6. Fósforo 2.5–4.5mg/dl
• Compensación por efecto fosfatúrico
de FGF-23 desde TFG menor a 60ml
• Retención con TFG menor a 30
mL/min.
• Medición Colorimétrica estandarizado
facilmente reproducible
Subexpresión de
• Hiperfosfatemia asociada a alta morbi-mortalidad
CaSR
↑FGF-23
7. Calcio 8.5–10.5 mg/dl
• Tiende a disminuir
• Compensación a expensas
de inducir alteraciones del
recambio óseo
• Método colorimétrico
• Corrección con Albumina
• No correlación entre
calcemia-Fx-mortalidad
8. Fosfatasa Alcalina
• Remueve Fosfato de proteinas y
nucleotidos
• Intestino, Placenta, Riñones
• Elevación → Descartar Hepatopatía
• Mayor valor en niños en crecimiento
• Puede Predecir Alto o Bajo remodelado
• Asociado a calcificaciones coronarias y
mortalidad en HD
• Método Colorimétrico
9. ↓ Masa Renal
- 1ἀhidroxilasa
Vitamina D
• Mortalidad
• ECV
• HPT2
• 25(OH)D
• Varios métodos de
↓ 25(OH)d3
tubular
ensayo
• Cromatografía líquida
de alta eficiencia
• RIA
• Quimioluminiscencia
10. Receptor de vitamina D (VDR).
• Ubicación nuclear.
• Su numero decrece por inestabilidad de ARNm en la uremia
• Su déficit de VDR produce resistencia a la acción inhibitoria de la vitamina D
sobre la síntesis de PTH y redunda en Hiperplasia.
Receptor-sensor de calcio (CaR).
• Ubicación citoplasma
• Sensa cambios mínimos en los niveles séricos de calcio.
• Calcio unido a los receptores del calcio y se deja de inhibir la secreción de PTH.
• Su déficit produce resistencia a la acción del inhibitoria del Ca sobre la glándula
paratiroidea y media la hiperplasia
Receptor para el FGF-23
• FGF-23 ejercer una acción inhibitoria sobre la glándula paratiroidea.
• En experimentos en animales urémicos y en muestras de paratiroides
hiperplásicas de pacientes urémicos se ha evidenciado una disminución de los
11. PTH:
• 84 aa
• Extremo carboxilo y amino
• Se fragmenta
• Predictor de Alto o Bajo
remodelado
• KDOKI: Nichols Allegra
• KDIGO: Variabilidad
Interensayos
• 1, 2, 3 Generación
13. Recomendaciones KDIGO
• Vigilancia en Adultos desde G3
• Chequeo mas frecuente en Px que reciben
tratamiento
• Vigilancia en niños a partir de G2
• Decisiones terapéuticas en base a tendencias y no en
base a valores aislados
• Corrección de Deficiencia de Calcidiol
• No se aconseja Producto CaxP
14.
15. Osteodistrofia Renal: desorden complejo en el que los ensayos
bioquimicos no predicen con exactitud la histologia osea
subyacente
Sintomas
• Dolor óseo lumbar, caderas,
piernas
• Artralgias / Fx / Deformidad
• Debilidad Muscular
Predictores
• PTH
• Fosfatasa Alcalina
No relación entre tipo histológico y manifestaciones clínicas, riesgo de fracturas y
calcificación arterial
16. Sistema TMV
Remodelado(T)
• Tasa de
formación de
Hueso
• Doble Marcaje
con
Tetraciclinas
• Hormonas,
Citoquinas
Mineralización(M)
• Cuan bien la
matriz colágena
se calcifica
• Medicion del
volumen de
Osteoide
• Tetraciclinas
• Def. Vit D
• Aluminio
• Bajo Ca y P
Volumen(V)
• Cantidad de hueso
por unidad de vol.
• Producto del
Balance entre
formacion-
Resorcion
• Contribuye a la
Fragilidad Osea
17. Osteitis Fibrosa
• Expresión de HPT
• Fibrosis de medula osea
• Formacion de quistes oseos
y erosiones oseas
• Dolor, Fragilidad osea,
• Resistencia a la EPO
18. Osteomalacia
• Acumulación de Osteoide
• Bajo Volumen Oseo
• Deficiencia de Vit D
• Intoxicación por Aluminio
Enfermedad Ósea Adinámica
• Mineralización y Volumen
Bajos
• Ancianos y Diabéticos
• Supresión Excesiva de PTH
• Aumento de Fx y C.V.
