Abstract
Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a common complication of CKD, associated with higher mortality in dialysis patients. Its impact in non-dialysis patients remains mostly unknown. We investigate the associations between parathyroid hormone (PTH), phosphate, and calcium (and their interactions) and all-cause, cardiovascular (CV), and non-CV mortality in older non-dialysis patients with advanced CKD.
We used data from the EQUAL study, which included patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries. Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV, and non-CV mortality. Models were sequentially adjusted for other mineral biomarkers, age, sex, country, eGFR, albumin, BMI, comorbidities and medications. Effect modification between biomarkers was also assessed.
In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH (aHR 1.12, 95%CI 1.03-1.23, p 0.01) and phosphate (aHR 1.35, 95%CI 1.00-1.84, p 0.05), but not calcium (aHR 1.11, 95%CI 0.57-2.17, p 0.76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality.
CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.
Effect sizes of CKD-MBD biomarkers on all outcomes. Hazard ratios (HR) for all-cause (A), CV (B) and non-CV (C) mortality associated with 1 SD increase in baseline and time-dependent biomarkers in unadjusted and sequentially adjusted models (I, unadjusted; II, adjusted for other mineral biomarkers; III, previous further adjusted for age sex and country; IV, previous further adjusted for eGFR; V, previous further adjusted for albumin; VI, previous further adjusted for BMI; VII, previous further adjusted for pre-existing comorbidities; VIII, previous further adjusted for medications). Abbreviations: BMI, body mass index; CV, cardio-vascular; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone.
The interaction between phosphate and calcium in affecting all-cause mortality. (A) Thick lines represent the HR for all-cause mortality based on calcium levels for different phosphate levels (1st,50th and 99th percentile). Orange bands represent 95% confidence intervals. (B) Thick lines represent the HR for all-cause mortality based on phosphate levels for different calcium levels (1st,50th and 99th percentile). Green bands represent 95% confidence intervals. (C) Heatmap of the risk of dying (the darker the color, the higher the risk) based on calcium and phosphate levels. For all plot's, fully adjusted models were used (baseline analysis to the left and time-dependent analysis to the right).
Comments