Cell-Specific Biomarkers in Renal Medicine and Research

Abstract

Histopathology is the gold standard for defining renal injury, but it is invasive, time-consuming and expensive, plus it is seldom used in subjects with mild renal injury. Using biomarkers linked to distinct, defined cell types and tissues provides a direct link to histopathology without its drawbacks, plus it provides increased sensitivity, and specificity. The nephron consists of several sections, each with its own specific biomarkers; therefore, by the use of a battery of tests injuries can be localised to distinct areas of it. Using urine samples simplifies repeated sampling from the same subject or animal leading to better defined toxicokinetics and disease monitoring.Serum creatinine is the most widely used renal biomarker in spite of its known shortcomings. Cell-specific biomarkers are more specific and sensitive and have been known for over 40 years, but they are still underused in renal medicine and research. In particular, while many studies have shown cell-specific biomarkers to be valuable in diagnosis, there are few studies where they have been used to guide therapy or linked to quantitative changes in the kidney. Furthermore, the great majority of cell-specific biomarkers are from the proximal tubule, which may have hindered research into the study of conditions where the distal tubules are affected. Recently, the range of biomarkers and their applications has been expanded by the introduction of indicators of cellular regeneration.This chapter will discuss how using biomarkers with a known cellular origin, renal effects may be found earlier and at lower levels of injury. Their use in both renal medicine and drug research will be presented. Knowledge of these existing markers lays the foundation for evaluation, comparison, and characterisation of new markers that will be identified in the future.

Abrogation of cisplatin‐induced nephrotoxicity by emodin in rats

“…role in CP-induced damage, and several antioxidants and thiol compounds have been reported to mitigate or protect against CP nephrotoxicity [8,29]. Here, we have confirmed that CP depletes renal GSH and other enzymes involved in scavenging of free radicals, and that pretreatment and concomitant treatment with emodin significantly reverses these changes.…”

“…GSH has been shown in several in vivo and in vitro studies to protect against CP nephrotoxicity, and CP is metabolized to a nephrotoxicant through a GSH‐conjugate intermediate [36]. Oxidative stress has been reported to play a role in CP‐induced damage, and several antioxidants and thiol compounds have been reported to mitigate or protect against CP nephrotoxicity [8,29]. Here, we have confirmed that CP depletes renal GSH and other enzymes involved in scavenging of free radicals, and that pretreatment and concomitant treatment with emodin significantly reverses these changes.…”

“…Renal injury by CP has been associated with oxidative stress, inflammation, and apoptosis [8,29]. Our results have shown remarkable and highly significant restoration of the markers of oxidative stress in renal tissues, viz GSH e, glutathione peroxidase, glutathione reductase SOD, and catalase activities.…”

“…Despite its other limitations (e.g., invasiveness), histopathological examination of the renal tissue is established to be the gold standard for defining renal injury [30]. Several workers have shown that CP‐induced apoptosis through different mechanisms [29], and that apoptosis – through the intrinsic (mitochondrial), extrinsic (death receptor), or extracellular signal‐regulated kinase pathways – is the main underlying mechanism in CP‐induced nephrotoxicity [7]. In this work, emodin markedly inhibited the CP‐induced apoptosis and renal tubular damage, confirming its effectiveness is abrogating CP nephrotoxicity.…”