Predicting progression in acute kidney injury

Last month the final study from my time at NIH was published. This study explored a promising, and relatively new, biomarker for acute kidney injury during critical illness. Although the biomarker had been previously tested in humans we were able to develop a potential refinement in a preclinical model.

During critical illness, such as sepsis, organ failure is a major complication increasing the risk of death. For the kidneys, treatment is limited to more focused management. This means avoiding further harm and keeping the patient alive long enough for kidney function to return.

The sooner kidney injury is detected the better the likely outcome but this can be surprisingly difficult. Some significantly improved options have been developed but further, even better, options are still desired. A new approach is giving the kidney something to do and measuring how well it performs. This idea is similar to the treadmill stress test commonly used to detect cardiovascular disease such as angina.

The test that was developed gave a dose of a drug called furosemide that is actively excreted by the kidneys and stimulates urine production. If the kidneys are healthy, the furosemide will be excreted and the amount of urine produced will increase. In a human clinical study this approach performed very well and there have been several subsequent studies in different settings.

Urine volume is altered by a variety of factors and we decided to investigate whether further improvements in performance would be possible by measuring furosemide excretion directly. When used in ideal conditions results were comparable. However, when we gave a drug called vasopressin that is commonly used to manage blood pressure during critical illness measuring urine volume gave erroneous results while furosemide excretion remained reliable.

The study is published in Critical Care Explorations and is freely available.

Circadian rhythm and variation in small extracellular vesicles

Exosomes have been an ongoing interest for several years. Beginning with my PhD in Edinburgh and continuing in my current position I have published several articles on exosomes. The field is also maturing with a growing appreciation for the complexities of exosomes and related vesicles. Exosomes are formed and released by a specific mechanism from cells. Once released exosomes are difficult to distinguish from other sources of similar vesicles. In many experimental settings it would be difficult to confirm an exosomal origin. To reflect this uncertainty the use of the term small extracellular vesicles was suggested following a broad consultation by the International Society for Extracellular vesicles.

We have recently published an article on two related investigations:

  1. the circadian pattern of small extracellular vesicle release in the urine
  2. possible methods for normalizing biomarkers derived from small extracellular vesicles

Circadian patterns, or rhythms, are natural oscillations in biological processes that repeat roughly every 24 hours. They are widely seen in biological systems but little is known about variations in exosome, or small extracellular vesicle, release. A circadian rhythm is just one source of variation that may contribute to the wide variability seen in biomarker studies of small extracellular vesicles. In this article we suggest that normalization by small extracellular vesicle number may help correct for some of the variability encountered.

Cryptography talk at DC Python

At the April meeting of DC Python I gave a talk on cryptography. A video of the event is now available on youtube.

DC Python is the local user group for the python programming language in the Washington, D.C., Maryland, and Northern Virginia area. I have been hosting a monthly event called Project Night with the group since 2015 and we have recently restarted a monthly talk event. All events can be seen on our meetup page.

My presentation was a summary of two of my recent posts on two factor authentication and partial passwords with an introduction to using cryptography in python.

The other presentation was given by Alan Swenson on JSON web tokens in flask. The video for his talk is also available.

Exploring the onset of acute kidney injury during sepsis

In an earlier post I discussed the damage sepsis can do. It has been a focus of many of the projects I have been involved with for the past few years even though the group I am with is tasked with studying kidney disease. We are interested in sepsis because it is a major cause of acute kidney injury.

We do not yet know all the details of this link. Knowing exactly when kidney function falls after sepsis and what triggers the fall could be very important. It would help in developing clinical procedures and therapies to manage patients with sepsis at risk of acute kidney injury.

I recently published a study exploring one potential cause of falling kidney function during sepsis. The kidney filters the blood and removes excess fluid, solutes, and toxins from the body. The blood passes through the glomerulus where fluid can leak out. The volume at this stage is very large and includes many good things the body wants to keep. This fluid then passes through other specialized structures including the tubules where most of the fluid and useful solutes are re-absorbed. To prevent the body from losing too much fluid if the tubules are not working there is a feedback loop that stops the glomeruli producing filtrate.

Using a genetic model I tested whether this feedback loop is activated during sepsis. The results have just been published in the American Journal of Physiology. Renal Physiology.

A partial password implementation

Whilst working on my previous post on two factor authentication I was reminded of the broad spectrum of approaches taken to security by many sites. I have one bank that does two factor authentication, another using the standard username/password combination for one factor authentication, and then another that asks for a username, a piece of personal information and then a partial password. In this case, three characters from a password.

Of these three approaches it is the last that seems the weakest. The piece of personal information includes things like the town you grew up in, the name of your first school, etc. These are not generally secret and could be discovered for most people by a bit of research. The partial password scheme seems only slightly stronger than a three character password.

I believe the partial password is intended to prevent a keylogger on your computer from compromising your entire password. This scheme is often paired with selecting characters from a dropdown menu, potentially providing additional protection. The idea is that by requesting different characters on each visit you would need to log in multiple times on a compromised computer before an attacker discovered your entire password.

I don't think such a system would be used in a new application today but I did wonder how such a scheme might be implemented.

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