Using Cellphone Photos for Medical Analyses

There's an app now for taking medical-grade selfies of a sort. Actually, they're selfies of urine dipsticks, useful for diagnosing and monitoring certain diseases and conditions.

Clinical diagnosis of certain diseases and conditions relies on simple dipstick analysis of a sample of urine. Typically, a paper dipstick that changes color when dipped in urine is compared to a color chart to determine the presence or absence of certain substances in the urine, such as glucose, blood, or protein. Diagnosis depends on a physical comparison of the color of the dipstick to a reference color chart.

It would be nice to be able to just take a photo of the dipstick and send it in to a health professional, so that diagnosis could be done remotely without the patient having to go to a clinic. But the problem with photo analysis of a dipstick is that the colors depend critically on lighting conditions and the angle at which the photo is taken. But now an app developed by an Israeli company called Healthy.io has gotten around that problem. First, a photo of the dipstick is taken against a proprietary color card. The app, called Dip.io, then color-corrects the background colors to mimic natural ambient light and reads the dipstick. The company hopes that Dip.io will provide patients and their physicians with an easy and inexpensive way to monitor certain diseases characterized by substances in the urine, such as diabetes (glucose), chronic renal failure and pre-eclampsia of pregnancy (protein), and urinary tract infections (blood).

The ability to standardize photographs for color and size opens up all kinds of possibilities. Take dermatological conditions, for example. If moles on the skin were photographed against a background card displaying objects of various sizes and colors, the results could again be standardized to allow long-distance diagnosis. The barriers to entry into this exciting new development in distance medicine are low (just the development of an app), so we can expect Healthy.io to have healthy competition in the future.

Disclosure: I have no financial interest in Healthy.io, nor do I expect to have one in the future. I'm just interested in new and interesting medical technologies.

First Child Born Without Kidneys

The first child ever to survive a condition called bilateral renal agenesis (the failure of kidneys to develop in the fetus) will be three years old this July. Young Abigail Beutler is the daughter of Congresswoman Jaime Herrera-Beutler from Washington state and her husband, Dan.

Bilateral renal agenesis occurs in about 1 in 5,000 pregnancies. In the past, such fetuses always died before birth. That's because the urine produced by the fetus's kidneys is the source of most of the amniotic fluid that bathes a fetus; without adequate amniotic fluid, the fetus's lungs fail to develop normally. Representative Herrera-Beutler's fetus (the future Abigail) was kept alive during gestation by an experimental procedure in which Rep. Herrera-Beutler received intra-abdominal injections of saline throughout late pregnancy, simulating amniotic fluid. The technique worked, and Abigail was born successfully on July 15, 2013.

But that was only the beginning of young Abigail's survival story. Because she was born without kidneys, she was on dialysis from birth until she was old enough for a kidney transplant. Fortunately, both of her parents were good matches for the transplant. On Feb. 8 of this year when she was 2 1/2 years old, Abigail received one of her father's kidneys. Both father and daughter are doing well.

Call it yet another lifesaving advance in medicine. We can probably expect the saline injection technique used in this case to become the standard treatment for fetuses diagnosed with bilateral renal agenesis.

Using "Incompatible" Kidneys for Transplant

Every year, hundreds of patients who need a new kidney die before a donated kidney (either from a living person or a cadaver) can be found for them. The basic problem is that the donated kidney has to be a good immunological match for the recipient (the patient) or his/her immune system will attack the donated kidney, ultimately causing it to be rejected. But before we blame the immune system for this problem, remember that the immune system protects us from infectious diseases precisely because it attacks foreign tissues and cells, such as bacteria.

Knowing how the immune system works, scientists think they may have found a way to circumvent the system so that any kidney could be used in any recipient. It would mean that a husband could donate to his wife, for example, or any friend could donate to a friend in need. This would be a huge advance, because the chance of a good immunological match between two unrelated individuals is around one in 100,000 or more.

In the procedure, called "desensitization", the patient's antibodies are filtered out of the blood. (They're replaced by an infusion of other antibodies to provide some temporary protection from infection.) After the kidney transplant, the patient's immune system slowly replenishes the patient's own antibodies, but for some reason these new antibodies are not as likely to attack the foreign (donated) kidney.

