Prevalence of CKD and its relationship to eGFR-related genetic loci and clinical risk factors in the SardiNIA study cohort

Abstract

The prevalence of CKD and of renal failure vary worldwide, yet parallel increases in leading risk factors explain only part of the differential prevalence. We measured CKD prevalence and eGFR, and their relationship with traditional and additional risk factors, in a Sardinian founder population cohort. The eGFR was calculated using equations from the CKD Epidemiology Collaboration and Modification of Diet in Renal Disease studies. With use of the Kidney Disease Improving Global Outcomes guidelines, a cross-sectional analysis of 4842 individuals showed that CKD prevalence was 15.1%, including 3.6% of patients in the high-risk and 0.46% in the very-high-risk categories. Longitudinal analyses performed on 4074 of these individuals who completed three visits with an average follow-up of 7 years revealed that, consistent with other populations, average eGFR slope was -0.79 ml/min per 1.73 m(2) per year, but 11.4% of the participants had an eGFR decline >2.3 ml/min per 1.73 m(2) per year (fast decline). A genetic score was generated from 13 reported eGFR- and CKD-related loci, and univariable and multivariable analyses were applied to assess the relationship between clinical, ultrasonographic, and genetic variables with three outcomes: CKD, change in eGFR, and fast eGFR decline. Genetic risk score, older age, and female sex independently correlated with each outcome. Diabetes was associated with CKD prevalence, whereas hypertension and hyperuricemia correlated more strongly with fast eGFR decline. Diabetes, hypertension, hyperuricemia, and high baseline eGFR were associated with a decline of eGFR. Along with differential health practices, population variations in this spectrum of risk factors probably contributes to the variable CKD prevalence worldwide.

Keywords: chronic kidney disease; clinical epidemiology; ethnicity; glomerular filtration rate; human genetics; renal function decline.

Figure 1.

Progressive decline in kidney function in all individuals and in different subgroups of patients of SardiNIA Study Cohort over a 7-year period. (A) Prevalence of renal function categories in the three visits. The eGFR was evaluated with the CKD-Epidemiology Collaboration formula. (B) Histograms for slope of eGFR. Significant slopes are in black. The numbers of individuals with positive or negative slopes are on the right and left, respectively. The rate of decline of eGFR, assessed in the same 4074 SardiNIA study cohort individuals who participated in all three visits, was −0.79 ml/min per 1.73 m² per year. The rates of decline of eGFR (ml/min per 1/73 m² per year) in subgroups were −1.41 in patients with diabetes, −1.09 in hypertensive patients, −1.06 in obese individuals, −1.87 in patients with baseline eGFR<60 ml/min per 1.73 m², and −0.52 in individuals without comorbid conditions. The rate of decline of eGFR of each subgroup is reported in the text. All data were adjusted for starting eGFR and included interaction terms between the risk factor and starting eGFR. “Normal” individuals are those without the comorbid conditions listed in Table 1.

Figure 2.

Prevalence of CKD risk categories in SardiNIA Study Cohort, adjusted by sex, according to KDIGO guidelines. CKD prevalences were 15.5% overall, 13.9% in men, and 16.6% in women. The eGFR was calculated using the CKD-Epidemiology Collaboration formula; CKD was staged as proposed by KDIGO.