Nutrition in Children With Chronic Kidney Disease: How to Thrive?

The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.

Paricalcitol and Extended-Release Calcifediol for Treatment of Secondary Hyperparathyroidism in Non-Dialysis Chronic Kidney Disease: Results From a Network Meta-Analysis.

CONTEXT: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. OBJECTIVE: The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD). METHODS: A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. RESULTS: Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed. CONCLUSION: This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.

Complications in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) is a widespread condition that predisposes patients to a myriad of complications, including cardiovascular disease, electrolyte and acid-base derangements, anemia, mineral-bone disease, and volume excess. The frequency of CKD complications increases with the stage of disease, becoming nearly ubiquitous in later stages. The complications of CKD have profound implications for patient management, laboratory monitoring, medication prescribing, and follow up. Management of CKD seeks to slow disease progression and mitigate the risks posed by these complications.

Bone mass protective potential mediated by bovine milk basic protein requires normal calcium homeostasis in mice.

OBJECTIVES: Milk provide protective effects against bone loss caused by an impaired calcium balance. Although the effects of some elements have previously been confirmed, the involvement of milk basic protein (MBP) in bone mineral metabolism remains poorly characterized. Moreover, the importance of mineral nutrition sufficiency to establish the effect of MBP must be evaluated. METHODS: First, to evaluate the physiological conditions required for MBP activity, we examined the bone and mineral phenotypes of mice that suffer from insufficient calcium absorption due to a lack of intestinal vitamin D signaling. Second, to determine whether vitamin D signaling affects the effect of MBP on bone resorption, in vitro osteoclastogenesis were assessed using bone marrow cells. RESULTS: In mice with systemic vitamin D receptor (Vdr) inactivation, dietary MBP supplementation was unable to normalize hypercalcemia and hyperparathyroidism and failed to rescue bone mineralization impairments. In contrast, calcium and bone homeostasis responded to MBP supplementation when Vdr inactivation was restricted to the intestines. Hyperparathyroidism in intestine-specific Vdr knockout mice was also improved by MBP supplementation, along with a decrease in bone resorption in response to the level of serum tartrate-resistant acid phosphatase 5b. These results corresponded with a reduction in tartrate-resistant acid phosphatase-stained osteoclast numbers and the eroded surface on the tibia. MBP treatment dose-dependently suppressed osteoclastogenesis in cultured bone marrow macrophages regardless of vitamin D activity. These effects of MBP were blunted when parathyroid hormone was added to the culture medium, which is in line with the in vivo phenotype observed with systemic Vdr inactivation and suggests that severe hyperparathyroidism limits MBP activity in the bone. CONCLUSIONS: Therefore, adaptive calcium homeostasis is an essential requirement when MBP exerts protective effects through the inhibition of bone resorption.

Metabolismo óseo-mineral en 4620 pacientes prevalentes en hemodiálisis crónica en argentina / Bone-mineral metabolism in 4,620 prevalent patients in chronic hemodialysis in argentina

RESUMEN Introducción: Las anormalidades del metabolismo óseo-mineral comienzan desde las primeras etapas de la enfermedad renal crónica, produciendo el desarrollo de enfermedad ósea y el aumento de la morbimortalidad de los pacientes. Objetivos: Conocer en una muestra representativa de nuestra población en hemodiálisis, la prevalencia de pacientes en rango objetivo de valores de parathormona, hiperparatiroidismo secundario y enfermedad ósea adinámica, de acuerdo con las guías KDIGO, evaluando, además, el uso de diferentes medicamentos en el control de estas alteraciones. Material y métodos: Participaron 39 centros de hemodiálisis de nuestro país, quienes enviaron las últimas determinaciones de calcio, fósforo y parathormona, y la medicación recibida en el manejo del metabolismo mineral. Resultados: Se incluyeron 4620 pacientes prevalentes en hemodiálisis, > 18 años, edad media 57 años, hombres 57,4%. Las medias fueron: calcemia 8,6 y fosfatemia 4,9 mg/dl. De esta población, el 56,7% y el 50,3% estaban en rango de calcemia y fosfatemia, respectivamente. La parathormona promedio fue 601 y la mediana 437 pg/ml. El 50,5% tenía parathormona en rango, el 15% por debajo de 150 y el 34,5% por encima de 600 pg/ml. En relación a la medicación, el 47% de la población recibió quelantes cálcicos, con extremos en su uso, que van desde el 4,5% al 8% en algunos centros, y del 83% al 94% en otros. El 28,8% recibió Sevelamer, calcitriol el 38%, paricalcitol el 11% y cinacalcet el 20%, siendo su uso variable según los centros del 3% al 52%. Conclusiones: La presencia de hiperparatiroidismo secundario es más frecuente que la deseada, probablemente vinculado a la dificultad en el uso adecuado de medicamentos.

