Hyponatremia and bone disease.

Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients, especially in those receiving medications that can cause hyponatremia. Furthermore, elderly patients with an unsteady gait and/or confusion should be evaluated for the presence of mild hyponatremia, and if present, treatment should be initiated. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and hyponatremia corrected, if present.

Mild prolonged chronic hyponatremia and risk of hip fracture in the elderly.

BACKGROUND: Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. METHODS: We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. RESULTS: Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 ± 5 mmol/L in hyponatremic patients and 139 ± 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. CONCLUSION: Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking.

Hypercalcemia secondary to granulomatous disease caused by the injection of methacrylate: a case series.

Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function.

Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification.

Morbidity and mortality of chronic kidney disease (CKD) patients are largely associated with vascular calcification, an actively regulated process in which vascular smooth muscle cells (VSMCs) change into cells similar to osteocytes/chondrocytes, known as trans-differentiation. Cellular and systemic response to low oxygen (hypoxia) is regulated by the prolyl hydroxylase/hypoxia-inducible factor (HIF)-1 pathway. Recent studies highlighted that hypoxia-mediated activation of HIF-1 induces trans-differentiation of VSMCs into bone-forming type through an increase in osteo-/chondrogenic genes. Inhibition of the HIF-1 pathway abolished osteochondrogenic differentiation of VSMCs. Hypoxia strongly enhanced elevated phosphate-induced VSMC osteogenic trans-differentiation and calcification. HIF-1 was shown to be essential for phosphate enhanced VSMC calcification. O2-dependent degradation HIF-1 is triggered by the prolyl hydroxylase domain proteins (PHD). Prolyl hydroxylase inhibitors, daprodustat and roxadustat, increase high phosphate-induced VC in VSMCs, stabilizing HIF-1α and activating the HIF-1 pathway in these cells. Whether the use of these PHD inhibitors to treat anemia in CKD patients will favor the development and progression of vascular calcification remains to be explored.

Kidney stone matrix proteins: Role in stone formation.

Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.

Is chronic hyponatremia a novel risk factor for hip fracture in the elderly?

Hip fractures represent a serious health risk in the elderly, with significant associated morbidity and mortality. There is now an emerging literature that suggests that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms: (i) it produces mild cognitive impairment resulting in unsteady gait and falls and (ii) it directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium. There is debate over the effect of hyponatremia on the production of osteoporosis, as one study found decreased bone mineral density (BMD) and another did not. Should we be screening for low serum sodium in patients with osteoporosis or assessing BMD in patients with hyponatremia? The final answer is yet to come from prospective studies that allocate elderly individuals with mild hyponatremia to receive active treatment or not for hyponatremia and see if this intervention prevents gait disturbances and changes in BMD reducing fracture risk. In the meantime, physicians caring for elderly patients must be aware of the association between hyponatremia and bone problems. As serum sodium is a readily available, simple and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients who take medications that can cause hyponatremia. Also, elderly patients with unsteady gait and/or confusion should be checked for the presence of mild hyponatremia and if present it should not be ignored. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and corrected if hyponatremia is present.

Metabolic diagnosis in stone formers in relation to body mass index.

It is known that several metabolic abnormalities that favor stone formation have a strong dependence on environmental and nutritional factors. The incidence and prevalence of kidney stone is increasing while there has been a parallel growth in the overweight/obesity rate, and epidemiologic studies have shown a significant association between overweight/obesity and increased nephrolithiasis risk. The aim of this study was to assess if metabolic abnormalities observed in stone patients differ in relation to their BMI. We evaluated 817 renal stone formers (459 men and 358 woman) in an outpatient setting. They were all studied with a standard protocol (two 24 h urine collections and serum parameters) and classified according to their BMI in normal, overweight and obese and according to age in <50 or >50 year old. In the whole population we found that 58.7% were either overweight or obese: 39.4% (n = 322) were OW and 19.3% (n = 158) were OB. The proportion of overweight was significantly higher among men than women. In women of all ages regardless of BMI, hypercalciuria was the most prevalent diagnosis. Hyperuricosuria increased its prevalence significantly only in overweight and obese women <50 years of age (p < 0.01). Hypercalciuria was the predominant diagnosis in normal weight men of both age groups. Hyperuricosuria was the most frequent abnormality in overweight and obese men followed by gouty diathesis and both increased their prevalence significantly from normal weight to obesity and in both age groups (p < 0.05 and <0.01). We conclude that the only abnormalities that increased their prevalence significantly with increasing BMI were hyperuricosuria and gouty diathesis, the first one in men of all ages and women under 50 years of age, while the second one only in men.

