Researchers have revealed how maintaining good kidney health can stop dangerous parasites from entering the body and weakening the immune system.
A research team from Instituto Gulbenkian de Ciência (IGC) in Lisbon have found that the kidney’s ability to recycle iron in the body is key to preventing malaria. The findings of the study, titled ‘A Protective Inter-Organ Communication Response Against Life-Threatening Malarial Anemia,’ may have important implications for the prognosis of infected patients and for the development of new treatment options for malaria.
Malaria can often lead to lethal outcomes related to kidney health, such as acute kidney injury. This is caused by the Plasmodium parasite, which transmits the disease through mosquito bites, infecting the host’s red blood cells.
The kidneys are vital in repairing red blood cells
Once it has entered the body, the parasite can multiply and cause anaemia by destroying red blood cells, which weakens the host’s immune system. In a healthy person, specialised cells in the immune system, called macrophages, recycle the iron released from damaged or old red blood cells to form new ones.
In an infected person, the capacity of these macrophages is quickly exhausted, damaging their kidney health. Once the body is unable to replace red blood cells, the patient is at a high risk of death. The IGC findings show that when acute kidney injury and anaemia occur simultaneously, the risk of death increases even further.
The researchers studied 400 patients hospitalised with malaria at Josina Machel-Maria Pia Hospital, in Angola, where malaria is a leading cause of death. Alongside this study, the researchers analysed iron metabolism in animal models.
“It is easy to understand, through its colour, that the mice we study get rid of the by-products of red blood cells’ destruction through urine,” explained Susana Ramos, co-leader of the study.
“We began to realise that these animals also had lots of iron in their urine, but they could not possibly be getting rid of it all, even more so because these sick mice do not eat enough to sustain the needed levels of this essential micronutrient. So, we thought there must be a population of kidney cells that reabsorbs and recycles iron, to maintain some degree of normality in these anaemic mice,” she continued.
Previous research has revealed that these cells, known as renal proximal tubule cells, are vital in eliminating the toxic by-products that promote severe forms of malaria. The team found that these kidney cells alter their genetic programme to absorb and store iron.
The researchers were surprised to find that the cells put the iron back in circulation, allowing for new red blood cells to form. “We were not expecting kidneys to have such an immediate role in re-establishing the development of these blood cells”, said Qian Wu, the first author of the study.
Kidney health affects the whole body
Due to their ability to store and redistribute iron, the kidneys can determine the outcome of this disease. To better understand why this is, the researchers created mice without ferroportin, the gene that allows kidney cells to export iron.
These mice developed severe anaemia and died, which showed how a simple cellular mechanism and good kidney health could have vital effects on the entire body. By re-establishing the circuit of iron and the number of red blood cells, the kidneys stopped the progression of anaemia, meaning that each organ received oxygen and continued to function after infection.
“This finding is a clear demonstration of how the metabolism of an infected host can be re-wired to determine the outcome of an infection, in this case, malaria”, explained the principal investigator Miguel Soares.
These findings could help researchers create better-personalised prognoses for infected patients. “People with some genetic mutations in this cellular iron exporter are less prone to develop severe anaemia”, Miguel added.
If a patient has poor kidney health and cannot export the iron they absorb, they will become dangerously susceptible to developing acute kidney injury and anaemia. The researchers have said they are currently working on new therapeutic strategies directed at this metabolic pathway.