ABSTRACT Introduction : Abnormalities of bone mineral metabolism begin from the early stages of CKD, causing the development of bone disease and increased morbidity and mortality of patients. Objectives: To know, in a representative sample of our hemodialysis patients, the prevalence of patients in the target range of PTH values, secondary hyperparathyroidism and adynamic bone disease according to the KDIGO guidelines, also evaluating the use of different drugs in the control of these alterations. Methods: 39 hemodialysis centers from our country participated, who sent the latest determinations of calcium, phosphorus and PTH and the medication received in the management of mineral metabolism. Results: 4620 prevalent hemodialysis patients > 18 years were included, mean age 57 years, men 57.4%. The means were calcemia 8.6 and phosphatemia 4.9 mg/dl. 56.7% and 50.3% were in the calcemia and phosphatemia range, respectively. The average PTH was 601 and the median 437 pg/ml. 50.5% had PTH in range, 15% below 150 pg/ml and 34.5% above 600 pg/ml. In relation to medication, 47% of the patients received calcium chelators with extreme use ranging from 4.5-8% in some centers to 83-94%. 28.8% received Sevelamer, calcitriol 38%, paricalcitol 11% and cinacalcet 20%, its use being variable according to the centers from 3% to 52%. Conclusion: the presence of secondary hyperpartyroidism was more frequent than desired, probably linked to the difficulty in the adequate use of medications.

Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study.

BACKGROUND: Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients. METHODS: Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), ß-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D. RESULTS: Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment. CONCLUSIONS: Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.

Serum magnesium, bone-mineral metabolism markers and their interactions with kidney function on subsequent risk of peripheral artery disease: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Few studies have investigated the association of magnesium levels with incident peripheral artery disease (PAD) despite emerging evidence of magnesium contributing to vascular calcification. Moreover, no data are available on whether the magnesium-PAD relationship is independent of or modified by kidney function. METHODS: A cohort of 11 839 participants free of PAD in the Atherosclerosis Risk in Communities Study at Visit 2 (1990-92) was studied. We investigated the association of serum magnesium and other bone-mineral metabolism markers [calcium, phosphorus, intact parathyroid hormone (iPTH) and intact fibroblast growth factor-23] with incident PAD using multivariable Cox proportional hazards regression. RESULTS: Over a median of 23 years, there were 471 cases of incident PAD. The hazard ratio for incident PAD in Quartile 1 (<1.5 mEq/L) versus Quartile 4 (>1.7 mEq/L) of magnesium was 1.96 (95% confidence interval 1.40-2.74) after adjustment for potential confounders. Lower magnesium levels were associated with greater incidence of PAD, particularly in those with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (n = 11 606). In contrast, the association was largely flat in those with eGFR <60 mL/min/1.73 m2 (n = 233) with P-for-interaction 0.03. Among bone-mineral metabolism markers, only higher iPTH showed an interaction with kidney function (P-for-interaction 0.01) and iPTH >65 pg/mL was significantly related to PAD only in those with eGFR <60 mL/min/1.73 m2. CONCLUSIONS: Lower magnesium was independently associated with incident PAD, but this association was significantly weaker in those with reduced kidney function. In contrast, higher iPTH levels were particularly related to PAD risk in this clinical population.

Hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease.

BACKGROUND: Few studies have examined the association between hepcidin, iron indices and bone mineral metabolism in non-dialysis chronic kidney disease (CKD) patients. METHODS: We reviewed the data of 2238 patients from a large-scale multicenter prospective Korean study (2011-16) and excluded 214 patients with missing data on markers and related medications of iron and bone mineral metabolism, hemoglobin, blood pressure and causes of CKD. Multivariate linear regression analysis was used to identify the association between iron and bone mineral metabolism. RESULTS: The proportion of CKD Stages 1-5 were 16.2, 18.7, 37.1, 21.6 and 6.4%, respectively. Per each 10% increase in transferrin saturation (TSAT), there was a 0.013 mmol/L decrease in phosphorus [95% confidence interval (CI) -0.021 to -0.004; P = 0.003] and a 0.022 nmol/L increase in logarithmic 25-hydroxyvitamin D (Ln-25OHD) levels (95% CI 0.005-0.040; P = 0.019). A 1 pmol/L increase in Ln-ferritin was associated with a 0.080 ng/L decrease in Ln-intact parathyroid hormone (Ln-iPTH; 95% CI -0.122 to -0.039; P < 0.001). Meanwhile, beta (95% CI) per 1 unit increase in phosphorus, Ln-25OHD and Ln-iPTH for the square root of the serum hepcidin were 0.594 (0.257-0.932; P = 0.001), -0.270 (-0.431 to -0.108; P = 0.001) and 0.115 (0.004-0.226; P = 0.042), respectively. In subgroup analysis, the relationship between phosphorus, 25OHD and hepcidin was strongest in the positive-inflammation group. CONCLUSIONS: Markers of bone mineral metabolism and iron status, including hepcidin, were closely correlated to each other. Potential mechanisms of the relationship warrant further studies.

Calcifilaxis en terapia de sustitución renal / Calcifilaxis in renal substitution therapy

Resumen La calcifilaxis es una de las complicaciones menos comunes de la enfermedad renal crónica avanzada, sobretodo en terapia de sustitución renal, se desconoce la fisiopatología exacta de aparición, pero se cree, que es por una alteración en el metabolismo óseo-mineral. Se describe un caso clínico, de un paciente con enfermedad renal crónica, que presentó como complicación grave calcifilaxis, llegando a dicho diagnóstico gracias a las imágenes características de dicha patología tomadas del banco del servicio de imagenología del hospital. En conclusión, la calcifilaxis, a pesar de ser una patología difícil de encontrar en la actualidad, debido al mejor control del metabolismo óseo-mineral, se debe considerar en aquellos pacientes con progresión rápida de la enfermedad renal y con presencia de lesiones calcificadas supurativas en extremidades.

Abstract Calciphylaxis is one of the less common complications of Chronic Advanced Kidney Disease, especially in renal replacement therapy, the exact pathophysiology of its appearance is unknown, but it is believed that it is due to an alteration in bone-mineral metabolism. We describe a clinical case of a patient with chronic kidney disease, who presented as a serious complication calciphylaxis, reaching this diagnosis thanks to the characteristic images of this pathology taken from the bank of the Hospital's imaging service. In conclusion, calciphylaxis, despite being a pathology difficult to find nowadays due to better control of bone-mineral metabolism, should be considered especially in those patients with rapid progression of renal disease and presence of suppurative calcified lesions in extremities.

Vitamin D abnormalities and bone turn over analysis in children with epilepsy in the Western Cape of South Africa.

