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

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. 

#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 8^th, 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.

View all Nephmadness posts on eAJKD here.

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

5.    Univ of Arkansas website

6.    Flume cast

7.    Med Page today headlines

8.    MedPage today

9.    Renal and Urology News

10.  Renalweb daily news

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.

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.

A nice review can be found here. 

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

Concept Map: Hereditary Amyloidosis and Renal involvement

Kidney MAPS: Volunteer opportunity

Kidney MAPS (Mentoring and Assessment Program for Students) was established by the American Society of Nephrology (ASN) to promote interest in nephrology careers through student-organized community screening programs that identify people at risk for diabetes and hypertension in medically under-served communities. Each chapter is supported by practicing nephrologists who volunteer their time and mentor medical students. 

The goal of Kidney MAPS is to recruit and mentor the next generation of nephrologists early in their careers by showing students the risk factors for chronic kidney disease, the effects of kidney disease on public health and the increasing need for medical professionals to help combat it.

Currently, ASN supports student chapters at Emory University, Indiana University and the University of Louisville.

In addition, as a part of Kidney MAPS, the ASN and chapters headquartered in the Kidney Week host city partners with the American Kidney Fund to host a Kidney Action Day screening event to kick-off Kidney Week each year. In 2013, the Emory University Kidney MAPS Chapter partnered with AKF to screen nearly 250 patients.

For more information about the Kidney MAPS program and learn how to establish chapter at your institution, please contact Lisa Bryan at lbryan@asn-online.org.