Transient benign hyperphosphatasemia due to COVID-19: the first case report.

OBJECTIVES: Coronavirus disease (COVID-19) rapidly spread worldwide in a few months and was declared as a worldwide pandemic by WHO in March 2020. Transient benign hyperphosphatasemia (THI) is a benign condition associated with marked elevation of alkaline phosphatase (ALP) without any other kidney, bone, and liver pathologies. CASE PRESENTATION: Herein, we report a previously healthy 16-month-old female patient who developed a secondary transient benign hyperphosphatasemia associated with SARS-CoV-2. Patient whole family's SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) results were positive. Since THI is a diagnosis of exclusion, other reasons that may cause ALP elevation should be ruled out. ALP activity decreased and turned to normal ranges within the following month. THI has been reported to be in association with various conditions. Its relationship with many viruses has been reported previously. CONCLUSIONS: If ALP elevation is detected in patients with COVID 19 due to the increasing number of infections, THI should be considered if there is no other accompanying pathology.

Resultados del tratamiento quirúrgico del hiperparatiroidismo primario en un país en vías de desarrollo / Outcomes of Primary Hyperparathyroidism Surgical Treatment in a Low-Middle Income Country

Introducción: El hiperparatiroidismo primario es una enfermedad común y con una distribución similar en todo el mundo. El propósito del estudio fue establecer si la presentación clínica y bioquímica, así como los resultados de su tratamiento quirúrgico, difieren en un país en vías de desarrollo, que no cuenta con todos los recursos diagnósticos y terapéuticos recomendados actualmente. Metodología: Análisis retrospectivo de pacientes operados por un mismo equipo, entre 1992 y 2015. Se obtuvo información sobre presentación clínica, resultados de estudios preoperatorios, procedimientos quirúrgicos, diagnóstico histopatológico y evolución postoperatoria. Resultados: Se operaron 55 pacientes con edad promedio de 45 años, 78% mujeres. El 65% eran sintomátcos. El valor promedio preoperatorio de calcio sérico fue 11.2 mg/dl, PTH 167.1 pg/ml, fósforo 2.6 mg/ dl, 25-hidroxi vitamina D 17.3 ng/ml y calcio urinario de 24 horas 294.7 mg. Al 59% se realizó estudios de localización preoperatoria. La sensibilidad del ultrasonido fue 57.14% y 75% para centellografa con tecnecio sestamibi. La positividad de los estudios de localización determinó el tipo de exploración quirúrgica (p=0.02). Se practcaron 27 (49%) exploraciones unilaterales y 28 (51%) bilaterales, resecando 47 (85.5%) adenomas solitarios y 3 ½ glándulas en 7 (12.7%) casos de hiperplasias. En 27 (36%) coexista patología tiroidea. Las tasas de curación, persistencia y recurrencia fueron 94.5%, 5.5% y 3.6% respectivamente. Conclusiones: La mayoría de nuestros pacientes operados son jóvenes y sintomátcos. La estrategia quirúrgica fue condicionada por los estudios de localización. Nuestras tasas de curación, persistencia y recurrencia son comparables a las reportadas.

Background: Primary hyperparathyroidism (HPTP) is a common disease with widespread distribution around the world. The aim of this study was to establish if clinical and biochemical disease characteristics and long term results differ in patents with HPTP in a low-middle income country without all recommended diagnostc and therapeutc resources. Methods: Retrospective collection of clinical diagnosis, biochemical, operative details, histology and long term results of all surgically treated patents with HPTP, from 1992 to 2015, by the same surgical team. Results: 55 patents with HPTP were analyzed. Average age is 45 years old with 78% of female patents. Sixty five percent were symptomatic. The mean preoperative serum calcium level was 11.2 mg/dl, PTH 167.1 pg/ml, phosphorus 2.6 mg/ dl, vitamin D 17.3 ng/ml and 24 hour urinary calcium 294.7 mg. Fifty nine percent of the patents had preoperative imaging. Ultrasound and sestamibi scan sensitivity was 57.1% and 75% respectively. Unilateral localization in preoperative imaging determined surgical exploration (p=0.02). Unilateral approach was used in 27 (49%) patents and bilateral in 28 (51%); 47 (85.5%) solitary adenomas and 7 (12.7%) 3 ½ gland resections of hyperplastic glands were performed. Thyroid pathology co-existed in 27 (36%) patients. Cure, persistence and recurrence rates were 94.5%, 5.5% y 3.6% respectively. Conclusions: In this study most of the patents were young and symptomatc. Surgical strategy was determined by preoperatve imaging. Cure, persistence and recurrence rates were comparable to published literature.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder.

Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

[Research progress on pharmacotherapy of calcific aortic valve disease].

