It All Adds Up

Protein-urine levels, blood-filtering rate and risk of acute kidney injury all related in kidney disease

/ Author:  / Reviewed by: Joseph V. Madia, MD

An article published by The Lancet shows that the risk of acute kidney injury, the rate at which kidneys filter blood, and the levels of protein in urine are all closely interrelated.

The study is by Dr Matthew James. University of Calgary, AB, and Dr Marcello Tonelli from the University of Alberta, Edmonton, AB, Canada, and colleagues.

Acute kidney injury (AKI—also known as acute renal failure), is a rapid loss of kidney function. AKI is common, often preventable, and associated with adverse short-term and long-term outcomes in various clinical settings. AKI needing dialysis is associated with in-hospital mortality, ranging from 30% to 80%, but even slight declines in kidney function are associated with excess mortality, extended length of hospital stay, and increased costs.

Low values of kidney filtration rate (or estimated glomerular filtration rate /eGFR) identify people with chronic kidney disease, and predispose people to acute kidney injury. Proteinuria (protein in the urine) is another marker of kidney disease that is inexpensive and readily available. Current guidelines for classifying risk of both chronic and acute kidney damage is based primarily on eGFR and does not consider proteinuria. In this new work, the authors aimed to investigate how eGFR and proteinuria jointly modified the risks of AKI and subsequent adverse clinical outcomes.

The study covered around 920,000 adults living in Alberta, Canada, between 2002 and 2007. Participants not needing chronic dialysis at baseline and with at least one outpatient measurement of both serum creatinine concentration (a measure of eGFR) and proteinuria (urine dipstick or albumin-creatinine ratio) were included. The authors assessed hospital admission with acute kidney injury, along with all-cause mortality and a composite kidney-related outcome of end-stage kidney disease or sustained doubling of serum creatinine concentration.

During median follow-up of 35 months, 6,520 (0.7%) participants were admitted with acute kidney injury. In those with eGFR>60 mL/min per 1.73 m² or greater (normal or nearly normal levels of filtration) the adjusted risk of admission with AKI was about four times higher in those with heavy proteinuria as compared to those without proteinuria. In fact, among those with >60 mL/min per 1.73 m² or greater and heavy proteinuria, the risk of admission with AKI remained 2 to 3 times higher than in those with reduced kidney filtration (eGFR 45-59.9 mL/min per 1•73 m² but no proteinuria). The adjusted rates of admission with AKI were even higher in participants with heavy dipstick proteinuria who also had lower levels of eGFR – and people with AKI were more likely to die than those without AKI, at all levels of eGFR and proteinuria.

The authors conclude: "These findings suggest that information on proteinuria and eGFR should be used together when identifying people at risk of acute kidney injury, and that an episode of acute kidney injury provides further long-term prognostic information in addition to eGFR and proteinuria."

In a linked Comment, Dr Morgan Grams, Johns Hopkins School of Medicine, Baltimore, MD, USA, and Dr Josef Coresh, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, say: "James and colleagues' impressive work buttresses mounting evidence that even small amounts of pre-existing proteinuria or albuminuria should be a red flag when assessing kidney-risk profiles. Future studies are needed to determine the link between albuminuria and potentially preventable forms of acute kidney injury, such as contrast-induced nephropathy; however, we are hopeful that increased awareness by physicians of all risk factors for acute kidney disease might stem its growing incidence. Urine dipsticks—a cheap, simple, and widely available diagnostic test—might just be what the doctor ordered for starting to reverse worldwide trends in acute kidney injury, a common and deadly disease."

Reviewed by: 
Review Date: 
December 6, 2010
Last Updated:
December 6, 2010