FGF-23 and Mortality Journal Club

FGF-23 and Mortality in Dialysis patients- Journal Club

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Curbside Consults

We often have asked these questions? and some of them have no answers in the literature and some have long winded opinions- and that's it.  These are practical questions that have come up at almost every institution. Take a look at some of them?
1. Do Dialysis patients need colonoscopies and mammograms?
2. When and how should immunosuppression be tapered in a failed transplanted kidney?
3. Should we give erythropoiesis stimulating agents to a dialysis patient who has cancer?
4.  When should a nephrectomy be done in a transplanted patient with a failed kidney?
5.  Is there a higher mortality in certain dialysis shifts?

Seminars in Dialysis August 2011 issue has these questions answered along with more such scenarios. This special issues is fantastic. It covers some major issues that we face all the time.
Take a look
http://onlinelibrary.wiley.com/doi/10.1111/sdi.2011.24.issue-4/issuetoc

It's official -- chocolate linked to heart health

It's official -- chocolate linked to heart health

Concept Map of MPGN pattern of Injury

Based on a recent post by the renal fellows network on MPGN pattern of injury and a landmark paper in Kidney International, here is a concept map of MPGN pattern of injury. Feel free to make comments to add or change things.
Ref: http://www.ncbi.nlm.nih.gov/pubmed/7723253
http://renalfellow.blogspot.com/2011/08/mpgn-think-different.html

Click on the image to enlarge it

NEJM article highlights Malpractice Risk by Specialty

A recent NEJM paper in August 2011 shows the rate of malpractice in different fields of medicine. They obtained physician-level data on malpractice claims from a large, physician-owned professional liability insurer that provided coverage to physicians in USA. The most common specialties in our data were anesthesiology, family general practice, and internal medicine.


What about Nephrology? Well from what I could gather: from their data:
1. Proportion of Physicians Facing a Malpractice Claim Annually was very less , less than 2% . Nephrology was on the bottom of the list. Appears that it is the least likely specialty to be sued in Internal Medicine based on their Figure 1. Pulmonary, Oncology, Cardiology were the most in Internal Medicine.


2. In the Amount of Malpractice Payments, according to Specialty- Nephrology couldn't even be listed as it had fewer than 30 payments.  
Kudos for hardworking and great physicians- Nephrologists!

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21848463

IN the NEWS:- Internet and Nephrology

Two recent reviews by the bloggers in Nephrology talks about how the field of Nephrology has embraced the internet and Web 2.0 tools. It goes through each of the social media networks and identifies the pros and cons of each of these tools.
First of it's kind- will allow for more sophisticated work to be done in this era of Web 2.0.







The two articles can be found at

http://www.ncbi.nlm.nih.gov/pubmed/21840099
http://www.benthamscience.com/open/tounj/articles/V004/12TOUNJ.pdf

Pseudo-nephrotic Syndrome

Severe Monocytosis (perhaps in CMML) causes marked lysozymuria - which can be confused and read as nephrotic range proteinuria and this is actually pseudo nephrotic syndrome.  This case report below mentions this confounder in measurement of proteinuria. Unclear if this would be an issue today as we have much more sophisticated measuring devices for albumin and total protein.

Ref:
http://www.annals.org/content/121/10/818.1.long
image source: Wikipedia.com

TOPIC DISCUSSION: Retinal-Renal Diseases

Retinal abnormalities in many inherited renal diseases is common. From CHARGE syndrome, Tuberous Sclerosis, Alports syndrome, LCAT deficiency, to Fabry's disease, VHL Syndrome and Amyloidosis are many diseases that this is noted.

Why is that is the question?
The 4 main reasons are:
1. Kidney and Retina develop at the same embryonic stages
2. The Glomerular filtration barrier is very similar to the design of the retinochoroidal junction.
3. Both glomurelus and chorioretina are large capillary beds
4. Both Podocytes( renal epithelial cells) and Retinal epithelial cells are similar in function and depend on cilia for their functions

A nice review is available on this topic in recent issue of JASN August 2011( has a detailed review of all the diseases and mechanisms)

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21372206
http://www.ncbi.nlm.nih.gov/pubmed/9457747
http://www.ncbi.nlm.nih.gov/pubmed/9227202

CLINICAL CASE 41: ANSWERS and SUMMARY

What is the best known successful treatment for Dialysis Associated Ascites?

