Research is the Key to a Cure

Currently there are more than 8000 people on the active waiting list for a kidney transplant, and 2400 more who are too ill to join the list. Research such as that supported by the St Peter’s Trust can help improve this situation, if the funding can be found.

As a result of major technological advances in science over the last forty years it has become possible to discover how our bodies are regulated at the level of the different microscopically small cells that make up our various tissues and organs, and which hold our genetic material. The cell is the smallest functional unit that can operate more or less independently in any organism, and a human being is made up of millions of cells. Research at the cellular level has been funded by the St Peter’s Trust for many years, and new findings have been reported by the scientists and clinicians the Trust has supported in diseases such as diabetes, renal stones, complications of renal failure, bladder malfunction and prostatic cancer.

We are funding: 
 

Kidney function at the cellular level

A healthy human kidney contains about one million nephrons in its tissue, in an organ 10-12 cms long.   It is the nephrons that do the work of filtering the blood that is constantly passing through the kidney, draining away the urine (excess water and unwanted chemicals) into the bladder via the ureters and returning some 99% of the fluid that enters the kidney back into the body’s system to enable it to continue functioning.   There are tubules within these tiny nephrons which control the chemical composition of the circulating fluid, with the aim of providing the body with what it needs to maintain good health.   But disorders can occur at a cellular level in this filtration system which prevent its smooth operation - resulting in damage to the kidneys and subsequently to other organs.    The following five projects are investigating such disorders.

 

 

                   Blood pressure management.    Regulation by the kidney of the amount of salt circulating in the body is vital in maintaining a healthy blood pressure. Certain recently identified enzymes present in the kidney might be a factor in stimulating the reabsorption of salt into the blood stream and this study is directed at understanding more about their significance in the process. (Prof. Unwin)

Polycystic kidney disease.     A study of a newly identified hormone and receptor system that is thought to be linked to the production in some individuals of multiple cysts in the kidney tissue that cause irreparable damage and prevent healthy kidney function. (Prof. Unwin).   In addition, Dr. Norman and Patricia Wilson are seeking to block the action of a particular protein that previous studies suggest is involved in the expansion of the cysts through abnormal growth of the cells lining them.
 

 

                   Investigation of the role of mitochondria (minute bodies in the cells which contain an enzyme responsible for energy production) in the processes taking place in the tubule. (Prof. Unwin, Dr. Hall)

 

                   A study of the sensory mechanisms in the cells that regulate the flow of fluids and the process of salt and water salvage. (Dr. King, Mr Goodey)

 

                   Kidney stones.   A study of oxalate and related chemicals absorbed from food and their role as a trigger for the formation of calcium oxalate crystals in the kidney, and subsequent stones.   (Dr. Robertson)

 

Chronic kidney disease affects over 3 million people in the UK, and recent research in the UCL Centre for Nephrology has identified an enzyme, DDAH1, in the kidney which appears to be closely linked to the decline in kidney function, possibly by setting off a scarring process.   Kidney cells will be cultured to examine the role of this enzyme in kidney injury to see if its inhibition could offer a new way of preserving kidney function.   (Dr. Norman and Dr. Wheeler)

 

The kidney filtration barrier is a very complex (although minute) structure created from several different cell types. Disruption to the structure of these cells alters the barrier and leads to the leakage of protein in the urine - a common feature of kidney disease.   The researchers have identified a family of proteins which may be important in maintaining the shape of the cells in the barrier and their function will be investigated in more detail in this project.   If it proves possible to modulate this pathway, that may provide a new therapy for kidney disease. (Dr. Connolly and Jenny Papakrivopoulou)   

 

          During the process of filtering the blood within the nephrons in the kidney tissue, a large proportion of the filtered sodium and potassium is selectively reabsorbed into the body’s bloodstream in the middle section of these tiny nephrons in an area known as the loop of Henle.   This project aims to determine how chemicals in the nephron, called nucleotides, act on receptors at this particular site and block or stimulate reabsorption of sodium and potassium, as the correct quantities of these chemicals in the bloodstream is vital to good health. (Prof. Unwin)  

 
 

Vasculitis. 

