Analysis of Chronic Kidney Disease Staging with Different Estimated Glomerular Filtration Rate Equations in Chinese Centenarians
The elderly population, particularly centenarians, represents the fastest-growing demographic globally, especially in China. This demographic shift has led to increased social and economic burdens associated with age-related diseases, including chronic kidney disease (CKD). Accurate estimation of glomerular filtration rate (GFR) is crucial for the early diagnosis, staging, and treatment monitoring of CKD. While the gold standard for GFR estimation involves invasive methods such as 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) isotope imaging, serum creatinine (Scr)-based equations have been developed as non-invasive alternatives. The most commonly used equations include the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 (BIS1) equations. However, these equations were not initially developed using large samples of elderly individuals, raising concerns about their accuracy in this population. This study aimed to investigate the differences in CKD staging using these equations in Chinese centenarians and to analyze the sources of discrepancy.
The study enrolled 966 centenarians from Hainan province, China, between June 2014 and December 2016. Demographic and clinical data, including age, gender, body mass index (BMI), waist-hip ratio, blood pressure, and blood biochemical parameters, were collected. GFR was estimated using the MDRD, CKD-EPI, and BIS1 equations. CKD staging was performed according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, which classify CKD into five stages based on eGFR values: stage 1 (eGFR ≥90 mL/min/1.73 m²), stage 2 (60 ≤ eGFR <90), stage 3 (30 ≤ eGFR <60), stage 4 (15 ≤ eGFR <30), and stage 5 (eGFR <15).
The study population had a median age of 102 years, with a majority being female (81.9%). Hypertension was the most prevalent condition (23.50%), followed by cardiovascular disease (4.04%). The general health status of the participants was relatively good, with low prevalence rates of severe conditions such as stroke (1.97%) and cancer (0.10%). Blood biochemical parameters, including Scr, serum uric acid (SUA), and serum urea, were measured, and eGFR was calculated using the three equations.
The agreement between the MDRD, CKD-EPI, and BIS1 equations was assessed using Bland-Altman plots and the k statistic. The mean difference between the MDRD and CKD-EPI estimates was 6.0 mL/min/1.73 m², with 95% limits of agreement ranging from -14.8 to 26.8 mL/min/1.73 m². The MDRD equation yielded higher eGFR values than the CKD-EPI equation in patients with CKD stage 1 and healthy individuals. The mean difference between the MDRD and BIS1 estimates was 18.0 mL/min/1.73 m², with 95% limits of agreement ranging from -3.0 to 38.9 mL/min/1.73 m². The MDRD equation consistently produced higher eGFR values than the BIS1 equation. The mean difference between the CKD-EPI and BIS1 estimates was 12.0 mL/min/1.73 m², with 95% limits of agreement ranging from -0.4 to 24.4 mL/min/1.73 m². The CKD-EPI equation yielded higher eGFR values than the BIS1 equation in patients with CKD stages 2 and 3.
The k values indicated substantial agreement between the MDRD and CKD-EPI equations (k=0.610), fair agreement between the CKD-EPI and BIS1 equations (k=0.253), and fair agreement between the MDRD and BIS1 equations (k=0.381). Staging based on the MDRD and CKD-EPI equations was consistent in 71.53% of patients, while staging with the CKD-EPI and BIS1 equations was consistent in 61.39% of patients. Staging with the MDRD and BIS1 equations was the least consistent, with only 44.41% of subjects classified similarly. Misclassification of CKD stage 2 was more frequent than misclassification of other stages, with the CKD-EPI equation showing higher misclassification rates for stages 2 and 5, and the BIS1 equation showing higher misclassification rates for stage 3.
The incidence rates of CKD stages varied significantly depending on the equation used. The MDRD and CKD-EPI equations produced similar results, with the highest incidence rates in stages 2 and 3. However, the BIS1 equation classified fewer patients into stage 2 (7.56%) and more patients into stages 3 (77.85%) and 4 (13.56%) compared to the MDRD and CKD-EPI equations. The MDRD equation classified more patients into stage 1 (9.73%) than the CKD-EPI and BIS1 equations (0.21% each). The incidence rates of stage 5 CKD were low across all equations (0.72% for MDRD, 1.14% for CKD-EPI, and 0.83% for BIS1).
Partial correlation analysis identified Scr, SUA, and gender as the most significant factors influencing the differences between the equations. Scr explained 10.96%, 41.60%, and 17.06% of the variability in the differences between the MDRD and CKD-EPI, MDRD and BIS1, and CKD-EPI and BIS1 equations, respectively. SUA explained 3.65% and 5.43% of the variability in the differences between the MDRD and CKD-EPI and MDRD and BIS1 equations, respectively. Gender was significantly associated with differences in all three comparisons, with women showing greater differences between the MDRD and CKD-EPI and MDRD and BIS1 equations, and men showing greater differences between the CKD-EPI and BIS1 equations.
The study concluded that the MDRD, CKD-EPI, and BIS1 equations cannot be considered interchangeable for estimating GFR in centenarians. The differences in eGFR estimates were most pronounced in the ranges corresponding to CKD stages 2 and 3, which could significantly impact clinical decision-making. Scr, SUA, and gender were identified as the most important factors contributing to the discrepancies between the equations. These findings highlight the need for a new GFR estimation equation specifically tailored for elderly individuals to avoid over- or underestimating kidney function and to ensure accurate CKD staging and management.
doi.org/10.1097/CM9.0000000000000079
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