Intense Hemodialysis	10 (17%)
Intense Ultrafiltration	9 (15%)
Kidney Transplantation	21 (36%)
Angiotensin Converting Enzyme Inibitors	0 (0%)
Repeated Paracentesis	4 (6%)
Albumin infusion with ultrafiltration	14 (24%)

Dialysis associated ascites is a rare phenomenon these days.  Usually happens 8-69 months on dialysis and most cases are of patients with Glomerular diseases or HTN. We don't see it that much these days as more efficient dialysis happens and causes of ESRD are non glomerular diseases.  Many pathologic mechanisms have been proposed. A recent review by myself on this topic sheds light into the this entity.


In terms of treatment:- All mentioned above modalities have been tried and can work but the most definitive treatment is kidney transplantation( as most of you picked).  Complete resolution of ascites with long term improvement in quality of life has been reported in 21 of 28 patients that were studied post transplant.

See below:
Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21801212
http://www.ncbi.nlm.nih.gov/pubmed/9715728

Topic Discussion: Uromodulin Associated Kidney Disease

1.A disease entity called family juvenile hyperuricemic nephropathy or medullary cystic kidney disease type 2 is something that we rarely encounter.  It is also called uromodulin storage or uromulin associated kidney disease.

2.Clinically: Uric acid associated damages- tophi, gout and ultimately chronic renal damage leading to dialysis by 4th decade. 

3. Chromosome 16p12 ( autosomal dominant)

4. It's a reduced excretion problem of urate( unclear why?)

5. Diagnosis can be made:- history of childhood gout, renal insuff without hematuria or proteinuria and bland urine sediment and family history of gout

6. Renal US might reveal cysts but NOT always

7. Allopurinol and ACEI or ARB treatment are only potential supportive measures.

Some interesting work is being done at certain centers around the country

Look at the lists below:

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21473025

http://www.ncbi.nlm.nih.gov/pubmed/21071970

http://www.ncbi.nlm.nih.gov/pubmed/15168406

Nephrology Crosswords-History of Nephrology

Check out the next installment in Nephrology Crosswords in Kidney International- Topic is History of Nephrology. - Authored by the blogger of history of nephrology blog- Neil Turner.

http://www.nature.com/ki/journal/v80/n5/index.html#Make-Your-Diagnosis
http://www.nature.com/ki/journal/v81/n1/abs/ki2011363a.html
http://www.nature.com/ki/journal/v81/n1/abs/ki2011364a.html

The "Nephrologist"as a patient advocate

Its often that we encounter many family situations and complex medical patients.  As Nephrologists, we are at a very unique opportunity to be the patient's best advocate.  In a busy day to day practice,sometimes we feel rushed and forget the humanism in medicine.  Its a tough situation. But, few words of compassion can go a long way in a difficult patient and family members.  Let's not forget that.

I urge you all to read this essay by a medical student( at that time). It is shocking and very revealing.
http://www.ncbi.nlm.nih.gov/pubmed/12431924

Related slightly to these topics are two very recent NY Times Blog posts
http://well.blogs.nytimes.com/2011/08/12/do-patients-have-the-toughest-job-in-medicine/?ref=health
http://well.blogs.nytimes.com/2011/08/11/letting-doctors-make-the-tough-decisions/

Worth a read

Mohan foundation: First of its Kind in ASIA

MOHAN FOUNDATION

Most physicians know, transplants just don’t begin or end with one person’s death. A whole mechanism has to come into play – to confirm that the dead person’s organ is healthy, that his or her family is willing to donate, that the grieving family’s religious and spiritual needs are met, that trained professionals offer grief counseling and information about organ donation in a non-judgmental way, that a patient waiting for an organ on a list is notified timely, that doctors are prepared to walk into the operating room at any time day or night when such an event occurs, that this altruistic process is not corrupted by money or favoritism, that the public is sensitized to the true nature of this process, that this process perpetuates and spreads through society and that awareness amongst the general public reaches a level of acceptance that a majority come forward to donate their organs after death.   

Every year thousands of patients in India die without an organ transplant. Others either slowly wither away under the weight of their disease while waiting, or sometimes turn to organ traffickers to buy organs from the poor who have been tricked into “donating” their kidneys. These donations are done under the table, in terrible hospitals, with bad hygiene and sanitary conditions leading to poor outcomes for both donor and recipient. It is a terrible situation with a great need that goes unmet because of the lack of organization critical to run an organ donation program.

And yet, the solution is right under our noses! Statistics show that in the West, almost 37,500 organs are transplanted annually from cadaver donors where donation rates are about 25-35 per million people. In India we are able to retrieve organs from only about 70- 100 donors annually because our donation rate is 0.08 per million. If we are able to increase our donation rate to 2-3 per million, it can take care of ALL the current needs for organs in India!

