T regulatory Cells: A short review

T regulatory cells have now come out and made a splash in the transplant world but also in the immunology and glomerular disease world.  Treg are usually CD4+, CD25+, CTLA4+.
A common misconception is that all are Foxp3 positive.  

There are many types of Tregs.

Natural kind that do express Foxp3 and CD25 and they usually are IL-2 dependent

Induced Tregs are induced in the periphery and can express Foxp3 but after development

Regulatory Tregs do not express Foxp3 and CD25. They depend on IL-10 on development.

IL-10 has always been associated with regulatory function.

Now given above information, immunology always is evolving and who knows what will be new in 2011.

Advagraf Study

There has been talk about using prograf once a day for quite sometime now.  When it is used once a day its a tacrolimus prolonged use and its called Advagraf.  A recent  multicenter, 1:1-randomized, parallel-group, noninferiority study compared the efficacy of twice a day tacrolimus to advagraf.; combined with steroids and low-dose mycophenolate mofetil without antibody induction, in 667 de novo kidney transplant recipients. 
Per paper:


Biopsy-proven acute rejection rate at 24 weeks  was 15.8% for Tacrolimus BID versus 20.4% for Tacrolimus QD (p = 0.182; treatment ).
Kaplan-Meier 12-month patient and graft survival rates were 97.5% and 92.8% for Tacrolimus BID and 96.9% and 91.5% for QD. 
Both treatment groups showed equally well-maintained renal function at 12 months  by GFR
Overall, it was not inferior to twice a day dosing.


The original Ref is at:
http://www.ncbi.nlm.nih.gov/pubmed/20840480

New Informative Transplant News Website

please check out www.transplantnow.com.
This is similar to Nephrology now and compiles latest articles in Transplantation from major journals and will allow for good compilation.

Many guidelines equal no guildelines for cardiac evaluation before renal tranplantation

The degree of cardiac testing for potential transplant recipients is highly variable and depends on the practices of the particular transplant center. Multiple guidelines have been proposed by experts in the field however there is a huge variability between each guideline. At the two ends of the spectrum are the KDOQI guidelines which suggest universal testing for CAD at regular intervals depending on risk, and the ACC/ AHA who recommend testing only for symptomatic patients or patients who can not achieve 4 mets of activity. A recent article in cJASN by Friedman et al. demonstrates this beautifully(1). The authors had performed cardiac testing in 87% of their patients then retrospectively applied the KDOQI, AST, Lisbon and ACC/AHA criteria to thier patients to assess how many would have been tested. Turns out that 100%, 92%, 68% and 20% would have been screened respectively. The authors discovered ischemic disease in 17 (10%) of their patients and 10 of them underwent revascularization (7 had single vessel PCI). KDOQI and AST guidelines would have picked up all of the cases, Lisbon criteria would have picked up 16 patients and ACC/AHA would have picked up 4 of the patients with ischemia. The problem is that it is not clear whether identifying ischemia or performing revascularization in such patients is of any benefit in reducing cardiovascular event rates! In fact there are well designed studies that show pre-surgical revascularization in all patients with ischemic heart disease does not reduce cardiovascular morbidity and mortality in patients undergoing major vascular surgery(2) - but of course these studies were not in dialysis patients...

What we need is a large multicenter randomized controlled trial to evaluate the potential benefit in pre-transplant cardiac testing +/- revascularization in reducing cardiac morbidity and mortality in patients undergoing renal transplantation - to settle the question once and for all.

Reference:
1. Friedman et al. A Call to Action: Variability in Guidelines for Cardiac Evaluation before Renal Transplantation. cJASN 2011;6:1185
2. McFalls et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351: 2795
2804, 2004