A new study published today in British Journal of Pharmacology has identified that a component of grapefruit and other citrus fruits, naringenin, successfully blocks the formation of kidney cysts.
Known as polycystic kidney disease, this is an inherited disorder which leads to the loss of kidney function, high blood pressure and the need for dialysis. Few treatment options are currently available.
The team of scientists from Royal Holloway University, St George’s, University of London and Kingston University London used a simple, single-celled amoeba to identify that naringenin regulates the PKD2 protein responsible for polycystic kidney disease and as a result, blocks formation of cysts.
“This discovery provides an important step forward in understanding how polycystic kidney disease may be controlled,” said Professor Robin Williams from the School of Biological Sciences at Royal Holloway.
“In the study, we have demonstrated how effective the amoeba Dictyostelium is in the discovery of new treatments and their targets. Having previously applied the same method of testing in our work into epilepsy and bipolar treatments, it is clear that this new approach could help us reduce reliance on animal testing and provide major improvements.”
To test how this discovery could apply in treatments, the team used a mammalian kidney cell-line, and triggered the formation of cysts in these cells. They were then able to block the formation of the cysts by adding naringenin and saw that when levels of the PKD2 protein were reduced in the kidney cells, so was the block in cyst formation, confirming that the effect was connected.
Dr Mark Carew, from the School of Pharmacy and Chemistry at Kingston University, said: “Further investigation is underway to understand the action of naringenin at the molecular level. This work will entail looking at the function of the PKD2 protein as a cell growth regulator.”
“Indeed, this study provides a good example of how chemicals identified in plants can help us develop new drugs for the treatment of disease,” added Professor Debbie Baines from St George’s, University of London.
What are simple kidney cysts?
Simple kidney cysts are abnormal, fluid-filled sacs that form in the kidneys. Simple kidney cysts are different from the cysts that develop when a person has polycystic kidney disease (PKD), which is a genetic disorder. Simple kidney cysts do not enlarge the kidneys, replace their normal structure, or cause reduced kidney function like cysts do in people with PKD.
Simple kidney cysts are more common as people age. An estimated 25 percent of people 40 years of age and 50 percent of people 50 years of age have simple kidney cysts.
What causes simple kidney cysts?
The cause of simple kidney cysts is not fully understood. Obstruction of tubules - tiny structures within the kidneys that collect urine - or deficiency of blood supply to the kidneys may play a role. Diverticula - sacs that form on the tubules - may detach and become simple kidney cysts. The role of genetic factors in the development of simple kidney cysts has not been studied.
“Autosomal dominant polycystic kidney disease affects between 1 in 10 people on dialysis and 1 in 8 with a kidney transplant. Kidney Research UK welcomes this publication that may provide hope for a future new treatment for polycystic kidney disease, alongside its own on-going research focusing on tackling this common genetic kidney disease,” said Elaine Davies, Head of Research Operations at Kidney Research UK.
Renal cysts occur in a variety of genetic diseases in adults and children, but “simple renal cysts” are commonly observed in normal kidneys. They are so common, it is difficult to consider them a disease. More and more people are being diagnosed with these lesions as we use more medical imaging technology such as ultrasound, X-ray and CT scanning. In one survey of people undergoing ultrasound for evaluation of non-kidney-related problems, 15 percent of men and 7 percent of women aged 50 to 69 had a renal cyst. One-third of men and 15 percent of women older than 70 had a renal cyst.
The initial radiologic appearance of most cysts determines what further evaluation is needed. The physician needs to accurately distinguish simple renal cysts from complex renal cysts. Simple cysts are round and have one wall, much like a ping pong ball. They rarely require treatment. Complex cysts have walls within the outer wall or are a collection of small cysts. The latter can harbor cancerous masses.
Many physicians use the Bosniak classification of renal cysts to determine follow-up. Observation of lesions is far more common than biopsy. Traditionally biopsy required removal and loss of the kidney. Biopsy can now be done with a needle through the skin using CT imaging to guide the needle. These needle biopsies were once discouraged but are now done in very specific circumstances.
Bosniak uses a complicated algorithm of CT scan characteristics such as size, density and perfusion to place cystic renal masses into one of five different categories. Bosniak categories I and II are generally simple cysts and do not require further evaluation. Some would repeat an ultrasound at six to 12 months to assure stability and a correct diagnosis.
The research was funded by a SWan (SouthWest London Academic Network) research grant.
Royal Holloway, University of London