PURPOSE: The effects of antiseizure medications (ASMs) on bone metabolism is inconsistent. Most studies are in high income settings and none from sub-Saharan Africa. METHODS: A hospital based cross-sectional study in a paediatric epilepsy service with a comparison group assessed vitamin D metabolism. RESULTS: Seventy-five children with epilepsy and 75 comparison group were recruited. Median age for children with epilepsy was 9 years (range 1-17 years) and controls 3 years (range 1-12 years). Vitamin D deficiency occurred in 11(16.2%) children with epilepsy versus 6 (8.8%) control group (p = 0.29). Vitamin D insufficiency occurred in 30 (44.1%) children with epilepsy compared to 27(39.7%) control group. Children on ASMs had lower mean vitamin D levels than the control group (p = 0.02). Children on enzyme-inducing ASMs had lower mean vitamin D levels (p = 0.08), vitaminD2 (p = 0.0018), vitaminD3 (p = 0.004), serum phosphate levels (p = 0.000), and higher mean parathyroid hormone levels (p = 0.03) compared to controls. There was no difference in dietary intake and ancestry, although the dietary content of both groups was low in vitamin D products. CONCLUSIONS: Low vitamin D levels were common in children from both groups, but statistically lower for the children on ASMs. Children on enzyme-inducing ASMs need screening for vitamin D deficiency. The literature supports extending this for all children on ASMs. This is the first study to report that children on enzyme-inducing ASMs have lower levels of Vitamin D2 and D3 levels, probably as result of increased destruction of vitamin D. Improved vitamin D intake for children in vulnerable settings is important.

Calcimimetics and Bundled Reimbursement.

Since 2011, the Centers for Medicare & Medicaid Services has provided reimbursement for renal dialysis services furnished to Medicare beneficiaries through a bundled payment system known as the Prospective Payment System. Medications that have no injectable equivalent, known as "oral-only medications," are currently excluded from the bundle and are paid separately through Medicare Part D. Thus, before the development of etelcalcetide, the first injectable calcimimetic, calcimimetics were reimbursed outside the bundle. Etelcalcetide's introduction and approval for use in Medicare triggered a transition payment for a minimum of 2 years that will eventually result in the incorporation of calcimimetics into the dialysis bundle. Consequently, providers may face incentives to reduce calcimimetic use when the transition period has expired. The complexity of bone-mineral management in conjunction with the paucity of evidence-based recommendations in this area makes it difficult to predict the impact of this transition. Because these medications are expensive, a poor transition could have financial ramifications for dialysis organizations and potentially patient health. To ensure that patients are not adversely affected, it is critical that Medicare incorporate these medications into the bundle carefully, with close monitoring of outcomes.

Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.

BACKGROUND AND AIMS: Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function. METHODS: Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus). RESULTS: During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m2). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile). CONCLUSIONS: Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.

Low versus high dialysate calcium concentration in alternate night nocturnal hemodialysis: A randomized controlled trial.

INTRODUCTION: Higher calcium dialysate is recommended for quotidian nocturnal hemodialysis (NHD) (≥6 nights/week) to maintain bone health. It is unclear what the optimal calcium dialysate concentration should be for alternate night NHD. We aimed to determine the effect of low calcium (LC) versus high calcium (HC) dialysate on cardiovascular and bone parameters in this population. METHODS: A randomized controlled trial where participants were randomized to LC (1.3 mmol/L, n = 24) or HC dialysate (1.6 or 1.75 mmol/L, n = 26). Primary outcome was change in mineral metabolism markers. Secondary outcomes included change in vascular calcification (VC) scores [CT abdominal aorta (AA) and superficial femoral arteries (SFA)), pulse wave velocity (PWV), bone mineral density (BMD) and left ventricular mass index (LVMI) over 12 months. FINDINGS: In the LC group, pre-dialysis ionised calcium decreased -0.12 mmol/L (-0.18-0.06, P = 0.0001) and PTH increased 16 pmol/L (3.5-28.5, p = 0.01) from baseline to 12 months with no significant change in the HC group. In both groups, there was no progression of VC in AA or SFA and no change in PWV, LVMI or BMD. At 12 months, calcimimetics were prescribed in a higher percentage in the LC vs. HC groups (45.5% vs. 10.5%) with a lower proportion of the HC group being prescribed calcitriol (31.5% vs. 72%). DISCUSSION: Although dialysate calcium prescription influenced biochemical parameters it was not associated with difference in progression of VC between HC and LC groups. An important finding was the potential impact of alternate night NHD in attenuating progression of VC and inducing stabilisation of LVMI and PWV.

