What I Am Reading: Free Market Edition

(by Pascale Lane) Jul 28 2014

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Sigrid Fry-Revere is a lawyer and a medical ethicist. She has played an advisory role to organ donation organizations in the US. Her latest work explores the kidney "exchanges" in Iran where a very different approach to organ donation has produced a surplus of living kidney donors.

The approach in most of the world has been to use deceased donors for transplantation as much as possible. Kidneys provide a unique opportunity for living donation, since most people have two and can live nicely with only a single organ. Our system requires these kidneys be donated from purely altruistic motives, usually because of relationships between the parties involved: husband - wife, parent - child, or other relations. When relatives or other close parties cannot donate, a donation "circle" can be set up. In this, one party cannot donate to their loved one, but they are a match for someone else whose relatives cannot donate. In the simplest setting, the donor exchange is paired; however, chains of up to 19 donors and recipients have now been orchestrated to give dialysis patients a better life.  While many donor expenses are covered by medical insurance, donating may have unseen expenses, including weeks out of work and the potential for complications of anesthesia and surgery.

Despite harvesting deceased organs, matching services for donor chains, and availability of dialysis, 20 to 25 people in the US die every day awaiting a kidney.

Iran has taken a different tactic to alleviate kidney shortages, namely paying organ donors. The powers that be in the US have assumed that this system is coercive and unfair. Dr. Fry-Revere decides that a program this successful is worth learning about. She spends several months on the road in Iran with an expatriate nephrologist, Dr. Bahar Bastani, a former colleague of mine at Saint Louis University. They bravely recorded video and audio interviews with doctors, nurses, donors, and recipients throughout Iran, generating the first account of this system by Western experts. The resulting book is The Kidney Sellers: A Journey of Discovery in Iran.

In Iran, the national government provides a cash payment for a kidney. Additional compensation varies by region. Most regional centers provide health coverage for a period of time for donors. The donor can then negotiate with the seller through the regional bureau for additional cash; if the recipient has no means to pay, the center can often tap donations for the funds needed.

Procedures vary from region to region. In the best situations, donors are carefully screened to make sure that their financial issues cannot be solved through other routes.  Potential donors interviewed in the book often had a debt to retire or needed capital to start a business; marriage often necessitated a cash infusion. Donors often expressed mixed emotions about the procedure. Many got their money, fixed their financial issues, and moved on with no regrets, but some felt guilt or shame that they had to sell an organ to make their lives better.

Recipients sometimes formed bonds with their paid donors, but for the most part this was a market transaction that ended when it ended. Many stated that they preferred a paid donation to an altruistic one from a relative; the latter would have left them indebted for life, while paying cash let them feel the debt was paid. They could then move on with better health and less guilt.

The book can be a bit repetitive at times, but it paints a wonderful picture of a society and system we know very little of. As I watch my own patients on dialysis, waiting months for a deceased donor kidney, I wonder if the Iranians just might have a good idea. I recommend reading this work for a thought-provoking take on our organ donation system.

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Is the Answer at the RIVUR? #NephJC

(by Pascale Lane) Jul 16 2014

This study will be discussed as part of the online, twitter-based Nephrology Journal Club on July 22,2014. More information about the workings of #NephJC can be found here.

The Problem of Reflux

Vesicoureteroreflux (VUR) occurs in approximately 10% of children overall, but about one-third of those with a febrile or otherwise symptomatic urinary tract infection (UTI). VUR is associated with an increased risk of renal "scars." Since it was first described in the 1960's, treatment of this backflow of urine from the bladder to the ureter has been recommended for all affected children. Surgery can create a competent valve at the vesicoureteral junction during voiding, but an early randomized trial showed that prophylactic antibiotics to prevent infection were just as effective as surgery in the scarring outcome.

Despite the recommendations for treatment for 50 years, permanent kidney failure attributed to VUR has not declined in the end-stage database of any country. Improved prenatal diagnosis of infant renal anomalies have allowed us to diagnose VUR in the first weeks of life, prior to any UTIs. Some children without UTIs still get renal scarring, leading some to suspect that "scars" may actually be areas of hypoplasia or other abnormal development due to an abnormal ureteric bud.

