Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]2D3). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]2D3 production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness.

Several factors contribute to renal-function decline in CKD patients, and the role of phosphate content in the diet is still a matter of debate. This study aims to analyze the mechanism by which phosphate, independent of protein, is associated with the progression of CKD. Adult Munich-Wistar rats were submitted to 5/6 nephrectomy (Nx), fed with a low-protein diet, and divided into two groups. Only phosphate content (low phosphate, LoP, 0.2%; high phosphate, HiP, 0.95%) differentiated diets. After sixty days, biochemical parameters and kidney histology were analyzed. The HiP group presented worse renal function, with higher levels of PTH, FGF-23, and fractional excretion of phosphate. In the histological analysis of the kidney tissue, they also showed a higher percentage of interstitial fibrosis, expression of α-actin, PCNA, and renal infiltration by macrophages. The LoP group presented higher expression of beclin-1 in renal tubule cells, a marker of autophagic flux, when compared to the HiP group. Our findings highlight the action of phosphate in the induction of kidney interstitial inflammation and fibrosis, contributing to the progression of renal disease. A possible effect of phosphate on the dysregulation of the renal cell autophagy mechanism needs further investigation with clinical studies.

Mineral and bone metabolism disorders are relatively common among patients with end-stage renal disease on maintenance hemodialysis. Corneal and conjunctival calcification is the main extravascular site for calcification. Recently, this form of calcification has been linked to vascular calcification. Secondary hyperparathyroidism can lead to high levels of calcium and phosphorus and increase the risk of calcification. Here, we report a case of a 38-year-old female with severe hyperparathyroidism who underwent eye examination before and after parathyroidectomy. Anterior segment optical coherence tomography showed an improvement in the number and size of ocular calcifications 6 months after surgery. This case calls attention to the importance of eye examination in patients on dialysis and brings the possibility of recovery of calcification in a short-term follow-up.

Purpose of reviewIn patients with chronic kidney disease (CKD), hyperphosphatemia is associated with several adverse outcomes, including bone fragility and progression of kidney and cardiovascular disease. However, there is a knowledge gap regarding phosphate balance in CKD. This review explores its current state, depending on the stage of CKD, dialysis modalities, and the influence of kidney transplantation.Recent findingsAdequate phosphate control is one of the goals of treatment for CKD-mineral and bone disorder. However, ongoing studies are challenging the benefits of phosphate-lowering treatment. Nevertheless, the current therapy is based on dietary restriction, phosphate binders, and optimal removal by dialysis. In the face of limited adherence, due to the high pill burden, adjuvant options are under investigation. The recent discovery that intestinal absorption of phosphate is mostly paracellular when the intraluminal concentration is adequate might help explain why phosphate is still well absorbed in CKD, despite the lower levels of calcitriol.SummaryFuture studies could confirm the benefits of phosphate control. Greater understanding of the complex distribution of phosphate among the body compartments will help us define a better therapeutic strategy in patients with CKD.

Introduction: Body composition is critical for the evaluation of patients with Chronic Kidney Disease (CKD) and can be obtained from either multifrequency bioelectrical impedance analysis (BIA) or dual-energy absorptiometry (DXA). Although the discrepancy between the results obtained from both methods has already been described, reasons are unknown, and might be related to secondary hyperparathyroidism, which is associated with bone loss. Methods: We have evaluated 49 patients (25 males and 24 females): 20 with CKD not on dialysis and 29 on maintenance hemodialysis [18 with severe hyperparathyroidism (HD-SHPT) and 11 submitted to parathyroidectomy (HD-PTX)]. All patients underwent DXA and BIA. Results: The median age and body mass index (BMI) were 49 years and 25.6 kg/m2, respectively. Patients exhibited low bone mineral content (BMC) measured by DXA, particularly those from the HD-SHPT group. The largest BMC measurement disagreement between DXA and BIA was found in the HD-SHPT group (p=0.004). Factors independently associated with this discrepancy in BMC measurement were serum phosphate (p=0.003) and patient group (p=0.027), even after adjustments for age, BMI, and gender (adjusted r2=0.186). PTX attenuated this difference. Discussion: BIA should be interpreted with caution in patients with SHPT due to a loss of accuracy, which can compromise the interpretation of body composition.

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Background and Aims Increased levels of parathyroid hormone (PTH) are associated with a negative impact on the bone-muscle axis including sarcopenia with muscle weakness and muscle atrophy and osteoporosis, and it is possible that treating hyperparathyroidism (HPT) can ameliorate these disturbances. However, the effects of parathyroidectomy (PTX) on muscle mass, strength and performance, and physical activity have not been thoroughly investigated. This study aims to evaluate the impact of PTX on muscle (mass, strength, and performance), physical activity, body fat and resting energy expenditure (REE) in patients on hemodialysis with severe HPT. Method We are prospectively evaluating muscle mass strength, performance and physical activity of 30 patients before and after 6 months of PTX by using Actigraph GT3X accelerometer, timed-up-and-Go (TuG), Sit-to-Stand-to-Sit (STS) and muscle strength tests [handgrip (HGS), supine (SP) and leg press (LP)]. Body composition changes were assessed by dual-energy x-ray absorptiometry (DXA), and REE was examined by indirect calorimetry. Results At 6 months after PTX, 11 patients who already completed the protocol, showed a significant drop in PTH [1445 (1363-1937) vs. 54 (23-132) pg/mL; p = 0.002] and alkaline phosphatase [306 (235-744) vs. 77.5 (52-100] U/L); p = 0.002], a significant increase of number of steps/day [4321 (3384 – 6317) vs. 5950 (3918 – 7159); p = 0.04] and improvements of strength tests: HGS (27 ±14 vs. 31 ±15 kg; p = 0.01); SP (27 ±15 vs. 31 ±17 kg; p = 0.01] and LP [27 (2-36) vs. 36 (24-89) kg; p 0.04]. In addition, there was a significant reduction of TuG [10 (8-15) vs. 8 (7-11) seconds; p = 0.01], and a tendency towards STS improvement [6 (0-7) vs. 8 (7-11); p = 0.06]. A significant increase in body weight (66 ± 12 vs. 68 ± 14 Kg; p = 0.02), body mass index [24 (21–26) vs. 26 (21–28) kg/m2; p 0.001], and bone mineral content (BMC) [1.8 (1.3-2) vs. 2.1 (1.7-2.7); p=0.002] was seen. However, lean body mass (LBM) decreased [40.4 (38-55) vs. 39 (37-51) Kg; p=0.001], whereas fat mass (FAT) increased [18 (17-28) vs. 24 (17–30) kg; p = 0.02]. No change was noted in skeletal muscle index (SMI) and in REE [1580 (1193–1988) vs. 1473 (1326 - 1786) kcal/day; p = 0.7). We noticed a tendency toward an increase in IGF-1 levels [180 (141-207) vs. 223 (151-281) µg/L; p = 0.08], but no significant variation was found in serum albumin, insulin and HOMA index. Conclusion In hemodialysis patients with secondary hyperparathyroidism undergoing PTX, there were marked improvements of muscular function and bone mass, but not of muscle mass. Our findings suggest that PTH-associated sarcopenia is mediated not only by a decrease in muscle mass but also by muscle dysfunction. The long-term effect of PTX on muscle status remains to be further examined.