Renal medicine

Birmingham has a large, multi-ethnic population, including some of the most deprived communities in the UK. The region within 50 miles of the centre of Birmingham comprises 10% of the UK population. Chronic kidney disease affects more than 10% of the adult population and the area has some of the highest rates of dialysis requirements in Europe.

The clinical service manages 1,040 patients on haemodialysis, including 200 people on home therapies. The unit manages 11 chronic dialysis units within the catchment area. It also provides renal services for a population of 1.7 million people and kidney transplantation for 150 people a year from a catchment area of 4.5 million.

Queen Elizabeth Hospital Birmingham (QEHB) provides large and comprehensive secondary and tertiary care services across all areas of medicine. To support this the hospital has a large acute kidney injury and plasmapharesis programme, with a 25-station acute dialysis unit and 54 inpatient beds.

There is tight integration between clinical work and research, with a commitment to research across a range of areas and a growing portfolio of projects under the direction of faculty members.

The renal research laboratories are based in the University of Birmingham’s School of Immunity and Infection, which has a reputation for internationally competitive research. The group recently moved into new research laboratories which are within the newly built QEHB. There are close collaborations with a large number of research groups across the campus.

The main current research areas are:

  • immune mediated renal disease
  • paraprotein related renal diseases
  • chronic kidney disease (CKD) (including epidemiology)
  • transplantation (immune and non-immune-mediated aspects)
  • cardiovascular disease in CKD
  • dialysis
  • acute kidney injury

Researchers within renal medicine also work closely with colleagues in cardiology through the Birmingham Cardio-Renal Group (BCRG).

Immune mediated renal disease

The renal research group has been at the forefront of research defining the molecular causes of vasculitis with a particular emphasis on the role of autoantibodies. Our group has identified how certain autoantibodies develop in patients with vasculitis.

Our research is designed to improve the long-term survival of these patients by reducing the rates of illness and death associated with both the disease and treatment.
Clinical trials in collaboration with the European Vasculitis Study Group (EUVAS) have focused on optimising the use of intensive immunosuppression for acute disease. This means using drugs to strongly suppress the immune system.

Clinical studies have targeted adverse events, especially infection, which are associated with the long-term use of immunosuppressants. Our team does this by identifying predictors of infection, investigating the role of secondary immunodeficiency, and investigating vaccine responses.

Paraprotein related kidney disease

We have sought to improve the management of patients with acute kidney injury (AKI) complicating multiple myeloma. AKI is a term used to describe any damage to the kidney, including harm caused by a physical injury, disease or condition. Multiple myeloma is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies.

Renal biopsies

Focusing on diagnostic aspects of care, we have recently identified the safety of renal biopsies in this population and identified the benefit of reviewing this histology both at presentation with renal failure and later in the patient’s management.

Serum free light chains (FLCs)

The group has shown the value of immunoassays, which are a specific type of laboratory test, to detect monoclonal proteins as a method for providing a rapid diagnosis and early initiation of treatment for these patients. Monoclonal proteins are antibodies found in large amounts in the blood or urine of people with multiple myeloma and other types of plasma cell tumors.

We have subsequently described the importance of achieving an early reduction in serum free light chains (FLCs) to enable renal recovery. FLCs are components of antibodies, with a typical antibody made up of both heavy chains and light chains. This work has lead to collaborations with the Mayo Clinic.

In seeking options to allow early reduction in FLCs, we described for the first time the removal of FLCs by haemodialysis.

International Kidney and Monoclonal Gammopathy Research Group

In late 2010 the group founded the International Kidney and Monoclonal Gammopathy Research Group, which brings together for the first time researchers in the field to allow multi-national collaborations. To date this includes opinion leaders from the UK, France, Greece, the United States of America and Spain.

Chronic kidney disease (CKD)

CKD is a condition which varies in seriousness from mild to severe. While most cases do not cause symptoms or progress to complete renal failure, it can be extremely serious and even life-threatening. CKD is also known as chronic renal failure.

Our team is carrying out cutting-edge research on CKD treatments, while also taking a strong interest in its causes. With access to large national and regional databases we are working with the University of Birmingham’s Division of Primary Care to better understand the current prevalence of CKD in the UK and to define the risks for people with known kidney disease.

We have also established animal models of CKD to address the dominant processes promoting progressive kidney disease, irrespective of the initial trigger.

RIISC

This group has established the Renal Insufficiency in Secondary Care (RIISC) cohort, which is a large multi-centre study to investigate the bioclinical determinants of progressive chronic kidney disease.

Stromal fibroblasts

The group is now focusing on the role of stromal fibroblasts, which are the primary producers of cells of the kidney. Using human observational studies, as well as laboratory work, we are helping to define the nature of stromal fibroblasts in fibrotic kidney disease and how this relates to progression of disease.