  According to a recent summary study, the 8-year survival rate of desensitized patients who received an incompatible kidney was 76%. That compares favorably to the 44% survival rate of a matched group of control patients who simply remained on the transplant list.

Transplanting HIV-Positive Organs

If all goes according to plan, there will soon be a significant increase in the number of human organs available for transplantation. That's because the United Network for Organ Sharing (UNOS), the system that oversees organ transplants in this country, has given final approval to begin transplanting organs from HIV positive donors into HIV recipients.

Twenty years ago, HIV-positive patients were not considered good candidates for organ transplantation because they were not expected to live very long. But over the years better treatment of HIV has meant that HIV-positive patients can live nearly a normal life. So although HIV-positive people are now eligible for organ transplants, there are not nearly enough HIV-negative organs available to satisfy a rapidly growing demand. (Traditionally, organs from donors who test positive for HIV are rejected because of the fear of transferring HIV to the recipient.)

Prior to 2013 it was illegal to even conduct research using HIV-positive organs. Then in 2013 the government passed the HIV Organ Policy Equity (HOPE) act, allowing such research for the first time. The research showed conclusively that HIV-positive organs could be effectively and safely transplanted into HIV-infected recipients. The first such transplant is likely to occur within months. The availability of HIV-infected organs dramatically increases the pool of organs available to HIV-positive recipients (they will now be eligible for organs that HIV-negative recipients are not). It will also improve the situation for potential recipients who are not HIV-positive, because there will be fewer HIV-positive recipients competing for the available HIV-negative organs.

It's win-win for all potential organ recipients, regardless of HIV status. The government should be congratulated for their vision on this one.

Should Kidney Donors be Compensated?

Is it time to seriously consider whether kidney donors should be paid? The idea has always been dismissed out of ethical concerns, but as the need for kidneys and the cost of caring of patients on dialysis continues to rise, opinions are beginning to change. Did you know, for example, that the cost of caring for patients on dialysis now consumes 7% of the entire Medicare budget? Are you aware that some countries DO now compensate kidney donors in one form or another, without any obvious negative consequences?

For an interesting and informative take on this issue, read the well-documented opinion piece in The New York Times by Tina Rosenberg. She covers the subject much better than I could here.

Illegal Human Organ Trafficking

It is illegal to sell or buy human organs in most countries. It is also against the principles of the Transplant Society and the International Society of Nephrology, whose joint Declaration of Istanbul states that organ trafficking and transplant tourism “ violate the principle of equity, justice, and respect for human dignity and should be prohibited.”

But where there’s money to be made, someone will try to make it. As the gap between the demand for kidneys and their supply (from cadavers or live donors) continues to widen, unscrupulous underground “businessmen” manage to bring desperate patients and willing sellers together, for money. If you can find one of these kidney brokers, the going price seems to be nearly $200,000 to buy a kidney, but less than $20,000 to sell one.

Kidney brokers are rarely caught and convicted, in part because they may not live on the same continent as the buyer and seller. So where exactly is the crime committed? Furthermore, brokers claim to enlist only altruistic donors who are not paid. They tell the potential buyer that the high price is to “cover expenses”. Donors are paid under the table and then coached to say that they are not doing it for money. No one really believes that, however, when the donor is from Costa Rica and the patient (a total stranger) is from Israel or the U.S. Desperate buyers are willing to turn a blind eye to the truth when their life is at stake. For a peek into this shadowy world, see the New York Times article on the subject or visit the Declaration of Istanbul website highlighted above.

Reasonable people have argued that the only way to eliminate the black market in human organs is to permit the buying and selling of organs, subject to controls to protect potential donors. They argue that thousands of lives could be saved every year. Whether buying/selling organs could be done without undue coercion of the poor is still an open question. At least one study in this country suggests that perhaps it could (this blog, April 26, 2010.) I’m not convinced, however, that the same results would hold in places where people are truly desperate, and not just below the average U.S. income. I’m reserving judgment on this idea for now.

