Early Markers of Nephrotoxicity

Abstract

The kidney is susceptible to a wide range of nephrotoxins which vary in their e¡ect from mild renal dysfunction to severe damage and end-stage renal failure. The identi¢cation of the presence of early renal damage, and also of individuals at risk of developing renal dysfunction, is important in order that corrective therapies can be applied at an early stage. However, glomerular ¢ltration rate (GFR) is unlikely to fall until 50% of nephrons have ceased to function. A major challenge is to provide measurements, both qualitative and quantitative, that give an early indication of the initial site of renal damage before gross deterioration in kidney function has occurred. Nephrotoxic exposure results in a cascade of events of gradually increasing severity. Initially, functional changes occur which, if exposure continues, then progress past a point of no return leading ultimately to renal failure. Most biomarkers measure the e¡ect of a toxin on the kidney, but some are insensitive, making it di⁄cult to measure accurately the extent to which the kidney has been exposed. Used selectively, biomarkers are able to give information on the stage and severity of the damage/disease process. To be useful, a biomarker should be easily measured by robust inexpensive procedures, which can be carried out on random or timed urine samples. The e¡ect of nephrotoxic agents is best assessed with a small battery of tests that can be followed by more specialized tests to con¢rm the severity and type of renal damage that has occurred.

Evaluation of snake envenomation-induced renal dysfunction in dogs using early urinary biomarkers of nephrotoxicity

“…In this view routine urinary marker assays are generally known to be better indicators of renal damage as the loss of urine concentrating ability is observed sooner than renal azotemia (Price, 2002). However, measured USG in this study, at both T0 and T1, was not significantly different from that in control dogs.…”

“…A variety of urinary biomarkers have recently been introduced ranging from proteins of low (LMW) to high molecular weight (HMW) which are helpful in the assessment of the localisation, extent and progression of renal injuries (Price, 2002;Smets et al, 2010;Maddens et al, 2011) . Among these biomarkers, the HMW proteins, such as urinary albumin (uAlb), immunoglubin G (IgG) and C-reactive protein (uCRP) are usually associated with glomerular damage, whereas detection of urinary retinol binding protein (uRBP) typically reflects tubular damage (Bernard et al, 1987;Price, 2002;D'Amico and Bazzi, 2003).…”

“…Among these biomarkers, the HMW proteins, such as urinary albumin (uAlb), immunoglubin G (IgG) and C-reactive protein (uCRP) are usually associated with glomerular damage, whereas detection of urinary retinol binding protein (uRBP) typically reflects tubular damage (Bernard et al, 1987;Price, 2002;D'Amico and Bazzi, 2003). uAlb has been demonstrated to be an indicator of early glomerular damage which precedes more severe proteinuria (Price, 2002;D'Amico and Bazzi, 2003;Smets et al, 2010). Two other HMW proteins which are also associated with a damaged glomerular barrier are uIgG and uCRP (Price, 2002;D'Amico and Bazzi, 2003).…”

“…uAlb has been demonstrated to be an indicator of early glomerular damage which precedes more severe proteinuria (Price, 2002;D'Amico and Bazzi, 2003;Smets et al, 2010). Two other HMW proteins which are also associated with a damaged glomerular barrier are uIgG and uCRP (Price, 2002;D'Amico and Bazzi, 2003). Retinol binding protein (RBP) belongs to the group of LMW proteins and is freely filtered through the glomerulus but subsequently reabsorbed by epithelial cells of the proximal tubules (Marinó et al, 2001).…”

Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi

“…Therefore, sensitive markers are necessary for the early diagnosis of renal dysfunction in canine babesiosis. Urinary markers may allow this and additionally have the capacity to quantify and localize the site of renal injury (Price, 2002). Immunoglobulin G (IgG), involved in the humoral immune response, and C-reactive protein (CRP), a major acute phase protein in dogs, are two high molecular weight (HMW) proteins, to which an intact glomerular barrier is impermeable (D'Amico and Bazzi, 2003).…”