Bone effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus.

Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone. Minimal increases in serum phosphate and magnesium that were within normal limits were seen with canagliflozin versus placebo. Canagliflozin was associated with increases in serum collagen type 1 beta-carboxy telopeptide (beta-CTX), a bone resorption marker, and osteocalcin, a bone formation marker. Decreases in total hip BMD were seen with canagliflozin 100 and 300 mg versus placebo after 2 years (-1.7%, -2.1%, -0.8%; differences of -0.9% and -1.2%), but not at other skeletal sites (normal age-related bone loss, ~0.5-1.0%/year). Changes in beta-CTX and total hip BMD were significantly associated with weight loss, which is known to increase bone resorption markers and decrease BMD. Canagliflozin was associated with a higher fracture incidence in an interim analysis of the CANagliflozin cardioVascular Assessment Study (CANVAS) in patients with a history or high risk of cardiovascular disease (incidence per 100 patient-years of 1.6, 1.6, and 1.1 with canagliflozin 100 and 300 mg and placebo), but not in other clinical studies of patients with T2DM. Fractures tended to occur as early as 12 weeks after initiating treatment and were primarily located in the distal parts of the upper and lower extremities. The reason for increased fracture risk with canagliflozin treatment is unknown, but is likely not related to a direct effect of canagliflozin on bone-related biomarkers. Data from ongoing canagliflozin studies, including CANVAS, will provide additional information on fracture risk in patients with T2DM.

PTH levels and not serum phosphorus levels are a predictor of the progression of kidney disease in elderly patients with advanced chronic kidney disease. / El nivel de la hormona paratiroidea (PTH) y no el de fósforo sérico es predictor de la progresión de la enfermedad renal en pacientes mayores con enfermedad renal crónica avanzada.

BACKGROUND: At present, there is a high incidence of elderly patients with advanced chronic kidney disease (CKD) and it is important to know the long term progression and the factors that influence it. OBJECTIVES: To analyse the progression of advanced CKD in elderly patients and the influence of bone-mineral metabolism. METHODS: Retrospective study of 125 patients ≥70years of age with CKD stages 4-5 who started follow-up from January 1, 2007 to December 31, 2008, showing the progression of CKD (measured by the slope of the regression line of the estimated glomerular filtration rate [eGFR] by MDRD-4) over 5years. RESULTS: Progression in the entire group (median and 25th and 75th percentiles): -1.15 (-2.8/0.17) ml/min/1.73m2/year, CKD-4: -1.3 (-2.8/0.03) ml/min/1.73m2/year, CKD-5: -1.03 (-3.0/0.8) ml/min/1.73m2/year; the slope of the regression line was positive in 35 patients (28%: CKD does not progress) and negative in 90 patients (72%: CKD progresses). Negative correlation (Spearman) (slower progression): PTH, albumin/Cr ratio and daily Na excretion (all baseline measurements). No correlation with eGFR, serum P, urinary P excretion, protein intake and intake of P (all baseline measurements). In the linear regression analysis (dependent variable: slope of progression): albuminuria and PTH (both at baseline measurements) influenced this variable independently. Logistic regression (progresses vs. does not progress): PTH, albuminuria and eGFR (all at baseline measurements) influenced significantly. CONCLUSIONS: In our group of elderly patients, impairment of renal function is slow, particularly in CKD-5 patients. Albuminuria and PTH at baseline levels are prognostic factors in the evolution of renal function.

