Academy of Diagnostics & Laboratory Medicine - Scientific Short

Is there utility for inflammatory biomarkers for the early diagnosis of chronic kidney disease

Marie Browne

The kidneys play an important role in homeostasis, they regulate the amount of water and salts present in the body by filtering blood through the nephrons. When the kidneys are not functioning efficiently, waste products and fluids begin to accumulate instead of being excreted which can cause serious health problems. Many conditions can affect the ability of the kidneys to carry out their vital functions. Some conditions can lead to a rapid (acute) decline in kidney function; other conditions lead to a gradual (chronic) decline. Chronic kidney disease (CKD) can go undiagnosed due to its asymptomatic nature and is described as a progressive loss in renal function leading to end-stage renal failure and death. Early diagnosis of CKD would slow the progression to total kidney failure. In many cases, CKD is associated with other medical conditions (i.e. hypertension, diabetes). Additional risk factors include obesity, older age, family history and ethnicity.

In order to classify patients with early CKD (Stages 1-3), Modification of Diet in Renal Disease (MDRD) guidelines suggest an estimated Glomerular Filtration Rate (eGFR) ≥ 90 ml/min/1.73m2 (based on the measurement of serum creatinine), with other evidence of kidney disease (proteinuria, haematuria, kidney inflammation). The complexity in diagnosing a patient with CKD at an early stage of disease has led to most patients not receiving a diagnosis until the disease has progressed to an advanced stage. There currently are no accepted methods for easily determining kidney disease at early stages. Inflammation plays a key role in the development and progression of CKD and identification of inflammatory markers in patients suspected of having CKD may play a useful role in the diagnosis of disease. Inflammation can be monitored through the presence of signalling molecules, such as cytokines, and their soluble receptors.

A recent investigative study aimed to identify soluble cytokine receptors; soluble tumor necrosis factor 1 (sTNFRI) and 2 (sTNFRII) as potential novel markers to aid diagnosis of CKD at early stages following a multi-analytical approach. This means that the two markers can be detected at the same time using a single serum sample as the tests sites for both of them define arrays on a biochip surface following data processing with the biochip analyser Evidence Investigator. Serum samples from 327 patients with CKD (stages 1-3) and from 139 healthy controls were taken and the concentrations of sTNFRI and sTNFRII were determined through the biochip platform. Serum creatinine was also measured to determine eGFR using the MDRD equation. Following statistical analysis, elevated levels of sTNFRI and sTNFRII were found in the serum of CKD (stages 1-3) patients compared to controls. Both markers presented a significant correlation with disease stage and eGFR.

Are these findings indicative of the potential utility of these inflammatory markers in diagnosing CKD at an earlier stage? Do they have a potential use as disease stratification markers? In addition, the biochip platform has the potential to incorporate further markers relevant to the study of early stages of CKD, which can facilitate even further the approach of an early diagnosis.

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Academy of Diagnostics & Laboratory Medicine Designation

Fellows of the Academy use the designation of FADLM. This designation is equivalent to FACB and FAACC, the previous designations used by fellows of the National Academy of Clinical Biochemistry and AACC Academy. Those groups were rebranded as Academy of Diagnostics & Laboratory Medicine in 2023.