Omar Mohammed Ramadhan, Basma A. Al-Mshhdani, Qadoori Zedan Khalaf

Mineral-axis heterogeneity in early acute kidney injury: A cross-sectional clustering analysis

Introduction

Mineral-axis heterogeneity in early acute kidney injury: a cross-sectional clustering analysis. Explore early mineral metabolism disturbances in acute kidney injury (AKI) and identify distinct biochemical profiles using clustering analysis. Discover heterogeneity independent of creatinine-based severity.

Abstract

The kidney plays an essential role in maintaining mineral homeostasis through regulation of calcium, phosphate, parathyroid hormone (PTH), and vitamin D metabolism. Although mineral disturbances are well established in chronic kidney disease, their early presentation in acute kidney injury (AKI) and their relationship to KDIGO-defined severity remain incompletely understood. This study aimed to evaluate early alterations in mineral metabolism within 24 hours of AKI diagnosis and to explore potential biochemical heterogeneity using clustering analysis. Methods. This cross-sectional study included 100 participants: 50 patients with AKI defined according to KDIGO criteria and 50 age- and sex-matched controls without AKI. Serum calcium, phosphorus, PTH, and 25-hydroxyvitamin D [25(OH)D] were measured within 24 hours of AKI diagnosis. Comparisons were performed between AKI patients and controls and across KDIGO stages. Unsupervised k-means clustering was applied to identify distinct mineral-axis profiles within the AKI group. Results. Compared with controls, patients with AKI had significantly lower calcium and 25(OH)D levels and higher phosphorus and PTH concentrations (all p < 0.0001). These disturbances were observed across AKI stages, without a consistent stepwise trend according to creatinine-defined severity. Clustering analysis identified two distinct mineral-axis profiles among AKI patients. The two-cluster solution explained 23.6% of total variability (R² = 0.236) and showed clear separation. Cluster membership was not associated with creatinine levels, AKI stage, urea concentration, or dialysis requirement, indicating biochemical heterogeneity independent of conventional severity classification. Conclusions. Early AKI is accompanied by significant disturbances in mineral metabolism that do not parallel creatinine-based staging. Distinct mineral-axis profiles can be identified within 24 hours of diagnosis, suggesting underlying biochemical heterogeneity. Further prospective studies are needed to determine the clinical and prognostic significance of these early mineral alterations.

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