The effects of amlodipine and platelet rich plasma on bone healing in rats.

AIM: The aim of this study was to evaluate the effects of calcium channel blocker (CCB) amlodipine (AML), platelet rich plasma (PRP), and a mixture of both materials on bone healing. MATERIALS AND METHODS: Fifty-six male Wistar rats were randomly divided into four groups: group A, tibia defect model with no treatment; group B, tibia defect model treated with AML, 0.04 mg daily by oral gavage; group C, tibia defect model treated with local PRP; group D, tibia defect model treated with local PRP and AML, 0.04 mg daily by oral gavage. RESULTS: At day 21, bone healing was significantly better in groups C and D compared to group A (P<0.05), but comparisons showed no statistically significant difference in group B (P>0.05). At day 30, groups B and C showed no statistically significant difference (P>0.05) compared to group A, but bone healing in group D was significantly better than in group A (P<0.05). Statistically, AML did not affect alkaline phosphatase (ALP) activity at 21 and 30 days (P>0.05), but PRP and AML + PRP increased ALP activity statistically (P<0.05). CONCLUSION: It can be concluded that AML had neither a positive nor a negative effect on bone healing, but when used in combination with PRP, it may be beneficial.

Evaluación del metabolismo óseo pre y postrasplante renal en niños y adolescentes / Pre and post-renal transplant bone mineral metabolism in children and adolescents

Introducción. La enfermedad renal crónica presenta efectos sobre el tejido óseo que se conocen como enfermedad renal crónica-trastorno mineral óseo. Los pacientes con trasplante renal también presentan trastornos óseos, aun con la función normal del injerto. Se han atribuido a los medicamentos inmunosupresores (esteroides e inhibidores de calcineurina). Por lo anterior, es necesario conocer la prevalencia y evolución de trastorno mineral óseo pre y postrasplante renal en los niños. El objetivo de este trabajo fue describir la prevalencia y el tipo de alteraciones de metabolismo mineral pretrasplante y su evolución postrasplante. Métodos. El estudio fue aprobado por el Comité de Ética e Investigación del hospital. Se obtuvo el consentimiento informado de todos los participantes. Participaron pacientes con enfermedad renal crónica menores de 18 años, estudiados para recibir un primer trasplante renal. Al momento del trasplante, así como a los 6 y a los 12 meses postrasplante, se realizó la antropometría completa y se colectó sangre para determinar creatinina, niveles en valle de tacrolimus, calcio, fósforo, magnesio y fosfatasa alcalina. Se midió la hormona paratiroidea intacta (PTH) al momento del trasplante. Resultados. Se incluyeron 31 pacientes con edad promedio de 14.6 ± 3.2 años y predominio del sexo femenino (52%). Todos recibieron inducción con basiliximab y triple esquema con prednisona, micofenolato de mofetilo y tacrolimus. En cuanto a los valores de PTH, 51.6% tuvieron cifras pretrasplante <150 pg/ml (sugestivo de lesiones óseas de bajo remodelamiento); 38.7%, >300 pg/ml (sugestivo de alto remodelamiento); y tan sólo 9.6% tuvieron PTH en los valores recomendados. Al comparar los valores pre y postrasplante, la creatinina sérica disminuyó en forma significativa, no hubo diferencia en el calcio sérico y fosfatasa alcalina, pero se encontró una disminución significativa en fósforo y magnesio. Doce pacientes (38.7%) presentaron hipofosfatemia postrasplante. Diez pacientes (32%) cursaron con hipomagnesemia. Todos incrementaron el valor z de peso en forma significativa. La función renal tuvo correlación positiva con el calcio sérico y negativa con el fósforo y el magnesio (p <0.05). Los niveles de tacrolimus tuvieron una correlación negativa con el magnesio sérico (r =-0.431, p <0.0001). Conclusiones. La velocidad de filtración glomerular al momento del trasplante tuvo una correlación negativa con el fósforo sérico basal y la concentración de tacrolimus, con el magnesio sérico. El crecimiento fue mejor en los pacientes que no presentaron hipofosfatemia durante el postrasplante. Es necesario vigilar y tratar oportunamente las alteraciones minerales en el postrasplante renal.