19. Indicaciones de Biopsia
1. Hipercalcemia e hipofosfatemia
inexplicables
2. Fracturas patológicas en ausencia o
ante un mínimo traumatismo
3. Enfermos sintomáticos (p. ej., con dolor
óseo inexplicable) en presencia de
parámetros clínicos incongruentes.
4. Enfermos con sospecha de enfermedad
ósea inducida por aluminio
5. Antes del inicio de tratamiento con
bifosfonatos
Guías S.E.N. 2011 Revista Nefrología 2011;31(Suppl 1):3-32
20. Densitometría Osea
• Método estándar para determinar la
densidad mineral ósea
• Cuello femoral y en columna
vertebral
• Proporciona información de cambios
en el contenido mineralóseo, pero no
del tipo de enfermedad ósea
subyacente
• Diálisis: En el radio distal es predictiva
• del riesgo de fractura y se
correlaciona negativamente con la
PTH
• No recomendado de Rutina (KDIGO)
22. • Los Pacientes con ERC y C.V son catalogados en el mas alto riesgo
Cardiovascular
• No hay Evidencia Clara de que protocolo diagnostico y terapeutico
hay seguir luego de obtener una prueba positiva para presencia de
calcificaciones vasculares
• Evitar Quelantes con Ca
23. Abdominal Aortic Calcifications Score- Kauppila
Abdominal aortic calcification in dialysis patients: results of the CORD study. Nephrol Dial Transplant 200; 23: 4009-15.
24. Adragao SCORE
El Puntaje
Adragao T, Pires A et al. Nephrol Dial Transplant. 2004 Jun; 19(6):1480-8
26. Grosor intima-media
• Detecta calcificaciones en
placas de ateroma
• La hiperfosfatemia se ha
asociado con aumento del
grosor íntima-media, rigidez
y calcificación vascular,
hipertrofia miocárdica y
mortalidad
Velocidad de onda de pulso
• medir la rigidez arterial.
• Correlación con el grado de
calcificación vascular
27. Calcinosis tumoral
• Calcificaciones masivas metastásicas en partes blandas
• Habitualmente periarticulares, que afectan a grandes articulaciones
• Se ha asociado a hiperfosforemia grave y prolongada
– Con producto Ca/P aumentado
– Uso abusivo de derivados de la vitamina D
• Suele cursar asintomática
• Se ha descrito compresión de nervios periféricos, limitación del
movimiento articular y síndrome febril asociado
• Masas tumorales duras, periarticulares y no dolorosas
Guías S.E.N. 2011 Revista Nefrología. Órgano Oficial de la Sociedad
Española de Nefrología.
35. PARATIROIDECTOMÍA
HPT2 con hipercalcemia no
iatrogénica resistente a las
alternativas médicas
Hiperparatiroidismo
primario en pacientes con
ERC
Pacientes con calcifilaxis y
PTHi superior a 500 pg/ml,
que no responden
rápidamente al tratamiento
con calcimiméticos
Guías S.E.N. 2011 Revista Nefrología 2011;31(Suppl 1):3-32
36. Conclusiones
• Ampliar el concepto de tratar la «osteodistrofia renal» a tratar la alteración óseo
mineral asociada con la enfermedad renal crónica» concebida como un síndrome
sistémico
• Las alteraciones óseo-minerales asociadas con la enfermedad renal crónica se
inician de modo precoz en el transcurso de la enfermedad renal
• Además del esqueleto, el sistema cardiovascular, entre otros, es uno de los más
importantes tejidos secundariamente afectados por las alteraciones óseo-minerales
asociadas a la enfermedad renal crónica.
• Las calcificaciones vasculares no son sólo un fenómeno pasivo de deposición de
calcio y fósforo sino que en la uremia se favorece, por distintos factores
• Los valores séricos de calcio y fósforo no son suficientes para el manejo de los
pacientes con alteraciones del metabolismo óseo-mineral
37. • Bibliografìa:
– Guias KDIGO 2009 paramanejo de EMO
– Comentario de KDOQI sobre KDIGO
– Guias Senefro 2011
– Guias KDOQI 2006
– Brenner, The Kidney
– Cohomprensive Clinical Nephrology
– Harryson´s Nephrology GRACIAS!!!
