CONSULT ROUNDS: Rising BUN only

Three common causes of rising BUN without serum crt rise are: ( in setting of normal GFR)

1. Steroid use
2. GI bleed
3. Tetracycline use

The third one is interesting. In 1972, experiments showed that rise in BUN was seen in some patients that got tetracyclines. The reason was due to anti anabolic effects of these class of drugs on amino acid incorportation into protein. Next time, you give democlocycline for SIADH, watch the BUN

Consult Rounds: Vancomycin induced renal toxicity

Why are we noticing more vancomycin induced renal injury these days? Is it because we are using more vancomycin as there are more resistant bugs or the trough levels have been raised to higher limits? Vancomycin-associated nephrotoxicity was reported in 0% to 5% of patients in the 1980s.  Initially, the first few reports many years ago of vancomycin induced renal damage was presumed to be from the impurities it carried that used to be called "Mississippi

Mud". As soon that was recognized, this was reduced.  

Treatment failures following vancomycin therapy in patients with methicillin-resistant Staphylococcus aureus infections have led to the utilization of higher doses of this antibiotic to achieve the trough concentrations of 10-20 μg/mL recommended by the Infectious Diseases Society of America clinical practice guideline. Vancomycin-induced renal toxicity was reported in 10-20 % and 30-40 % of patients following conventional and high doses of vancomycin therapy, respectively . Injury appears to be oxidative stress related.

Risk factors:

High level >20
Over 4g/day dose
Concomitant nephrotoxin on board
>7 days of treatment
ICU admission

Another study found rates of dialysis higher as well in those cases, but most reversible

What is the pathology in most of these cases?

ATN
Accelerated ATN ( as some authors called it)

AIN ( can be from any drug)

In The News: Patients know better

Two boston unit patients were asked about their perceptions on their prognosis and their likelihood of transplantation. With a chart review and a survey of both patients and their nephrologists, the authors compared the physicians expectations of 1 and 5 year survival and transplant candidacy to the patient's expectation. 
What did they find?
"In this single center study, patients were more optimistic then their nephrologists regarding survival at 1 and 5 years and transplant candidacy. In their sample, patients' expectations about 1-year survival were more accurate than those of their nephrologists, but their longer-term survival expectations dramatically overestimated even their 2-year survival rates."
Implications:
There has to be better communication of nephrologists and their patients on dialysis re this perception. As our ability to accurately prognosticate for seriously ill patients continues to advance, we need to learn to be better communicators to our patients. 

Check out the full study at JAMA

Open access journals: is this the future? Or not?

In terms of high impact journals, nephrology is on the lower end of the impact factor scale compared to our counterparts in hematology/oncology and cardiology.  An emerging option for publishing scientific data is open access journals.  This form of information sharing is beginning to penetrate the publishing/academic world.  While open access allows for all to view the article without paying for fees to the journal- are they offering quality articles? What do nephrologists think about open access journals?

First and foremost, why would an author want their work published in an open access journal?

Many reasons exist:-
 1. Rapid turn-around and availability to the world to view.
 2. The manuscript was rejected by traditional journals.
 3. E xperiment a different form of publishing. 

Are “non” PubMed ‘able journals in nephrology worthy for consideration of academic promotion? For now, it is unclear what “promotion” committees thinks of manuscripts that appears in these journals. 

Let’s take a few of these journals for example:   

Plos One:. Interestingly Plos One has a decent impact factor (4.0 in 2011) and the turnaround time appears to be quick (told to give review back in 10 days). The peer review is still a standard process (i.e. blinding reviews) like any other journal.  Great outlet, popular, PubMed’able – but comes with a cost for publishing in it.  Nephrology papers have been published in these journals. Check out this interesting commentary by an author. Here is Wikipedia’s view on Plos One

F1000 research: This is the newer journal. The concept is interesting. Peer review is open (meaning everyone including the author knows who the reviewer is) and happens after your manuscript is online.  The peer review is open for all to view and comment as well.  Great outlet, novel concept, they state it is PubMed’able (but I could not do it yet)- hopefully it’s coming soon.  How fair can a peer review be if this is open for all to review?  I think it’s very hard when a review is not anonymous to be honest in the review. But let’s see what scientists will think of this journal.  Another downside- cost for publishing in it. Many have voiced their concerns regarding this journal. Here is another one.

The table below I created reviews some common Open access novel journals in nephrology. Be your own judge

Journal Name and Link	Type of Articles	Cost involved?	Pubmed indexed( Y/N)
BMC Nephrology	Original investigations, basic and clinical, case reports, review articles	US $1950 after acceptance	Yes
International Journal of Nephrology	Original research, review articles	US $1000  after acceptance	Yes
International Journal of Nephrology and Renovascular disease	Original( basic and clinical), review, case reports	Cost but no amount disclosed on website	Yes
The Open Urology and Nephrology Journal	Case reports, reviews, images	Not disclosed on website	No
Journal of Nephrology and Therapeutics	Reviews, Original( basic and clinical), case reports	Yes, varied from 900-1300 based on type of article	None I found on pubmed but on their website it says NIH funded studies will be pub med indexed
Nephrology Reviews	Reviews	Yes, 500 Euro	No
Open Journal of Nephrology	Original articles( clinical), reviews, case reports	Yes, US $500	No
Journal of Nephrology and renal transplantation	Reviews, original articles( clinical)	Not disclosed on website	Found one article in 2009 indexed in pubmed, rest not
World Journal of Nephrology and Urology	Case reports, original articles( clinical), letters	Not disclosed upfront on website	No
Clinical Nephrology and Urology Science	Case reports, reviews, original articles( clinical)	US $300	No

A few obvious advantages of open access journals include the free access to scientific papers regardless of affiliation with a subscribing library, lower costs for research in academia and industry, in addition to improved access for the general public and higher citation rates for the author. Here is a view by someone on top nephrology journals.

The major concern is damage to the peer review process. Peer review is extremely important for good science. Eventually a bad paper can be published somewhere, but sometimes good papers can get published in low impact journals as well.  Publishing quality is important and unclear to me how the open access is preserving that.  PLoS and BioMed Centeral journals are regarded well among the open journals.  Hoax papers have been published in some open access journals. A list of questionable open access journals that promotions committee needs to be worried about have been listed at this website. Wonder if there is one for nephrology. We should likely come up with a list.

Recently, the NY times had done an interesting article on exploitation of scientists for use of such journals that charge significant amount for publishing. At least, the good quality opens mention this up front. Many of the low quality ones later distinguish themselves. Even Nature had a dark side talk on this.

So, you decide what you would do? Would love to hear nephrology community thoughts on this.

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.