Pulsating glomeruli

It seems incredible now that it was only in 1998 that it was conclusively proven that the podocyte plays a vital role in the prevention of albuminuria. At that time mutations in NPHS1, encoding nephrin, were found in 49 patients from Finland with congenital nephrotic syndrome. Up to that point, the podocyte was thought to play a secondary role in the glomerular filtration barrier. Since then, multiple mutations in different podocyte proteins have been identified in association with proteinuria. The table below (taken from a recent Nature Reviews Nephrology article) summarizes the podocyte-related genes that have been associated with albuminuria (click to enlarge).

Orthodoxies continue to be challenged - the old model of podocytes that are fixed in place is being replaced by one where podocytes are constantly moving, being shed and replaced. The video below is from a remarkable paper where the authors have used GFP to visualize podocytes in mouse glomeruli. The pulsatile nature of glomerular contractions is notable and fascinating.

Oral Dialysis

It's an important anniversary for the Brigham and Women's Hospital and as a result there are events planned in all departments of the hospital over the next year. Not to be left out, the Renal Division invited some senior nephrologists to come and talk about their experiences with the world of early dialytic therapies and we had a special Grand Rounds presentation this morning on the topic.

John Merrill was one of the early pioneers of dialysis (and has been called the father of dialysis). He was an advocate for the use of dialysis at a time when many believed that it was unethical and experimental. I realized during the lecture this morning that reviewing the published literature of Dr Merrill would be a good way to learn the history of the dialysis. The first paper that I came across was published in 1949 and describes the early experience using the modified Kolff kidney in the Brigham to treat both AKI and metabolic disorders. My favorite quote from this article comes from a postscript added to the paper by a discussant which suggests an alternative means of dialyzing a patient as an alternative to "in vitro hemodialysis" as HD was then termed:


DR. J. EDWIN WOOD, JR. [Charlottesville, Virginia] : We are fortunate
to hear this excellent presentation and view quantitative results with the
artificial kidney.
It may be interesting to compare results from upper intestinal lavage
with the ones just presented. With a Miller-Abbot tube about three feet
below the pylorus and a Levine tube down to the pylorus we can wash
through and recover a large quantity of suitable lavage fluid in a twentyfour
hour run. Actually, we have been able to remove by this method
as high as 11.9 to 23.2 grams of urea nitrogen in twenty-four hours, and
from 90 to 102.5 mEq of potassium at the same time.
Dr. Thorn's artificial kidney obviously accomplishes the desired result
in a shorter period but intestinal lavage removes enough in twenty-four
hours to warrant serious consideration.

I'm glad that this is not one of the alternatives that we are offering patients today.

(Picture from Flickr user Rob Koopman via Wikipedia)

Does that taste bad? - Part 2

Following on from yesterday's post about turtles who may have a taste of urine in their mouths, here's an interesting historical diversion about doctors who, in the past, intentionally drank urine to diagnose disease. An article in Scientific American gave us this picture of a "urine wheel" which, by correlating the taste, smell and appearance of the urine, was a valuable diagnostic tool in the 16th century. The classic diagnosis associated with tasting the urine was of course diabetes but it is by no means the only one. 

Edible geography collected various other urine wheels.

Picture originally from Nature.

Does that taste bad?

Better known as a delicacy in the Far East, the Chinese softshell turtle has generated some interest in the Nephrology world because of its unusual means of urea elimination. A paper was recently published in the Journal of Experimental Biology in which the authors described the process of urea excretion in these interesting animals. The primary habitat of the turtle is seawater, and saltwater marshes and swamps. As a result, most of the water in that environment is hyperosmolar such that eliminating urea via the kidneys could lead to excessive water losses. It had been previously noted that the turtles have a tendency to submerge their heads in water for prolonged periods. The researchers attached plastic bags to the cloacae of the turtles but, to their surprise, found that the urea concentration in the water where they submerged their heads was higher that that of the collected urine. 

The turtles have buccopharyngeal villiform processes in their mouths that contain active urea transporters. They take water into their mouths and spit it out again in order to excrete urea waste. A transporter was isolated from the buccal mucosa that had a 70% homology with mouse and human UT-A2. This transporter was not present in the kidneys of the turtles indicating a lesser role for the kidneys in urea transport. The average urea concentration of the saliva was 36mmol/L as opposed to 2.4mmol/L in the serum. After an IP injection of a urea load, the serum concentration increased to 45mmol/L while the saliva concentration increased to an impressive 614mmol/L.

This evolutionary adaptation may have allowed them to invade this hostile environment. 

CKD Guidelines

AJKD this month has an extended editorial section on the KDOQI guidelines for CKD. It is now 10 years since these guidelines were introduced and their impact on nephrology has been significant, not least due to the fact that many more patients are now recognized as having early CKD that may have been missed in the past. These patients with moderately reduced GFRs, while unlikely to progress to ESRD, still have a significantly increased risk of cardiovascular morbidity and mortality. 

The articles comprise a series of commentaries written by members of the editorial board of AJKD and examine the impact of these guidelines on the NKF itself, research, primary care, clinical laboratories (which now routinely report eGFRs) and the practice of nephrology around the world.

Vividiffusion

"The physicians are now constructing a machine capable of doing the work necessitated by a volume of blood circulating the a body weighing up to 20 pounds and, inasmuch as they have determined to their own satisfaction that the procedure is not inimical to life, there is no reason why it should not be applied to human beings when the occasion arises"

This line is from a 1914 article that appeared in the New York Times describing the work of John Abel who experimented in dialyzing dogs at Johns Hopkins in Baltimore. Cotton-based hoses, leech extracts for anticoagulation, glass tubes, salt, water, science and determination set the foundation for what would become a life-saving procedure.

Below see a video clip of the first recorded dialysis - performed on a dog in 1915 - a classic silent movie. The dog survived!

Posted by Kassem Safa, MD