A novel look at hyponatremia in the alcoholics

Tavare and Murray in a recent NEJM image had an interesting case of hyponatremia correction. The case highlights development of central pontine myelinolysis(CPM) despite slow correction of hyponatremia.  CPM is known to occur in alcoholism, liver disease and malnourishment in the absence of hyponatremia, hypokalemia or hypophosphatemia. 

We wanted to suggest an algorithm that can be used in settings where alcoholics present with moderate to severe hyponatremia with similar symptoms as presented in this case and are at risk of CPM.  The figure below is a novel algorithm that uses brain imaging to help us guide the therapy for moderate to severe hyponatremia in alcoholics.  

If the patient is symptomatic with seizures, the correction of hyponatremia should be promptly started.  If the patient is asymptomatic  or with milder symptoms and is encephalopathic ( with several  confounding  etiologies : hyponatremia, alcoholism, liver disease), a MRI of the brain should be performed. If the MRI confirms cerebral edema, hyponatremia should be treated with the usual slow rate of correction of 6-9mmol/L per 24 hours.  If the MRI confirms CPM, the correction of hyponatremia should be put on hold.  

We hypothesize that often the hyponatremia  in alcoholics is  chronic  and correction, regardless of the rate, might cause harm in these patients.

We welcome comments from experts on this concept. 

Kenar D. Jhaveri, MD
Rimda Wanchoo, MD
Alessandro Bellucci, MD

Nephrologists as Super Heroes

When somebody asks me what nephrologists are, I usually respond with ‘superheroes.’ Sure, my perspective may be a bit skewed since I write for a comic series, and yes, superheroes may not be the first thing that pops into one’s mind when discussing the kidney. But in clinical practice, nephrology is a multidisciplinary field within medicine that requires deep knowledge of numerous organ systems. Acid-base disorders, dialysis, oncology, rheumatologic diseases, and transplantation are just some of the subjects in which a budding nephrologist gains expertise. Combine this prowess with the everyday challenges of providing primary care to chronic kidney disease patients, one can’t help but think of nephrologists as ‘superheroes’ in medicine.

When intensivists are struggling with an ABG, who do they call? The nephrologist. When cardiologists are struggling with hypertension and volume management, who do they call? The nephrologist. When endocrinologists are baffled by unexplained hypercalcemia, who do they call? You get the picture. Superheroes are wanted---and needed---in order to save the day.

You would think that young residents would be clamoring to don their capes and join the field of nephrology. But on the contrary, interest in nephrology has steadily been declining in recent years. According to Dr. Warren Kupin of U-Miami, the field of nephrology is suffering from an ‘acute fellowship insufficiency’, with fewer than 50% of programs filling their open fellowship positions, and some large academic programs going without even a single fellow. This lack of interest can be attributed to perceptions that this field is too complex, or perhaps to a lack of exposure to nephrology in residency. We may see ourselves as superheroes, but in actuality we are perceived more as “mutants” by the rest of the medical profession.

The mutants of X-Men are a group of individuals that were born with superhuman powers, but needed guidance, direction and purpose in order to flourish. They were constantly being targeted for their distinct abilities and talents that no humans could ever dream of possessing. The X-Men frequently had to fight for their mere survival. While on the pathway to annihilation, a bright light shined over these mutants. A gentleman by the name of Professor X would fill the void and provide mentorship to these troubled youth. He was a scholar and a role model for his students. It was through him alone that the X-Men were able to hone their powers for the good of mankind and recruit other mutants to Xavier’s Academy for Gifted Youngsters. Had it not been for the mentorship of Professor X, the mutants would have surely fallen into extinction.

Simply stated, we need more Professor Xs in nephrology. There needs to be a drive from within the field itself to demonstrate the attractiveness of our specialty. A systematic approach towards creating interest in our field must be undertaken to draw in the next generation of renal specialists. One way to make nephrology appealing to medical students and residents is through effective mentorship and education from the people within.