But India doesn’t have its UNOS.

MOHAN Foundation

MOHAN (Multi Organ Harvesting Aid Network) Foundation is a not for profit organization that leads this mission to facilitate deceased organ donation in India. Since the inception in 1997, MOHAN have facilitated the donation of over 2000 organs and tissues. The core objectives are to create awareness about organ donation, to counsel the families of “brain dead” victims about donating their loved ones’ organs, to train transplant coordinators on the nuances of counseling, to coordinate organ donations with hospitals and patients, to lobby with government to pass appropriate legislation that will promote organ donation and to ensure that all this is done in an ethical and transparent manner.

Mohan will have a booth this year at ASN 2011.

Learn about the UNOS like foundation of India- MOHAN 

To be part of this or see what is going on visit www.mohanfoundation.org 

 Dr. Anirban Bose

NephroPlus, a new email group to join for discussion of Technology in Medicine

TRIBE AKI Consortium

Acute kidney injury is at a very exciting stage. The troponin for renal disease is almost near to be found.  Creatinine as we all know is not the best marker for detecting early renal disease. Follow the following link developed at researchers at Yale to study this problem. All recent publications can be found at this website
http://www.yale.edu/tribeaki/index.shtml

Consult Rounds: Alkalemia causing Metabolic Acidosis

Can severe metabolic or resp alkalemia lead to Metabolic Acidosis?
Yes it can!!

Metabolic alkalosis, if from vomiting or diuretic use can be associated with a small increment of anion gap ( around 4-6meq/L) and this is ofcouse if no other disorder has been identified.  Why? Largely due to increase in albumin and some due to other increase in anionic proteins.  

Serum anion gap does not change notably in acute respiratory alkalosis, but small increases up to 3meq/L have been observed in chronic respiratory alkalosis.  

Alkalemia also causes glycolysis in the liver and a mild lactic acidosis (seen in our patient). In addition, in a volume contracted patient, the change in anion gap can be due to the change in valence of circulating proteins to preserve extracellular volume.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/401925

http://www.ncbi.nlm.nih.gov/pubmed/17699401

http://www.ncbi.nlm.nih.gov/pubmed/18974769

IN THE NEWS: Rituximab Targeting Podocytes in Recurrent FSGS

Rituximab might be working in a non B cell mediated manner in FSGS recurrence post transplant.
A new study by Fornoni et al showed this in an elegant way.
Some summary points

1. 41 patients were studied, post transplant and 14 were controls and remaining received rituxian as part of their induction.
2. Fewer podocytes with SMPDL-3b protein in biopsies from recurrent FSGS were found.
3. Serum from patients with recurrent FSGS had a decrease in both SMPDL -3b and sphingomyelinase activity.
4 They predicated that rituximab preserves SMPDL-3b expression in podocytes.
5.The above part was prevented with anti CD20 treatment.
6. They studied SMPDL-3b protein, cytoskeleton remodeling in cultured normal human podocytes that had been exposed to patient sera with or without rituximab.
7. Over-expression of SMPDL-3b or treatment with Anti CD20 was able to prevent recurrent FSGS and showed preservation of cytoskeleton.
8.These data suggest that modulation of the sphigolipid related proteins might be playing a role in causing recurrent FSGS and perhaps anti CD20 agents are inhibiting this process in a B cell independent fashion.

Key: SMPDL= sphingomyelin phosphdiesterase acid like.

ref:
http://www.ncbi.nlm.nih.gov/pubmed/21632984

IN THE NEWS: SuPAR circulating Factor for FSGS

Finally, the circulating factor in FSGS has been likely identified. Take a look at the most recent Nature paper by Wei et al. Some summary points:

1. Serum soluble urokinase receptor (suPAR) is elevated in 2/3 of the patients with FSGS
2. It is not elevated in other proteinuric glomerular diseases
3. Higher concentrations before transplantation- might suggest risk of recucurrence
4. Mouse models showed that elevated suPAR caused FSGS like pathology ( foot process effacement)
5. SuPAR decreased with plasmapheresis.

What is suPAR:- it is normal to have some amount of it as it is responsible for neutrophil trafficking.
Interestingly, it is elevated in HIV and some cancers- hmmm? perhaps a factor in HIV associated FSGS as well?
Can this be used as a marker? Perhaps- and even as a predictor of recurrence?
Can galactose bind to this circulating factor? Perhaps?...
What about the other 1/3 of FSGS?

