#155 - Chris Sonnenday, M.D.: The history, challenges, and gift of organ transplantation

KEYPOINTS

• 01

  Transplantation is a young field

  The first kidney transplants were done in the 1950s, and the first liver, heart and lung attempts in the 1960s. Chris Sonnenday, a transplant surgeon at the University of Michigan who trained with Attia at Johns Hopkins, notes that when they were residents in the 1990s, much of today's practice had been operational for only about a decade. Much of his current work was invented in the 1990s and early 2000s.

• 02

  The first successful kidney transplant avoided the immune system

  Joseph Murray performed it in 1954 at what is now Brigham and Women's Hospital, between identical twins, and later won the Nobel Prize. Michigan's first kidney transplant, in 1963, was also between twin sisters; the programme recently celebrated its 5,000th. In the 1960s and 1970s, some published series reported patient mortality of 50–70% after kidney transplantation, not just graft loss.

• 03

  Cyclosporine was the turning point

  Matching by blood type and the HLA system helped, but one-year graft survival was still only about 60–70% with the best regimens of the time. Cyclosporine, a fungal compound that Sir Roy Calne showed prevented rejection in preclinical models, interferes more selectively with T-cell activation after an antigen is presented. Both men agree its spread through the 1980s and early 1990s is what made transplantation work.

• 04

  A transplant beats dialysis within months

  For similar patients, the survival curves for dialysis and transplantation cross within about 90–250 days, even counting surgical risk and the start of immunosuppression. After that, dialysis 'loses'. Dialysis only became widely funded through a rider to the Medicare legislation.

• 05

  Living-donor kidneys outperform deceased-donor kidneys

  Deceased-donor organs go through brain death or circulatory death, cold storage, transport and 6–72 hours of ischaemia. Living donation is an elective operation in side-by-side operating rooms. The laparoscopic donor nephrectomy, pioneered at Hopkins by Louis Kavoussi and Lloyd Ratner, made donating easier, and US volume grew to about 18,000–20,000 kidney transplants a year.

• 06

  Paired exchanges widen access

  A willing but incompatible donor can swap with another pair. Swaps began in the 1990s and took off in the 2000s. Sonnenday describes a recent day when he and a colleague each removed a donor kidney, both kidneys were shipped to other institutions, and two kidneys came back that afternoon for their own recipients. Donor and recipient operations are now completely decoupled. Attia raises the catch: trading a healthy young kidney for a 75-year-old's isn't an equal exchange.

• 07

  Paying for organs remains unresolved

  Organ donation has been treated as a gift, grounded in donor autonomy. The worry about an open market is that it could coerce economically disadvantaged people into selling organs. Sonnenday calls it a frequently debated, never-resolved question.

• 08

  Attia wants kidney decline caught early

  Rising prediabetes and metabolic syndrome are driving chronic kidney disease. A GFR in the low 40s may be acceptable in someone in their early 70s, but Attia argues that blood pressure of 130/85 is 'not really acceptable'. It could take someone from a GFR of 95 to 85 in a decade, which he considers too steep a decline.

• 09

  Organ allocation and the line around death

  Organs are coordinated by 58 organ procurement organisations (OPOs). Geographic variation has fallen, so the sickest patients get transplanted quickly wherever they live. That system, which Attia found unjust 20 years ago, is fairer now. But 'medium-sick' patients wait behind sicker ones, which shows the need for more donors. Death must be declared by a separate team, using brain-death criteria or tests showing blood flow to the brain has stopped. Otherwise organ procurement could be seen as hastening death.

• 10

  Liver transplant indications are shifting

  Hepatitis C, often acquired in the 1970s and silent for decades, dominated liver transplants for about 20 years. Old drugs worked in only 15–30% of patients, and the virus always recurred after transplant, but it is now curable. Fatty liver disease (NAFLD/NASH) is predicted to become the leading indication by around 2030. Alcohol-related liver failure has also exploded, often in people in their 20s and 30s.