Tuesday, April 29, 2014

CONSULT ROUNDS: IVIG and hyponatremia

What’s the relationship here?

In the 1990s, a paper in NEJM described the first relationship of the two.  Pseudohyponatremia has been classically described with intravenous gamma globulins. Pseudohyponatremia is a laboratory artifact due to hyperlipidemia or hyperproteinemia. Intravenous infusion of immune globulin increases the protein load and as a result the protein phase of serum is higher. Depending on the type of laboratory test used, some centers might note a low Na. Usually, the serum osmolarity then would be normal clinching the diagnosis.

Another mechanism that has been proposed is a form of hypertonic hyponatremia – the one you would see in mannitol or hyperglycemia.  most IVIG preparations contain significant amounts of sucrose or maltose leading to the increased osmolarity and leading to fluid shifts leading to hyponatremia. The magnitude of the Na drop might depend on renal function as well and clearance of sucrose.

Finally, a dilutional variant has been noted as well ( Sosm would be low) and you would have a true hyponatremia due to the volume of IVIG infusion that leads to a form of water intoxication.

Take a look at this case series that combines the latter to mechanisms in their presentations of IVIG induced hyponatremia.  Here is another case report.

Sunday, April 27, 2014

An inspiring story of a medical student interested in Nephrology

A recent study in CJASN 2014 aimed to determine the association of body mass index (BMI) with access to kidney transplantation in men and women.  While the study highlighted some very important points, we should notice that the second author on the manuscript is a medical student. Her name is Elizabeth Hendren from University of British Columbia, MD Candidate, Class of 2015

I had the opportunity to ask her a few questions.

“What was your role in the project that has the current manuscript in CJASN?

Elizabeth: “For this study I performed the background literature review, helped the statisticians with the data analysis and then presented the data at the American Transplant Congress in 2013 - providing feedback from that session into the final abstract.”

How did the ASN grant help you with this study and in general regarding research opportunities?

Elizabeth: “The ASN grant actually helped with two summer's worth of research.  I worked with  Howard Yan who was a 2012 recipient on a biopsy project and he was the one who let me know about the grant. I then applied in 2013 to work on an exciting survey idea for living donors and their willingness to enter the paired exchange.  I actually was a clinical trials coordinator for the same research group before medical school, but this project funding was my first foray into planning my own research project from the start.”

Are you interested in pursuing a career in Nephrology?

Elizabeth: “At this point I am planning on Internal medicine, and probably Nephrology.  I'm trying to keep my options open within Internal Medicine at this point. Nephrology excites me in particular because of the amazing mentorship.  In particular, I remember meeting Dr. Segev and Dr. Ratner at ATC 2013.  I had read countless papers by these two authors and to have them talk to me and talk about their research was so inspiring! I felt like I was talking to celebrities.

Locally, I've also had great mentorship through Drs. John and Jag Gill but also through allof our staff nephrologists and many of the residents.  I am so happy to go to our research office at the end of a long day and know I will always leave with more knowledge than when I entered.  Luckily, I also love the physiology, the biochemistry and immunology that build the fundamentals of Nephrology.”

Thanks Elizabeth for being so passionate about what you do and continue on this passion in whatever career path you take.

Wednesday, April 23, 2014

Carfilzomib induced renal injury: mechanism of action?

Multiple myeloma is the second most common type of hematologic malignancy. 

Carfilzomib is a second-generation epoxyketone proteasome inhibitor that is approved for treatment of relapsed and refractory multiple myeloma. Phase 2 trials have reported that 25% of treated patients have renal adverse effects. Pre-renal/vasoconstriction-related insult from this chemotherapy agent has been documented.

Recently, even a case of tumor lysis syndrome has been reported with this agent. According to the product labeling, the frequency of tumor lysis syndrome (TLS) is less than 1% in patients treated with carfilzomib. Is it possible then to prevent AKI via pre treatment with allopurinol and or rasburicase?

Also being presented at NKF 2014 e poster and a recent publication is the use of N-acetyl-l-cysteine to partially mitigated the renal injury upon re-challenge in case of carfilzomib related AKI. This case report hypothesizes that acute renal injury from carfilzomib is caused by vasoconstriction of the renal vessels, which may be prevented by N-acetyl-l-cysteine.

More can be learned about the mechanism of renal injury if biopsy proven cases are published. Thus far no biopsy proven AKI cases have been reported in the literature. 

image source: www.cancer.gov

Monday, April 14, 2014

Clinical Case 82: Answers and Summary

Which oral magnesium preparation has the highest amount of elemental magnesium content?

Milk of magnesia
  4 (11%)
Magnesium citrate
  7 (19%)
Magnesium oxide
  13 (36%)
Magnesium chloride
  5 (13%)
Magnesium lactate
  3 (8%)
Magnesium carbonate
  4 (11%)

Magnesium oxide  has the highest ( 61%) elemental magnesium; 242mg in a 400mg tablet
Milk of Magnesia Or Magnesium Hydroxide  has the second highest ( 42%).
Mg Carbonate has 24%
Mg Citrate has 16% elemental Mg
MgCl has 12%
Mg lactate has 10%

Other ones not listed are Mg gluconate that has 5% elemental Mg, Mg aspartate HCl that has 10%
Mg glycerophosphate that has 10% as well.

Check out a nice review article in AJKD by Ayuk and Gittoes on management of hypomagnesemia. 