Check out the ref at:
http://www.ncbi.nlm.nih.gov/pubmed/21804539

Green tea and Tacrolimus

Its seems like tacrolimus gets in trouble with lot of things.  Since its a substrate for the P450 system, it is good to monitor with any new medication.
Recent report suggests that green tea might increase tacrolimus levels. In this particular case discussed in AJKD, poor metabolism was also a culprit but green tea is something to watch out for.

Take a look
http://www.ncbi.nlm.nih.gov/pubmed/21787983

Consult Rounds: High Uric Acid

Uric acid elevations are frequently noted in patients with renal insufficiency as a clearance related problem.
We also note seriously high uric acid levels in patients with tumor lysis syndromes or large tumor burdens.
HCTZ can also do it.


What about tissue hypxia? Changes in oxygen tension has been associated with modulation of purine turnover.  
Rat and human studies have shown that uric acid levels in hypoxia are much higher than normoxia and hyperoxia.  There is a correlation that hypoxia results in greater purine catabolism and leading to increased production of uric acid. Hence we often see lactate levels correlating well with uric acid levels in sepsis.

Few ref:
http://www.ncbi.nlm.nih.gov/pubmed/8470901
http://www.ncbi.nlm.nih.gov/pubmed/20730463
http://www.ncbi.nlm.nih.gov/pubmed/17067515
http://www.ncbi.nlm.nih.gov/pubmed/17269363

Topic Discussion: Non glucose based solutions for Peritoneal Dialysis

Glucose based solutions are standard for PD.
Two non glucose based are also available: Icodextrin and amino acids.

1. EAPOS trial compared retrospectively on membrane function and it showed stable membrane function and better UF with the icodextrin arm
2. Exposure to hyperglycemia and subsequent effects of glucose absorption are less with these agents
3. No side effects are noted with these agents
4. No clinical data are present to support use of amino acids as membrane protectors
5. Cost of above agents are a lot and hence not used much in USA.

Something to ponder about
Check out the recent Seminars in Dialysis review on this topic by Peter Blake
http://www.ncbi.nlm.nih.gov/pubmed/21801231
http://www.ncbi.nlm.nih.gov/pubmed/16720998
http://www.ncbi.nlm.nih.gov/pubmed/15780118

The Art of Medicine: Let’s Not Lose It In Nephrology

The Art of Medicine: Let’s Not Lose It In Nephrology

CLINICAL CASE 40: ANSWERS AND SUMMARY

Besides phosphate metabolism, what other functions does the klotho gene have associations with?

insulin resistance	5 (11%)
thyroid disease	0 (0%)
aging	35 (81%)
development of the hypothalamus	0 (0%)
sensory neuron development	3 (6%)

Interesting history regarding Klotho. The gene actually was first identified as a aging suppressor gene that extended life span before it got its glory in FGF 23 and phosphate regulation. So Aging is the right answer.  Klotho is also an obligate co receptor to FGF 23( which suppresses phosphate reabsorption and 1,25 Vit D synthesis in the kidney).

Klotho actually means "who spun the thread of life".  The klotho knockout mouse has the following finding:

faster aging, hypogonadism, growth retardation, atrophy of skin, cognition impairment.

The transgenic Klotho mice have increase in lifespan. FGF 23 def mice are similar to Klotho def mice and hence the relation came about.  Some studies show that it is the phosphate retention that causes extensive aging like features. It is not surprising that it is the phosphate that really makes the big difference in CKD and dialysis patients.  

Interesting concepts

Check out ref:

http://www.ncbi.nlm.nih.gov/pubmed/19329831

http://www.ncbi.nlm.nih.gov/pubmed/21164022

http://www.ncbi.nlm.nih.gov/pubmed/21496980

TOPIC DISCUSSION: Adequacy of Dialysis HD vs. PD

For PD, the weekly goal is 1.7 which divided into 7 days is below 0.3 (if we were close to 2) and for HD the kt/v goal is 1.2 every treatment which divided into 2 days will give approx 0.6 per day so  questions arise?- 
Why are goals different and howcome the outcomes are same?

The goals to be achieved during hemodialysis are typically higher beacuse the 24 hour solute clearance that we get with PD is more "efficient" and gets more convective/middle molecular clearance. Comparable efficiency of all solute clearance on HD can only be achieved with higher kt/v for each treatment since they are short and intermittent in other words hemodialysis is less efficient if you will.