medwireNews: Patients with low estimated glomerular filtration rate (eGFR), either based on creatinine alone or combined with cystatin C, and albuminuria have an increased risk for adverse kidney outcomes, cardiovascular diseases, and hospitalizations, indicates an individual participant data meta-analysis of more than 27 million adults.
Lower eGFR categories (≤89 vs 90–104 mL/min per 1.73 m2) and higher urine albumin-to-creatinine ratio (UACR) categories (10 to ≥1000 vs <10 mg/g) were consistently associated with an increased risk for each of 10 adverse outcomes, with the risk heightening in line with worsening eGFR and UACR categories.
The adverse outcomes studied were incident kidney failure with replacement therapy, acute kidney injury, hospitalization, coronary heart disease, heart failure, stroke, atrial fibrillation, peripheral artery disease, all-cause mortality, and cardiovascular death.
“The pattern of associations persisted irrespective of age, sex, diabetes, and cardiovascular disease and were stronger for eGFR based on creatinine and cystatin C compared with eGFR based on creatinine alone,” say Morgan Grams (New York University, USA) and fellow members of the CKD Prognosis Consortium in JAMA.
“This work supports recent recommendations to increase the use of cystatin C in clinical practice.”
Data on eGFR categories based on creatinine alone were available for 27,503,140 participants from 114 cohorts. They had a mean age of 54 years and 51% were women. The mean eGFR at baseline was 90 mL/min per 1.73 m2. In all, 33% of patients had albuminuria measured, at a median UACR of 11 mg/g.
The researchers report that over a mean follow-up of 4.8 years, the incidence of each of the adverse outcomes was significantly increased even in people with the mildest levels of kidney disease, namely those with a UACR below 10 mg/g and an eGFR of 45–59 mL/min per 1.73 m2 versus 90–104 mL/min per 1.73 m2.
The adjusted hazard ratios (HRs) for this group ranged from 1.2 to 1.6 for cardiovascular outcomes, including 1.4 for cardiovascular mortality. The adjusted HR was 1.3 for all-cause mortality, 3.5 for acute kidney injury, and 12.7 for kidney failure with replacement therapy.
Hospitalization (HR=1.3) was the most common adverse event, occurring at a rate of 161 per 1000 person–years in those with a UACR below 10 mg/g and an eGFR of 45–59 mL/min per 1.73 m2. This compared with 79 events per 1000 person–years in those with an eGFR of 90–104 mL/min per 1.73 m2, giving a significant excess absolute risk of 22 events per 1000 person–years, the researchers report.
The findings were similar for the 721,394 individuals from 20 cohorts whose eGFR levels were based on creatinine and cystatin C (mean age 59 years, 53% were women). In this group, the mean eGFR was 88 mL/min per 1.73 m2, the mean follow-up was 10.8 years, and approximately 44.4% of individuals in this population had measures of albuminuria, with a median UACR of 9 mg/g.
The researchers stress, however, that the relative risk associations between eGFR and the adverse outcomes were stronger and more linear with the addition of cystatin C. They say that a U-shape in the risk for adverse outcomes seen with the highest and lowest eGFR levels based on creatinine alone “may indicate imprecision and systematic overestimation of GFR among people who progress to adverse events.”
In addition, a difference in relative risks for the adverse outcomes between the two measures was observed in adults aged 65 years or older, leading the researchers to suggest that “when clinically available, additional use of cystatin C could better identify high-risk individuals, particularly among older populations.”
Higher categories of UACR, that is, above 10 mg/g, in the absence of reduced eGFR were also associated with significantly increased risks for each adverse outcome, even at a mildly higher category of 30–299 mg/g, highlighting the importance of albuminuria in risk assessment, despite its low rate of inclusion in medical records, say Grams and team.
Indeed, they found that among individuals in the reference eGFR category of 90 to 104 mL/min per 1.73 m2, those with a high UACR of 300–999 mg/g had an adjusted excess risk for mortality of 17 deaths per 1000 person–years and a 5-year survival rate of 91%, which the researchers say is “comparable with that of stage 1 colon cancer.”
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