Polyclonal and monoclonal free light chains

Recently we have started to evaluate the possible role of polyclonal free light chains (FLCs) in progressive CKD. Monoclonal FLCs are well described for their ability to drive processes which promote excess fibrous tissue development within the kidney.

We are studying the idea that polyclonal FLCs may actually be contributing to progressive fibrosis and overall patient outcomes in some cases of CKD.

This work includes clinical studies which have demonstrated that polyclonal FLCs independently predict overall survival and loss of renal function in patients with CKD. Additionally this work has been supported by laboratory work through collaboration with a group led by Paul Sanders in Birmingham, Alabama, which is further exploring the potential role of FLCs in renal scarring.

Renal transplantation

Research interests focus on improving the outcomes of renal transplantation through clinical and translational strategies. This research involves close co-operation with the hospital’s world-renowned renal transplant team.

Many of these studies involve clinical phenotyping of transplanted cohorts, which means observing patients who have received or donated kidneys to measure the way their genes influence their clinical outcomes.

The group is looking for correlations between all risk factors and outcomes to identifying novel diagnostic tools to predict long-term outcome.

Role of caveolin-1

Recently, the group has successfully identified a link between variation within the caveolin-1 gene of transplant donors, and subsequent graft failure rates.

Caveolin-1 is a gene which is believed to play a role in building the caveolae plasma membrane, which is part of most cells. We are exploring the role of caveolin-1 in renal fibrosis, which is a condition in which excess fibrous connective tissue is grown in the kidneys. The group is exploring the role of nutrition in outcomes.

Non-polymorphic HLA derived peptides

The human leukocyte antigen (HLA) system is the collective name for a large number of genes which are involved in the immune system function in humans. HLA produces particular types of proteins which are part of the exterior of cells, enabling the body to recognise those cells as its own.

When a person receives a transplanted organ from another person, this is called an allograft. The body usually recognises the HLA-derived cells on the allograft as being “alien” and the immune system is triggered to attack the foreign cells. This is why transplant patients receive immunosuppressant drugs; without such drugs the body rejects the organ.

We have identified immune responses to non-polymorphic HLA derived peptides, which are fragments of proteins, to be associated with chronic allograft dysfunction. This observation allows for the development of standardised tests of cellular immunity to guide long-term patient management.

ABO incompatible transplantation

Most renal transplants are carried out between patients whose blood group is compatible, because the body is more likely to reject an organ which is of a different blood type. However, a process can be used to remove the blood group antibodies in a patient before and after the transplant.

An important area of research for us is a multi-centre observational study of the outcomes of ABO incompatible transplantation in the United Kingdom.

Cardiovascular disease and chronic kidney disease

Chronic kidney disease is associated with increased cardiovascular risk, and heart failure and arrhythmias are the biggest causes of cardiovascular death in this population.

Increased arterial stiffness is a hallmark of CKD and is associated with adverse changes in cardiac structure and function which may make a patient more likely to suffer cardiovascular death.

These changes are already apparent in early kidney disease, which is highly prevalent in the developed world. It is important for us to understand the complex mechanisms underlying increased arterial stiffness in chronic kidney disease, because it will enable us to develop new strategies to prevent or reverse the damage and reduce the rate of cardiovascular disease in patients with CKD.

Main areas of work:

  • Role of aldosterone in cardiovascular disease
  • Abnormal phosphate handling as a cardiovascular risk factor
  • Impact of mild uraemia on cardiovascular structure and function
  • Inflammation, chronic viral infection and immunosuppression as modulators of cardiovascular risk

Acute kidney injury (AKI)

This group is evaluating treatment options for patients with rhabdomyolysis, which is frequently complicated by AKI. Rhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. When the tissue cells break down, one of the proteins which is released into the bloodstream is called myoglobin, which is harmful to the kidneys and may lead to AKI.

Severe AKI is associated with prolonged hospital admission and reduced patient survival.

The group has started to use laboratory work and mathematical models to test the clinical benefit of providing rapid removal of myoglobin by a process called protein permeable dialysis.

Dialysis

The dialysis research group focuses on three main areas:

  • The utility of new generation high-cut off dialysis membranes
  • Establishing a prospective cohort of dialysis patients (the VISION cohort) for identifying the bioclinical determinants of outcomes in people with end-stage kidney disease
  • Service models for the delivery of home therapies

Peritoneal dialysis

The main area of research interest is in the prevention and treatment of peritoneal catheter exit site complications. The team has recently been awarded an NIHR Research for Patient Benefit Grant to carry out a multicentre RCT using a steroid impregnated tape to treat overgranulation tissue.

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