Sandra Yin

May 15, 2012

May 15, 2012 (Washington, DC) — A commonly used urine dipstick can predict acute kidney injury (AKI), according to findings presented here at the National Kidney Foundation (NKF) 2012 Spring Clinical Meetings.

After adjustment for confounders, researchers found that patients who developed dipstick proteinuria had more than double the risk of developing AKI in the first 72 hours of admission than those who did not (odds ratio [OR], 2.3, 95% confidence interval, 1.4 to 3.8).

"Dipstick proteinuria is a cheap, simple, rapid, noninvasive, and widely available diagnostic test that could serve as an early biomarker of AKI in critically ill septic patients," lead researcher Javier Neyra, MD, an internal medicine resident at Henry Ford Hospital in Detroit, Michigan, told Medscape Medical News.

Checking for dipstick proteinuria is a component of the routine urinalysis. In septic patients, it is commonly used to identify whether an infection originated in the urinary system. AKI occurs in nearly 3 of 10 patients with severe sepsis and microalbuminuria, and has been noted in up to 87% of septic patients.

Proteinuria in patients with acute or severe sepsis is to be expected, Dr. Neyra said. Animal studies have shown that in sepsis, tubular damage in the kidney means that reabsorption of protein is impaired. Other recent studies have suggested that a gene that can be activated in sepsis might secrete more protein.

To determine how good an early biomarker of sepsis-related AKI de novo dipstick proteinuria is, the researchers retrospectively analyzed data from 328 patients with severe sepsis who were admitted to the intensive care unit at Henry Ford Hospital from January 2004 and July 2011 and who underwent dipstick proteinuria testing on admission. Patients whose baseline serum creatinine level was above 1.5 mg/dL and who had dipstick proteinuria within 3 months of the index admission date and common causes of false-positive dipstick proteinuria, such as urinary tract infection or gross hematuria, were excluded from the study.

Serum creatinine increased at least 0.3 mg/dL in 64% of patients within the first 72 hours of admission. New-onset dipstick proteinuria was found in 114 (54%) of those patients (P < 0.001; positive predictive value, 75%) and in 91 of 166 (55%) patients with AKI, based on Acute Kidney Injury Network criteria (P = 0.002; positive predictive value, 60%).

It is important to identify biomarkers that are sensitive and specific and that provide timely and early diagnosis of AKI, Dr. Neyra said. The traditional approach of relying on serum creatinine levels to detect AKI in septic patients can delay its diagnosis, he explained, in part because creatinine production from muscle is lower in septic patients. In addition, septic patients receive aggressive intravenous fluid administration, which can dilute serum creatinine.

NKF president Lynda Szczech, MD, MSCE, FASN, FNKF, medical director of pharmacovigilance at Pharmaceutical Product Development, a contract research organization based in Morrisville, North Carolina, told Medscape Medical News that the performance of the dipstick proteinuria is "remarkably good."

The tool, Dr. Szczech said, can detect who is most susceptible to AKI and help providers intervene early and prevent it from developing. She acknowledged that it is not perfect, but explained that all the other biomarkers that people are trying to develop have similar issues. This is "a really cheap, easy, routinely measured adjunct to serum creatinine and is actually a brilliant observation on how to use something that we would use anyway."

Creatinines are a notoriously bad marker for kidney function, noted Dr. Szczech. A person could have both kidneys taken out one day, but the manifestation of injury wouldn't be immediately apparent, because creatinine levels might not be elevated for 24 hours or more, she explained.

Biomarkers are not totally reliable, she said; baseline renal stress can lead to elevations in people who do not go on to develop kidney injury. Biomarkers might also not be elevated in people who go on to develop AKI. "None of the biomarkers are perfect," she said.

"We're still looking for the troponin of the kidney." When troponin goes up, you know you've had a heart attack. If it doesn't go up, you haven't had a heart attack, she explained. Although researchers are looking at promising biomarkers, they will probably "only have promise when used in a panel so they can complement each others' weaknesses," she added.

Dr. Neyra has disclosed no relevant financial relationships. Dr. Szczech works for Pharmaceutical Product Development.

National Kidney Foundation (NKF) 2012 Spring Clinical Meetings. Poster 17. Presented May 10, 2011.

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