A New Drug for Type 2 Diabetics

In normal people, insulin causes sugar to be taken up by cells, especially in muscle, liver, and fat.  But in Type 2 diabetics, insulin loses its effectiveness, and as a result too much sugar remains in the blood.  Most of the drugs currently used to treat diabetes improve cells’ ability to take up sugar from the bloodstream, thereby lowering the blood sugar level back toward normal.

Now there’s a new drug that works in an entirely different way.  Invokana was developed based on a basic knowledge of how the kidneys handle blood sugar.   Normally, all of the sugar that is filtered in the kidneys is reabsorbed back into the bloodstream; none is excreted in the urine.  It’s nature’s way of conserving energy (sugar).  The mechanism of sugar reabsorption involves sugar transport “pumps” (comprised of certain proteins) in cells of the renal tubules.   Invokana blocks those sugar transport pumps, so some of the some of the filtered sugar is not reabsorbed.   Instead, it is excreted from the body in the urine.  In diabetics (whose blood sugar is too high), that's a good thing, because it lowers the blood sugar level.

One of the potential side effects of Invokana is a slight loss of weight.  That makes sense when you think about it; sugar lost in the urine equals calories lost.  In diabetics who are also overweight, that could be a good thing.   But I see a real danger here; what if people are led believe that Invokana would work as a diet pill (“just pee those extra calories out!”) and a black market develops for it?

I hope that doesn’t happen.  There’s no data yet to prove that Invokana would result in enough weight loss to make a dieter happy.  More importantly, in a person with a normal blood sugar level to begin with, Invokana might lower blood sugar to dangerously low levels.   Unfortunately, people are willing to believe some pretty crazy things when marketers (black-marketers or otherwise) give them just a grain of truth.

Economic Theory is Applied to Kidney Donations

In 2012 the Nobel prize in economics was awarded to economist Alvin Roth and mathematician Lloyd Shapley, for their work in developing algorithms for efficient computerized matching of individuals with unique needs with other similar individuals or institutions. Their algorithms have been used to match employers with employees; hospitals with doctors seeking residencies; students with schools; even kidney donors with kidney recipients.

That’s right; kidneys. Matching donors to recipients is not all that easy, because although a donor may want to donate to a specific recipient (say a relative, or a spouse), often they can’t because the tissue match is not good enough. That’s where Dr. Roth and his computer algorithm come in. By entering all available potential donors and recipients into a computer file and then applying a matching algorithm based on each donor and recipient’s tissue type, the best possible match can be found for each donor and for each recipient, even though they might not even be aware of each other. The donor may end up donating to an unknown and unrelated recipient, but in exchange the recipient will get a kidney from another, also unrelated, donor. The effect is the same as if the donor had donated directly to his/her specific recipient of choice!

Dr. Roth’s matching algorithm was first applied to kidney donations back in 2004 by the New England Program for Kidney Exchange (NEPKE). The method worked so well that NEPKE was later folded into the current national kidney matching system, United Network for Organ Sharing (UNOS). Since 2004 Dr. Roth’s method of matching has resulted in over 2,000 kidney donations, most of them between unrelated donors and recipients.

Sarah Murnaghan had Two Lung Transplants

Well, it didn’t have to happen, but it did; Sarah Murnaghan’s first lung transplant on June 12 failed almost immediately. She was put back on the organ transplant list, and three days later she was given a second set of adult lungs.  Her condition is improving now.  But here’s the irony; in all the talk in the past several weeks over the landmark case that she represented (adult lungs given to a 10-year-old child), the pubic was unaware that it was her second pair of lungs that have helped her to get better. That fact only became widely known on June 28, nearly two weeks after the second transplant.

The basic problem with transplanting adult lungs into children is that the lungs need to be “resized” to fit the child.  It adds another level of risk to what is already a fairly risky procedure. That’s one of the reasons that the organization that oversees transplants, the Organ Transplant and Procurement Network (OTPN), had a policy of not approving adult lungs for transplant into children under 12 years old.  But Sarah’s parents sued, and so the OTPN decided to keep its “Under 12 rule” but create a special review option for one year to consider exceptions on a case by case basis.  So now we have a precedent that may embolden the parents of other needy children to sue for what they want.  We should all be happy that young Sarah survived the surgeries and is doing well, but make no mistake; that means that the two sets of lungs didn’t go to someone else.