            When I was in medical school, I was assigned to a nephrologist as my attending physician for much of my internal medicine rotation. This was my first real exposure to what I would come to find as my life’s calling. I was intrigued by the complexities of renal physiology and its application in practice. I was excited by the life saving procedures of catheter placement and emergent hemodialysis in the emergency room and ICU. I was challenged by the detective work involved with diagnosing glomerular diseases. Now, in fellowship, my passion for the field has been furthered by being a part of the kidney transplant team.

            It is time we all do our part and take on the tradition of actively engaging and mentoring young physicians in the field of nephrology. Medical students and residents should be encouraged to rotate through nephrology electives with inspiring clinicians and passionate educators. By motivating a new trainee to consider a career in nephrology, you become more than a role model- you become a superhero. In the words of Professor X, “when you can access all that, you’ll possess a power no one can match. Not even me.”

Post by Dr. Khurram Mehtabdin, NSMC intern, who is a graduate of Syracuse University and TouroCOM NY. He completed his residency in internal medicine at Flushing Hospital Medical Center and is in his nephrology fellowship at the Northwell Health and Hofstra Northwell School of Medicine. Khurram is the co-creator of the comic book series Zindan, available at TheLastAnsaars.com

Nephmadness 2016 Begins today

As each of you might be aware, NephMadness (now in its 4th year) is a way to promote our field to residents and medical students while each of us learn at the same time. NephMadness celebrates all things nephrology during the entire month of March (National Kidney Month). NephMadness (brought to you by the AJKD blog, the official blog of the American Journal of Kidney Diseases) is an online game that invites everyone to predict the "winners" of competing medical concepts.

Like in March Madness, where fans try to pick the winner of the NCAA Basketball Tournament, NephMadness provides brackets for participants to fill out online (click here for the submission site) and then compete with a worldwide community of peers. Winners of each “game” are determined by a majority vote of nephrologists we call the “blue ribbon panel”

• Dan Weiner
• Scott Gilbert
• Nancy Adams
• Jeffrey Berns
• David S. Goldfarb
• Melanie Hoenig
• Roger Rodby

The medical concepts—or "teams"—are divided into eight regions highlighting different aspects of nephrology. They are:

1. Hypertension Region: Raymond Townsend
2. Palliative Care and Nephrology Region: Christian T. Sinclair
3. International Nephrology Region: Professor Vivekanand Jha
4. Missteps in Nephrology Region: Mark Rosenberg, MD
5. Transplant Nephrology Science Region: Milagros (Millie) Samaniego, MD
6. Recreational Drugs and the Kidney Region: Mark A. Perazella, MD, FACP
7. Pediatric Nephrology Region: John D. Mahan, MD
8. Statistics in Nephrology Region: Perry Wilson, MD MSCE

Detailed scouting reports with background information is all provided at the blog. How do you pick the winner of each match. Simple, just select the medical concept that in his/her best medical judgment holds the most significant and promising benefit for the future of nephrology, weighting evidence-based medicine over eminence-based medicine.

NephMadness begins March 10th (World Kidney Day) and entries are collected until March 23rd when the game begins at roughly the same pace as the real NCAA tournament.

Winners of the concept matchups will be determined by a blue-ribbon panel of nephrologists and physicians. Those who guess the most correct matchups correctly will have a chance to win AJKD/NephMadness swag, textbooks, and fame!

Go to www.ajkdblog.org to review the scouting reports for each concept or go to the bracket submission site to place your votes.

Detective Nephron Returns with another electrolyte case

Check out this month's issue of ASN Kidney News
http://www.asn-online.org/publications/kidneynews/archives/2016/KN_2016_03_mar.pdf

Monoclonal Gammopathy and end organ damage ( Skin, Nerves, Cornea and more):- it’s not just the kidney.

While MGUS and Kidney disease is now a finding well described in the literature, why not other organs?

It is quite possible that there is end organ damage to other organs from these small set of B cell or plasma cell clones if there is kidney damage.