Healing of subtrochanteric atypical fractures after strontium ranelate treatment.

Oral bisphosphonates comprise the most widely prescribed class of antiosteoporotic drugs. Recent reports, however, suggest a link between prolonged bisphosphonate use and atypical low-energy, subtrochanteric fractures. We describe the clinical course of two patient treated for a long term with different bisphosphonates who developed subtrochanteric atypical fractures. They were treated initially with intramedullary rodding without pain disappearance or healing of the fracture. Strontium ranelate, a new orally administered agent for the treatment of osteoporosis, was given to these patients with complete closure of the fracture and pain disappearance after a few months. We conclude that based on the chronology of fracture healing and pain disappearance of our patients and published evidence that strontium ranelate can accelerate fracture healing in a rat model, that strontium ranelate had a positive anabolic effect that contributed to fracture healing that produced the secondary disappearance of pain.

Role of claudins in idiopathic hypercalciuria and renal lithiasis.

Paracellular transport in the kidney is mediated by a family of proteins located in the tight junctions called claudins which confers its ionic selectivity. Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations. In the thick ascending limb of Henle (TALH) calcium is reabsorbed by a paracellular channel formed by Claudin-16 and-19. Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability. On the other hand, Claudin 14, that is also located in TALH, inhibits the paracellular permeability of Claudin-16 to calcium. Recent wide genomic association analysis studies have detected four common synonymous variants (genetic polymorphisms of a single nucleotide, SNPs) at the locus of Claudin-14 gene that were significantly associated with the presence of renal lithiasis. Another study of wide genomic association and nephrolithiasis was carried out in the general population but including chromosome X, where claudin-2 gene is located. They detected nine SNPs that had a significant association with renal lithiasis risk. A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study.

Background: Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production. Methods: We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR. Results: Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8-18.4] mg/dl vs. 6.6 [IR 1.6-14.0] mg/dl, p < 0.01) and ferritin levels (median 649 [IQR 492-1,168] ng/dl vs. 393 [IQR 156-1,440] ng/dl, p = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52-10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33-9.49], p < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14-4.34) and adjusted (HR 2.76, 95%CI:1.88-4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, p < 0.01). Conclusion: Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04493268.

Sarcopenia in hemodialysis patients from Buenos Aires, Argentina.

OBJECTIVES: Sarcopenia is the loss of skeletal muscle mass and function that occurs with aging that can lead to greater morbidity and mortality. Chronic kidney disease and hemodialysis (HD) favors the development of sarcopenia. We studied the prevalence of sarcopenia and its components using European Working Group on Sarcopenia in Elderly People 2 proposed criteria and risk factors for its development in HD patients. METHODS: In 100 adult HD patients, we evaluated: hand grip strength (HGS), muscle mass by dual energy X-ray absorptiometry and physical performance (gait-speed and sit-stand test). RESULTS: Sixty patients were male and 40 were female; mean age 55.6 years. Prevalence of sarcopenia was 16% (11.1% in males and 25% in females; P = 0.05); 7% had severe sarcopenia. Prevalence of low HGS was 33% in males and 28% in females; low muscle mass was 30% in males but 70% in females and low physical performance 23% in males and 45% in females. Falls were reported by 23 patients. Patients with lower HGS had a higher prevalence of falls in the last year (40% two or more falls; P = 0.03). Only females with sarcopenia had lower bone mineral content. Neither age, body mass index, time on dialysis, or prevalence of diabetes predicted sarcopenia. CONCLUSIONS: A significant proportion of dialysis patients had sarcopenia, more frequent in females. Low HGS was associated with a higher prevalence of falls. Only females with sarcopenia had lower bone mineral content.

Chronicity of Uncorrected Hyponatremia and Clinical Outcomes in Older Patients Undergoing Hip Fracture Repair.