When it comes to such rare and precious resources as human organs, the decisions regarding who gets them are likely to remain contentious. This is worth talking about; who should decide, and how should they decide? The OPTN’s special review option is set to expire in one year unless the full board of directors votes to keep it.  I’ll be interested to see what they do.  

Transplanting Adult Organs Into Children

On June 12 a young cystic fibrosis patient named Sarah Murnaghan finally received a much-needed transplant of an adult lung. What makes this news is that Sarah is only 10 years old.

Adult lungs are not readily available for transplant, and children’s lungs are just plain rare. Because children are smaller than adults, adult lungs have to be resized to fit them, adding an additional level of risk of failure. Therefore the organization that oversees transplants, the Organ Procurement and Transplantation Network (OPTN), had developed a policy of not considering adult lung transplants for children under the age of 12. But following an urgent request by her parents, last week, a federal judge ruled that younger children should be eligible for adult lungs, opening the way for Sarah to receive her lungs and for other children to be considered as well.

Not everyone is happy about the new development. For years, the OPTN has done its best to allocate scarce organs equitably and fairly. The recent ruling disturbs some people because it implies that seeking help from the courts (as Sarah’s parents did) is a legitimate way to deal with what are clearly complex medical and ethical decisions. I’m as glad as anyone that little Sarah was saved by a lung transplant. But given that there are too few transplantable organs available, do we want medical professionals and ethicists to make such decisions based on certain principles of fairness and medical effectiveness, or do we want the decisions made by judges and lawyers based on who shouts the loudest?

You decide.

Obesity and Kidney Donation

Over 90,000 patients with advanced renal failure are waiting for a suitable kidney for a transplant. There are simply too few cadaveric kidneys available, and not enough suitable living donors, either.

Live donor kidney donation is considered safe for persons who are in good health. Long-term follow-up studies of persons who donated kidneys as long as 50 years ago have shown past donors live just as long as one would expect. To ensure that donors are not put at risk, potential kidney donors are screened for good health before they are allowed to donate.

Persons who are obese may be rejected as potential kidney donors even though they are otherwise in good health. That’s because obesity is a known risk factor for kidney disease later in life. There are no hard-and-fast weight limits to be allowed to donate a kidney because no one knows whether donating a kidney would actually increase an obese person’s chances of kidney disease later in life. Nevertheless, many kidney transplant centers aren’t willing to take the risk. More than half of all kidney transplant centers set a Body Mass Index (BMI) of 35 as an upper limit for an acceptable donor; 10% set the limit even lower, at a BMI of 30.

According to a presentation at a recent clinical meeting of the National Kidney Foundation, one transplant center found that 37% of its potential living kidney donors were obese (BMI>30) and another 22% were morbidly obese (BMI>35). Although the morbidly obese potential donors received nutritional counseling and follow-up, fewer than 15% lost enough weight and eventually were allowed to donate a kidney.

Obesity is on the rise in this country. It’s a shame that the potential pool of living kidney donors, never large enough to begin with, may shrink even further with the rise in obesity.

Another Way to Increase Organ Donations

As I’ve pointed out numerous times, there’s a critical shortage of cadaveric organs for transplantation into patients whose own organs have failed them. That’s why the news this month that Facebook would allow its members to list their organ donation status on their Facebook page was such welcome news. The hope is that social pressure, or at least the knowledge that their friends were doing it, would convince more people to become potential organ donors.

Researchers interested in organ donations are looking into other ways to increase organ donations as well. In one recent experiment, about half of all drivers arriving at a driver’s license renewal office to renew their license were shown a five-minute iPod video addressing common concerns about organ donation. The other half of the drivers did not see the video. Then in an exit poll, all drivers were asked to show the organ donor status written on their new licenses. 84% of the drivers who saw the video consented to be organ donors, compared to 72% of the group that did not see the video.

