Biomarkers in Nephrology: Core Curriculum 2013

Abstract

The clinical assessment and management of patients with known or suspected kidney disease has been aided for decades by biomarkers, a term defined by a National Institutes of Health (NIH) working group as "A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention." The characteristics of an ideal biomarker are given in Box 1. Historically, the first biomarker of kidney disease was the finding on physical examination of interstitial edema or ascites, a condition termed dropsy, that was not specific to what eventually became recognized as kidney failure but that rather encompassed a number of clinical conditions including congestive heart failure and cirrhosis. More objective biomarkers in the early days of nephrology included the examination of the urine sediment, followed by measurement of the blood urea nitrogen concentration and the serum creatinine concentration. Recently, there has been an explosive growth in the search for more sensitive, specific, and prognostically accurate biomarkers to assist in the care of patients with or at risk of kidney disease. In this review we aim to discuss both conventional and novel biomarkers of kidney disease in the settings of acute kidney injury (AKI), chronic kidney disease (CKD), nephrotoxin exposure, and glomerulonephritis. An anatomical localization of these biomarkers along the nephron is shown in figure 1. Additional Readings CONVENTIONAL BIOMARKERS OF KIDNEY FUNCTION AND DISEASE Modern definitions of CKD and AKI emphasize a stage of decreased glomerular filtration rate (GFR), and a stage of kidney damage, defined as structural or functional abnormalities before a decline in GFR. Corresponding biomarkers include filtration markers, such as

Association of Urinary Injury Biomarkers with Mortality and Cardiovascular Events

“…Less than 1% of KIM-1, 5.25% of IL-18, 5.8% of albuminuria, and 5.9% of urine creatinine values were set to the lowest detection limit. Mean age of the populationwas 74 years, 49% of participants were men, 41% of participants were black, 24% of participants had diabetes, and 22% of participants had prevalent coronary heart disease (CHD); 17% of participants had eGFR cys ,60 ml/min per 1 (Table 1). Participants with higher urinary KIM-1/creatinine (cr) were more likely to be white, have diabetes or CHD, have higher levels of C-reactive protein (CRP) and UACR, and have lower levels of serum albumin and eGFR cys .…”

Dialysis Vascular Access Intervention and the Search for Biomarkers

“…Delivering on that promise requires, at least, that candidate biomarkers fully measure up to and meet specific and discerning criteria. 19 Serum indoxyl sulfate levels are, thus, a long way from consideration as a biomarker that will aid in determining whether a stenosing AVG will thrombose after intervention and when to intervene. Nonetheless, like prior observations showing that plasma levels of asymmetric dimethylarginine correlate with the risk for restenosis after angioplasty of AVFs, 20 the study of Wu et al 9 identified a specific uremic toxin linked with a particular postintervention outcome and will likely stimulate the search for others.…”

Cistatina C: Um Marcador de Função Renal Promissor em Doentes com Lúpus Eritematoso Sistémico?

“…3,4 A TFG pode ser medida através da clearance de um marcador de filtração exógeno, sendo o gold standard a medição da clearance urinária da inulina durante uma infusão intravenosa contínua. Outros marcadores exógenos possíveis são o iotalamato, o iohexol ou o ácido etilenodiamino tetra-acético (EDTA).…”

“…Constitui um bom marcador de função renal pois não se liga a proteínas e não é metabolizada no rim, sendo filtrada livremente no glomérulo. 3 Contudo, possui reconhecidas limitações, já que a sua concentração sérica não depende exclusivamente da TFG, mas é influenciada largamente por outros factores fisiológi-cos, sendo a taxa de produção da creatinina proporcional à massa muscular. A sua excreção não depende exclusivamente da filtração glomerular, ocorrendo secreção tubular proximal (10 -20%), bem como eliminação extra-renal pelas bactérias da flora gastrointestinal, sendo que estes mecanismos se tornam mais importantes com o declínio da função renal, permitindo manter a concentração sérica da creatinina dentro de valores normais até uma diminuição muito significativa da TFG (cerca de 60 mL/min/1,73 m 2 ) -faixa cega da creatinina.…”

“…4,6 Procurou-se ultrapassar a variabilidade inter-individual da produção da creatinina através do desenvolvimento de equações que melhoram o cálculo da TFG, através da inclusão diversos factores antropométricos, das quais são exemplo a fórmula de Cockroft-Gault, a do estudo Modification of Diet in Renal Disease (MDRD) e a do Chronic Kidney Disease Epidemiology Collaboration (CDK-EPI). 3,6,7 Segundo a KDIGO (2012), a equação recomendada para calcular a TFG é a equação da creatinina do estudo CKD--EPI 2009 (CKD-EPI creat ), pois demonstrou ser mais exacta e precisa e ter menos viés comparativamente à equação do estudo MDRD, especialmente para TFG mais elevadas. 2,8 Como marcador alternativo de TFG tem sido investigada a cistatina C, uma proteína não glicosilada de baixo peso molecular, pertencente à família dos inibidores das cisteinoproteases, produzida, a ritmo constante, por todas as células nucleadas, livremente filtrada nos glomérulos renais, e por fim reabsorvida e metabolizada nos túbulos proximais.…”