Kidney Disease Biomarkers

Kidney Disease Biomarkers

There has been considerable interest in studying novel biomarkers in chronic kidney disease (CKD) beyond the conventional clinical indices, such as serum creatinine, blood urea nitrogen, and urine protein or urine albumin. The motivation for this is similar to what has been outlined in other articles in this issue of ASN Kidney News.

Evolution of the biomarker concept

The search for biomarkers in body fluids is evolving into a broader quest for molecular phenotyping of tissue and disease reclassification. The original biomarker concept was too limited, failing to recognize that the interpretation of the molecular changes in body fluids requires a molecular understanding of the diseased tissue.

Cirrhosis is a major contributor to the burden of disease in society, and much of the morbidity and mortality associated with cirrhosis is due to the complications of portal hypertension. Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis, occurring in up to 20 percent of hospitalized patients (1). Despite the high rate of AKI in this patient population, there is often a delay in early diagnosis of AKI.

Over the past decade there has been an explosion of research investigating biomarkers of acute kidney injury (AKI). The research was borne out of the desire to replace serum creatinine, and in part urine output, as for a variety of reasons both serve as suboptimal tools in the diagnosis of acute renal tubular injury. The biomarker movement has been assisted by internationally accepted, standardized, consensus definitions of AKI.

Renal insufficiency is prevalent and clinically relevant in the setting of congestive heart failure. When admitted for acute decompensation, on average 1 out of 5 patients has a rise in serum creatinine, 1 out of 10 requires some form of dialysis, and 1 out of 20 requires long-term renal replacement therapies (1). These startling observations highlight the fact that adequate renal function plays a pivotal role in the clinical stability of heart failure.

Contrast-induced acute kidney injury (CI-AKI) is a common condition that is associated with serious, adverse short- and long-term outcomes. Despite substantial advancements in our understanding of CI-AKI, the capacity to effectively risk-stratify patients, diagnose incipient renal injury before elevations in serum creatinine (SCr) manifest, and identify patients at highest risk for adverse downstream events is limited.

Clinicians view kidney disease as a continuum where kidney failure results from a combination of patient susceptibility factors (diabetes, hypertension, or low nephron mass) combined with episodes of kidney injury (acute kidney injury [AKI]). Clinicians use traditional biomarkers such as serum creatinine, urine output, and albumin as indices of kidney function to diagnose, prognosticate, implement therapy, and monitor progression. These traditional biomarkers are far from ideal.

ASN Kidney News gratefully acknowledges KN Editorial Board member Edgar Lerma for his contribution as editor of this special section.

A biomarker is defined as a characteristic that can be objectively measured and evaluated as an indicator of normal biologic or pathogenic processes of pharmacological responses to a therapeutic intervention (1). Examples of biomarkers are proteins; lipids; microRNAs; genomic, metabolomic, or proteomic patterns; imaging determinations; electrical signals; and cells present on a urinalysis. This issue will focus primarily on serum and urine proteins.