Background: Chronic hyponatremia is a risk factor for hip fracture but remains uncorrected in most patients. This study evaluated if preoperative chronicity of uncorrected hyponatremia influences outcomes after hip fracture repair. Materials and Methods: Evaluated were older patients hospitalized for hip fracture repair between 2007 and 2012 with plasma sodium measured at admission and ≥1 preadmission outpatient measurement. Patients were classified as being normonatremic (NN; plasma sodium 135-145 mmol/L), chronic prolonged hyponatremia (CPH; ≥2 consecutive plasma sodium values <135 mmol/L over >90 days), or recent hyponatremia (one plasma sodium <135 mmol/L within 30 days before admission with previously normal plasma sodium). Length of hospital stay, in-hospital death, post-operative complications, 30-day readmission, and long-term mortality were the evaluated outcomes. Multivariable Cox regression was used to evaluate the association of hyponatremia status with outcomes. Results: Among 1,571 eligible patients, 76.7% were NN, 14% had CPH, and 9.1% had RH. Compared with NN patients, CHN patients were older and had more prior heart failure, alcoholism, and anticonvulsant drug use. In multivariable analyses, neither CPH or RH was associated with hospital length of stay, in-hospital or 30-day death, or 30-day readmission, while RH was associated with post-operative sepsis [adjusted odds ratio (aOR) 1.84, 95% CI: 1.01-3.35). Only CPH was independently associated with long-term all-cause death (OR 1.53, 95% CI: 1.12-2.09). Conclusions: Hyponatremia affects nearly 25% of patients undergoing hip fracture repair. Preoperative chronic untreated hyponatremia is associated with increased post-operative mortality following surgical repair of a hip fracture in older patients. Future studies should evaluate if correction of hyponatremia could decrease long-term mortality after hip fracture repair.

The role of zinc in urinary stone disease.

In recent years, the role of trace elements in lithogenesis has received steadily increasing attention. It is well documented that some trace elements can influence the morphology and speed of the crystallization process. Zinc has been found in significant amounts in calcium stones relative or organic stones (uric acid and cystine), probably substituting calcium in crystals because of their similarity in charge and size. High Zn levels are present in carbapatite of Randal's plaques suggesting that zinc could promote calcium phosphate deposition in the medullar interstitium. Large-scale epidemiological studies have found an association of increased dietary zinc intake with increased risk of nephrolithiasis in adults but not in adolescents. Most studies examining urinary zinc levels in adults have reported increased urinary Zn excretion in stone formers. In an experimental model of organic crystal formation produced by silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn excretion have shown to reduce crystal formation in the lumen of the Malpighian tubules. This is curious because this is not a model of calcium stone formation. Finally, zinc supplementation has been associated with increased admissions for urinary lithiasis in men, but no change in calcium stone formation in children. Perhaps, some of these contradicting findings can be explained in part by the in vitro effect of zinc on the type and amount of calcium phosphate formed: At low concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate, octacalcium phosphate, and apatite, and at higher concentrations, it promoted the formation of amorphous calcium phosphate. Thus, further studies are needed to see whether manipulation of Zn metabolism can inhibit calcium stone formation.

Nuevas estrategias terapéuticas para tratar la hiperfosfatemia en la IRC: foco en la absorción intestinal / New therapeutic strategies to treat hyperphosphatemia in CRF: focus on intestinal absorption

RESUMEN El manejo de la hiperfosfatemia de los pacientes con insuficiencia renal crónica en diálisis permanece como un desafío. A pesar de utilizar un enfoque multifacético que incluye la restricción dietética, la remoción de fósforo por la diálisis y el uso de quelantes de fósforo, esta estrategia múltiple no logra reducir los niveles de fósforo en más de 2 mg/dl. El control de fósforo de los pacientes en diálisis es fundamental en razón de la relación monotónica entre los niveles séricos de fosfato y el incremento del riesgo cardiovascular. Por lo tanto, hay una necesidad de explorar nuevas estrategias para reducir los niveles séricos de fosfato a niveles normales. Recientes avances en nuestra compresión de los mecanismos que subyacen a la homeostasis del fósforo sugieren que el transporte gastrointestinal del fósforo podría ser un objetivo. Recientemente se han desarrollado inhibidores de los cotransportadores sodio fosfato del intestino y se ha revalorizado el uso de la nicotinamida, en su formulación de liberación prolongada, que también actuaria por ese mecanismo. También se han drogas como el tenapanor, que inhibiendo el intercambiador sodio/hidrogeno isoforma 3 del enterocito, disminuyen la absorción paracelular de fósforo.