The original study showed equivalent results from surgery and antibiotic prophylaxis, but it included no untreated control group to assess the strategy of intermittent treatment of  UTIs when they occurred. The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial set out to determine if long-term prophylaxis prevented recurrence of UTIs, occurrence of "scars," or contributed to antimicrobial resistance.

The Study

The study was a randomized, double-blind, placebo-controlled trial of prophylaxis with trimethoprim-sulfamethoxazole (TMPS). Children were screened and enrolled after 1 or 2 febrile or otherwise symptomatic UTIs, including positive culture. Bagged urine samples were not allowed. Children in the study ranged in age from 2 months to 6 years and had grades I to IV VUR (severe grade V patients were excluded). Exclusion criteria included other urinary abnormalties, chronic kidney disease, inability to take TMPS, and other selected medical issues.

Studies included dimercaptosuccinic acid (DMSA) scans at baseline and 1 and 2 years later. These scans (the gold standard for kidney scars) were read and scored centrally by two pediatric nuclear medicine radiologists.

Treatment failure was defined as:

  • 2 febrile UTIs
  • 1 febrile and 3 symptomatic UTIs
  • 4 symptomatic UTIs
  • New or worsening "scars" at 1 year

The Results

Baseline characteristics of the children enrolled can be seen here. No significant differences on any parameter existed between the treatment and control groups. Time to first febrile or symptomatic UTI after trial enrollment is shown below:

Figure2

As shown in the paper’s figure 2 above, the two groups separated significantly within the first 6 months of treatment, with TMPS prophylaxis clearly preventing UTIs. By the end of 2 years, approximately one quarter of the placebo group had experienced an infection, while only half that many in the prophylaxis group had fallen ill.

A number of potential modifying factors were assessed for impact on the results, shown in the figure below:

Figure 3

As shown prophylaxis was more valuable for children who presented with febrile, as opposed to symptomatic but afebrile, UTI. Bowel and bladder dysfunction, determined via a standardized survey, also favored the use of TMPS.

Renal “scars” showed no difference throughout the study. Rectal swabs showed no significant difference in the rate of resistance of E. coli to TMPS between the prophylaxis and control groups.

Remaining Questions

Clearly antibiotic prophylaxis reduces the risk of recurrence of UTIs in children with VUR. However, about 75% of children receiving placebo had not suffered a recurrence after 2 years of study. UTIs cause discomfort, school absence, and lost work for parents; even after this trial we have no evidence of long-term damage prevention through the use of TMPS. Antibiotic resistance does not seem to be a big problem in this patient population.

So the question remains: what should we do about VUR?

In my mind, the question is still open. Many families today have qualms about long-term exposure to these medications. Other families dread missing a UTI and would far prefer to take the antibiotic. The tolerance of the family for illness vs the small risks of prophylaxis often prove to be a big factor driving therapy.

That leaves us each a lot of flexibility in our approach to VUR. My personal preference is to watch most cases without prophylaxis initially. Those who have further UTIs in the first few months after diagnosis are encouraged to start prophylaxis and consider surgical treatment. Those without significant recurrences receive follow-up on a regular basis. All of this requires ongoing discussion with the parents and input regarding their tolerance for urinary symptoms.

The pediatric nephrology community hoped that RIVUR would answer our managment questions about VUR. It would appear that we still have more we need to know.

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Better than the BBB

(by Pascale Lane) Jul 09 2014

Our bathroom needs some work on the walls.

We have some peeling and chipped paint, some holes that need repair. The toilet paper holder was not appropriately anchored. It looks like our predecessors in the house glued one bracket to the wall when it pulled out. Its now unstable, to say the least.

I got a couple of recommendations for painters, and I had one come by yesterday for an estimate. She came in the house, and the cat came out to sniff her feet. Dottie, the feline, then rubbed her ankles and presented her belly for a rub.

How can I not hire someone who gets that kind of approval from the cat?

