Searching for the causes of kidney failure

Why do humans and other mammals have two kidneys, but only one heart and one brain?
“Because the kidneys are so important, of course!” says Diana Karpman – partly joking and partly serious. As a consultant and professor in nephrology, she really does think these organs are among the most essential in the body.

Karpman

Diana Karpmans work has been very rewarding.

In a healthy individual, the kidneys lead a rather obscure life. But a person with kidney disease, which could be due to a congenital malformation or a result of infection, knows how important they are. Kidney failure is a serious condition that affects the entire body and can eventually be fatal.

Diana Karpman founded the unit for paediatric nephrology – dealing with kidney disease in children – at SUS in Lund, which currently treats around one thousand young patients per year. She also runs her own research team, specialising in the molecular mechanisms behind kidney failure. Her long working days can sometimes stretch into nights, when the deadline for a crucial application or an important research article is approaching.

Her work has been very rewarding, however. Last year, Region Skåne declared paediatric nephrology in Lund the 2015 “Centre of Excellence in Health” and, in the spring, Diana Karpman was elected to the Royal Swedish Academy of Sciences and appointed a Wallenberg Clinical Scholar.

A Wallenberg appointment means a five-year research grant totalling SEK 15 million, intended to give the recipient researcher respite from the merry-go-round of applications and a chance to invest in more long-term projects. Besides Diana Karpman, another LU medic, cardiovascular researcher Olle Melander, was among this year’s five Wallenberg Clinical Scholars.

“The grant enables translational research into the causes of kidney failure – raising research questions from patient cases, studying them in the lab and transferring the answers back in the form of better treatment methods”, says Diana Karpman.

One of her research questions concerns the connection between EHEC infections in the intestine and kidney failure. EHEC (Enterohaemorrhagic Escherichia coli) is a bacterium which causes severe intestinal infections; in 10–15 per cent of all patients, it can also lead to kidney failure and death. What is strange is that the EHEC bacterium binds to the mucous membrane in the intestine but does not spread into the bloodstream. If the bacteria stay in the intestine, how can they affect the kidneys?

“The bacterium releases a toxin, a poisonous substance, in the intestine. This binds to blood cells, from which small blisters called vesicles gradually detach. These carry the toxin to the kidneys”, says Diana Karpman.

She believes that the same mechanism is at play in other cases as well, such as when inflammation in the blood vessels leads to kidney failure. In these cases too, small vesicles may carry damaging substances to the kidneys.

The blood cells “hiving off” small blisters full of toxins and inflammatory substances is probably important for the blood cells themselves. Therefore, the process must not be interfered with at that stage, according to Diana Karpman. Instead, she wants to try to prevent the vesicles from penetrating the kidneys and damaging them.

“We have actually found a lot of substances capable of slowing this process down. They are well-known substances which in certain cases are already used as therapeutic drugs”, she says.

Doctors who have specialised in paediatric nephrology have a positive task in the sense that kidney damage can be reduced through active treatment. In serious cases, children with kidney disease can get a new kidney through transplantation, if a parent or grandparent donates a kidney.

“One can transplant an adult kidney into a child as young as one or two years old. It takes more space in the abdomen than the child’s own kidney, so the other organs have to move up, but it usually works”, says Diana Karpman.

That a two-year-old grandchild should get a 60-year-old kidney from a grandparent can seem strange, but it isn’t unusual these days. And the donated kidney lasts longer in its new environment.

“All the hormones and growth substances present in the child’s body are good for the transplanted kidney. It actually gets rejuvenated, so it can function well for several decades before a new transplant may become necessary”, explains Diana Karpman.

Text: Ingela Björck

Photo: Gunanr Menander

Kidney facts: The kidneys are two bean-shaped organs, around 10–13 cm long in an adult. Their primary function is to clear harmful substances and waste products from the body, but they also help to regulate blood pressure, to stimulate the formation of red blood cells and generate hormones, among other things.

The kidneys have a large reserve capacity: it is only when the kidney function is severely impaired, around a tenth of its normal state, that a patient needs dialysis or transplantation.

Clinical graduate school: Diana Karpman is also course director for the Faculty of Medicine’s clinical graduate school, a seven-week training programme for physicians who are part-time doctoral students. The programme includes theory of science, gender perspectives, basic research methodology, drug testing, statistics, presentation techniques and ethics. Each participant is assigned a personal mentor.