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Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.
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RESUMEN El manejo de la hiperfosfatemia de los pacientes con insuficiencia renal crónica en diálisis permanece como un desafío. A pesar de utilizar un enfoque multifacético que incluye la restricción dietética, la remoción de fósforo por la diálisis y el uso de quelantes de fósforo, esta estrategia múltiple no logra reducir los niveles de fósforo en más de 2 mg/dl. El control de fósforo de los pacientes en diálisis es fundamental en razón de la relación monotónica entre los niveles séricos de fosfato y el incremento del riesgo cardiovascular. Por lo tanto, hay una necesidad de explorar nuevas estrategias para reducir los niveles séricos de fosfato a niveles normales. Recientes avances en nuestra compresión de los mecanismos que subyacen a la homeostasis del fósforo sugieren que el transporte gastrointestinal del fósforo podría ser un objetivo. Recientemente se han desarrollado inhibidores de los cotransportadores sodio fosfato del intestino y se ha revalorizado el uso de la nicotinamida, en su formulación de liberación prolongada, que también actuaria por ese mecanismo. También se han drogas como el tenapanor, que inhibiendo el intercambiador sodio/hidrogeno isoforma 3 del enterocito, disminuyen la absorción paracelular de fósforo.
ABSTRACT Management of hyperphosphatemia in patients with chronic renal failure on dialysis remains challenging. Despite using a multifaceted approach that includes dietary restriction, phosphorus removal by dialysis, and phosphate binders, these multiple strategies fail to reduce phosphorus levels by more than 2 mg/dL. Phosphorus control in dialysis patients is essential due to the monotonic relationship between serum phosphate levels and increased cardiovascular risk. Therefore, there is a need to explore new strategies to reduce serum phosphate levels to normal levels. Recent advances in understanding the mechanisms underlying phosphorus homeostasis suggest that the gastrointestinal transport of phosphorus could be a target. Inhibitors of intestinal sodium phosphate cotransporters recently developed, and using of nicotinamide, in its prolonged release formulation, which would also act by this mechanism, has been revalued. There have also been drugs such as tenapanor, which, by inhibiting the isoform three sodium/hydrogen exchanger of the enterocyte, decreases the paracellular absorption of phosphorus.
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Morbidity and mortality of chronic kidney disease (CKD) patients are largely associated with vascular calcification, an actively regulated process in which vascular smooth muscle cells (VSMCs) change into cells similar to osteocytes/chondrocytes, known as trans-differentiation. Cellular and systemic response to low oxygen (hypoxia) is regulated by the prolyl hydroxylase/hypoxia-inducible factor (HIF)-1 pathway. Recent studies highlighted that hypoxia-mediated activation of HIF-1 induces trans-differentiation of VSMCs into bone-forming type through an increase in osteo-/chondrogenic genes. Inhibition of the HIF-1 pathway abolished osteochondrogenic differentiation of VSMCs. Hypoxia strongly enhanced elevated phosphate-induced VSMC osteogenic trans-differentiation and calcification. HIF-1 was shown to be essential for phosphate enhanced VSMC calcification. O2-dependent degradation HIF-1 is triggered by the prolyl hydroxylase domain proteins (PHD). Prolyl hydroxylase inhibitors, daprodustat and roxadustat, increase high phosphate-induced VC in VSMCs, stabilizing HIF-1α and activating the HIF-1 pathway in these cells. Whether the use of these PHD inhibitors to treat anemia in CKD patients will favor the development and progression of vascular calcification remains to be explored.
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Paracellular transport in the kidney is mediated by a family of proteins located in the tight junctions called claudins which confers its ionic selectivity. Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations. In the thick ascending limb of Henle (TALH) calcium is reabsorbed by a paracellular channel formed by Claudin-16 and-19. Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability. On the other hand, Claudin 14, that is also located in TALH, inhibits the paracellular permeability of Claudin-16 to calcium. Recent wide genomic association analysis studies have detected four common synonymous variants (genetic polymorphisms of a single nucleotide, SNPs) at the locus of Claudin-14 gene that were significantly associated with the presence of renal lithiasis. Another study of wide genomic association and nephrolithiasis was carried out in the general population but including chromosome X, where claudin-2 gene is located. They detected nine SNPs that had a significant association with renal lithiasis risk. A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.
