Abstract Background and Aims Secondary hyperparathyroidism (SHPT) is one of the most common complications in patients with chronic kidney disease (CKD). The prevalence of SHPT progressively increases with the severity of CKD, affecting approximately 50-70% of patients on hemodialysis (HD). SHPT significantly impacts morbidity, mortality, hospitalization risks, healthcare costs, and the quality of life of CKD patients, making its management of paramount importance in this population. A positive serum phosphorus (P) balance is one of the critical determinants of SHPT, and the management of P levels in HD patients revolves around nutritional therapy, medications, and optimal kidney replacement therapy (KRT). Numerous studies have explored the role of KRT in P control among prevalent HD patients. However, whether the reduction of P achieved during KRT affects parathyroid hormone (PTH) levels is still a matter of debate. Currently, a direct evaluation of the relationship between intra-HD P reduction and PTH levels is lacking. Method We conducted a retrospective observational study on the prevalent HD population at the Division of Nephrology, University Hospital of Verona, from January to December 2022. We Included clinically stable adult patients undergoing HD for over 6 months, with multiple recorded visits during the follow-up. Demographic, clinical, laboratory, and medication data were collected. Time-varying variables were updated at each study visit. Food intake was assessed through a 3-day food record (HD day, non-HD day, and weekend day). Patients were instructed to maintain their usual ideally low-phosphate diet and to meticulously record and weigh all foods and preparations consumed. This assessment was conducted every 4 months during the observation period. From the 3-day food records, the dietary phosphorus intake was calculated using a national database and reported as mg of P per day. A dietitian evaluated dietary questionnaires. The primary outcome of interest was PTH levels. The absolute intra-HD change in P (intra-HD ∆P), defined as the difference between pre- and post-HD P levels, served as the main exposure. Multivariable adjusted linear mixed models were used to investigate the relationship between intra-HD ∆P and PTH levels. Potential confounders were included in the following three models of hierarchical adjustment: (i) Model 1, unadjusted; (ii) Model 2, adjusted for age and sex; (iii) Model 3, adjusted for all covariates in Model 2 plus URR, HD modality, active vitamin D, phosphate binders, calcimimetics, comorbidities. Since the relationship between intra-HD ∆P and PTH is influenced by the pre-HD P, all models were adjusted for pre-HD P. The association between PTH and intra-HD ∆P was also assessed in a subgroup of patients who provided a valid dietary diary. A multivariable linear mixed model adjusted for all covariates in Model 3 plus dietary phosphorus intake was used to assess this association. Results A total of 211 patients contributed to 904 study visits. A significant and positive relationship was observed between intra-HD ∆P and pre-HD P (β = 0.76, 95% CI 0.75, 0.78, p < 0.001) and urea reduction ratio (β = 0.38, 95% CI 0.35, 0.41; p < 0.001) (Figure). An increase in intra-HD ∆P was significantly and independently associated with low PTH levels (β = −0.17, 95% CI −0.30, −0.03; p = 0.016; Table). Overall, 86 out of 211 patients provided valid dietary data. The relationship between intra-HD ∆P and PTH levels was confirmed after additional adjustment for dietary P intake (p = 0.041). Conclusion The extent of intra-HD P reduction significantly correlates with low PTH levels. Strategies focused on optimizing or enhancing depurative efficiency in KRT can exert a substantial impact on managing positive phosphorus balance and secondary hyperparathyroidism (SHPT). The assessment of intra-HD P reduction may play a pivotal role in the management and follow-up of SHPT in HD patients.
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Jun 1, 2024
Pierre Singer 
Open Access