Editor's Notes
Brenner 2021: Metabolismo calcio fosforo
Brenner 2240: Tratamientos de Met min oseo
When the love falls, Love me, bellas lullaby, stay with me, new moon
Brenner 2021: Metabolismo calcio fosforo
Brenner 2240: Tratamientos de Met min oseo
Hiperfosfatemia eleva PTH por: Pi may affect the regulation of intracellular calcium in parathyroid cells, resulting in the inhibition of arachidonic acid synthesis and cytosolic phospholipase A2. Second, Pi may also increase cell proliferation and growth through transforming growth factor-α (TGF-α) mediated via the epidermal growth factor receptor.29 Third, hyperphosphatemia also reduces the expression of the calcium-sensing receptor (CaSR),30 thereby decreasing the ability of the parathyroid gland to respond to changes in ionized calcium. Fourth, studies have also revealed the presence of cytosolic proteins in the parathyroid gland that bind the 3′ untranslated region (3′UTR) of the PTH mRNA and prevent degradation, thus stabilizing the mRNA. Efecto del Fósforo sobre la secreción de FGF23. Last, hyperphosphatemia indirectly increases PTH by inhibiting the activity of 1α-hydroxylase, thereby reducing the conversion of 25(OH)D to 1,25(OH)2D. This reduction in 1,25(OH)2D directly leads to increased PTH secretion
Initial studies clearly demonstrated high levels of FGF23 in patients with CKD3
Unlike calcium, a major component of phosphorus is intracellular, and factors such as pH and glucose can cause shifts of phosphate ions into or out of cells,
thereby altering the serum concentration without changing the total body phosphorus.
Phosphorus is routinely measured in clinical laboratories with colorimetric methods in automated machines. There are quality control standards used by clinical laboratories. Thus, the assay is generally precise and reproducible. Levels will be falsely elevated with hemolysis during sample collection. In healthy individuals, there is a diurnal variation in both serum phosphorus levels and urinary phosphorus excretion. Epidemiologic data suggest that Pi levels above the normal range are associated with increased morbidity and mortality in patients with CKD.
In the presence of hypoalbuminemia, there is an increase in ionized calcium relative to total calcium; thus, total serum calcium may underestimate the physiologically active (ionized) serum calcium. A commonly used formula for estimating ionized calcium from total calcium is the addition of 0.8 mg/dl (0.2mmol/l) for every 1 g decrease in serum albumin below 4 g/dl (40 g/l). This ‘corrected calcium’ formula is routinely used by many dialysis laboratories and in most clinical trials. Unfortunately, recent data have shown that it offers no superiority over total calcium alone and is less specific than ionized calcium measurements
In Total serum calcium tends to decreaseduring the course of CKD as a result of phosphate retention and decreased production of 1,25-dihydroxyvitamin D (calcitriol) from the kidney, decreased intestinal calcium absorption, and skeletal resistance to the calcemic action of PTH, but the levels of free calcium remain within the normal range in most patients (Fig. 81.3)3 as a result of compensatory hyperparathyroidism.
Because calcium is a major regulator of PTH secretion, persistent hypocalcemia is a powerful stimulus for the development of hyperparathyroidism and also contributes to parathyroid growth
Estos mecanismos de compensación puede llegar a normalizar la calcemia y la fosfatemia temporalmente, lo hace a expensas de inducir alteracionesdel recambio óseo14.
