Association between CKD-MBD biomarkers and symptom burden in older patients with advanced CKD: Results from the EQUAL study

Background:Patients with advanced chronic kidney disease (CKD) develop numerous symptoms, with a multifactorial origin. Evidence linking mineral disorders (CKD-MBD) and uremic symptoms is scant and mostly limited to dialysis patients. Here we aim to assess the association between CKD-MBD and symptom burden in non-dialysis CKD patients. Methods:We used data from the European Quality study, which includes patients aged >= 65 with eGFR <= 20 ml/min/1.73m2 from six European countries, followed up to five years. We used generalized linear mixed-effect models to determine the association between repeated measurements of parathyroid hormone (PTH), phosphate and calcium with the overall symptom number (0-33), the overall symptom severity (0-165), and the presence of 33 CKD-related symptoms. We also analyzed subgroups by sex, age, and diabetes mellitus, and assessed effect mediation and joint effects between mineral biomarkers. Results:The 1396 patients included in the study had a mean of 13 +/- 6 symptoms at baseline, with a median overall severity score of 32 (IQR 19-50). The association between PTH levels and symptom burden appeared U-shaped with a lower symptom burden found for mild-to-moderately increased PTH levels. Phosphate and calcium were not independently associated with overall symptom burden. The highest symptom burden was found in patients with a combination of both severe hyperparathyroidism and severe hyperphosphatemia (+2.44 symptoms (0.50, 4.38), P=0.01). The association of both hypocalcemia and hyperphosphatemia with symptom burden seemed to differ by sex and age. Conclusions:In older patients with advanced CKD not on dialysis, mild-to-moderately increased PTH was associated with a lower symptom burden, although the effect size was relatively small (less than one symptom). Neither phosphate nor calcium were associated with the overall symptom burden, except for the combination of severe hyperphosphatemia and severe hyperparathyroidism which was associated with an increased number of symptoms.