Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD-results from a placebo-controlled randomized trial.

BACKGROUND: Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. METHODS: The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. RESULTS: A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6-49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4-5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval -39.2, 36.4), P = 0.65] or CPP-II [-18.3% (95% confidence interval -40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. CONCLUSIONS: Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.

Outcomes following parathyroidectomy for secondary hyperparathyroidism in patients with chronic kidney disease: a single-centre study.

BACKGROUND: Surgical parathyroidectomy may be required for severe and refractory secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD). Parathyroidectomy is associated with long-term survival benefit despite an increase in short-term morbidity and mortality. Global variation in practice exists, with limited Australian data on outcomes following parathyroidectomy. AIM: To evaluate clinical outcomes of patients with chronic kidney disease undergoing surgical parathyroidectomy for secondary hyperparathyroidism. METHODS: We conducted a retrospective study of patients who underwent parathyroidectomy for SHPT between January 2010 and December 2019 at a single tertiary referral centre in Melbourne, Australia. Biochemical markers and medications were assessed 12 months pre- and post-surgery. Clinical outcomes, including hospital readmission, cardiovascular events and mortality were assessed following surgery. RESULTS: During the 10-year study period, 129 patients underwent parathyroidectomy for SHPT (mean age 50.7 ± 15 years; 109 (85%) on dialysis). Significant immediate post-operative complications were seen in eight (6%) patients, requiring admission to the intensive care unit (n = 6) or return to theatre (n = 2). Within the first 6 months, 24 (19%) patients required hospital readmission. Within 12 months post-parathyroidectomy, 100 (78%) and 103 (80%) patients experienced at least one episode of hypercalcaemia (corrected calcium >2.6 mmol/L) or hypocalcaemia (corrected calcium <2.1 mmol/L) respectively. Over a 12-month period, there were six (5%) deaths and eight (6%) patients experienced a major cardiovascular event. CONCLUSION: Significant fluctuations in serum calcium levels are common post-parathyroidectomy; however, long-term morbidity and mortality in our cohort were lower than previously reported, highlighting that parathyroidectomy in a carefully selected cohort is safe for severe SHPT refractory to medical treatment.

Reduction of Calciprotein Particles in Adults Receiving Infliximab for Chronic Inflammatory Disease.

Patients with chronic inflammatory diseases (CID) experience accelerated loss of bone mineral density, which is often accompanied by increased vascular calcification. These disturbances can be attenuated by therapies for inflammation, such as the tumor necrosis factor inhibitor infliximab. Calciprotein particles (CPP) are circulating colloidal aggregates of calcium and phosphate together with the mineral-binding protein fetuin-A, which have emerged as potential mediators of vascular calcification. The precise origins of serum CPP are unclear, but bone turnover may be an important source. In this longitudinal observational study, we studied patients with CID undergoing treatment with infliximab to assess the temporal relationship between bone turnover and circulating CPP. Ten patients with active CID receiving infliximab induction therapy and an additional 3 patients with quiescent CID on maintenance infliximab therapy were studied for 8 weeks with repeated measures of bone turnover markers as well as CPP (calciprotein monomers [CPM], primary CPP [CPP-I], and secondary CPP [CPP-II]). Therapeutic response was appraised using validated disease activity scores. At baseline, those with active CID had elevated markers of bone resorption and suppressed bone formation markers as well as higher CPM and CPP-I compared with those with quiescent CID. In responders, there was an early but transient reduction in resorption markers by week 1, but a more sustained increase in bone formation markers compared with non-responders at week 8. This was accompanied by reductions in CPM (ß = -6.5 × 103 AU [95% CI -11.1, -1.8], p = 0.006) and CPP-I (ß = -23.4 × 104 particles/mL [95% CI -34.8, -11.9], p < 0.001). In contrast, no significant changes in any markers were observed in non-responders or those receiving maintenance therapy. Thus, CPP have a dynamic association with changes in bone turnover in response to infliximab therapy, adding to accumulating evidence of the role of bone as a determinant of systemic levels. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone microarchitecture in patients undergoing parathyroidectomy for management of secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) leads to complex bone disease, affecting both trabecular and cortical bone, and increased fracture risk. Optimal assessment of bone in patients with CKD is yet to be determined. High-resolution magnetic resonance imaging (MRI) can provide three-dimensional assessment of bone microarchitecture, as well as determination of mechanical strength with finite element analysis (FEA). METHODS: We conducted a single-centre, cross-sectional study to determine bone microarchitecture with MRI in CKD patients with SHPT undergoing parathyroidectomy. Within two weeks of surgery, MRI was performed at the distal tibia and biochemical markers of SHPT (parathyroid hormone [PTH] and alkaline phosphatase [ALP]) were collected. Trabecular and cortical topological parameters as well as bone mechanical competence using FEA were assessed. Correlation of MRI findings of bone was made with biochemical markers. RESULTS: Twenty patients with CKD (15 male, 5 female) underwent MRI at the time of parathyroidectomy (16 on dialysis, 3 with functioning kidney transplant, one pre-dialysis with CKD stage 5). Median PTH at the time of surgery was 138.5 pmol/L [39.6-186.7 pmol/L]. MRI parameters in patients were consistent with trabecular deterioration, with erosion index (EI) 1.01 ±â€¯0.3, and trabecular bone volume (BV/TV) 10.8 ±â€¯2.9%, as well as poor trabecular network integrity with surface-to-curve ratio (S/C) 5.4 ±â€¯2.3. There was also evidence of reduced cortical thickness, with CTh 2.698 ±â€¯0.630 mm, and FEA demonstrated overall poor bone mechanical strength with mean elastic modulus of 2.07 ±â€¯0.44. CONCLUSION: Patients with severe SHPT requiring parathyroidectomy have evidence of significant changes in bone microarchitecture with trabecular deterioration, low trabecular and cortical bone volume, and reduced mechanical competence of bone.