Serum calcium levels are routinely measured in clinical laboratories using colorimetric methods in automated machines. There are quality control standards utilized by clinical laboratories. Thus, the assay is generally precise andreproducible. In healthy individuals, serum calcium is tightly controlled within a narrow range, usually 8.5–10.0 or 10.5 mg/dl (2.1–2.5 or 2.6mmol/l), with some, albeit minimal, diurnal variation.52 However, the normal range may vary slightly from laboratory to laboratory, depending on the type of measurement used patients with CKD stages 3 to 5, no data support an increased risk of mortality or fracture with increasing serum calcium concentrations
Alkaline phosphatases are enzymes that remove phosphate from proteins and nucleotides, functioning optimally at alkaline pH. Measurement of the level of t-ALP is a colorimetric assay that is routinely used in clinical laboratories in automated machines, with quality control standards routinely used. The enzyme is found throughout the body inthe form of isoenzymes that are unique to the tissue of origin. Highest concentrations are found in the liver and bone, but
the enzyme is also present in the intestines, placenta, kidneys, and leukocytes. Specific ALP isoenzymes to identify the tissue source can be determined after fractionation and heat inactivation, but these procedures are not widely available in clinical laboratories. Bone-specific ALP (b-ALP) is measured
with an immunoradiometric assay. Elevated levels of t-ALP are generally due to an abnormal liver function (in which case, other tests are also abnormal), an increased bone activity, or bone metastases. Levels are normally higher in children with growing bones than in adults
También de forma precoz se observa un descenso discreto pero significativo del calcitriol (1,25[OH]D3) en pacientes con ERC, secundario a:
1. Pérdida de masa renal, que ocasiona menor disponibilidad de 1-alfa-hidroxilasa.
2. Descenso del filtrado glomerular, que conlleva disminución de la 25(OH)D3 tubular. La 25(OH)D3 debe ser filtrada por el glomérulo para alcanzar el túbulo contorneado proximal y allí penetrar por endocitosis dentro de la célula (con la intervención de la megalina, un receptor endocítico situado en la membrana apical).
3. Retención de fósforo, que disminuye la síntesis renal de calcitriol, directa o indirectamente, a través del aumento del FGF-23.
El déficit de síntesis de calcitriol disminuye la absorción intestinal
de calcio. Este fenómeno ocurre precozmente ya en
estadios 2 y 3 de ERC.
Vitamin D deficiency in patients with CKD stages 3 and 4 is associated with increased PTH and low BMD. In dialysis patients, vitamin D deficiency is associated
with mortality in incident dialysis patients and increased cardiovascular events in peritoneal dialysis patients. These studies support the concern raised by the NKF K/DOQI guidelines that low calcidiol levels in patients with CKD may contribute to the etiology of secondary hyperparathyroidism. The international KDIGO guidelines recommend measurement of 25(OH)D levels, but conclude that there are insufficient data to suggest an optimal level in CKD patients while noting there is also no reason to assume that CKD patients would require different levels for non-endocrine effects of vitamin D. However, we lack definitive studies demonstrating that treatment with vitamin D leads to improvement in secondary hyperparathyroidism or other diseases common in patients with CKD.
a) La acción de la vitamina D sobre la PTH es mediada por este receptor, que es un receptor citosólico.
b) Con la progresión de la ERC el número de VDR decrece, el propio estado urémico puede disminuir la estabilidad
del ARNm VDR, produciendo un descenso en los niveles de proteína del receptor. Además, «toxinas
urémicas» disminuyen el paso del complejo VDR-vitamina D al núcleo y su unión al elemento de
respuesta del ADN7.
c) El déficit de VDR produce resistencia a la acción inhibitoria de la vitamina D sobre la síntesis de PTH.
d) La hiperplasia de las glándulas paratiroides se acompaña de disminución en la densidad de VDR. En estados
avanzados de hiperplasia, «hiperplasia nodular», la disminución de los VDR es muy marcada.