ABSTRACT Management of hyperphosphatemia in patients with chronic renal failure on dialysis remains challenging. Despite using a multifaceted approach that includes dietary restriction, phosphorus removal by dialysis, and phosphate binders, these multiple strategies fail to reduce phosphorus levels by more than 2 mg/dL. Phosphorus control in dialysis patients is essential due to the monotonic relationship between serum phosphate levels and increased cardiovascular risk. Therefore, there is a need to explore new strategies to reduce serum phosphate levels to normal levels. Recent advances in understanding the mechanisms underlying phosphorus homeostasis suggest that the gastrointestinal transport of phosphorus could be a target. Inhibitors of intestinal sodium phosphate cotransporters recently developed, and using of nicotinamide, in its prolonged release formulation, which would also act by this mechanism, has been revalued. There have also been drugs such as tenapanor, which, by inhibiting the isoform three sodium/hydrogen exchanger of the enterocyte, decreases the paracellular absorption of phosphorus.

Is the renal kallikrein-kinin system a factor that modulates calciuria? / ¿Es el sistema calicreína/quinina renal un factor modulador de la calciuria?

Renal tubular calcium reabsorption is one of the principal factors that determine serum calcium concentration and calcium excretion. Calcium excretion is regulated by the distal convoluted tubule and connecting tubule, where the epithelial calcium channel TRPV5 can be found, which limits the rate of transcellular calcium transport. The dynamic presence of the TRPV5 channel on the surface of the tubular cell is mediated by an endosomal recycling process. Different intrarenal factors are involved in calcium channel fixation in the apical membrane, including the anti-ageing hormone klotho and tissue kallikrein (TK). Both proteins are synthesised in the distal tubule and secreted in the tubular fluid. TK stimulates active calcium reabsorption through the bradykinin receptor B2 that compromises TRPV5 activation through the protein kinase C pathway. TK-deficient mice show hypercalciuria of renal origin comparable to that seen in TRPV5 knockout mice. There is a polymorphism with loss of function of the human TK gene R53H (allele H) that causes a marked decrease in enzymatic activity. The presence of the allele H seems to be common at least in the Japanese population (24%). These individuals have a tendency to greater calcium and sodium excretion in urine that is more evident during furosemide infusion. Future studies should analyse if manipulating the renal kallikrein-kinin system can correct idiopathic hypercalciuria with drugs other than thiazide diuretics.

Evaluation of cortical bone by peripheral quantitative computed tomography in continuous ambulatory peritoneal dialysis patients.

Several studies have suggested an increased prevalence of osteopenia in dialysis. Peripheral quantitative computed tomography (pQCT) is a new technique that allows the noninvasive evaluation of trabecular and cortical bone separately. The aim of the study was: (1) to evaluate cortical bone by pQCT in continuous ambulatory peritoneal dialysis (CAPD) patients and compare the data with that obtained in healthy controls; and (2) to correlate cortical bone parameters with bone mineral density (BMD) of the lumbar spine and femoral neck and total bone mineral content (TBMC). Cortical bone parameters were obtained in 22 CAPD patients and 27 healthy individuals at the distal radius using a Stratec XCT 960 pQCT machine. In the dialysis patients, we also determined BMD and TBMC by bone densitometry. Dialysis patients, compared with controls, showed a significant reduction in volumetric cortical BMD (VcBMD) (p = 0.04) and cortical thickness (cThk) (p < 0.0001) with a significant increase in radial total cross-sectional area (TA) (p = 0.006), endosteal circumference (p < 0.0001), and buckling ratio (p < 0.0001). In CAPD patients, total time on dialysis correlated negatively with radial total BMD (p < 0.01) and VcBMD (p < 0.01). Age correlated positively with TA (p < 0.01), endosteal (p < 0.01), and periosteal circumferences (p < 0.01). Serum intact parathyroid hormone (PTH) levels correlated positively with endosteal (p = 0.04) and periosteal perimeter (p = 0.01). Total alkaline phosphatase correlated negatively with VcBMD (p < 0.01), and positively with endosteal perimeter (p = 0.02). Total bone mineral content correlated significantly with radial cortical content (p < 0.001), cross-sectional cortical area (cA; p < 0.001), and cThk (p < 0.01) but not with total radial BMD, VcBMD, or buckling ratio. No correlations were found between radial cortical parameters and BMD measured at the lumbar spine or femoral neck. We conclude that dialysis patients show cortical osteopenia with marked cortical thinning partially mediated by PTH action on bone. Total bone mineral content correlated with various radial cortical parameters (content, area, and thickness) but not with others. No correlations were found between cortical bone parameters measured at the peripheral skeleton with areal bone density measured at the axial skeleton. These findings suggest that pQCT may be a new tool in the assessment of bone fragility in dialysis patients.

