Proteinuria Lowering Can Adversely Affect Some CKD Patients

MEMPHIS, TN — Proteinuria-lowering interventions in patients with advanced chronic kidney disease (CKD) should be implemented cautiously, considering the potential for adverse outcomes, according to a new study led by researchers from the Memphis, TN, VAMC.

According to the report, published in the Journal of the American College of Cardiology, those patients with the lowest levels of urine microalbumin-creatinine ratio (UACR) experienced higher mortality and worse progression of CKD.1

In general, the authors write, “The risk of adverse outcomes associated with lower levels of proteinuria has been found to be linearly decreasing with even low-normal levels of microalbuminuria.” They say they embarked on their research because it was unclear “whether comorbid conditions change these associations.”

For the study, the researchers examined the association of urine microalbumin-creatinine ratio (UACR) with mortality and the slopes of estimated glomerular filtration rate (eGFR) in a nationally representative cohort of 298,875 VA patients. They focused on associations of UACR with all-cause mortality overall and in subgroups of patients with and without diabetes mellitus, hypertension, cardiovascular disease, congestive heart failure, and advanced CKD.

They found that very low levels of UACR were linearly associated with decreased mortality and less progression of CKD overall: adjusted mortality hazard ratio and estimated glomerular filtration rate slope (95% confidence interval [CI]) associated with UACR ≥200 μg/mg, compared to <5 μg/mg were 1.53 (95% CI: 1.38 to 1.69, p < 0.001) and -1.59 (95% CI: -1.83 to -1.35, p < 0.001).

“Similar linearity was present in all examined subgroups, except in patients with CKD in whom a U-shaped association was present and in whom a UACR of 10 to 19 was associated with the best outcomes,” the authors note, adding, “The association of UACR with mortality and with progressive CKD is modified in patients with CKD, who experience higher mortality and worse progression of CKD with the lowest levels of UACR.”

1. Kovesdy CP, Lott EH, Lu JL, Malakauskas SM, Ma JZ, Molnar MZ, Kalantar-Zadeh K. Outcomes associated with microalbuminuria: effect modification by chronic kidney disease. J Am Coll Cardiol. 2013 Apr 16;61(15):1626-33. doi: 10.1016/j.jacc.2012.11.071. PubMed PMID: 23500283; PubMed Central PMCID: PMC3625505.

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