PTH is cleaved to an 84-amino-acid protein in the parathyroid gland, where it is stored with fragments in secretory granules for release. Once released, the circulating 1–84-amino-acid protein has a half-life of 2–4 min. The hormone is cleaved both within the parathyroid gland and after secretion into the N-terminal, C-terminal, and midregion fragments of PTH, which are metabolized in the liver and in the kidneys. There has been a progression of increasingly sensitive assays developed to measure PTH over the past few decades (Figure 6). Initial measurements of PTH using C-terminalassays were inaccurate in patients with CKD because of the impaired renal excretion of C-terminal fragments (and thus retention) and the measurement of these probably inactive fragments. The development of the N-terminal assay was initially thought to be more accurate but it also detected inactive metabolites. The development of a second generation of PTH assays (Figure 6), the two-site immunoradiometric assay—commonly called an ‘intact PTH’ assay—improved the detection of full-length (active) PTH molecules. In this assay, acaptured antibody binds within the amino terminus and a second antibody binds within the carboxy terminus.61 Unfortunately, recent data indicate that this ‘intact’ PTH assay also detects accumulated large C-terminal fragments,commonly referred to as ‘7–84’ fragments; these are a mixture of four PTH fragments that include, and are similar in size to, 7–84 PTH.62 In parathyroidectomized rats, the injection of a truly whole 1- to 84-amino-acid PTH was able to induce bone resorption, whereas the 7- to 84-amino-acid fragment was antagonistic, explaining why patients with CKD may have high levels of ‘intact’ PTH but relative hypoparathyroidism at the bone-tissue level.6365 Thus, the major difficulty in accurately measuring PTH with this assay is the presence of circulating fragments, particularly in the presence of CKD. Unfortunately, the different assays measure different types and amounts of these circulating fragments, leading to inconsistent results.66 More recently, a third generation of assays has become available that truly detect only the 1- to 84-amino-acid, fulllength molecule: ‘whole’ or ‘bioactive’ PTH assays (Figure 6). However, they are not yet widely available and have not been shown convincingly to improve the predictive value for the diagnosis of underlying bone disease67 or other serum markers of bone turnover,68 in contrast to at least one report that suggested that levels of 1–84 PTH or the 1–84 PTH/large C-PTH fragment ratio may be a better predictor of mortality in CKD stage 5 than standard ‘intact’ PTH values.69 Therefore, the Work Group felt that the widely available second-generation PTH assays should continue to be used in routine clinical practice at present.
PTH has long been considered a surrogate marker for bone disease, and the ability to predict low and high turnover disease
was the rationale for the target range of 150 to 300 pg/ mL in the NKF K/DOQI guidelines for stage 5D CKD.46 Unfortunately, the assay used, Nichols Allegra, is no longer available, and a study demonstrated that iPTH levels within a range of 150 to 300 pg/mL are not predictive of underlying bone histology. the KDIGO guidelines considered that levels of iPTH less than 2 and greater than 9 times the upper limit of normal for the PTH assay (<130 and >585 pg/mL for most kits that have a upper normal limit of 65 pg/mL) and values within that range should be interpreted by evaluating trends, with interventions if the trends are consistently going
up or down.49 However, it is important to recognize that no randomized clinical trials have demonstrated that treatment to achieve specific PTH level results in improved outcomes.
PTH has long been considered a surrogate marker for bone
disease, and the ability to predict low and high turnover disease
was the rationale for the target range of 150 to 300 pg/
mL in the NKF K/DOQI guidelines for stage 5D CKD.46
Unfortunately, the assay used, Nichols Allegra, is no longer
available, and a study demonstrated that iPTH levels within
a range of 150 to 300 pg/mL are not predictive of underlying
bone histology.
the KDIGO guidelines considered that levels
of iPTH less than 2 and greater than 9 times the upper
limit of normal for the PTH assay (<130 and >585 pg/mL for
most kits that have a upper normal limit of 65 pg/mL) and
values within that range should be interpreted by evaluating
trends, with interventions if the trends are consistently going
up or down.49 However, it is important to recognize that no
randomized clinical trials have demonstrated that treatment
to achieve specific PTH level results in improved outcomes.
The bone response to PTH, however, is not consistent, and there is evidence for skeletal resistance to PTH in patients
with CKD–MBD. The results of studies that reported correlations between PTH and bone-formation rates are shown in Figure 14,
which shows the wide variabilities seen in different situations.69,99,108,111,146,210224 The older studies tended
to find better correlations between PTH and bone-formation rates, whereas more recent studies show poor correlations. This follows a trend for associating findings of adynamic bone disease with high PTH levels. The reasons for poor correlations between PTH and bone formation are not clear, but could involve differences in the assays for PTH, secular changes in the dialysis
population with more diabetic and elderly patients SINTOMAS: Aches and pains are common manifestations,
often nonspecific in nature, and occur in the lower back, hips,
and legs, aggravated by weight bearing. Acute, localized bone
pain can also become manifested and may be suggestive of acute
arthritis. Pain around joints may be caused by acute periarthritis,
which is associated with periarticular deposition of calcium phosphate
crystals, especially in patients who suffer from marked
hyperphosphatemia. The symptoms may be confused clinically with gout or pseudogout and often respond to nonsteroidal antiinflammatory
drugs (NSAIDs). The gradual onset of muscle
weakness is also common in patients with ESRD. Many factors
are probably involved in its pathogenesis, including hyperparathyroidism
and abnormalities of vitamin D. The arthropathy
associated with b2-microglobulin amyloidosis (see later discussion)
should be considered in the differential diagnosis in very
long term dialysis patients.
