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Calcium (Ca) binds to proteins and other substances in the blood, with only about half being ionized. Physiologically, ionized calcium (Ca+) possesses biological activity. However, since it binds to proteins like albumin, total Ca levels appear lower than actual when albumin is reduced. Therefore, during hypoalbuminemia, the Pyne formula is used. Although inaccuracies in this correction formula have been noted for some time, in clinical practice, albumin is measured each time, and Pyne's formula is used when albumin is low.
In 2025, Noémie et al. reported that unadjusted Ca correlated more strongly with Ca+ than Pyne's formula Ca. However, while the data included chronic kidney disease (CKD) patients, no stratified analysis was performed. CKD patients often complicates with hypocalcemia. However, no reports have compared Ca+ with serum total Ca (unadjusted Ca), leaving uncertainty about directly applying the above data. We aim to detect correlations between Ca+, unadjusted Ca, and Pyne's fomula Ca in CKD, and to identify factors influencing these correlations.
From cases where blood sampling was performed in our hospital's nephrology department, we extracted blood test results and performed linear regression analysis separately for Ca+ and uncorrected Ca/Pyne’s formula Ca. We evaluated the results using the correlation coefficient R. We also conducted hierarchical evaluations for other parameters such as chronic kidney disease stage and phosphorus to examine factors related to correlation. SPSS (IBM) was used for analysis.
A total of 8,998 blood test results were available. After removing duplicates, 1,898 cases were analyzed. For patients with multiple blood tests, the first test result was evaluated. Overall, Ca+ and unadjusted Ca showed a significant correlation (R = 0.434, p < 0.001, 95%CI 0.397-0.470). This correlation was stronger than that between Ca+ and Pyne’s fomula Ca(R = 0.260, p < 0.001, 95%CI 0.218-0.302). When analyzed by CKD stage, in CKD stage 5, the correlation with uncorrected Ca was R = 0.696 (p < 0.001, 95% CI 0.640–0.745), and with Pyne’s formula Ca was R = 0.521 (p < 0.001, 95%CI 0.442–0.592). At all other stages, unadjusted Ca showed a stronger correlation with ionized calcium than Pyne’s formula Ca (Stage 4: unadjusted Ca R=0.581, Pyne’s formula Ca R=0.280; Stage 3b: unadjusted Ca R=0.451, Pyne’s formula Ca R=0.148; Stage 3a: unadjusted Ca R=0.480, Pyne’s formula Ca R=0.263.).
Furthermore, analysis of the hierarchical structure based on serum phosphorus levels revealed that the correlation between Ca+ and adjusted Ca strengthened as serum phosphorus levels increased. (0
Discussion: Unadjusted Ca showed stronger correlation than Pyne’s formula Ca across all stages. The correlation between Ca+ and un unajusted Ca increased as stage progressed. While multiple causes are possible, the stronger correlation between Ca+ and unadjusted Ca with rising phosphorus suggests hyperphosphatemia associated with advancing renal failure may be a contributing factor. Furthermore, many cases showed decreased Ca+ levels around stage 3a. Ca+ is known to decrease over time after blood collection, suggesting measurement timing could introduce bias.
In CKD patients, albumin-corrected calcium correlates less strongly than uncorrected calcium, suggesting that unadjusted Ca was the practical alternative to ionized calcium.
