Clinical Research Directory

Osteoporosis & Renal Disease: Research in Primary Health Care Services

Osteoporosis, a silent and multifactorial systemic skeletal disorder, severely compromises bone strength and significantly increases the risk of fragility fractures. Despite its high prevalence (affecting \~10% of Portuguese over 50), it remains critically underdiagnosed and undertreated, with over 80% of fragility fractures occurring in untreated individuals. Chronic Kidney Disease (CKD) profoundly exacerbates bone fragility, giving rise to CKD-associated osteoporosis, a complex skeletal disorder often integrated within CKD-Mineral and Bone Disorder. This systemic dysregulation of mineral metabolism not only impairs bone quality but also actively promotes vascular calcification and significantly elevates cardiovascular disease risk, underscoring a critical kidney-bone-vascular nexus. Despite these well-established links, CKD-associated osteoporosis is similarly underdiagnosed and undertreated, partly due to diagnostic challenges related to Bone Mineral Density interpretation and therapeutic hesitancy in this complex patient population. This multi-phase observational study is designed to address the significant public health challenges posed by osteoporosis and by osteoporosis associated with CKD in Portugal, particularly among individuals aged 40 years to 90 years. The study aims to enhance understanding of disease prevalence, identify diagnostic and treatment gaps, and evaluate management trajectories, while emphasizing the intricate interrelationships among bone health, renal function, and cardiovascular risk.

The CPH-MBD Cohort

Persons with chronic kidney disease (CKD) have a 3-fold increased risk of bone fracture and a 10-fold increased risk of cardiovascular disease than the general population. These increased risks are related to the disturbances in the mineral metabolism, and this clinical entity is termed Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD). The overall aim of the present project is to explore factors that may predict or associate with the development of bone and cardiovascular disease in patients with CKD and hopefully provide insight into underlying mechanisms and pathophysiological pathways for future treatment and prevention. In a sub study investigators aim to explore the calcium and phosphate balance in patients with CKD and describe how these associate with each other as well as with kidney function (eGFR).

Medium Cut-Off and High-Flux Membranes on Mineral and Bone Metabolism in Hemodialysis Patients

This study aims to compare the effects of medium cut-off (MCO) and high-flux hemodialysis membranes on mineral and bone metabolism biomarkers in patients receiving maintenance hemodialysis. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by disturbances in biomarkers such as fibroblast growth factor-23 (FGF-23) and sclerostin, which are associated with bone turnover, vascular calcification, and adverse clinical outcomes. This is a single-center, prospective, randomized, open-label, two-sequence, two-period crossover clinical study. Thirty adult patients receiving maintenance hemodialysis will be randomized to receive either MCO membrane treatment followed by high-flux membrane treatment or the reverse sequence, with each treatment period lasting three months. Serum FGF-23 and sclerostin levels will be measured at baseline, Month 3, and Month 6. Additional assessments will include pulse wave velocity (PWV), body composition monitoring (BCM), handgrip strength, health-related quality of life (KDQOL-36), pruritus severity (UP-Dial), and pain assessment (SF-MPQ). The study will evaluate whether MCO membranes provide additional benefits compared with conventional high-flux membranes regarding CKD-MBD-related biomarkers and patient-centered outcomes.

Reducing Inflammation to Improve Vascular and Bone Outcomes With Low-dose Colchicine in CKD

The overall objective of this pilot randomized clinical trial is to determine whether low-dose Colchicine (LoDoCo) improves vascular disease including vascular calcification, peripheral arterial disease (PAD), and chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers in patients with chronic kidney disease (CKD) stage 3 over a 12-month intervention period, compared with usual care. Successful completion of this study will generate critical preliminary data to support a larger clinical trial aimed at evaluating inflammation-targeted therapies to mitigate CKD-MBD, including vascular calcification and related PAD, as well as osteoporosis, ultimately reducing cardiovascular events and mortality in patients with CKD. Additionally, this work has the potential to redefine the diagnostic framework for CKD-MBD.

Phosphate Assessment in Chronic Kidney Disease Patients Study

The proposed pilot feeding study aims to explore novel pathways in phosphate metabolism and identify new biomarkers, as well as to develop a compound index for assessing phosphate overload with high validity and reliability. Investigators will address the following specific aims: 1). To explore novel pathways of phosphate metabolism and assess the influence of CKD status on these metabolic pathways. 2). To identify novel biomarkers for phosphate overload that reflect changes in dietary phosphorus intake. 3). To develop a compound phosphate overload index that measures dietary phosphorus intake with high validity and reliability. This study will provide novel insights into phosphate metabolism and the assessment of phosphate overload in CKD patients. This investigation aims to provide preliminary data to further studies for the development of reliable biomarkers in CKD patients, which could contribute significantly to early interventions and improve health outcomes.

The Effect of REgulation of PArathyroId hoRmone in Patients With Chronic Kidney Disease to Investigate the Change in Bone Mineral Density

The prevalence of chronic kidney disease (CKD) in the adult population is estimated to 10%. CKD increases risk of bone fractures, cardiovascular disease and death. The main role of parathyroid hormone (PTH) is to regulate mineral metabolism, including the calcium and phosphate homeostasis. PTH increases as the kidney function declines, and at end stage kidney disease almost all patients have disturbances in the mineral metabolism. Decreasing bone mineral density is associated with risk of fracture, both in background population and in patients with CKD. For decades, treatment with activated vitamin D, phosphate binders, and calcium supplements has been used for patients with chronic kidney disease and elevated parathyroid hormone, but treatment targets have varied greatly over the years, reflecting the lack of randomized clinical trials with clinical important end points. The purpose of The REPAIR-CKD trial is to determine if treatment of hyperparathyroidism improves the bone mineral density in patients with chronic kidney disease. During this trial it will also be evaluated if it is feasible to obtain a difference in PTH levels when targeting two different levels of PTH. Further this trial will explore if a difference in PTH influences on arterial stiffness, muscle mass, muscle function, bone histology and health related quality of life.