Sunday, April 13, 2014

#NephMadness 2014- the aftermath

The contributors of eAJKD, the official blog of the American Journal of Kidney Diseases,
experimented again this year with the same concept of March madness- called Nephmadness.  The goal was to create a game online to increase interest in nephrology. Starting on selection Sunday to April 8th, this contest exposed the novel concepts in nephrology to many readers of social media and non social media in nephrology. 
are experimenting with a novel application of social media in medical education.

In Dec 2013, Joel Topf proposed to redo the magic he had proposed in 2013. He asked Matt Sparks and myself to see if were ready for this. But this year, we thought big and broader. With the help of eAJKD and AJKD staff, the www.nephmadness.com was created.  Following that, brackets were designed and professional look to it enhanced its appeal compared to last year’s version.  Time crunch to write posts and educational material began end of Feb 2014 till selection Sunday. Meanwhile, selecting bracket leaders and content experts was a fun and fulfilling task.  It branded Nephmadness to a different level.  Once the posts were in, editing was performed by content experts and we were all set for Selection Sunday.  The games began after that and Joel’s summary on this can be found here. 
            We hope this game enticed fellows, residents and medical students to understand nephrology better and appreciate its importance in medicine. While the game was a success from a numerical standpoint compared to last year( 260 participants from around the world), we yet don’t know if it did what we intended it to do.. educate and create interest in nephrology? Perhaps it did ?  What we know is that there was a domino effect. The amount of posts on the topic in the social media world was far more than last year and interest in learning about this from non nephrologists was intriguing. 

This year we also had involved content experts to edit the posts and contents under their expertise making it more peer review quality.
However, in NephMadness, the teams are nephrology concepts. The field is divided into eight regions, each with a content expert:
§  Regeneration: Stuart Shankland
§  Acute kidney injury: Sarah Faubel
§  Electrolytes: Helbert Rondon
§  Kidney Stones: David Goldfarb
§  Biologics: Jonathan Hogan
§  Toxins: Warren Kupin
§  Hypertension: George Bakris
§  Renal replacement therapy: Glenn Chertow

This year, Joel Topf and Matt Sparks took off with a bang and two new members Warren Kupin and Edgar Lerma joined us in this momentous effort.

When you google “ Nephmadness 2014” the following posts on this topic appear

1.    KevinMd.com
2.    Renal fellow network parts 1-8 on their reviews.
3.    Duke University promoting it.
4.    Pro Med Network
6.    Flume cast
8.    MedPage today

Personally, I couldn’t find anything to this caliber ever done in Nephrology, not alone in Medicine!  For many things nephrologists have been the first to do—look at uptodate.com and who founded that.  I am glad and happy to be part of the Nephmadness team and hope folks learned while they played along.

Monday, April 7, 2014

Topic Discussion: Hemo peritoneum in PD

Etiologies for Bloody Peritoneal Dialysate( as little as 2ml in a 1L PD solution will make it turn fully red)
Catheter related causes: Erosion of mesenteric vessel by Tenckhoff catheter
Obstetric and gynecologic: Menstruation, Ovulation,Hemorrhagic luteal cyst,Ovarian cyst rupture, Pregnancy (uterine tear)
Intra-abdominal: Renal cyst rupture, Acquired cystic kidney disease, Autosomal dominant polycystic kidney disease ,Liver or liver cyst rupture,Hepatic tumors,Hepatocarcinoma, Liver metastasis, Splenic rupture, Splenic infarct, Aneurysm rupture, Pericardiocentesis, Radiation, Colonoscopy
Bleeding diatheses: platelet dysfunction, Anemia
Infection: Cytomegalovirus infection, Peritonitis
Other: Retroperitoneal hematoma, Iliopsoas spontaneous hematoma

What to do while determining cause?
1.      Several rapid PD exchanges are performed to determine if bleeding is persistent or is an acute event( vasoconstriction from rapid exchanges helps control bleeding)
2.      Most of the causes are menstruation related or a capillary rupture. 
3.      Correct any coagulopathy ( uremic or bleeding diathesis)
4.      Addition of heparin 500 U/L PD fluid is recommended to prevent catheter malfunction due to a clot obstructing the flow of dialysate.
5.      With persistent hemoperitoneum, imaging might be needed.

Saturday, April 5, 2014

Plasma exchange for central pontine myelinolysis?

As we know that a complication of overcorrection of hyponatremia is central pontine myelinolysis(CPM). Once it happens, what can be done to improve the neurological complications?

A recent case report shines light into an older treatment approach from 1990s- plasma exchange. In this case report, a patient received IV bicarbonate therapy for distal RTA from sjorgen’s syndrome and Na corrected from 140s to 170s in 24 hours and then few days later leads to CPM .
Two days of 4+ liters of plasma exchange were done with albumin and FFP replacement. Two days following the treatment, the neurological symptoms improved.  The sodium level also was getting staying stable.

So how does one treat CPM? – besides preventive strategies

There have been some animal  studies investigating the benefits of re-inducing hyponatremia in the case of rapid  overcorrection of hyponatremia in order to avoid osmotic demyelination. So bring the Na back down again to allow for the change to be mitigated.  What about plasma exchange? This was first attempted in 1999 Lancet paper that showed that 3 patients were successfully treated with plasma exchange ( but in those cases were for weeks compared to the above case for only 2 sessions)

Another case report exists in use of this strategy in a liver transplant patient with CPM.
One more in the neurology literature  adds to this potential treatment.
 Myelin toxic compounds may be removed by plasma exchange due to their high molecular weight and preventing the further damage is the suggested mechanism.

Would it be worth doing plasma exchange while correcting for hyponatremia simultaneously in high risk patients? – such as the alcoholic beer potemanias? Some food for thought.

Image source: wikipedia.com

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