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Cálculos Renais , Litíase , Cálcio/metabolismo , Claudina-2 , Claudinas/genética , Claudinas/metabolismo , Humanos , Hipercalciúria/genética , Cálculos Renais/genéticaRESUMO
OBJECTIVES: Sarcopenia is the loss of skeletal muscle mass and function that occurs with aging that can lead to greater morbidity and mortality. Chronic kidney disease and hemodialysis (HD) favors the development of sarcopenia. We studied the prevalence of sarcopenia and its components using European Working Group on Sarcopenia in Elderly People 2 proposed criteria and risk factors for its development in HD patients. METHODS: In 100 adult HD patients, we evaluated: hand grip strength (HGS), muscle mass by dual energy X-ray absorptiometry and physical performance (gait-speed and sit-stand test). RESULTS: Sixty patients were male and 40 were female; mean age 55.6 years. Prevalence of sarcopenia was 16% (11.1% in males and 25% in females; P = 0.05); 7% had severe sarcopenia. Prevalence of low HGS was 33% in males and 28% in females; low muscle mass was 30% in males but 70% in females and low physical performance 23% in males and 45% in females. Falls were reported by 23 patients. Patients with lower HGS had a higher prevalence of falls in the last year (40% two or more falls; P = 0.03). Only females with sarcopenia had lower bone mineral content. Neither age, body mass index, time on dialysis, or prevalence of diabetes predicted sarcopenia. CONCLUSIONS: A significant proportion of dialysis patients had sarcopenia, more frequent in females. Low HGS was associated with a higher prevalence of falls. Only females with sarcopenia had lower bone mineral content.
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La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)
Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)
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Humanos , Animais , Camundongos , Hormônios Neuro-Hipofisários/biossíntese , Arginina Vasopressina/efeitos adversos , Ocitocina/uso terapêutico , Osteoblastos/fisiologia , Osteoclastos/fisiologia , Osteogênese , Osteoporose/terapia , Hormônios Neuro-Hipofisários/fisiologia , Arginina Vasopressina/antagonistas & inibidores , Arginina Vasopressina/biossíntese , Arginina Vasopressina/fisiologia , Arginina Vasopressina/uso terapêutico , Ocitocina/biossíntese , Ocitocina/efeitos adversos , Ocitocina/fisiologia , Transdução de Sinais , Densidade Óssea , Densidade Óssea/efeitos dos fármacos , Receptores de Ocitocina/biossíntese , Receptores de Ocitocina/fisiologia , Estradiol/uso terapêutico , Estrogênios/fisiologiaRESUMO
Background: Chronic hyponatremia is a risk factor for hip fracture but remains uncorrected in most patients. This study evaluated if preoperative chronicity of uncorrected hyponatremia influences outcomes after hip fracture repair. Materials and Methods: Evaluated were older patients hospitalized for hip fracture repair between 2007 and 2012 with plasma sodium measured at admission and ≥1 preadmission outpatient measurement. Patients were classified as being normonatremic (NN; plasma sodium 135-145 mmol/L), chronic prolonged hyponatremia (CPH; ≥2 consecutive plasma sodium values <135 mmol/L over >90 days), or recent hyponatremia (one plasma sodium <135 mmol/L within 30 days before admission with previously normal plasma sodium). Length of hospital stay, in-hospital death, post-operative complications, 30-day readmission, and long-term mortality were the evaluated outcomes. Multivariable Cox regression was used to evaluate the association of hyponatremia status with outcomes. Results: Among 1,571 eligible patients, 76.7% were NN, 14% had CPH, and 9.1% had RH. Compared with NN patients, CHN patients were older and had more prior heart failure, alcoholism, and anticonvulsant drug use. In multivariable analyses, neither CPH or RH was associated with hospital length of stay, in-hospital or 30-day death, or 30-day readmission, while RH was associated with post-operative sepsis [adjusted odds ratio (aOR) 1.84, 95% CI: 1.01-3.35). Only CPH was independently associated with long-term all-cause death (OR 1.53, 95% CI: 1.12-2.09). Conclusions: Hyponatremia affects nearly 25% of patients undergoing hip fracture repair. Preoperative chronic untreated hyponatremia is associated with increased post-operative mortality following surgical repair of a hip fracture in older patients. Future studies should evaluate if correction of hyponatremia could decrease long-term mortality after hip fracture repair.
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In recent years, the role of trace elements in lithogenesis has received steadily increasing attention. It is well documented that some trace elements can influence the morphology and speed of the crystallization process. Zinc has been found in significant amounts in calcium stones relative or organic stones (uric acid and cystine), probably substituting calcium in crystals because of their similarity in charge and size. High Zn levels are present in carbapatite of Randal's plaques suggesting that zinc could promote calcium phosphate deposition in the medullar interstitium. Large-scale epidemiological studies have found an association of increased dietary zinc intake with increased risk of nephrolithiasis in adults but not in adolescents. Most studies examining urinary zinc levels in adults have reported increased urinary Zn excretion in stone formers. In an experimental model of organic crystal formation produced by silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn excretion have shown to reduce crystal formation in the lumen of the Malpighian tubules. This is curious because this is not a model of calcium stone formation. Finally, zinc supplementation has been associated with increased admissions for urinary lithiasis in men, but no change in calcium stone formation in children. Perhaps, some of these contradicting findings can be explained in part by the in vitro effect of zinc on the type and amount of calcium phosphate formed: At low concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate, octacalcium phosphate, and apatite, and at higher concentrations, it promoted the formation of amorphous calcium phosphate. Thus, further studies are needed to see whether manipulation of Zn metabolism can inhibit calcium stone formation.
