GVHD after Kidney transplantation? Can this happen?

GVHD is mainly associated with allogenic hematopoietic stem cell transplantation, and occurs much less frequently after transplantation of immunologically active solid organs such as liver and small intestine. GVHD after solid organ transplantation(SOT) is a very rare and frequently lethal complication caused by the engraftment and proliferation of allograft-associated lymphocytes in the immunosuppressed recipient, with subsequent immune-mediated attack by donor-origin effector cells directed against HLA-disparate host tissues. SOT-GVHD occurs most frequently following small bowel and liver transplantation, followed by lung and kidney transplantation in decreasing order of frequency. Risk factors for SOT-GVHD are the quantity of lymphoid tissue in the donor organ, greater degrees of HLA match between donor and recipient and recipient age over 65 years. Given there are immune system related tissue when one does solid transplants such as small bowel or liver is not uncommon.

80 cases of GVHD after liver transplant were reported in 2008, with published incidence rates of 1-2%.  worldwide. GVHD is the consequence of an immunologic reaction of engrafted lymphoid cells against the tissues of the host. It is known that transient lymphocyte chimerism occurs in recipients of SOT, and in fact it is thought to be necessary for the establishment of organ tolerance; however, lymphocyte chimerism usually rapidly decreases over time so that by the third postoperative week not allowing the risk of GVHD.

Only 4 cases of kidney transplantation associated GVHD ( what I found) have been reported. Typical symptoms and signs of GVHD are skin rash, severe diarrhea, and the elevation of total bilirubin, but these findings were often attributed by drug reactions or infections. These may make the delay of GVHD diagnosis.  The earliest time frame reported is 17 days after transplantation and latest up to 240 days following it.  Majority of those cases presented with diarrhea or rash and 50% mortality.

Specific tests have been used in diagnosis of GVHD. One is detection of macrochimerism which was defined as more than 1% donor nucleated cells in the peripheral blood of recipient, and the other is single-tandem repeat (STR) DNA analysis which quantifies relative amounts of different DNA in a single tissue sample.  A gastrointestinal source based disease usually reveals apoptotic cells in the endoscopy or colonoscopy findings.

A recent article discusses a case report from Korea. The other 3 cases have been from Japan and USA.

http://www.ncbi.nlm.nih.gov/pubmed/16627604

http://www.ncbi.nlm.nih.gov/pubmed/9496741

http://www.ncbi.nlm.nih.gov/pubmed/19917421

IN the NEWS: The Ott Kidney

A recent article from the Harvard Medical School scientists in Nature shocked the nephrology and transplantation world.

Dr Ott, a CT surgery resident at Harvard, who has bio engineered other organs, along with his team bio engineered a kidney of  rat in his lab and then transplanted it to test in the rat and it shows signs of "working"

The researchers used a shortcut to engineer the kidneys—starting with a scaffold of collagen, which is what remained after living cells were washed away from another rat’s kidney. They then seeded this matrix with a cocktail of cells, including kidney cells from newborn rats, which grew into a functioning organ.

His lab has been working on this for past few years. Check out their website.

A video to their experiment can be found here as well.

Few interesting points from the study.

1. ECM was left in place as a scaffold, and cells were bleeched and then seeding was via giving endothelial cells via artery and epithelial cells via ureter.  Perhaps that scafolding is what makes that epithelial cell then become differentiated to a podocyte?- not clear

2. They showed that after perfusion, and transplantation, the kidney made urine.. but GFR was 30 fold lower than the control or cadveric transplantation. Unclear to me what time frame they used to get that CrCl.  

3. What about mesangial cells? - how to they form in this structure

4. It was nice they showed polarity of some of the cells- that was cool

5. Proof of concept- nicely done and will lay foundation for many more studies to perfect this idea. 

Bravo to the team led by a CT surgeon in making this a headway for us nephrologists and transplant surgeons. 

Nephmadness going along way!!

In March 2013, the eAJKD team was introduced to a novel idea by Dr Joel Topf on creating the biggest social media competition in history( definitely in nephrology)- Nephmadness.  With Dr Matthew Sparks and myself involved, and then Drs. Vinay Nair and Kellie Calderon joining along, the project grew to enormous heights. Few highlights I might mention.

1. It was fun creating the educational documents that were descriptions of the most historical movements in nephrology.
2. Seeing the social media and nephrology community vote on their top 32, 16 and eventually to the final 2 was a lot of fun.
3. This was a great way of promoting nephrology. Yes, the scientists out there might say- no "p" value and there is no data that showed this helped promote nephrology --- it is a passionate project that promoted nephrology in social media world regardless of the measured impact.
4. Here is the unplugged version of Nephmadness that you can find on the eAJKD final review of this mega mission.
5. In addition, Dr Topf gave a GRAND ROUNDS on this topic already and discussed the journey of creating Nephmadness( check it out on his blog) -worth looking at the first PDF.

To all involved in Nephmadness- a special shout out and thank you
To all involved in Nephrology- this is a special tribute to you all- scientists, researchers, clinicians, fellows, and patients.

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