Bone deformities may occur in patients with severe hyperparathyroidism,
particularly in children. In adults, deformities arise as
a consequence of fractures, sometimes induced by brown tumors
(see later discussion); the axial skeleton is most commonly
affected. This can lead to kyphoscoliosis or chest wall deformities.
Slipped epiphysis may occur in children, and frank rachitic features
are occasionally evident. Growth retardation is also common
in children, and although some improvement has been shown
with calcitriol, this has not been the universal finding.
Extraskeletal calcifications are frequently encountered in
patients with advanced CKD and are aggravated by persistent
elevation of the calcium-phosphate product. Most commonly,
vascular calcifications are seen, but calcifications may also occur
in other sites, such as the lung, myocardium, and periarticular
areas (Fig. 81.8).
In the skin, hyperparathyroidism can be manifested as pruritus
(discussed in detail in Chapter 84). Rarely, it can also underlie
the development of calciphylaxis, or calcific uremic arteriolopathy
(discussed in detail in Chapter 84; see Figs. 84.6 and 84.7)
Given these pathophysiological and diagnostic
differences, the definition of ‘osteoporosis’ in adults is most
appropriate only for those with CKD stages 1–3; in later CKD
stages, those with low BMD should be designated as having
‘CKD–MBD with low BMD.
Fractures occur
more commonly in elderly patients, in women, in diabetic
patients, in those using glucocorticoids, and in those with a
longer exposure to dialysis. Fractures are also common in
elderly patients with CKD stages 3–4 (Supplementary Table 5).
Hip fractures were seen two to three times more often than in
persons without CKD.
To clarify the interpretation of bone biopsy results in the evaluation of renal osteodystrophy, it was agreed by KDIGO to use three key histologic descriptors—bone turnover, mineralization, and volume (i.e., the TMV system)—with any combination of each of the descriptors possible in a given specimen (Table 54-4).1 The TMV classification scheme provides a clinically relevant description of the underlying bone pathology as assessed by histomorphometry, which in turn helps define the pathophysiology, and thereby guide therapy. Turnover reflects the rate of skeletal remodeling, which is normally the coupled process of bone resorption and bone
formation. It is assessed with histomorphometry by dynamic measurements of osteoblast function using double-tetracycline
labeling. Bone formation rates (BFRs) and activation frequency (Ac.f ) represent acceptable parameters for assessing bone turnover. Bone turnover is affected mainly by hormones, cytokines, mechanical stimuli, and growth factors that influence
the recruitment, differentiation, and activity of osteoclasts and osteoblasts. It is important to clarify that although BFR is frequently similar to bone resorption rate, which cannot be measured directly, this is not always true. An imbalance in these processes can affect bone volume. For example, excess resorption over formation leads to negative bone balance and decreased bone volume.
Mineralization reflects how well bone collagen becomes calcified during the formation phase of skeletal remodeling. It is assessed with histomorphometry by static measurements of osteoid volume and osteoid thickness and by dynamic, tetracycline-
based measurements of mineralization lag time and osteoid maturation time. Causes of impaired mineralization include inadequate vitamin D nutrition, mineral (calcium or Pi) deficiency, acidosis, and bone aluminum toxicity. Volume indicates the amount of bone per unit volume of tissue. It is assessed with histomorphometry by static measurements of bone volume in cancellous bone. Determinants of bone volume include age, gender, race, genetic factors, nutrition, endocrine disorders, mechanical stimuli,
toxicities, neurologic function, vascular supply, growth factors, and cytokines. This new classification is consistent with the
current commonly used classification system210 but provides more information on parameters other than turnover.
and resorption rates: if the overall bone formation rate is
higher than the overall bone resorption rate, the bone is in
positive balance and the bone volume will increase. If
mineralization remains constant, an increase in bone volume
would also result in an increase in BMD and should be
detectable by dual-energy X-ray absorptiometry (DXA).