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What I'm Watching: Steampunk MacGyver

(by Pascale Lane) Jun 30 2014

Murdoch Mysteries have captured my attention for the past month or so. The setting is the late 1890s in Toronto where Detective William Murdoch employs the latest scientific techniques to catch criminals. He is assisted by a young Constable prone to flights of fancy. For example, when they fight a microwave death ray (aided by Tesla, of all people), Constable George Crabtree immediately perceives its commercial potential for food preparation. When reminded of the size of the equipment, he speculates that in the future, houses may have a room dedicated to "potato cooking." On another case, as the Detective maps the potential murder weapons and murderers in a model of a grand home, the Constable sees the potential for a board game in the proceedings.

The series includes strong women as well. The original coroner is a woman, as is her eventual replacement. Various romantic entanglements occur over time, of course. Right now, my interest has been captured by the efforts of the women physicians to distribute information about contraception. Discussing periodic abstinence or any other strategy to plan pregnancy was quite illegal. Yup, these ladies get to see the jail cells from both sides of the bars.

This plot line seems especially important at the moment when the rights of women to control their fertility are coming under fire from so many directions.

The first 3 seasons can be streamed via Netflix; all available episodes can be streamed from Amazon as well.

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Update from the Waterbath

(by Pascale Lane) Jun 27 2014

My husband really appreciates the flavors I can achieve with the new sous vide setup. I do find it annoying that he now walks into the kitchen and asks what I'm annealing for dinner.

Tonight's menu includes pork tenderloin and corn on the cob, both completed via sous vide. Photos will go up on twitter.

Happy weekend, all!

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Dinner Dare: Under Pressure

(by Pascale Lane) Jun 25 2014

At last week's meetings of the American Diabetes Association, we stayed at The Intercontinental and dined at Luce, their restaurant featuring sous vide cooking. Literally meaning "under vacuum" in French*, this cooking technique involves sealing ingredients in a bag and then cooking in a constant temperature water bath for prolonged periods of time.

Think about how we usually cook a piece of meat. We expose it to temperatures far above those at which we will consume it, either on a grill or in an oven. We then wait until the interior reaches a temperature at which proteins coagulate and bacteria are killed. Often this means overcooking the exterior of the meat. With sous vide, the meat can be cooked to the temperature desired. Most pathogenic bacteria can be killed at these lower temperatures; it just requires a longer period of time. In addition to avoiding the dried, overcooked exterior, the sealed cooking chamber keeps the flesh moist and allows seasonings to fully permeate the meat.

Sous vide won't give you a crusty carmelized exterior or crispy poultry skin, but these can easily be added just before serving with a quick trip on the grill or a blast from a kitchen torch.

Halibut with Citrus Buerre Blanc - Click for recipe

After a couple of delicious meals at Luce, I began reading more about the technique. Soon my own water oven was en route. Last night I cooked my first real meal with it, using a recipe from Sous Vide Supreme Blog, a valuable resource for ideas with this technique. Three halibut fillets were sandwiched between slices of grapefruit and lemon in a 1-qt vacuum bag with cubed cold butter. These were cooked in the water bath at 132 degrees F for 20 minutes, producing moist flaky fish with a light citrus flavor. While the fish cooked, I made a citrus buerre blanc starting with the juice from the grapefruit and lemon not used for slicing:

Citrus Beurre Blanc (From Sous Vide Supreme Blog)
Yields: 1 cup (8 fl oz/237 ml)

INGREDIENTS

  • 2 tablespoons (1 fl oz/30 ml) dry white wine
  • 1 tablespoon (0.5 fl oz/15 ml) fresh grapefruit juice
  • 1 tablespoon (0.5 fl oz/15 ml) fresh lime juice
  • 1 tablespoon (0.5 fl oz/15 ml) fresh lemon juice
  • 1 tablespoon (0.5 fl oz/15 ml) fresh orange juice
  • 1 small shallot, finely minced
  • ½ teaspoon sea salt
  • 8 ounces (226 g) cold butter, cut into 16 cubes

INSTRUCTIONS

  1. In a medium saucepan bring wine, citrus juices and shallots to a boil. Reduce to about 1 ½ tablespoons (0.8 fl oz/23 ml) of liquid.

  2. Reduce the heat to the lowest setting. Pull the saucepan from the heat and whisk in 2 cubes of butter; as it melts whisk in one more piece.