Sevelamer carbonate reduces the risk of hypomagnesemia in hemodialysis-requiring end-stage renal disease patients.

BACKGROUND: Sevelamer has been associated with less progression of vascular calcifications. This effect could be due to a reduction in serum phosphate levels but also to other additive effects. Magnesium has been also shown to prevent vascular calcification but the effect of sevelamer on serum magnesium levels has not been thoroughly evaluated. Our aim was to analyze whether the use of sevelamer reduces the risk of hypomagnesemia in hemodialysis (HD)-requiring end-stage renal disease patients. METHODS: All prevalent patients from the dialysis unit of the Hospital Italiano de Buenos Aires as of 1 June 2015 were evaluated. They were on three times per week bicarbonate/citrate-buffered HD. They were not receiving phosphate binders or magnesium-containing drugs. The average of three successive monthly magnesium serum levels was considered as the baseline magnesium concentration. Sevelamer carbonate use was retrieved from the patient's clinical records. RESULTS: One hundred and fifty-one patients were included. A large proportion of individuals were on proton pump inhibitors (PPIs) (66%) and more than 50% were using sevelamer carbonate. Serum magnesium levels were significantly higher in those receiving sevelamer compared with those who did not (2.05 ± 0.3 versus 1.8 ± 0.4 mg/dL; P < 0.05). A larger proportion of individuals receiving sevelamer were among those with normal serum magnesium (P = 0.02), while among those with hypomagnesemia, a larger proportion were on PPIs. In the multivariate model including the use of PPIs, sevelamer carbonate resulted in an independent protective factor for hypomagnesemia (odds ratio: 0.44; 95% confidence interval: 0.21-0.87). CONCLUSIONS: Hemodialysis patients receiving sevelamer show higher serum magnesium levels and a reduced risk of hypomagnesemia. This effect remains even after adjustment for PPI use. This effect could contribute to the still controversial superiority of sevelamer in preventing vascular calcifications.

Vascular calcifications in chronic kidney disease: are there new treatments?

Cardiovascular disease is extremely common in patients with end-stage renal disease (ESRD) and accounts for at least 50% of deaths among these patients. Vascular calcifications (VC) have been recently implicated as a possible cause of this excess cardiovascular mortality. Medial calcification is a striking feature of vascular disease in patients with ESRD. The traditional view that VC is a degenerative and passive process has been seriously challenged, based on strong evidence suggesting that VC is an active and highly regulated process similar to bone formation. Different data support the notion that elevated levels of phosphorus and/or other uremic toxins may play an important role by transforming vascular smooth muscle cells into osteoblast-like cells, which can produce bone matrix proteins. This nidus can then mineralize if the balance of pro-mineralizing factors outweighs inhibitory factors. The advent of newer noninvasive screening tests have generated great interest for screening patients with ESRD for vascular calcifications. Control of serum phosphorus with sevelamer, a recently developed non-calcium, non-aluminum phosphate binder, have attenuated or arrested progression of coronary artery and aortic calcifications compared to treatment with calcium-based binders. Amino bisphosphonates, have shown to completely inhibit soft tissue calcifications, calciphylaxis and prevent death in animal models. The first generation bisphosphonate, etidronate, reduces the progression of coronary artery calcifications patients receiving long-term hemodialysis and intravenous pamidronate has produced a rapid improvement of calciphylaxis. In conclusion, VC is a widespread phenomenon in patients with ESRD with important cardiovascular consequences. A better understanding of the processes of VC is leading to therapies to retard or improve this phenomenon and will probably have an important impact on patient mortality.