Although both cortical and cancellous bone volumes decrease
in typical idiopathic osteoporosis, these compartments are
frequently different in patients with CKD. For example, in
dialysis patients with high PTH levels, the cortical bone
volume is decreased but the cancellous volume is increased.93
Los niveles elevados de Ca, P y CaxP promueven la formacion y crecimiento de nucleos de cristales de hidroxiapatita. La hidroxiapatita es el principal componente mineral de los huesos. El origen de las celulas responsables de la mineralizacion en
la pared vascular es la celula muscular lisa vascular (CMLV) y no a celulas pasajeras, como la célula de estirpe osteoblástica que participa en el proceso de mineralizacion. El cotransportador de fosfato dependiente de sodio, NaPi, cuyo subtipo Pit-1 se encuentra presente en las CMLV, es un factor importante en la mediacion de esta diferenciacion osteocondrogenica. Niveles altos de fosforo estimula la actividad del cotransportador y la carga, mientras niveles elevados de calcio induce la expresion de mRNA de Pit-1. El
aumento de la expresion de genes osteogenicos provoca la secrecion de moleculas minerales (vesiculas de matriz, proteinas ligadoras de calcio, fosfatasa alcalina y matriz extracelular rica en colageno) (17) (Figura
2). La mayoria de los investigadores estan de acuerdo en el rol esencial
de la CMLV en el proceso de la calcificación celular y hay muchos mecanismos
que cooperan y amplifican esta respuesta de transformación
an assessment for vascular calcification is warranted in some patients. These
may include, but are not limited to, patients with significant
hyperphosphatemia requiring a differentiated high-dose
phosphate-binder therapy, patients on a transplant waiting
list, and any patient in whom the caring physician decides
that a knowledge of the presence of vascular calcification may
impact therapeutic decision making.
In 1986 Witteman et al.[7] reported the relationship between aortic calcification and cardiovascular mortality. More recent data also support this observation.[8] A system for quantification of calcification was described by Kauppila et al.[9] in a subgroup of participants of the Framingham heart study. It relies on lateral lumbar radiographs and the calculation of the abdominal aortic calcification (AAC) score. The predictive value of this method for cardiovascular events and mortality was validated in a large cohort of 2500 subjects in the Framingham heart study.[10,11] Recently, the AAC score was shown to correlate well with electron beam computer tomography (EBCT) scores of coronary arteries in chronic hemodialysis patients.[12] AAC may also be associated with all-cause and cardiovascular mortality in ESRD
Predicdictor of cardiovascular death, cardiovascular hospitalizations
and vascular disease in dialysis patients and was
an independent predictor of arterial stiffness evaluated by
pulse wave velocity and pulse pressure
Brenner 2021: Metabolismo calcio fosforo
Brenner 2240: Tratamientos de Met min oseo
Tratamiento dirigido a controlar las concentraciones séricas de fósforo y calcio
4.10. Los quelantes de fósforo que contienen calcio son efectivos para disminuir las concentraciones séricas de fósforo.
Sin embargo, su uso puede asociarse con hipercalcemia y con una mayor incidencia de calcificación vascular
(2C)(SLANH).
4.11. Se recomienda restringir la dosis de quelantes de fósforo que contienen calcio hasta un máximo de 1.500 mg de
calcio elemental/día (1B)(SLANH). También se recomienda restringir o evitar el uso de quelantes de fósforo con calcio
en presencia de hipercalcemia, calcificaciones vasculares, enfermedad ósea adinámica o niveles persistentemente
bajos de PTHi (2C)(KDIGO).
4.12. Los quelantes de fósforo que contienen aluminio no deberían usarse (1C)(SLANH).
4.13. En pacientes con ERC 3-5 con fósforo sérico normal o elevado, sugerimos no exceder la ingesta de
fósforo en la dieta de 800-1.000 mg/día, de forma aislada o en combinación con otros tratamientos
(2D)(SLANH).