Background. Information regarding chronic kidney disease-mineral bone disorder (CKD-MBD) in children who undergo renal transplant is scarce. Despite successful renal transplantation, bone disorders have been described and attributed to immunosuppressive drugs (steroids and calcineurin inhibitors). Therefore, it is important to determine the prevalence and outcome of bone mineral disorders pre- and post-renal transplant. The aim was to describe the prevalence and type of bone mineral disorders in children pre-renal transplant and outcomes. Methods. The Institutional Review Board and Ethics Committee approved the study. Signed consent/assent was obtained from all participants. Patients <18 years of age and under investigation for a first renal transplant were invited to participate. At transplant and 6 and 12 months after transplantation, anthropometric data were collected and blood samples were collected for serum creatinine, slope levels of tacrolimus, serum calcium, phosphorus, magnesium and alkaline phosphatase. Intact parathyroid hormone (PTH) was measured before transplant. Results. Thirty-one patients were included with a mean age of 14.6 ± 3.2 years. Females represented 52%. All received induction with basiliximab and triple maintenance therapy with prednisone, mycophenolate mofetil and tacrolimus. Pre-transplant PTH values were <150 pg/ml in 51.6%, suggestive of low turnover bone lesions, 38.7% had PTH >300 pg/ml, suggestive of high turnover bone lesions and only 9.6% had PTH between 150 and 300 pg/ml. When pre- and post-transplant studied parameters were compared, serum creatinine was statistically lower during follow-up. No difference was found in serum calcium and alkaline phosphatase, but magnesium and phosphorus values were significantly lower after transplant. Twelve patients (38.7%) had post-transplant hypophosphatemia and required supplementation. Ten patients (32%) had hypomagnesemia, seven of them with concomitant hypophosphatemia. Z-score for weight increased significantly after renal transplant; nevertheless, only patients with no hypophosphatemia during follow-up improved their Z-score for height. Glomerular filtration rate had a positive correlation with serum calcium and a negative correlation with phosphorus and magnesium (p <0.05). Tacrolimus slope levels had a significantly negative correlation with serum magnesium (r =-0.431, p <0.0001). Conclusions. Glomerular filtration rate had a negative correlation with serum phosphorus at transplant. Tacrolimus slope levels had a negative correlation with magnesium serum values. Patients with no hypophosphatemia during the first year had better growth than those with hypophosphatemia. It is important to monitor and opportunely treat bone mineral disorders in children who undergo transplantation.

Efeitos endócrinos e metabólicos das drogas antiepilépticas / Endocrine and metabolic effects of antiepileptic drugs

As drogas antiepilépticas (DAE) são utilizadas por um enorme contingente de pessoas em todo o mundo - tanto no tratamento das epilepsias como para outros fins - frequentemente por um longo tempo. Por essas razões, torna-se fundamental o conhecimento sobre os potenciais efeitos adversos desses medicamentos, muitos deles envolvendo vários aspectos hormonais e metabólicos que devem ser do conhecimento do endocrinologista. Nesta revisão, foi abordada a relação das DAE com anormalidades no metabolismo mineral ósseo, balanço energético e peso corporal, eixo gonadal e função tireoideana, além de ter sido revisado o papel terapêutico dessas medicações no tratamento da neuropatia diabética.

The antiepileptic drugs (AED) have been widely used for a great deal of people - in the treatment of epilepsy and other diseases - throughout the world. Continuous and prolonged use of AED may be associated with adverse effects in different systems, including a variety of endocrine and metabolic abnormalities. In this review, the relationship of AED with alterations in bone mineral metabolism, energy balance and body weight, gonadal function and thyroid metabolism was revised, as well as their clinical utility in the treatment of diabetic neuropathy.

