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1. In this prospective cohort study involving patients with chronic kidney disease (CKD), those with urine albumin levels on the higher side of normal had a greater risk of disease progression compared to those with lower urine albumin.

2. Patients with higher albuminuria also had a greater incidence of overt kidney failure compared to their lower albuminuria counterparts.

Evidence Rating Level: 2 (Good)

Study Rundown: It is well-established in the literature that excessive albumin secretion into the urine is closely linked to heightened risks for kidney failure. While people with a urine albumin-creatinine ratio (UACR) of <30 mg/g are considered to be within the normal range, this threshold was defined over four decades ago based on population variance and not necessarily performance characteristics or clinical utility. Since then, even microalbuminuria has been linked to adverse renal and cardiovascular outcomes, suggesting that there may be a continuous relationship between UACR and risk. This study evaluated the risk gradient of CKD progression among patients with existing renal insufficiency and baseline normoalbuminuria. It was found that those with higher baseline UACRs were significantly more likely to experience CKD progression and kidney failure compared to those with lower baseline UACRs. These effects persisted after adjustment for demographic and clinical characteristics, including body mass index, diabetes status, cardiovascular disease history, and baseline estimated glomerular filtration rate (eGFR). This study had several limitations, such as the observational design, using a single spot UACR for inclusion, and the high prevalence of medications with renal effects. However, this study boasted a long follow-up duration and a high participant retention rate. Overall, these results suggest that higher levels of albuminuria within the normal range may still confer additional risks for CKD progression.

Click here to read the study in AIM

In-Depth [prospective cohort study]: This multicenter observational study utilized data from 1629 adult patients who were enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study and had both an eGFR of 20-70 mL/min/1.73 m² and a UACR of less than 30 mg/g. The primary outcome was chronic kidney disease progression, defined as either a 50% decline in eGFR or incident kidney failure (initiation of dialysis therapy or kidney transplantation). The secondary outcome was kidney failure alone. The mean age was 60.2 years; 52.0% were women, and 54.3% were White. Median UACR was 6.9 mg/g (IQR, 4.0 to 14.2 mg/g), and mean eGFR was 49.6 mL/min/1.73 m2 (SD, 14.7). Over a median follow-up of 9.8 years, 182 individuals developed CKD progression and 99 developed kidney failure. Median baseline UACRs were higher in participants who developed CKD progression (12.0 vs. 6.5 mg/g) and kidney failure (15.5 vs. 6.6 mg/g) compared with those who did not. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% Confidence Interval [CI], 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for persons who had UACRs of 0 to less than 5, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Using the low UACR group as a reference, the hazard ratios for the medium and high UACR groups were 1.37 (CI, 0.89 to 2.10) and 2.61 (CI, 1.69 to 4.02), respectively. For kidney failure alone, the corresponding 10-year adjusted cumulative incidences were 3.8% (CI, 1.8% to 5.7%), 5.0% (CI, 3.3% to 6.7%), and 10.1% (CI, 7.5% to 12.8%). This corresponded to hazard ratios of 1.40 (CI, 0.75 to 2.62) and 3.42 (CI, 1.88 to 6.20). In summary, this study revealed that there may be some prognostic value to assessing albuminuria levels within the normal range.

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