eAJKD's #Neph Madness

Welcome to Neph Madness: the ultimate Nephrology competition of the best accomplishment in Nephrology. 

March Madness and Kidney Awareness Month leading to the NephMadness.
Blend it with NCAA Men's tournament and we shall crown the next champion- the greatest nephrology advancement
Check out the next 2 weeks in eAJKD for the winner

Play along the fun game and in the midst- learn the history of Nephrology!!.
http://ajkdblog.org/category/nephrology-madness/

Medical student perspective on Nephrology

Happy World Kidney Day!  The theme this year is kidney attack or Acute Kidney Injury. In the US, the nephrology community is facing a different form of attack.  There is a nephrology workforce angina.
While we have postulated what could be the reasons for many residents not choosing the field for variety of reasons, two medical students( American and German) in a recent editorial highlight their reasons and concerns regarding the field of nephrology.

Two medical students celebrate nephrology with it's wholesome experience. Medical students need to see the entire nephrology experience ( and not just inpatient) and need to have knowledge of the gratifying longitudinal experience of nephrology.
Let's take a pledge this World Kidney Day

1. To showcase nephrology( both inpatient and outpatient) to medical students around the world
2. To showcase the positive research opportunities in this field of medicine
3. To showcase them that nephrologists are good teachers and make great clerkship faculty cohorts
4. To showcase them the best organ of the human body

Topic Discussion: Renal injury biomarkers

Finding a troponin for renal injury has been the quest for the last 10 years for many researchers in Nephrology. A recent article in AJKD nicely summarizes this quest in a core curriculum review. The lead author is from the renal fellow network.

Some key points:
1. Most biomarkers that have been discovered in the recent years have been mainly looking at proximal tubular injury and glomerular permeability.
2.While creatinine and albuminuria are always considered conventional, it was interesting to see that they included cystatin C as a conventional marker as oppose to novel. Clinically, doubt the use of this marker has blossomed yet.
3. Most common settings most of the newer markers have been checked are: post cardiac surgery, intensive care unit settings and contrast nephropathy
4. The best part of the paper is the discussion of urinary versus serum biomarkers and how in certain cases urinary markers could be most helpful but there could be contamination. Serum biomarkers are excellent to have during anuric settings but are they specific for kidney injury?
5. There are many tables that are good to review to go over most of the new markers that have been evolving in the last 5 years.

Kidney TREKS: ASN's new venture for medical students

A product of the ASN workforce committee's efforts to increase interest in nephrology is Kidney TREKS- the medical student course in physiology that could potentially spark interests among budding nephrologists. Regardless of the choice of specialty these students choose, attending this spectacular course will enhance their understanding of physiology and science. Also, for more references and details check the ASN trainees page.

In the News: LG3 and the Transplanted kidney

Antibodies have always been the biggest concern in transplantation. During vascular rejection, there is endothelial cell damage. The apoptotic endothelial cells release a fragment of perlecan referred as LG3.  

A recent study in the AJT identified a novel antibody that may be playing a role in vascular form of antibody mediated rejection. The authors call this anti-LG3, an antibody that some patients produce to attack a protein that plays an important role in vascular repair and regeneration, LG3. In these patients, the secretion of LG3 by the new kidney stimulates the activity of these antibodies which attack and injure the blood vessels of the transplanted organ, and the normal healing process of the transplanted organ is impaired. Patients who experienced vascular rejection had elevated anti-LG3 titers pre and posttransplantation compared to subjects with interstitial form of rejection( cellular) or stable graft function significantly respectively.  The authors also confirmed these findings with mice data. Collectively, these data identify anti-LG3 antibodies as novel accelerators of immune-mediated vascular injury and obliterative remodeling. One prior animal study showed similar findings. 

Do we have a new marker for potential vascular rejection? What is the data on LG3 in other forms of endothelial injury namely CNI induced TMA or other forms of endothelial damage? Then again, the perlecans are altered in certain genetic diseases that don't quite fit the role they play in transplantation. 

Topic Discussion: Genetic Diabetes Insipidus

The arginine vasopressin gene (AVP gene), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])—provide the basis for understanding of three different hereditary forms of “pure” diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephrogenic diabetes insipidus (NDI), and non–X-linked NDI(AD and AR), respectively. Four main categories can be considered. 

Neurohypophyseal diabetes insipidus: Autosomal Dominant, they retain some limited capacity to secrete AVP during severe dehydration, and the polyuro-polydipsic symptoms usually appear after the first year of life, when the infant’s demand for water is more likely to be understood by adults. 

Delayed onset of disease and can get worse with age.  The gene mostly involved is AVP gene. 

X-linked NDI: Affected male patients do not concentrate their urine after administration of AVP. Because this form is a rare, recessive X-linked disease, female individuals are unlikely to be affected, but heterozygous female individuals can exhibit variable degrees of polyuria and polydipsia because of skewed X chromosome inactivation.  The gene mostly involved is AVP2 gene. V2 receptors have been tried as chaperone medications as a trial to help overcome the misfolding that happens as a result of the gene mutation and helps in NDI.

Autosomal recessive NDI: Some cases have been identified. They have defect in the AQP2 gene.

AQP2 mutations that are responsible for autosomal recessive NDI are characterized by misrouting of the misfolded mutant proteins and are trapped in the endoplasmic reticulum.
Autosomal Dominant linked NDI: Both males and females affected. A patient who presented shortly after birth and it is a defect in the AQP2 channel gene. 

A nice review can be found at JASN and NDT

Pathology and Nephrology: A combined force!

The rise of renal pathology: a recent review in AJKD refers to the role of the renal pathologists in the care of the kidney patient. Truly a dedicated article to the nephro-pathologists in the world who are truly making a difference in nephrology care. Their presence at the nephrology national meetings is always felt as a strong positive influence and force.

Some interesting historical points from the review:
1. The first pathologist who used nephron dissection as a primary means for studying renal diseases was Dr.Jean Oliver
2. Kidney biopsies were used for tumors as early as 1930s
3. The earliest reports to use in renal diseases were in 1950s by Dr. Iversen and Brun from Denmark
4. Pirani-Kark and Muehrcke team from Univ of Chicago did the first groundbreaking clinical-pathological studies to start the era of kidney disease pathology.
5. The CIBA symposium ( London) in 1961 was the first nephrology-pathology meet that sparked enthusiasm and exchange of ideas and experience of leaders worldwide in this field.
6. Hepinstall's Pathology of the Kidney became the landmark book for nephro-pathology.  Dr RH Hepinstall from Great Britain wrote the first edition in 1966. He also served as president of the American Society of Nephrology in 1972. Yes, he is one of the two pathologists who served as the president of ASN.
7. Dr. Ramzi Cotran served as ASN president in 1995.

Check out the entire manuscript at AJKD.