Relationship between serum osteoprotegerin levels and bone mineral metabolism in women / 대한내과학회지

BACKGROUND: Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. The relationship between circulating OPG levels and female bone status in human populations is unclear. Thus, the aim of this study was to investigate the relationship between circulating OPG levels and bone mineral metabolism in Korean women. METHODS: ubjects were 287 women aged 37~73 (mean age, 51.5 yr). Serum concentrations of OPG were determined by ELISA. Biochemical markers of bone turnover and follicle stimulating hormone (FSH) were measured by standard methods. Bone mineral density at lumbar spine and femur neck were measured by dual energy X-ray absorptiometry. RESULTS: e observed a significant positive association between circulating OPG levels and urine calcium excretion (r=0.128; p<0.05). Although circulating OPG levels were not significantly correlated to urine deoxypyridinoline levels (r=0.105; p=0.076), but there was a weak trend in it. We found that mean OPG levels were about 11% greater in postmenopausal women (mean +/- SD, 1358.5 +/- 380.0 pg/mL) than in premenopausal women (1228.8 +/- 407.7 pg/mL; p<0.001). There was a significant positive relationship between circulating OPG levels and serum FSH levels (r=0.172; p<0.01). There was a non-significant relationship between circulating OPG levels and bone mineral density at lumbar spine and femur neck. CONCLUSION: In conclusion, our data shows that the circulating OPG levels are associated with urine calciumexcretion and serum FSH levels in Korean women. These data suggest that OPG may be an important paracrine mediator of female bone metabolism in human populations.

Relationship between Serum Osteoprotegerin-Receptor Activator of NF-kappaB Ligand Levels and Bone Mineral Metabolism in Men / 대한내분비학회지

BACKGROUND: Osteoporosis is a growing health problem, not only in women, but in men also. Sex hormones and insulin-like growth factor-I (IGF-I) have been shown to be the major determinant in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine, which acts as a decoy receptor for the receptor activator of the NF- B ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis in animal models. The relationship between the OPG-RANKL system and male bone status in human populations is unclear. The aim of this study was to investigate the relationship between circulating the OPG-RANKL system and bone mineral metabolism in 80 Korean men. METHODS: The subjects of this study were 80 men aged between 42 and 70 (mean age, 54.5 yr). The serum concentrations of OPG and RANKL were measured by ELISA. The serum concentrations of estradiol, total testosterone, IGF-I and biochemical markers of bone turnover were measured by standard methods. The bone mineral densites (BMD) at the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry. RESULTS: A significant correlation was observed between the serum OPG/RANKL ratios and osteocalcin levels (r=-0.229, p<0.05). The serum OPG levels were significantly correlated to the femoral neck BMD (r=-0.227, p<0.05). The mean value of the serum OPG was found to be greater in patients with osteoporosis at the femoral neck (mean SD, 4.72.1 pmol/L) than in subjects with a normal BMD (3.30.9 pmol/L, p<0.05). The serum RANKL/OPG ratios were significantly positively correlated to the serum estradiol level (r=0.401, p<0.001). Also, there was a significant negative correlation between the serum OPG and estradiol levels (r=-0.288, p<0.05). In a multiple regression analysis, the BMI, serum OPG and RANKL levels, and the serum IGF-I level were identified as significant predictors of the femoral neck BMD. In another multiple regression analysis, only the serum estradiol level was identified as a significant predictor of the serum OPG level. CONCLUSION: In conclusion, our data show that the serum OPG and RANKL levels are partly associated with bone mineral metabolism, and are related to the endogenous estrogen levels in human male populations. Therefore, the possibility exists that the OPG-RANKL system may be a mediator of the estradiol in male bone metabolism. However, there have been few study published on the relation between the serum OPG and estradiol levels in men. Further studies are needed to clarify this relationship