The Largest Meta-analysis on Global AKI Incidence

This month, the Clinical Journal of the American Society of Nephrology (CJASN) published a meta-analysis on the epidemiology and global incidence of acute kidney injury (AKI) last month. 

Dr. Bertrand L. Jaber and his colleagues from Tufts University School of Medicine included 312 published cohort studies (between 2004 and 2012) with 49 million adult and pediatric patients, from over 40 countries across all continents.

Incidence of AKI:

• The pooled incidence rate of AKI was 10.7% using all the 312 studies. However, in a subgroup analysis of 154 studies that used a KDIGO-equivalent AKI definition, the pooled incidence rate of AKI was 23.2%.
• The highest pooled incidence rate of AKI was found in ICU to be 37%, followed by cardiac surgery 24%.
• The pooled incidence rate of AKI was higher in countries south versus north of the Equator (27% vs 22%, respectively), and higher in countries that spent more than 10% of its GDP on total health expenditure vs those countries that spend less than 5% (25% vs 14%).

Incidence of AKI-associated mortality:

• The pooled incidence rate of AKI-associated mortality was 23%.

Ancillary findings:

• There were 269 studies of adults, 42 studies of children, and 1 study combining adults and children.
• There were 62% retrospective cohort studies, 35% prospective cohort studies, and 3% post hoc cohorts derived from clinical trials.
• Sample size of individual studies on adults ranged from 500 to 12 millions, and on children varied from 64 to 60 thousands.
• The mean age ranged from 23 to 80 years for adults and from 0 to 13 years for children.
• Studies from high-income countries represented 87% of the studies included in this meta-analysis

Comment:

This is a landmark meta-analysis in the area of AKI epidemiology. It is the first and largest meta-analysis of AKI incidence that include both adults and pediatric patients from allover the world. Beside the surprising findings that AKI occurs around the world, there has been a disparity in the representation of certain countries in this meta-analysis, simply due to the lack of published evidence from these countries. The findings of high AKI incidence in high-income countries warrant further investigations to identify the causes and develop solutions. However, I believe that the low incidence from countries that spend less than 5% of their GDP on health expenditure could be false. This could be attributed to the underdiagnosis of AKI from lacking nephrology-trained physicians. Besides, lack of scientific publications in this area could contribute to the potentially false low incidence, in my opinion.

Jaber et al conclude:

“…discussions should encourage providers to design better hospital-based health care delivery systems that focus on the prevention, early detection, and treatment of AKI, improve patient safety, and ultimately, preserve kidney health and well-being while mitigating the long-term costly burden of CKD."

Eating Fish is Associated with Decreased All-Cause Mortality in Older Adults

Mozaffarian and his colleagues published a paper recently in the Annals of Internal Medicine analyzed data from 2692 U.S. adults aged 74 years (±5 years) without prevalent cardiovascular diseases at baseline, who participated in the National Heart, Lung, and Blood Institute (NHLBI)-funded cohort, The Cardiovascular Health Study (CHS). The investigators measured the blood circulating levels of 3 types of long-chain omega-3 polyunsaturated fatty acids (omega-3 PUFAs); eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). These were measured from the blood that was collected from the participants in 1992. They then followed them longitudinally for 16 years (1992 through 2008) to evaluate the relationship with total and cause-specific mortality and incident fatal or nonfatal CHD and stroke.

The authors found that the individual levels of EPA, DPA, and DHA, and their total levels (omega-3 PUFA) were associated with lower total mortality across three robust models of adjusted Cox proportional hazards models (age, gender, various demographic and co-morbid conditions, and dietary factors):

       The participants in the higher quintile of the total omega-3 PUFAs had 27% lower risk 

       The participants in the higher quintile of EPA had 17% lower risk 

       The participants in the higher quintile of DPA had 23% lower risk

       The participants in the higher quintile of DHA had 20% lower risk

All results were statistically significant with narrow 95% confidence internals.

For cause-specific mortality, and using the same adjustment models of the total mortality risk data, total omega-3 PUFAs, and most of the individual levels of the three subtypes, were associated with cause-specific mortality. Total omega-3 PUFAs was associated with: 

       35% lower risk from cardiovascular mortality

       40% lower risk from coronary heart disease mortality

       45% lower risk from arrhythmic coronary heart disease (CHD) mortality

       28% lower risk from non-arrhythmic CHD mortality

       40% lower risk from stroke mortality

       28% lower risk from total fatal and nonfatal CHD mortality

       17% lower risk from nonfatal myocardial infarction mortality

       25% lower risk from total fatal and nonfatal stroke mortality

       37% lower risk from Ischemic stroke mortality

This data strongly suggests that fish consumption or fish oil supplementation would reduce both total mortality and cause-specific mortality in older adults. The steepest dose-response relationship between the circulating blood levels of omega-3 PUFAs and the decreased risk came from as low as 400 mg per day dietary intake, or two servings of fatty fish per week. This will lead to an average increase of about 2 more years of life in those with higher levels compared to those with lower levels.

My opinion:

This conclusion is supported by the robust statistical analyses with adjustment to many confounders, as well as a quantification of the omega-3 PUFAs rather than the amount of fish intake from Food Frequency Questionnaires (FFQ) or similar tool. Despite some limitations in this paper, it is a landmark paper in supporting increased fish intake to decrease the risk of mortality in older adults.