Apparently just a little effort to address people’s concerns about organ donation goes a long way toward convincing people to donate. Although the increase in willingness to donate after seeing the video was just 12 percentage points overall, that 12% is the equivalent of more than 40% of the 28% of drivers in the control group who chose not to donate after not seeing the video.

Facebook Encourages Organ Donations

Every year, nearly seven thousand of the people who are waiting for an organ transplant in the U.S. die before they ever receive an organ. The sad truth is that the number of organs available for transplant is falling farther and farther behind the growing demand for organs. Most states permit or even encourage persons to make their wishes regarding organ donation known on their driver’s licenses. And yet, fewer than half of all adults have indicated that they would be willing to be an organ donor in the event of their untimely death.

In what some people see as a move from social networking into social engineering, Facebook announced last week that it would encourage its members to list their donor status on their Facebook pages. Experts in the field of organ donation are pleased. It’s one thing to decide in private to be an organ donor – its quite another to make a public statement by announcing it to all of your friends. The hope is that peer pressure will cause some of the 160 million Facebook members in the United States (and 900 million worldwide) to join the organ donation bandwagon, adding millions of persons to the potential organ donor pool.

I’d like to see that happen. Though I’m not a Facebooker, I am proud to be a a potential organ donor. How about you?

Advertising for a Kidney on Craigslist.org

A 28-year-old Florida woman who desperately needed a kidney transplant made a plea last summer on Craigslist.org for a person willing to donate one to her, according to an article in USA Today. After the local television channel picked it up as a news story, she received over 800 inquiries and finally found a willing donor who was a good match - a 23-year-old woman who lived nearby. The two women traveled together to the hospital for psychosocial evaluations and medical tests. Eventually the hospital gave its approval, and the donation/transplant was performed in December. Both women are doing well.

Placing an ad on Craigslist or other Web site for a kidney is a bit unusual, but not illegal as long as the donor is not paid for the kidney. The donor’s medical expenses can be paid, but no other compensation is allowed. The reason for the psychosocial evaluations is to ensure that the motivation of the donor is purely altruistic and that he/she knows all of the possible medical and psychosocial risks. 

The only benefit to an altruistic organ donor is the knowledge that they have done something truly selfless for another person. And for a rare few, that apparently is enough. How rare? Less than 2% of all living donors are strangers to the recipient.

Kidney Disease and African Sleeping Sickness

Natural selection can actually favor an otherwise harmful allele of a gene, if that allele somehow confers a survival advantage in some individuals and populations. The one textbook example of this phenomenon has always been sickle cell disease, a genetically inherited disease that results in deformed red blood cells and can lead to early death. Sickle cell disease is prevalent in persons of African ancestry because the allele that causes sickle cell disease also protects the person with that allele from malaria, a disease which is widespread in Africa.

Now there’s a second example of this phenomenon. Researchers have found that two different alleles for a gene involved in the production of a blood protein; a) are associated with a rare inherited kidney disease, and b) protect against the parasite that causes African sleeping sickness. Not surprisingly, the two abnormal alleles and the kidney diseases they cause are four to five times more common in African Americans than in persons of European descent.

Researchers are wondering how many other genetic diseases we’ll find that also confer protective advantages against certain infectious diseases. Researchers are also hoping to develop new treatments for African sleeping sickness that are based on the proteins these abnormal alleles produce.

How Safe is Live Kidney Donation?

It’s been about 60 years since the first live kidney donor operation. There have been scattered reports that kidney donation is safe, but most published studies have been limited in scope and used inappropriate control groups against which to compare mortality statistics.

A recent report strengthens the hypothesis that live kidney donation is relatively safe. The report compares mortality data for essentially all 80,347 live kidney donors in the United States between 1994 and 2009 to a carefully matched control group of people who were eligible to donate but were not asked to do so. Mortality statistics were followed in both groups for up to 12 years (median 6.3 years) after donation by the live kidney donor group.

The results indicate that there is a small risk of death from the surgical procedure itself, as would be expected of any similar major surgical procedure. Early post-surgical (three-month) mortality was 3.1 per 10,000 kidney donors, compared to 0.4 deaths in the control group over a similar three-month period. After that, however, there were no differences in survival between the donor and control groups out to 12 years.