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Urolitíase/metabolismo , Zinco/metabolismo , Animais , Cristalização , Suplementos Nutricionais , Humanos , Urolitíase/epidemiologia , Urolitíase/etiologia , Zinco/urinaRESUMO
Hip fractures represent a serious health risk in the elderly, causing substantial morbidity and mortality. There is now a considerable volume of literature suggesting that chronic hyponatremia increases the adjusted odds ratio (OR) for both falls and fractures in the elderly. Hyponatremia appears to contribute to falls and fractures by two mechanisms. First, it produces mild cognitive impairment, resulting in unsteady gait and falls; this is probably due to the loss of glutamate (a neurotransmitter involved in gait function) as an osmolyte during brain adaptation to chronic hyponatremia. Second, hyponatremia directly contributes to osteoporosis and increased bone fragility by inducing increased bone resorption to mobilize sodium stores in bone. Low extracellular sodium directly stimulates osteoclastogenesis and bone resorptive activity through decreased cellular uptake of ascorbic acid and the induction of oxidative stress; these effects occur in a sodium level-dependent manner. Hyponatremic patients have elevated circulating arginine-vasopressin (AVP) levels, and AVP acting on two receptors expressed in osteoblasts and osteoclasts, Avpr1α and Avpr2, can increase bone resorption and decrease osteoblastogenesis. Should we be screening for low serum sodium in patients with osteoporosis or assessing bone mineral density (BMD) in patients with hyponatremia? The answers to these questions have not been established. Definitive answers will require randomized controlled studies that allocate elderly individuals with mild hyponatremia to receive either active treatment or no treatment for hyponatremia, to determine whether correction of hyponatremia prevents gait disturbances and changes in BMD, thereby reducing the risk of fractures. Until such studies are conducted, physicians caring for elderly patients must be aware of the association between hyponatremia and bone disorders. As serum sodium is a readily available, simple, and affordable biochemical measurement, clinicians should look for hyponatremia in elderly patients, especially in those receiving medications that can cause hyponatremia. Furthermore, elderly patients with an unsteady gait and/or confusion should be evaluated for the presence of mild hyponatremia, and if present, treatment should be initiated. Finally, elderly patients presenting with an orthopedic injury should have serum sodium checked and hyponatremia corrected, if present.
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Envelhecimento/metabolismo , Fraturas Ósseas , Hiponatremia , Osteoporose , Fraturas Ósseas/etiologia , Fraturas Ósseas/metabolismo , Humanos , Hiponatremia/complicações , Hiponatremia/metabolismo , Osteoporose/etiologia , Osteoporose/metabolismoRESUMO
BACKGROUND: Sevelamer has been associated with less progression of vascular calcifications. This effect could be due to a reduction in serum phosphate levels but also to other additive effects. Magnesium has been also shown to prevent vascular calcification but the effect of sevelamer on serum magnesium levels has not been thoroughly evaluated. Our aim was to analyze whether the use of sevelamer reduces the risk of hypomagnesemia in hemodialysis (HD)-requiring end-stage renal disease patients. METHODS: All prevalent patients from the dialysis unit of the Hospital Italiano de Buenos Aires as of 1 June 2015 were evaluated. They were on three times per week bicarbonate/citrate-buffered HD. They were not receiving phosphate binders or magnesium-containing drugs. The average of three successive monthly magnesium serum levels was considered as the baseline magnesium concentration. Sevelamer carbonate use was retrieved from the patient's clinical records. RESULTS: One hundred and fifty-one patients were included. A large proportion of individuals were on proton pump inhibitors (PPIs) (66%) and more than 50% were using sevelamer carbonate. Serum magnesium levels were significantly higher in those receiving sevelamer compared with those who did not (2.05 ± 0.3 versus 1.8 ± 0.4 mg/dL; P < 0.05). A larger proportion of individuals receiving sevelamer were among those with normal serum magnesium (P = 0.02), while among those with hypomagnesemia, a larger proportion were on PPIs. In the multivariate model including the use of PPIs, sevelamer carbonate resulted in an independent protective factor for hypomagnesemia (odds ratio: 0.44; 95% confidence interval: 0.21-0.87). CONCLUSIONS: Hemodialysis patients receiving sevelamer show higher serum magnesium levels and a reduced risk of hypomagnesemia. This effect remains even after adjustment for PPI use. This effect could contribute to the still controversial superiority of sevelamer in preventing vascular calcifications.
