Description

We are concerned about the world's largest potential group of chronic kidney disease.

According to statistics of the World Health Organization, about 1.2 million people died of kidney disease in 2015 worldwide, which is 32% higher than that in 2005. Among them, diabetes and hypertensive patients are the largest potential victims of chronic kidney disease. Of the new ESRD patients in the United States in the past 10 years, 58% are from diabetes and hypertension patients. If we do not intervene in patients with early-stage hypertension or diabetes, it will cause a dramatic deterioration of renal function with a mortality rate up to 90%. However, if the patient's kidney status can be monitored at any time, with early detection and timely medical treatment, up to 70% of the disease may be reversed. Therefore, it is of great social significance to monitor the renal status of patients with early-stage hypertension and diabetes.

At this stage, the excretion rate of urinary microalbumin (mALB) is mainly used to diagnose diabetic nephropathy and hypertensive nephropathy. Although the detection method is relatively perfect, it has the following disadvantages:

1. The accuracy and specificity of mALB in diagnosing DN are not high, and urinary tract infection and other factors can increase the excretion rate of urinary albumin, resulting in high misdiagnosis and missed diagnosis.
2. When the mALB is abnormal, DN has progressed to Phase III. It is not sufficient to use this indicator to monitor the occurrence and development of DN.
3. Renal impairment in hypertension occurs first in the renal tubules, and then in the glomerulus. Urine microalbumin mainly reflects glomerular filtration impairment and is not sensitive to renal tubular injury.

We use β₂M for high sensitivity monitoring of the kidneys.

In order to solve the problems in the above detection methods, we conducted a multi-study investigation to find a new type of indicator β₂M which has higher sensitivity to early kidney damage. β₂M is a small molecule globulin produced by lymphocytes, platelets, and polymorphonuclear leukocytes. It can be freely filtered from the glomerulus and is absorbed by the proximal tubular in 99.9% . Under normal condition, the excretion of β₂M in urine(U-β₂M) is very small which is no more than 0.25mg/L. U-β₂M excretion is increased in early urine of diabetic patients with stage I hypertension and diabetes. With the deepening of the renal damage, β₂M accumulates in patients and continue increase. Therefore, the detection of U-β₂M in patients with a risk of kidney disease, such as diabetes and hypertension, can achieve real-time monitoring of the condition of the kidneys, as well as the discovery of early nephropathy to prevent irreversible damage to the kidneys.

What kind of a work we want to complete?

Patients with diabetes for about 5 years or those with Hypertension for 5 to 10 years are at high risk of chronic kidney disease and are at risk of renal impairment at any time. Since diabetics and hypertensives are usually treated at home in early stages , routine blood and urine tests are rarely performed and the U-β₂M indicator is unknown. This has led many patients to miss the opportunity for early intervention and control. Our work enables these patients to easily monitor their own renal function status at home through the U-β₂M test. In addition, we can use mobile devices to conduct a brief analysis of the patient's renal function and give medical advice.

For U-β₂M we developed a suitable detection method

In this project, we combined strongly specific nanobodies with high-sensitivity liquid crystal detection to develop a visual detection method, thereby enabling accurate quantification or semiquantification of microgram-levelU- β₂M. Firstly, we use nanobody to specifically bind to β₂M. Compared with conventional antibodies, nanobody is a smaller molecular,less susceptible to denaturation, but still has intact antigen binding properties. In addition, nanobodies can be expressed by E. coli , which make the cost of production is greatly reduced. What's more, we use the birefringence of liquid crystal molecules. The liquid crystal application that we are familiar with is liquid crystal display, but this is to change the arrangement of the liquid crystal molecules through the electric current, thus show different light signals. Here, we modify the liquid crystal cell substrate with antibodies. After combining antigens, the micro-environment of the liquid crystal cell platform changes, resulting in a significant difference in color or brightness , the visualization of detection is achieved.

This project will propose a low-cost, portable and visible method for monitoring early renal injury and provide medical advice for patients with hypertension and diabetes.