O'Hare AM (VA Seattle HSR&D Center of Excellence (COE)), Gupta I
(VA Seattle HSR&D COE), Maynard C
(VA Seattle HSR&D COE), Rodriguez RA
(VA Puget Sound HCS, Division of Nephrology)
The presence and amount of urinary albumin is known to correlate with mortality risk. However, it is not known whether the prognostic significance of albuminuria varies with the patient’s level of kidney function. Our goal was to determine whether albuminuria was associated with a similar relative risk of death among patients with different levels of kidney function.
Using the VA Decision Support System (DSS) Laboratory Results File, we identified all patients who underwent at least one urine protein, urine creatinine, and serum creatinine measurement within a 90-day period between October 1, 2003 and September 30, 2006 (n=309,118). Level of renal function (estimated glomerular filtration rate or eGFR) was calculated using the modification of diet in renal disease (MDRD) formula based on serum creatinine, age, sex, and race. We excluded patients with an eGFR < 15. Death data were obtained from the VA Vital Status file with follow-up through September 1, 2007. We used a Cox proportional hazard model to measure the association of urinary albumin with time to death.
Among patients included in this cohort, 64,599 (21%) had microalbuminuria (30-299 mg/g) and 9,563 (3%) had macroalbuminuria ( > =300 mg/g). Among those with macroalbuminuria, this was low grade (300-9999 mg/g) in 7,087 (74%), intermediate grade (1000-2999 mg/g) in 2,031 (21%) and high grade ( > =3000 mg/g) in 445 patients (5%). Among patients with either micro- or macroalbuminuria, 35% had moderate or severe chronic kidney disease (CKD) defined as an eGFR < 60. After adjustment for age, race, sex, and eGFR, there was a strong graded association between level of albuminuria and risk of death (hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.50, 1.58) for microalbuminuria; HR 1.96 (CI 1.84, 2.07) for low grade albuminuria, HR 2.56 (CI 2.31, 2.84) for intermediate grade albuminuria, and HR 3.05 (CI 2.49, 3.74) for high grade albuminuria). However, the prognostic importance of urinary albumin differed by level of eGFR (P for interaction < 0.001). The association of microalbuminuria with death was strongest for patients with an eGFR > =60 and became progressively attenuated at lower levels of eGFR. In patients with severe CKD (eGFR < 30), these associations were modest and not statistically significant (microalbuminuria (HR 0.99, CI 0.87, 1.12), low grade albuminuria (HR 1.18, CI 0.98, 1.42), intermediate grade albuminuria (HR 1.16, CI 0.91, 1.48) and high grade albuminuria (HR 1.33, CI 0.88, 2.02)).
The prognostic importance of micro- and macroalbuminuria is modified by level of kidney function (eGFR).
Primary care providers and nephrologists should be aware that the value of urinary albumin measurements in discriminating between patients at high and low risk for death is greatest among patients with normal kidney function and more limited in the presence of moderate or severe CKD.