With the population aging and declining incidence of rheumatic heart disease, calcific aortic valve disease (CAVD) has become the most frequent valve disease and the common cause of aortic valve replacement. Patients with CAVD need to cope with a deteriorating quality of life and valve replacement is the only effective clinical option for the patients. Therefore, early pharmacotherapy is of great significance in prevention or slow-down of the progression of CAVD. For years CAVD was considered to be a passive wear and tear process of valves, but now it is recognized as an active and multi-factorial process. Histopathologic studies have revealed that inflammation, disorder of calcium and phosphorus metabolism and dyslipidemia are involved in the process of CAVD. Clinical trials of CAVD pharmacotherapy have been carried out based on those histopathologic studies. Statin, renin-angiotensin inhibitors and anti-osteoporosis drug are well studied in recent years. This article reviews the recent research progress of the pharmacotherapy for CAVD.

Associations of dietary phosphorus intake, urinary phosphate excretion, and fibroblast growth factor 23 with vascular stiffness in chronic kidney disease.

OBJECTIVE: Elevated serum phosphate concentrations are established risk factors for cardiovascular disease and mortality in chronic kidney disease (CKD). Independent associations of other indices of phosphorus metabolism, such as phosphorus intake, urinary phosphate excretion, or hormones that regulate these systems, like fibroblast growth factor 23 (FGF23), with markers of cardiovascular disease in CKD, have been studied in less detail. DESIGN: Cross-sectional study. PARTICIPANTS: Seventy-four adult CKD patients with mean creatinine clearance of 51 ± 19 mL/minute. OUTCOME: Augmentation index (AI)--a surrogate marker of arterial stiffness. RESULTS: Although serum phosphate varied little across quartiles of creatinine clearance, average daily phosphorus intake and 24-hour urinary phosphate excretion decreased from highest to lowest quartile (by 31% and 60%, respectively, P for trend <.05). FGF23 was associated with serum phosphate (r = 0.24, P = .03) and creatinine clearance (r = -0.4, P = .001), but not with dietary phosphorus or 24-hour urinary phosphate excretion (P > .05 for both). Older age, higher systolic blood pressure, female gender, and black race were independently associated with increased AI. In contrast, there were no associations of serum phosphate, dietary phosphorus intake, urinary phosphate excretion, or FGF23 with AI in multivariate-adjusted models. CONCLUSIONS: In this sample of patients with CKD, established risk factors for arterial stiffness, but not mediators of phosphorus metabolism, were associated with increased AI. In addition, there were no significant associations between FGF23 and dietary phosphorus or urinary phosphate excretion. Future studies are needed to determine the main factors associated with elevations in FGF23 in CKD and to further assess the association of disordered phosphorus metabolism with subclinical markers of vascular disease.

Disturbance of inorganic phosphate metabolism in diabetes mellitus: its impact on the development of diabetic late complications.

The pathogenesis of diabetic late complications (DLC) is multifactorial. Studies of mechanisms leading to early functional microvascular changes in retina and kidneys point towards a disturbance in the metabolism of inorganic phosphate (Pi) in diabetes. Since tissue hypoxia and reduced high energy phosphates may be important factors in the development of DLC, the influence of Pi concentration on the metabolism and function of the erythrocytes and renal tubular cells, as well as the relationship of the concentration of Pi to total oxygen consumption, have been reviewed. While extensive research data in non-diabetic conditions support the suggestion, that the Pi concentration is a determining factor in regulation of metabolism and rate of oxygen consumption, diabetes shows the opposite behavior. In diabetes, the highest oxygen consumption is associated with the lowest concentration of Pi. Many conventionally-treated juvenile diabetic patients respond as if their tissues were in a state of chronic hypoxia. A disturbance in phosphate handling occurs in the kidney tubules, where the excessive sodium-dependent glucose entry in diabetics depolarizes the electrochemical sodium gradient and consequently impairs inorganic phosphate reabsorption. Similar changes may occur in other cells and tissues in which glucose entry is not controlled by insulin, and particularly in poorly-regulated diabetic patients in whom long-term vascular complications are more likely.