The results support the hypothesis that there is no long-term mortality risk associated with live kidney donation except for the usual risks of surgery. Presumably a follow-up study will be done in years ahead to extend the definition of “long-term” to beyond 12 years.

Paying Living Donors for a Kidney

Arguments against paying living donors for a kidney generally focus on two ethical concerns; 1) that payments might induce a potential donor to ignore the risks associated with kidney donation, and 2) that payments might exploit poor people, who would have a greater incentive to donate than wealthier persons.

To test these concerns, a team of researchers polled 342 potential donors in Philadelphia. The study found that potential donors’ perception of the risk of kidney donation is completely unaltered by how much money is offered for their kidney ($0, $10,000, or $100,000). The study also found that although a potential donor’s willingness to donate is influenced by money (more money, more willingness to donate), the effect of money was the same across all income strata. In other words, there was no evidence that payments would either induce donors to ignore risk or specifically exploit poor people.

Based on these data, perhaps payments should be offered to donors on a trial basis. It’s worth knowing whether potential donors’ actual choices would be the same as their hypothetical choices on a survey.

Encouraging Organ Donations

Fewer than 40% of all adults have signed a donor card or other legal document indicating their willingness to donate their organs after death. Perhaps it’s a form of avoidance, but for whatever reason we just don’t seem to get around to it. "Presumed consent" laws are one solution, but some people find presumed consent laws objectionable on the grounds that they are a form of religious discrimination. Under presumed consent, it's people who do not wish to donate (perhaps for religious reasons) who must make their wishes known in advance, not the other way around.

One innovative and eminently fair solution is to require everyone to make their wishes known. Its called “mandated choice”. In the State of Illinois, every person over the age of 18 who renews a driver’s license must answer the question, “Do you wish to be an organ donor?” The state now has a donor signup rate of 60%. Several other states (Pennsylvania, for one) ask the question as well, but it's for informational purposes only. In Illinois, the answer is considered legally binding, meaning that relatives cannot later overturn it.

Buying/Selling Kidneys

A Brooklyn businessman named Levy-Izhak Rosenbaum was arrested in New Jersey in 2009 for allegedly trying to broker the purchase of a kidney for $160,000. According to the criminal complaint filed against him, Mr. Rosenbaum told an undercover agent that he could arrange for a live kidney donor from Israel, and that they would then fabricate a fictitious “relationship” between the donor and the recipient so that the hospital in the U.S. would not become suspicious.

The Rosenbaum case is just one example of the shadowy black market in human organs worldwide. The World Health Organization estimates that about 10% of the more than 60,000 kidneys transplanted each year come from living donors who have sold their kidneys strictly for money. The temptation is hard to resist, especially for donors from poor countries where the choice may come down to selling a kidney or selling a child. The practice is not even illegal in some countries (Pakistan is an example), and as a result those countries are rapidly developing thriving “transplant tourism” enterprises.

What, if anything, could be done about the shortage of organs for transplantation?

Steve Jobs' New Liver

It’s not official, but there are reports in the news media that Steve Jobs, CEO of Apple computers, received a liver transplant recently at an undisclosed location in Tennessee (The New York Times, June 23; “A Transplant That is Raising Many Questions”).

Normally, patients who need an organ transplant place themselves on the transplant list of one of eleven regional Organ Procurement Organizations (OPOs) in the U.S. Waiting times can vary. When an organ becomes available the regional OPO offers it to a patient already on its list, with the highest priority given to the sickest patients and those who have been on the list the longest time.

Most patients sign up for the transplant list at only one OPO, because insurance companies will only pay for an organ transplant performed in a person’s “home” OPO. Nevertheless, patients who are willing to pay for the transplant themselves (and with access to a plane so they can get to the hospital within six hours) can increase their odds for a transplant by placing themselves on the transplant lists of several different OPOs simultaneously. No one has said whether or not Mr. Jobs was on more than one list at the time of his transplant, or how long he waited for his new liver.

For a discussion of whether the current organ allocation system is fair, see “How Should We Allocate Scarce Organs?” in Human Biology 5th ed., pp. 368-369.