Abstract BACKGROUND AND AIMS Recently, a growing number of studies have reported a close relationship between high serum calcium and low serum magnesium with vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for enhanced progression of kidney disease nevertheless, the knowledge remains scarce. The aim of this study is to evaluate the role of the calcium/magnesium ratio as a risk factor in CKD progression. METHOD Observational, prospective study involving 693 patients (f = 371, m = 322) with stage 4 and 5 CKD. Patients were divided into two groups, according to the development of end-stage renal disease (ESRD): G1 (n = 541), who did not undergo renal replacement therapy and G2 (n = 152), who had started renal replacement therapy (RRT). Several laboratory parameters were measured: haemoglobin, eGFR (MDRD), albumin, cholesterol, magnesium and mineral metabolism markers (PTH, calcium and phosphorus). Baseline characteristics were analysed and compared using Student%u2019s T-test for continuous variables and chi-squared test for categorical variables. Multivariate Cox regression analysis was used to identify independent factors associated with RRT initiation. A modified Poisson regression with robust error variance was used to estimate the cumulative relative risk for RRT initiation. RESULTS The mean age and estimated glomerular filtration rate (eGFR) of the study population was 70.09 ± 12.51 years and 19.91 ± 8.11 mL/min, respectively. Comparing the two groups, G2 had a significantly lower serum levels of Hb (11.75 versus 10.95 g/dL, P = 0.000), calcium (9.34 versus 8.95 mg/dL, P = 0.000), magnesium (1.92 versus 1.40 mg/dL, P = 0.0001), albumin (4.00 versus 3.88 g/dL, P = 0.03) and cholesterol (183.17 versus 172.39 mg/dL, P = 0.01) and a higher serum levels of phosphorus (3.88 versus 4.69 mg/dL, P = 0.0001), calcium/magnesium ratio (5.73 versus 7.56, P = 0.0001) and PTH (209.71 versus 338.84 pg/mL, P = 0.0001). In univariate Cox regression analysis, age, haemoglobin, eGFR, calcium, magnesium, phosphorus, calcium-magnesium ratio and PTH correlate with onset of RRT, which were further tested using a multivariate COX regression model. The results showed a clear relationship between high levels of phosphorus (HRa = 1.638, P = 0.001) and calcium-magnesium ratio (HRa = 1.292; P = 0.002), and low levels of magnesium (HRa = 0.761, P = 0.005) and eGFR (HRa = 0.934; P = 0.0001) were independent risk factors to start depurative techniques. Additionally, Poisson regression analysis showed that high calcium-magnesium ratios (aPR = 1.986; 95% CI 1.026–3.051; P = 0.002), high phosphorus levels (aPR = 1.607; 95% CI 1.324–1.950; P < 0.0001) and low levels eGFR (aPR = 0.927; 95% CI 0.891–0.964; P < 0.0001) were associated with a cumulative risk for initiation of RRT. CONCLUSION Our results suggest that the calcium/magnesium ratio is an independent predictive factor for the initiation of renal replacement therapy. Further studies are required to validate the use of this novel marker as a predictor of CKD progression.