Association between ckd-mbd and symptom burden in older patients with advanced ckd - results from the equal study

Background and Aims Patients with advanced chronic kidney disease (CKD) typically develop a constellation of various non-specific symptoms known as the uremic syndrome. This symptom burden affects patients’ quality of life and is one of the most relevant reasons for initiating dialysis. Several factors are thought to be involved in symptoms development, including mineral bone disorder (CKD-MBD). However, evidence linking deranged mineral biomarkers and CKD symptoms is mostly limited to few symptoms in dialysis patients. We studied the association between PTH, phosphate and calcium and the overall symptom burden in a cohort of elderly non-dialysis patients with advanced CKD, during 5 years of follow up. Secondly, we investigated whether these biomarkers are specifically associated with a wide spectrum of CKD-related signs and symptoms. Method We used data from the EQUAL study, which includes patients aged ≥65 with eGFR ≤20 ml/min/1.73m2 from six European countries. Symptoms were repeatedly assessed at 6-month intervals through a questionnaire on 33 CKD-related signs and symptoms. Generalized linear mixed models were used to study the association between mineral biomarkers and the overall symptom number (range 0–33), the overall symptom severity (range 0–165, with higher scores indicating higher severity), the probability of having each symptom and its severity (range 1–5). Models were adjusted for age, sex, Charlson Comorbidity Index, kidney function, albumin, hemoglobin and CKD-MBD medications. Results At baseline, the 1396 patients included in the study had a mean (SD) of 12.6 (±6.4) symptoms and a median symptom severity score of 32 [19-50], with the most prevalent symptoms being fatigue, loss of strength, muscle cramps, bone pain, swelling in legs, dry skin, and sexual disorders. Among the mineral biomarkers, only PTH had a significant association with the overall symptom number and severity. Furthermore, a doubling in PTH was associated with an increased probability of reporting shortness of breath (OR 1.13 [1.01, 1.27], p 0.03) and decreased probability of loss of strength (OR 0.90 [0.81, 1.00], p 0.05). Both PTH and phosphate had significant U-shaped associations with gastrointestinal symptoms (decreased appetite, nausea, and vomiting). A doubling in phosphate level was linearly associated to the severity of muscle cramps (β 0.20 [0.06, 0.36], p 0.007) and bone pain (β 0.24 [0.09, 0.39], p 0.002), in patients who experienced these symptoms. Phosphate was also non-linearly associated with the probability of having trouble falling asleep. One mmol/L increase in calcium was associated with both a decreased probability of having muscle cramps (OR 0.50 [0.25, 0.98], p 0.04) and its severity (β -0.43 [-0.69, -0.17], p 0.001). Conclusion Serum levels of PTH are associated with the overall symptom burden in older non-dialysis patients with advanced CKD, and PTH, phosphate, and calcium are specifically and independently associated with some of the individual symptoms in this population.