Glomerular Filtration Function Decline, Mortality, and Cardiovascular Events: Data from the Strong Heart Study

Background Rapid kidney decline is associated with mortality and cardiovascular disease, even in the absence of CKD. American Indians (AI) have particularly high burden of kidney disease, cardiovascular disease, and stroke. This study aims to examine extreme loss in glomerular function in this population in association with clinical outcomes. Methods The Strong Heart Study, a large longitudinal cohort of adult AI participants, collected plasma creatinine at three examination visits between 1989 and 1999. Intraindividual regressions of eGFR provided linear estimates of the change in kidney function over this time. Surveillance with physician adjudication identified mortality and cardiovascular events between visit three through to 2017. Results Mean change in eGFR was loss 6.8 ml/min over the 10-year baseline (range: -66.0 to +28.9 ml/min). The top 1 percentile lost approximately 5.7 ml/min per year. Participants with extreme eGFR loss were more likely to have diabetes (95% versus 71%), hypertension (49% versus 33%), or longer smoking history, among smokers (19 pack-years versus 17 pack-years). CKD (eGFR <60 ml/min) was associated only with mortality, independent of slope: HR, 1.1; 95% CI, 1.0 to 1.3. However, extreme loss in eGFR (>20 ml/min over baseline period) was associated with mortality, independent of baseline eGFR: HR, 3.5; 95% CI, 2.7 to 4.4, and independently associated with composite CVD events and CHF: HR, 1.4 and 1.7; 95% CI, 1.1 to 1.9 and 1.2 to 2.6, respectively. Conclusions This is the first examination of decline in eGFR in association with mortality and CVD among AIs. The implications of these findings are broad: clinical evaluation may benefit from evaluating change in eGFR over time in addition to dichotomous eGFR. Also, these findings suggest there may be aspects of renal function that are not well marked by clinical CKD, but which may have particular relevance to long-term renal and vascular health.