Functions of the kidneys

The kidneys are complex and delicate organs that perform a number of roles. In addition to the function that we all associate them with of filtering and excreting waste products from the blood (notably urea from protein breakdown and creatinine from muscle use), they also regulate fluid and water balance to maintain hydration, balance electrolytes and minerals, manage blood pressure and fluid volumes, as well as being involved in endocrine functions such as producing hormones (e.g. erythropoietin) and activating vitamin D, converting calcidiol into calcitriol, thereby helping the body to absorb calcium and phosphorus for bone strength.

Factors that affect kidney function and the importance of testing kidney function

Kidney function can be affected by chronic systemic diseases (e.g. diabetes, hypertension and cardiovascular disease), glomerular and autoimmune diseases (e.g. glomerular nephritis, IgA nephropathy, lupus nephritis, etc), inherited and genetic conditions (e.g. polycystic kidney disease, Alport syndrome, Fabry syndrome) and damage from structural, infectious and toxic causes (e.g. kidney infections, kidney stones, chronic use of certain medication, acute kidney injury). And this is not an exhaustive list, by any means.

Some of the main reasons for monitoring kidney function are to detect chronic kidney disease early, stage kidney disease severity, manage conditions (diabetes and hypertension) that risk damaging the kidneys and guide safe medication dosing to prevent kidney damage.

Tests for kidney function

Assessing kidney function is actually very difficult and the challenges involved are eloquently discussed by Bjornstad et al. [1]. Checking kidney function usually revolves around testing glomerular filtration rate (GFR), which can either be measured (mGFR) or estimated (eGFR). In general, in clinical practice, assessment of kidney function relies on eGFR by testing serum creatinine and/or serum cystatin C levels. In the last decade or so, the use of urinary cystatin C (uCysC) as a biomarker for renal impairment has emerged, as levels of urinary uCysC are low in normal conditions but elevated in conditions that reflect renal dysfunction or tubule damage. Using urine as a specimen is particularly attractive in resource-limited settings; however, the usual methods of analysis involve a particle-enhanced turbidimetric immunoassay, particle-enhanced nephelometric immunoassay and enzyme-linked immunosorbent assay (ELISA), all of which require highly trained staff and expensive facilities – usually centralized labs. Therefore, as yet, analysis of uCysC has been unsuitable for application as a point-of-care test.

Point-of-care device for measuring uCysC

Recently, however, Pang et al., have developed a device that allows a rapid test for point-of-care monitoring of uCysC [2]. The device consists of two chambers: a trapezoid sampling module and a result visualization part. The device is held vertically and dipped into the urine specimen, where capillary action draws a fixed volume into the sample chamber and is pinned at a vent. During this process, uCysC binds to anti-CysC-antibody-linked magnetic microbeads (MMBs) as well as anti-CysC-antibody-linked non-magnetic polystyrene microbeads (PMBs) forming MMB–uCysC–PMB complexes. Turning the device horizontally unpins the meniscus and the solution flows into the result visualization module. The MMB–uCysC–PMB complexes and any free MMBs are retained by a magnet, while free PMBs flow into the visualization channel, resulting in a red bar that indicates a length-based visual quantification of the uCysC level. The device has been validated and shows strong concordance with the gold-standard ELISA method, and “demonstrates suitable sensitivity, excellent selectivity against potential urinary interferents, and robust performance across a physiologically relevant pH range”. The device, does indeed provide a rapid, POC test for uCysC, suitable monitoring kidney health where centralized lab facilities are unavailable. Care will need to be taken, though, as possible confusion could be caused by the length of the red results line being inversely proportional to the concentration of uCysC.