Utilización nutritiva de fósforo en el transcurso de la anemia ferropénica nutricional / Nutritive utilization of phosphorus during the course of nutritional ferropenic anaemia

Se ha estudiado el efecto de la evolución de la anemia ferropénica nutricional sobre la utilización digestiva y metabólica de fósforo en tres periodos 20, 30 y 40 días. Los animales de experimentación han sido 48 ratas macho de la raza Wistar albina que se dividieron en 6 grupos: tres grupos controles(C) y tres grupos ferrodeficientes (FD) que recibieron una dieta AIN 93G con contenido normal (45mg Fe/kg dieta) o con un bajo contenido de hierro (5 mg/Fe Kg dieta) respectivamente durante 20, 30 ó 40 días. Se ha encontrado un aumento significativo en la utilización digestiva y metabólica de fósforo en el transcurso de la anemia ferropénica nutricional, efecto que se va haciendo más patente a medida que evoluciona la ferrodeficiencia. Este incremento en la utilización nutritiva de fósforo es debido principalmente al mecanismo pasivo de absorción de fósforo que opera principalmente en el yeyuno-íleon y es predominante en situación de anemia ferropénica nutricional(AU)

The evolution of the nutritional iron deficiency anemia on the digestive and metabolic utilization of phosphorus has been studied during three periods: 20, 30 and 40 days. 48 male Wistar albino breedrats were divided in 6 groups: three control groups (C) and three Fe-deficient groups (FD) receiving AIN 93G with normal-Fe content (45 mg /kg diet) or with a low-Fe content (5 mg/Kg diet) respectively during 20, 30 ó 40 days. A significant increase in the digestive and metabolic utilization of phosphorus has been found in the course of the nutritional iron deficiency anemia, effect that become more pronounced as the ferrodeficiency is instaured. This increase in the nutritive utilization of phosphorus is due mainly to the passive mechanism of phosphorus absorption which operates principally in the jejunum-ileum and is predominant in situation of nutritional iron deficiency anemia(AU)

Calcinosis pulmonarmetastásica / No disponible

No disponible

Calcinosis tumoral en pediatría: reporte de un caso clínico y revisión de la literatura / Tumoral calcinosis in young children: report of a case and literature review

We report a case of tumoral calcinosis in young girl, a quite infrecuent condition, caused by a hereditary dysfunction of phosphate regulation. Our aims are to review imaging signs (plain radiography ultrasound, Computed Tomography and nuclear medicine) and clinical and laboratory findings as well. Finally we made a literature search, oriented to help in diagnosing this disease, specially regarding images.

Presentamos el caso de una niña preescolar portadora de calcinosis tumoral, entidad infrecuente, causada por una disfunción hereditaria en la regulación de la excreción de fosfatos. Damos a conocer los hallazgos radiológicos (radiografía simple, ultrasonografía, tomografia computada y cintigrafía ósea), así como también hallazgos clínicos y laboratorio del caso, además de revisar la literatura para una breve actualización de esta condición, especialmente en lo que respecta al diagnóstico y las imágenes.

Optimising the treatment of hyperphosphatemia and vascular calcification in chronic kidney disease.

Accelerated atherosclerosis and vascular calcifications (VC) play a central role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD) patients. Mineral metabolism disorders and increased serum calcium-phosphate product have been recently investigated as inducing factors of cardiovascular calcification. In fact, cardiovascular disease in renal failure appears greatly associated with bone metabolism alterations. Recently, the treatment of hyperphosphatemia in CKD patients changed from either calcium- or aluminium-based phosphate-binders to new free-calcium and aluminium phosphate binders, such as sevelamer hydrochloride and lanthanum carbonate. Therefore, control of serum phosphate in CKD patients becomes crucial in preventing increases in calcium-phosphate product, secondary hyperparathyroidism and ultimately VC.

Emerging drugs for hyperphosphatemia.

Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.

Phosphate metabolism in the setting of chronic kidney disease: significance and recommendations for treatment.

Phosphorus is an essential mineral that plays a crucial role in cell structure and metabolism. In living organisms, phosphorus exists surrounded by four oxygen atoms to form phosphate (PO(4)). Within cells, PO(4) regulates enzymatic activity and serves as an essential component of nucleic acids, adenosine triphosphate, and phospholipid membranes. Outside cells, PO(4) primarily resides in bone and teeth as hydroxyapatite. A small amount of inorganic PO(4) circulates in serum, with levels balanced by gastrointestinal intake, renal excretion, and a set of specific hormones. Under normal conditions, PO(4) is excreted through the kidneys. Among patients with end stage renal disease (ESRD) receiving chronic dialysis, circulating PO(4) levels typically rise to levels well above the normal laboratory range. Higher serum PO(4) levels are strongly associated with arterial calcification and mortality in this setting. Among predialysis patients with chronic kidney disease (CKD), phosphaturic hormones enhance renal PO(4) excretion to maintain serum PO(4) levels within the high-normal laboratory range. Recently, high-normal serum PO(4) levels have been associated with cardiovascular (CV) events and mortality among individuals who have CKD and among those who have normal kidney function. This review discusses PO(4) metabolism in the context of CKD, examines associations of PO(4) levels with adverse outcomes in the CKD setting, and suggests treatment strategies for moderating serum PO(4) levels.

