TOPIC DISCUSSION: SIADH diagnosis

We always struggle to diagnosis this entity in few cases of hyponatremia. Measurement of AVP can prove challenging due to problems of ordering and time it takes to come back. Measurement of copeptin( a 39 amino acid glycopeptide) which is derived from the same precursor peptide as AVP and released in equimolor amounts as AVP might be measurable.  Is that been studied? You bet!

In this one prospective observational study, 106 consecutive hyponatremic patients were classified based on their history, clinical evaluation, and laboratory tests. In patients and 32 healthy control subjects, plasma copeptin concentration and standard biochemical parameters were tested for their utility of diagnosing SIADH.

Plasma copeptin levels were significantly higher in patients with hypo- and hypervolemic hyponatremia compared with SIAD (P < 0.005, respectively) and primary polydipsia (P < 0.001). The copeptin to U-Na ratio differentiated accurately between volume-depleted and normovolemic disorders (area under the receiver-operating characteristic curve 0.88, 95% confidence interval 0.81-0.95; P < 0.001), resulting in a sensitivity and specificity of 85 and 87% if a cutoff value of 30 pmol/mmol was used.  This ratio differentiated between volume-depleted and normovolemic disorders resulting in good specificity and sensitivity in this one study. It did better than copeptin alone as well. Another small swiss study felt that it added very little to the sodium balance information. I guess not much out in the literature. Lets see where this story unfolds and how this becomes real in clinical use.

Ref

http://www.ncbi.nlm.nih.gov/pubmed/18984663

http://www.ncbi.nlm.nih.gov/pubmed/21990032

Complement Component Quiz

Match the following complement components with their function in the complement cascade

C5a	Membrane attack complex
DAF	Initiates the alternative complement pathway
C5b-9	Initiates the classical complement pathway
Factor H	Byproduct of the classical complement pathway
C5	Potent inflammatory mediator
C1q	Membrane bound complement regulatory protein
C4d	Blockade of this complement component is the treatment for PNF
C3b	Deficiency results in atypical HUS

Good Luck
Answers provided in 1 week

Questions by Dr. Vinay Nair
Mt Sinai, Transplant Division
New York, USA

World Kidney Day Crosswords Answers

Kindey F Answers

ASN2011: Dialysis Mortality

SOME TEACHING POINTS FROM ASN 2011 Pre course on Dialysis Care

We all know that mortality is very high for incident hemodialysis and could reach as high as 50%. 

Hakim et all showed in a retrospective study in looking at Fersenius data. They looked 10 years back and found out that those with the highest mortality had catheters. One conclusion could be that these deaths could be  infectious complications. It behooves us therefore to prevent these kind of deaths. 

Unfortunately people had these catheters and died despite the fact that thery were followed by nephrologists for more than six months.

Bradbury et al, AJKD, 2009 showed that mortality decreased by 36% and 29% when catheter was changed to AVF, and AVG respectively; and mortality increased by 80% when permanent access was changed to a catheter.

What are some reasons to this suboptimal care: 

Late referal to nephrology, priamary avf failure, patient-induced delays and in-decisions, etc. (NDT)

Patients were reluctant bc of fear of needels and fear of surgery and prior failures of fistulas.

Our job as nephrologists is to prevent these deaths and spend the time and energy to convince patients get AVF or AVG.

Post from

Dr.Azzour Hazzan

Hofstra NSLIJ Nephrology

 

Topic Discussion: Nano Medicine ( ASN 2011)

Nano medicine  was one of the topics presented at ASN 2011. What is that?

Dr.Chan described it very well for us at the ASN meet.

It is the science of application of nano techology principles in biology principals. If one thinks of a single atom, that is called the atomic state.  If we have 26 atoms, that is the bulk state. Anywhere in-between 6-19 atoms, is the tunability state.  Hence in this part of the molecule's structure of growth, it can be used to tube physical and biological properties. That is the nano state of the particle(sub micron size).  The intersection of particles and directed energy is a rich source of novel and useful technology that is only recently being realized for medicine. One of the most promising applications is directed drug delivery.

These particles have tremendous potential for actively disrupting their environment for altering transport properties and unloading drugs.

Nano is actually the same size as DNA and protein. Hence one advantage of such technology is to introduce relevant size particles to specific body parts and have effect( chemo, biology. etc)

Example. Make a particle that is 60 nm and get to the target site of the tumor.  Then can be used for imaging purposes or delivering chemotherapy.  It is in clinical phase trials for invivo cancer, diagnostics as well, and in research phase in cardiovascular diseases, diabetes and pathology.

The limitations are:  delivery is poor- 5percent and the particle can stay in body for MONTHS. 

So toxicity in unclear. 

Nevertheless, nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. Technically,  nano carries can do drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. But not sure if this is clinically able to happen. The leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB).  Finally, direct in vivo imaging of nanomaterials is possible leading to provide real-time tracking of those nanocarriers. 

But this can open up a whole area of research in Renal diseases in terms of podocyte biology and perhaps even renal imaging of certain smaller structures.  

Interesting concept.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/22059114

http://www.ncbi.nlm.nih.gov/pubmed/20199661

ASN2011: Complement related disorders

This ASN, there was a series of talks regarding complement glomerulopathy and the use of certain newer agents for treatment. Dr Licht discussed this in detail in one of the talks.

Bottom line

1. MPGN pattern of injury is seen in complement related glomerular diseases.
2. DDD is now part of C3 glomerulopathies
3. Complement factor H antibodies, complement factor B antibodies have been associated with C3 glomerular disease since they will enhance c3 conversion and eventually affect the alternate pathway.
4. Genetic forms such as mutations in Factor H, CFHR5, C3 polymorphisms were also noted in that case.
5. It is possible that what we used to call perhaps C3 only post infectious GN or resolving post infectious GN was really C3 glomerulopathy.
6. Treatment is plasma exchange as there might be antibody that exists ( if you think there is)
7. Complement inhibition is the key- and the only drug we have is eculizumab ( 4 doses 900mg IV per week and 1200mg per week following that for 4 doses):- but expensive
8. Overall, there is a paradigm shift happening in introduction of these disorders.

eAJKD : Nephrology and the Internet

Check out the new post on eAJKD blog regarding Nephrologists and the Internet

http://ajkdblog.org/2011/11/15/the-nephrologists-and-the-internet/