
The FONT study describes an ongoing trial that compares anti TNF, anti PPAR and galactose as the modalities to the treatment of FSGS.
Initial Phase 1 trials were produced recently in key journals. The next phase is still on the way.
What is also interesting is that this study has started a network amongst investigators to study diseases, the first of its kind in renal diseases. More studies that form networks should be done and allow more multicenter trials to occur.
Links to the FONT trial papers.
http://www.ncbi.nlm.nih.gov/pubmed/19932542
http://www.ncbi.nlm.nih.gov/pubmed/19932542