  3. Set the pan over the lowest heat setting and continuously whisk one piece of butter into the mixture at a time, making sure that each piece is melted prior to adding the next.

  4. Pull the saucepan off of the heat when the last piece is melted.

  5. Spoon immediately onto serving plates and top with fish. Alternatively drizzle over the top of fish.

A sauce this rich and delicious deserves to adorn more than perfect fish, so I put brown rice on the side to soak up some of its loveliness. Served with a green salad and a melange of red raspberries, blackberries, and white nectarines for dessert, it made a refreshing late meal when my husband's plane got in an hour late.

I will be experimenting with my new water bath and posting recipes this summer. So far, sous vide is a winner; I have never been able to produce fish this delicious any other way!


 

*Yes, a vacuum really isn't pressure, but you get the air out of the bag with a negative pressure. Work with me here...

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Name That Demon!

(by Pascale Lane) Jun 23 2014

DemonThe Roman Catholic church rolls out saints on a regular basis, even though I rarely encounter anything remotely resembling saintly behavior in my daily life. However, demonic tendencies seem downright mundane, yet we do not denote it with any sense of shame...or achievement. Today I present my nominees for demons capable of transient possession to help explain some of the bad behavior we encounter on a regular basis. Please add your nominees in the comments.

Declinus Barometrus

This imp possesses my cat just before and during storms, leading her to race through the house like someone is about to bathe her. When excluded from my presence old DB produces howls such that one can only imagine a feline on fire, thus allowing her into the bedroom where she disrupts sleep ALL. NIGHT. LONG. The demon leaves with the thunder, and the cat immediately becomes cuddly as if to make up for her fears. Regular indifference resumes with the first light of day...

Ragius Stockcarus

A less benign devil, Ragius displaces the normally friendly soul of most Oklahomans the minute they slide behind the wheel of a car. Displays at first seem mild, like "rolling" stops or a bit of extra speed through the school zone. Once on the interstate, the full rage and horrible glory of RS can be felt, as normal drivers feel compelled to pretend they are on the Texas Speedway, going for the win. Exorcism of this spirit merely requires turning off the auto's engine and stepping away from the vehicle.

Reviewerus Treyus

Scientists who normally judge others with a fair and impartial mind become unreasonable fonts of minutiae and additional experiments once this bad boy enters their beings. Five years of experiments become mere preliminary data when the eyes are clouded by the third reviewer from the netherworld. If it's your manuscript under review, you better pray that your editor has the power to sense this evil presence, since good judgement is really the only countermeasure.

What other modern demons need to be named?

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Getting the Floor

(by Pascale Lane) Jun 19 2014

Daenerys-Targaryen-game-of-thrones-23107710-1600-1200Women often have trouble getting our voices heard in meetings. Our attempts to speak can be thwarted in a number of ways, and if we interrupt the way men do we are aggressive bitches. I cannot embed the video, but you can click over and watch my new solution:

Targaryen-Style

Of course, we tend to frown on bloodshed in the twenty-first century. For more practical advice, I recommend this post in Inc.  with eleven suggestions for being heard. Not as dramatic as Daenerys Stormborn. Perhaps not as effective.

But infinity more acceptable outside of Westeros.

Because we all cannot be Mothers of Dragons.

 

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Fair Warning

(by Pascale Lane) Jun 11 2014

Tomorrow I am off into the friendly skies again, headed for that city on the bay for the 74th Scientific Sessions of the American Diabetes Association. That means my posts for the next week or so will involve diabetes and its complications, especially kidney disease.

Other random shiny objects sometimes catch my attention when I travel, so get ready for those as well.

 

 

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Oh, Crap!

(by Pascale Lane) Jun 05 2014

Insert your favorite term for fecal material in the title. That defines my week covering our inpatient service. Once again, we have more E. coli causing bloody (literally-not used in the British sense) diarrhea and more hemolytic uremic syndrome. This condition plus assorted other weirdness have once again moved blogging waaaaay down my To-Do List.

Feel free to start your own discussion in the comments. Someone may as well use this corner of the internet for a bit!

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