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Introduction: Adjusting drug dose levels based on equations that standardize the estimated glomerular filtration rate (eGFR) to a body surface area (BSA) of 1.73 m2 can pose challenges, especially for patients with extremely high or low body mass index (BMI). The objective of the present study of patients with CKD and diabetes was to assess the impact of deindexing creatinine-based equations on estimates of kidney function and on the frequency of inappropriate prescriptions of oral antidiabetic drugs (OADs). Methods: The prospective CKD-REIN cohort is comprised of patients with eGFR <60 mL/min/1.73 m2. The inclusion criteria for this study were the use of OADs and the availability of data on weight, height and serum creatinine. We compared data for three BMI subgroups (group 1 <30 kg/m2; group 2 30-34.9 kg/m2; group 3 ≥35 kg/m2). Inappropriate prescriptions (contraindicated or over-dosed drugs) were assessed with regard to the summary of product characteristics and the patient's kidney function estimated with the 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, the 2021 CKD-EPI equation, the Modification of Diet in Renal Disease (MDRD) equation, the European Kidney Function Consortium (EKFC) equation, their deindexed estimates, and the Cockcroft-Gault (CG) formula. The impact of deindexing the equations was evaluated by assessing 1) the difference between the indexed and deindexed eGFRs, and 2) the difference in the proportion of patients with at least one inappropriate OAD prescription between the indexed and deindexed estimates. Results: At baseline, 694 patients were receiving OADs. The median BMI was 30.7 kg/m2, the mean BSA was 1.98 m2, and 90% of patients had a BSA >1.73 m2. Deindexing the kidney function estimates led to higher eGFRs, especially in BMI group 3. The proportion of patients with at least one inappropriate prescription differed greatly when comparing indexed and deindexed estimates. The magnitude of the difference increased with the BMI: when comparing BMI group 1 with BMI group 3, the difference was respectively -4% and -10% between deindexed 2021 CKD-EPI and indexed CKD-EPI. Metformin and sitagliptin were the most frequent inappropriately prescribed OADs. Conclusion: We highlight significant differences between the BSA-indexed and deindexed versions of equations used to estimate kidney function, emphasizing the importance of using deindexed estimates to adjust drug dose levels - especially in patients with an extreme BMI.
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Background: The association between hypo- and/or hypermagnesaemia and cardiovascular (CV) outcomes or mortality has shown conflicting results in chronic kidney disease (CKD) and has been conducted on total magnesium (tMg) levels. Thus, the objectives of the present study were to (i) describe the serum ionized Mg (iMg) concentration in patients at various CKD stages, (ii) measure the correlation between iMg and tMg concentrations, (iii) identify their associated factors and (iv) determine whether serum tMg and/or iMg concentrations are associated with major adverse cardiovascular events (MACE) and mortality before kidney replacement therapy in CKD patients. Methods: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort of CKD patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Baseline iMg and tMg serum concentrations were centrally measured. Adjusted cause-specific Cox proportional hazard models were used to estimate hazard ratios (HRs) for first MACE and for mortality. Results: Of the 2419 included patients, median age was 68 years, and the mean eGFR was 34.8 mL/min/1.73 m2. Concentrations of serum iMg and tMg were strongly correlated (r = 0.89, P < .001) and were independently associated with eGFR. The adjusted HR [95% confidence interval (CI)] for MACE associated with the baseline serum tMg level was 1.27 (0.95; 1.69) for patients in Tertile 1 and 1.56 (1.18; 2.06) for patients in Tertile 3, relative to patients in Tertile 2. The HR (95% CI) of death according to serum tMg concentration was increased in Tertile 3 [1.48 (1.11; 1.97)]. The adjusted risk for MACE and mortality (all-cause or CV) associated with the baseline serum iMg level was not significantly different between tertiles. Conclusions: Our analysis of a large cohort of patients with moderate-to-advanced CKD demonstrated that individuals with higher serum tMg concentrations, although still within the normal range, had a greater likelihood of MACE and mortality. However, serum iMg levels were not associated with these outcomes.