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Proteinuria Helps Predict Kidney Injury

Nov 24, 2010

Proteinuria, in addition to estimated glomerular filtration rate (eGFR), predicts an increased risk of acute kidney injury, investigators reported….

The risk of acute kidney injury quadrupled in patients who had a normal GFR but heavy proteinuria by dipstick measurement. Rates of hospital admission for acute kidney injury and injury requiring dialysis remained high for all values of estimated GFR.

Matthew T. James, MD, of the University of Calgary, and colleagues reported in a poster presentation at the American Society of Nephrology meeting that the risk of clinically relevant loss of kidney function after acute kidney injury increased for all patients except those with the lowest eGFR and heaviest proteinuria at baseline.  

In addition, “long-term mortality increased after acute kidney injury at all levels of eGFR and proteinuria,” the investigators wrote in their conclusion. 

“These findings show 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,” they added. 

Lower eGFR predisposes patients to acute kidney injury, and proteinuria also is a marker of kidney disease. How the two parameters jointly affect the risk of acute kidney injury and associated outcomes is unclear. 

To address the issue, James and colleagues performed a cohort study involving 920,985 adults residing in Alberta between 2002 and 2007. The study included individuals not requiring dialysis at baseline who also had at least one outpatient measurement of serum creatinine concentration and proteinuria. By means of hospital administrative codes, the investigators identified hospital admissions for acute kidney injury. 

Participants were categorized by eGFR measurements: ≥60, 45 to 59.9, 30 to 44.9, and 15 to 29.9 mL/min/1.73 m2. Proteinuria was classified as normal (urine dipstick negative), mild (trace or 1+), or heavy (≥2+). In sensitivity analyses, the investigators used the dipstick categories and albumin-creatinine ratio categories of normal (less than 3 .4 mg/mmol), mild (3.4 to 33.9 mg/mmol), and heavy (>33.9 mg/mmol).

Outpatient dipstick and albumin-creatinine ratio measurements in the six months before and after the eGFR measurement were used to establish baseline proteinuria and albuminuria. The review of medical records showed that 74,363 patients had both a dipstick measurement and albumin-creatinine ratio determination. 

During a median follow-up of 35 months, 6,520 study participants had hospital admissions for acute kidney injury. An additional 615 participants had acute kidney injury requiring dialysis. 

In participants with an eGFR of 60 mL/min/1.73 m2 or greater, heavy proteinuria by dipstick was associated with an adjusted risk of admission of 4.4 compared with participants who had no proteinuria. Heavy or moderate proteinuria increased the admission rate for acute kidney injury across the entire range of eGFR values. 

Analysis of 27,595 deaths that occurred during follow-up showed that patients admitted for acute kidney injury had a higher mortality compared with participants who did not have the disorder. Acute kidney injury was associated with increased mortality across the spectrum of eGFR values. 

Acute kidney injury (AKI) also increased the risk of the composite outcome of progression to end-stage renal disease or doubling of serum creatinine. However, the association decreased with heavier baseline proteinuria or lower baseline eGFR (P<0.0001 for trend). For patents with baseline eGFR <30 mL/min/1.73 m2 and heavy proteinuria, hospital admission for acute kidney injury did not increase the rate of the composite renal outcome. 

In their poster presentation, James and colleagues noted that “eGFR and proteinuria in combination modify the risk of AKI, as well as the risks of death or progressive kidney function loss following acute kidney injury. These findings suggest that proteinuria and eGFR should be incorporated into systems for predicting the risk for acute kidney injury or its consequences.” 

Limitations of the study cited by the authors included potential for misclassification; use of algorithms for acute kidney injury with high specificity but low sensitivity; assessment of eGFR, proteinuria, and comorbidities prior to admission — thereby excluding how changes during the hospitalization might have influenced outcome — and inability to exclude confounders such as use of drugs with effects on the kidney. 

Practice Pearls: 

  • Explain that a large Canadian observational study found that dipstick measurement of proteinuria added to estimated glomerular filtration rate (eGFR) helped to predict admission for acute kidney injury.

  • Note that heavy proteinuria was linked to admission for acute renal injury across all eGFR levels.

James MT, et al “Glomerular filtration rate, proteinuria, and the incidence and outcomes of acute kidney injury” ASN 2010; Abstract SA-PO2053

James MT, et al “Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study” Lancet 2010; DOI: 10.1016/S0140-6736(10)61271-8