A recent review in the corneal world found a case series of what we could call MIDD in the cornea. Seven patients were identified with corneal immunoglobulin deposition. The structures they found are similar to crystalline structures. Some of them looked like immunotactoid, some fibrillary and some amyloid. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenström macroglobulinemia. Authors suggest treating underlying MGUS or paraprotein disease. Few patients, this was the first systemic presentation of the disease.  What a great observation!!  If it can effect small renal vessels, why not the eye!

What other organs?

Skin: The association between Necrobiotic xanthogranuloma(NXG) and paraproteinemia is well documented in 2009. 11-48% had paraprotein disease as myeloma. The most common is IgG kappa more than lambda. However, the skin lesions in NXG could represent reactive inflammation and are not associated with the presence of monoclonal plasma cells or multiple myeloma.

Powell et al also described initially eight patients with pyoderma gangrenosum and monoclonal gammopathy showed that all patients except one had an IgA paraproteinemia. Seven patients have had a benign course and multiple myeloma has developed in one. In seven patients, the onset of thepyoderma gangrenosum preceded the detection of the monoclonal gammopathy. Since then, more cases have been associated with MGUS.

Syndromes:

Besides POEMS syndrome, which has been well described in the literature, others are :

TEMPI syndrome, a syndrome that was mentioned in NEJM that had a constellation of findings: Telangiectasias,elevated erythropoietin level and erythrocytosis, monoclonal gammopathy(IgG kappa), perinephric fluid collections and intrapulmonary shunting.  Since it’s initially discovery, chemotherapy and HSCT have been used for treatment of this entity.

Schnitzler's syndrome, initially described in 1974 is an uncommon condition defined by chronic urticaria and monoclonal IgM gammopathy. A study done in 2002 found 56 cases of Schnitzler's syndrome reported to date. The absence of lymphoproliferative disease in this condition is typical, but nine patients have progressed to develop lymphoplasmacytic neoplasias, particularly waldenstrom's macroglobulinemia.

So, besides MGRS, MGUS might have other distant organ effects from small noxious B cell clones. Perhaps, this needs to be defined more and treated more like MGRS.  It might be interesting to see the cases of ITG and fibrillary GN – if they have corneal findings and other end organ damages that we might be missing given these novel associations. We might be looking at a more systemic disease. 

We might be entering a new era in the paraprotein world.

New Biopsy Proven Renal toxicities in the Onconephrology World

BRAF inhibitors have revolutionized the treatment of melanoma recently.  While vemurafenib has had several reported cases of AKI, no biopsy proven cases of dabrafenib induced AIN have been reported. A recent review summarizes the renal toxic effects with BRAF inhibitors.  Early on, the injury likely is AIN and much later in treatment-likely ATN.  Finally, a biopsy proven case of AIN just got published with dabrafenib. This helps illustrate that the effects are more immunologic affecting the interstitial comportment. In addition, steroids improved the damage. Re-challenge didn’t allow for recurrence of AIN. 

BRAF inhibitor related toxicity summary

Allergic interstitial disease

Acute tubular necrosis

Proximal tubular damage

Hypophosphatemia

Hyponatremia

Hypokalemia

Sub nephrotic range proteinuria

Also, anti  CTLA-4 agents such as ipilimumab have known to have similar AIN like effects in the kidney. Lupus like nephritis also has been reported. Most recent, a biopsy proven AIN with minimal change disease was reported with this agent.  

Glomerular diseases reported thus far with this agent are:- Lupus like nephritis( membranous GN pattern), MCD and other autoimmune nephritis( but more likely AIN).

In the NEWS: Training in Lung Ultrasound for nephrologists

Recent studies and posts in nephronpower have shown the importance of lung ultrasound in clinical care in nephrology. A recent letter in Kidney International by our fellow and faculty highlight this important skill as part of training for both fellows and faculty.

While renal sonography might be more sophisticated imaging technique requiring more training, lung sonograms should become part of your physical examination.  It should help one assess volume status better.

Take a look at this letter in KI.  

Image source: www.ultrasoundpodcast.com