Patients with moderate and advanced chronic kidney disease (CKD) who have a very low urine microalbumin-creatinine ratio (UACR) experience worse CKD progression and higher mortality, according to a study.

In contrast, a very low UACR is associated with decreased likelihood of renal function decline and death among individuals without CKD, the study of nearly 300,000 U.S. veterans found.

Compared with a UACR less than 5 µg/mg, a UACR of 10-19 was associated with a 23% and 62% decreased risk of CKD progression among subjects with an estimated glomerular filtration rate (eGFR) of 30-44 and 15-29 mL/min/1.73 m2, respectively, investigators reported online ahead of print in the Journal of American College of Cardiology. By comparison, the risk of eGFR decline associated with a UACR of 10-19 versus less than 5 was increased by 9%, 19%, and 7% among subjects with an eGFR of 90 or higher, 60-89, and 45-59, respectively.

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The researchers, led by Csaba P. Kovesdy, MD, of Memphis VA Medical Center, observed a similar pattern with respect to mortality. Compared with a UACR less than 5, a UACR of 10-19 was associated with a 19% decreased risk of death among subjects with an eGFR of 15-29 compared with a 19%, 32%, and 11% increased risk of death among individuals with an eGFR of 90 or higher, 60-89, and 45-59, respectively.

“Explaining the different associations seen in advanced CKD necessitates the understanding of what the meaning of a high and low UACR is,” the authors pointed out. “The most commonly accepted theory is that UACR represents both a cause and a consequence of vascular damage.”

A possible explanation for the CKD-related findings is that UACR is a marker of intraglomerular pressure, and the different association patterns observed in some subgroups may represent their decreased ability to adapt to lower renal perfusion pressures, Dr. Kovesdy and his colleagues explained. CKD patients have an inability to autoregulate end-organ perfusion pressure in the face of lower blood pressure due to a combination of small blood vessel changes related to the older age and comorbid conditions found in these patients, they stated. This could result in ischemia. “Therefore, it is possible that a low UACR identifies patients at high risk for ischemic end-organ damage among those with advanced CKD,” the authors wrote.