                   Inflammation of the small blood vessels - systemic vasculitis - can lead to damage to their lining and narrowing and blockage.   The condition is difficult to diagnose, so organs may be severely affected by the time treatment is started, and even with therapy there is a high rate of permanent kidney failure.   The vasculitis is thought to be an autoimmune disease and associated with an antibody called ANCA which causes some of the organ injury.   But not all ANCA have equal effect.   This study will investigate whether or not this variability is important in determining why some people develop severe vasculitis in their lungs and kidneys, while others have a mild form of the disease.    (Dr. Little)

 
 

Bladder disorders

                  Bladder cancer in its aggressive and advanced forms is associated with many genetic changes in the affected tissue.   A gene labelled EEF1E1 is thought to behave as a tumour suppressor gene in many cancers and this project will investigate the role of EEF1E1 in bladder cancer and assess whether or not it has a clinical use as a biomarker in detecting the disease.   If it can be shown that a biomarker, or panel of biomarkers, can reliably detect bladder cancer cells in the patient’s urine, this would avoid the need for cystoscopy - which is invasive, expensive and carries some risks. (Dr. Gurung, Prof. Kelly)

 

Prostate cancer
 A clinical trial is being undertaken of minimally-invasive ways of treating prostate cancer, including high intensity focused ultrasound - HIFU.   (Mr. Emberton and Mr. Udin)

                    

                   Assessment of a non-invasive way of detecting and imaging precisely the sites of prostate cancer with a new form of ultrasound - histoscanning - and an advanced new form of multi-functional magnetic resonance imaging - MRI.   (Mr. Emberton and Mr. Udin)

 

 

Genetics
The genetic basis of stone disease - a Kidney Stone Research Consortium project established to study whether or not there is an inherited tendency for an individual to develop kidney stones. (Prof. Kleta)

                   

                   Membranous nephropathy.    The research group has been offered access to biopsy tissue from a large number of proven cases across the UK which could help it to identify genes involved in this devastating disease and develop new treatments for the condition, which is found in approximately 2 in 10,000 people.   Membranous nephropathy may be a disease originating within the kidney or it may be linked to other conditions, particularly those caused by a disturbance of the immune system. It produces inflammation and thickening of the filtering system within the nephrons in the kidney tissue, leading progressively to malfunction and eventual kidney failure with the associated need for dialysis or transplantation.    Its occurrence in families points to a genetic origin for the disorder.   (Prof. Kleta)

                    

                   Inherited kidney diseases have been found that have passed through several generations of specific extended families.   The suggestion is that there is a particular gene fault in each family.   The project is aimed at identifying the genes involved and then comparing the effects in the various families and with unaffected people in order to find out who might be at risk of these diseases. (Prof. Maxwell and Prof. Unwin)

                    

                   A group of patients with unique teeth and kidney problems has been identified by Prof. Kleta’s research team.   These problems are caused by a gene defect that it is important to investigate, because understanding what went wrong in these patients will provide insights into how calcium is handled by the body - both in the teeth (where their strength is determined by this gene’s function) and the kidneys (where it can be involved in stone formation).     (Prof. Kleta, Prof. Unwin, Dr. Zdebik)

                    

 

Congenital conditions

                   Development of a database to track through adolescence and adult life the complex congenital urological conditions originally treated in childhood.   (Mr. Wood)

                    

 

Kidney transplantation

                   Urinary tract infection is a worrying complication of renal transplant and it can damage the new kidney.   Regrettably, routine tests for urinary infections are insensitive and do not identify the disorder in all cases.   But more comprehensive, sensitive and accurate methods are now available as an alternative.   These have indicated that bacteria may be hiding in the cells of the urinary tract and are not being picked up by the routine tests. This project will use the new techniques to see if this is so in the renal transplant patients.   (Dr. Harber)

                    

                   Kidney transplant is an excellent treatment for kidney failure, but it can be adversely affected by the body’s reaction to introduced tissue, which may lead to loss of the new organ unless immunosuppressive drugs are used.   This project seeks to investigate the function and importance of a specific protein, called mannose receptor, found on a set of white blood cells which may prevent rejection without the need to increase the degree of immunosuppression being undertaken.   (Dr. Salama)

 

"I am part of a clinical trial for a treatment of polycystic kidney disease (PKD), which causes the kidneys to grow larger due to cysts growing on them, affecting the renal function of the kidney and can eventually result in dialysis or a kidney transplant. I found out that I had inherited PKD from my father after the birth of my first child. I was referred to a consultant but found out that there still was no treatment for PKD apart from living a healthy life style by reducing salt intake and keeping an eye on my blood pressure. My kidneys would slowly decline until I would reach dialysis; in addition I knew that my children have a 50% chance of having this passed on from me through my genes. Despite initial concerns, my second child was born without any complications.