Thirty-month follow-up of coronary artery calcification in hemodialysis patients: different roles for inflammation and abnormal calcium-phosphorous metabolism?

BACKGROUND: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. Coronary artery calcification (CAC) is considered a marker of atherosclerosis and coronary artery disease (CAD). The CAC progression and factors that influence it were evaluated during a 30-month period. METHODS: Forty HD patients without a history of CAD were enrolled into the study. CAC score was assessed with conventional CT repeated every six months. The circulating factors of phosphorous, calcium, calcium-phosphorous product, intact parathyroid hormone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, lipoprotein-alpha, albumin, high sensitivity C-reactive protein, and fibrinogen were measured monthly. Hypertension and calcium intake during the study period were taken into account as well. RESULTS: At baseline, CAC score was correlated with age and duration of HD therapy. From all evaluated factors, CAC initiation was influenced only by older age and C-reactive protein. CAC, when it was started, was aggravated continuously and was influenced only by elevated serum phosphorous and calcium-phosphorous product. Hypertension, lipid profile, and calcium intake did not affect CAC initiation or progression. CONCLUSIONS: Once CAC progression starts, it is an uninterrupted process. The roles of inflammation and abnormal calcium-phosphorous metabolism in CAC differ. Inflammation is the major factor that contributes in CAC initiation. Elevated serum phosphorous and calcium-phosphorous product accelerates CAC progression.

Mineral metabolism and aging: the fibroblast growth factor 23 enigma.

PURPOSE OF REVIEW: The regulation of phosphate homeostasis was thought to be passively mediated by the calciotrophic hormones parathyroid hormone and 1,25(OH)2D3. This article summarizes the emerging trends that show an active regulation of phosphate homeostasis by fibroblast growth factor 23 (FGF-23) - a process fairly independent of calcium homeostasis - and how altered mineral ion metabolism may affect the aging process. RECENT FINDINGS: A major breakthrough in FGF-23 biology has been achieved by the demonstration of strikingly similar physical/biochemical phenotypes of Fgf-23(-/-) and klotho hypomorph mice, which eventually led to the identification of klotho as a cofactor in FGF-23 and its receptor interactions. Furthermore, FGF-23 has emerged as a counter regulator of the renal 1alpha(OH)ase and sodium-phosphate cotransporter activities to modulate phosphate homeostasis. Finally, studies point towards a role of dentine matrix protein 1 in affecting phosphate homeostasis, in coordination with FGF-23. SUMMARY: Recent mouse genetic studies have broadened our understanding of biochemical/molecular pathways involved in phosphate homeostasis, and linked FGF-23 to such regulation. Understanding the molecular interactions of essential calcium and phosphate regulators will enhance our knowledge of the coordinated regulation of mineral ion metabolism, and will help to redefine the molecular pathology of age-associated lesions accompanied by abnormal mineral ion metabolism such as vascular calcifications and osteoporosis.

Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice.

Fibroblastic growth factor 23 (FGF23) regulates renal phosphate reabsorption and 1alpha-hydroxylase activity. Ablation of FGF23 results in elevated serum phosphate, calcium, and 1,25-dihydroxyvitamin D3 [1,25(OH)(2)D] levels; vascular calcifications; and early death. For determination of the independent roles of hyperphosphatemia and excess vitamin D activity on the observed phenotypic abnormalities, FGF23 null mice were fed a phosphate- or vitamin D-deficient diet. The phosphate-deficient diet corrected the hyperphosphatemia, prevented vascular calcifications, and rescued the lethal phenotype in FGF23 null mice, despite persistent elevations of serum 1,25(OH)(2)D and calcium levels. This suggests that hyperphosphatemia, rather than excessive vitamin D activity, is the major stimulus for vascular calcifications and contributes to the increased mortality in the FGF23-null mouse model. In contrast, the vitamin D-deficient diet failed to correct either the hyperphosphatemia or the vascular calcifications in FGF23 null mice, indicating that FGF23 independently regulates renal phosphate excretion and that elevations in 1,25(OH)(2)D and calcium are not sufficient to induce vascular calcifications in the absence of hyperphosphatemia. The vitamin D-deficient diet also improved survival in FGF23 null mice in association with normalization of 1,25(OH)(2)D and calcium levels and despite persistent hyperphosphatemia and vascular calcifications, indicating that excessive vitamin D activity can also have adverse effects in the presence of hyperphosphatemia and absence of FGF23. Understanding the independent and context-dependent interactions between hyperphosphatemia and excessive vitamin D activity, as well as vascular calcifications and mortality in FGF23 null mice, may ultimately provide important insights into the management of clinical disorders of hyperphosphatemia and excess vitamin D activity.