improved testing for the early detection of renal disease
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Our laboratories are involved in the development of new innovative tests as well as the improvement of currently available tests used for the screening, early detection, and monitoring of Renal Disease.

For information on current projects, please click the links below:

Investigating Biomarkers of Progressive Renal Disease and Screening of Nephrotoxic Agents

Urine Retinol Binding Protein: Development of a new monoclonal antibody based assay to identify tubular proteinuria patients with kidney stones and diabetes

Investigating Biomarkers of Progressive Renal Disease and Screening of Nephrotoxic Agents

Different factors may initiate or contribute to the process of Chronic Kidney Disease (CKD); in areas such as Western Europe and North America diabetes and hypertension are the major causes whereas in other parts of the world the aetiology is different with industrial pollutants or naturally occurring substances contributing greatly.

The prevalence of CKD in the UK is believed to be as high as 5- 10%; generally when this diagnosis is made the patient may have lost approximately 50% of their kidney function. However, at this point, for the majority of patients, it is often uncertain whether they will progress to complete loss of kidney function resulting in Established Renal Failure (ERF) or to determine how rapidly they might progress.

This on-going project seeks to identify novel markers and mediators of disease that may serve as useful non-invasive biomarkers of CKD progression; particularly, but not exclusively, in diabetic patients.

In parallel to the work investigating urinary biomarkers we have been seeking to establish useful panels of markers of renal damage and nephrotoxicity that can be used in our in vitro assays to test substances potentially harmful to the human kidney. Using both established and novel markers we are comparing nephrotoxic medicines such as calcineurin inhibitors and certain antibiotics with pollutants such as cadmium and biological agent such as aristolochic acid. From this data we will be able to construct a powerful screening tool that can used to quantitatively and qualitatively measure renal damage of exogenous agents.

If you would like further information on this project please contact Sarah.Yates@helierscientific.co.uk or mark.dockrell@swtirr.org.uk, or visit www.helierscientific.co.uk
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Urine Retinol Binding Protein: Development of a new monoclonal antibody based assay to identify tubular proteinuria patients with kidney stones and diabetes

Retinol binding protein (RBP) is a low molecular weight protein (LMWP). RBP4, the major circulatory form is bound to retinol and pre-albumin. The free form and that bound to retinol retinol is freely filtered at the glomerulus and reabsorbed by proximal tubule cells. Failure of reabsorption of proteins due to disorders of the proximal tubule leads to increased excretion in the urine, so called tubular proteinuria. RBP4 occurs in the serum in several configurations: as holo-RBP4 (RBP4 bound retinol); apo-RBP4, which remains after the release of retinol; RBP4-L, which is truncated at one C-terminal leucine molecule (Leu-183); and RBP4-LL, which is truncated at a second leucine molecule (Leu-182 and Leu-183) . The relative binding of these forms to pre-albumin is not known. Therefore their contribution to the total amount filtered through the kidney is not known and in previous assays using polyclonal antibodies affinity for different forms of RBP is not known.

A recently described assay using monoclonal antibodies to RBP has the potential for being technically more robust. It was shown to have much wider dynamic range, better linearity on dilution and almost equimolar recognition of different forms of RBP in urine. It is therefore likely to be more sensitive and specific for the detection of minor degrees of proteinuria found in patients with kidney stones and diabetes.
We aim to set up and evaluate the monoclonal assay on equipment that is already in the routine use in our laboratory for other tests.

Our main objective is to develop a more sensitive assay to detect tubular proteinuria in patients with kidney stones; although important to detect, the incidence of tubular proteinuria is low in these patients. We will therefore use urine samples from patient with type 2 diabetes mellitus known to have significant excretion of LMWP's to evaluate the assay. Patients with diabetes with microalbuminuria may have raised urine RBP which is possibly glomerular in origin. Patients with type 2 diabetes without microalbuminuria may have raised RBP which is likely to be tubular.

If you would like further information on this project please contact: Rashim.Salota@esth.nhs.uk, Marta.Lapsley@esth.nhs.uk or mark.dockrell@swtirr.org.uk.
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