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BACKGROUND: Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. METHODS: We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. RESULTS: Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 ± 5 mmol/L in hyponatremic patients and 139 ± 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. CONCLUSION: Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking.
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Fraturas do Quadril/etiologia , Hiponatremia/complicações , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de RiscoRESUMO
Una pérdida de la mitad de la masa renal no necesariamente tendrá la mitad de la tasa de filtración glomerular (TFG), es decir, no hay una correlación exacta entre la reducción de masa renal y la pérdida de función renal. La (TFG) es un índice necesario para diagnóstico, seguimiento de pacientes con deterioro de la función renal, chequeos epidemiológicos, ajuste de dosis de drogas nefrotóxicas o de eliminación renal, estadificación de la enfermedad renal crónica, etc
Loss of half renal mass does not necessarily correspond to half of glomerular filtration rate (GFR), meaning that there is not an exact correlation between renal mass reduction and loss of renal function. The GFR is a necessary index for: diagnosis; follow-up of patients with renal injury; epidemiological controls; nephrotoxic drugs dose adjustment or renal elimination drugs; chronic renal disease stratification, etc
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Humanos , Taxa de Filtração Glomerular , Testes de Função RenalRESUMO
Una pérdida de la mitad de la masa renal no necesariamente tendrá la mitad de la TFG, es decir, no hay una correlación exacta entre la reducción de masa renal y la pérdida de función renal. La tasa de filtración glomerular (TFG) es un índice necesario para diagnóstico, seguimiento de pacientes con deterioro de la función renal, chequeos epidemiológicos, ajuste de dosis de drogas nefrotóxicas o de eliminación renal, estadificación de la enfermedad renal crónica, etc.En esta actualización se analiza brevemente los principales métodos utilizados con el fin de estimar el filtrado glomerular, algunas de sus fortalezas y debilidades. El empleo de la tasa de filtración glomerular estimada en estudios epidemiológicos ha contribuido a generar controversias de envergadura que más que resultar en un avance científico, han producido larguísimas discusiones como producto de sofismas y desvíos por estos cálculos.Debería replantearse el aplicar ecuaciones de estimación de la TFG en estudios de laboratorio en la población, dada la imperfección de las mismas y a las dificultades en la interpretación de los resultados para el médico clínico no especialista en la materia.
The loss of half the renal mass does not necessarily imply half the Glomerular Filtration Rate (GFR), meaning that there is not an exact correlation between renal mass reduction and renal function loss. GFR is a necessary index for diagnosis and to establish chronic renal disease stages, followup of renal failure patients, epidemiological studies, adjustment of nephrotoxic drugs or renal excretion drugs, among other uses.This update briefly analyzes the principal methods used in order to estimate glomerular filtration, some of its strengths and weaknesses.The use of estimated GFR in epidemiological studies has contributed to generate a wide scale of controversies that instead of contributing to scientific progress, have produced endless discussions because of misleading argumentations and deviations for these calculations.Equations applied for estimating GFR in population studies, should be reconsidered, given their imperfection and the difficulty for clinicians, who are not specialists on the subject, to interpret the results.
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Masculino , Feminino , Humanos , Taxa de Filtração GlomerularRESUMO
Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.
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Hipercalciúria/complicações , Cálculos Renais/etiologia , Doenças Metabólicas/complicações , Adulto , Argentina/epidemiologia , Feminino , Humanos , Hipercalciúria/epidemiologia , Hipercalciúria/urina , Cálculos Renais/epidemiologia , Cálculos Renais/urina , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/urina , Pessoa de Meia-IdadeRESUMO
Increased cardiovascular morbidity and mortality has been associated with the hyperphosphatemia seen in patients with end-stage chronic kidney disease (CKD). Oral phosphate binders are prescribed in these patients to prevent intestinal absorption of dietary phosphate and reduce serum phosphate. In prospective observational cohorts they have shown to decrease all-cause and cardiovascular mortality risk. Different problems have been associated with currently available phosphate binders as positive calcium balance and impaired outcomes with calcium-based phosphate binders or increased costs with non-calcium-based phosphate binders. Iron-based phosphate binders represent a new class of phosphate binders. Several iron-based phosphate binders have undergone testing in clinical trials. Ferric citrate (JTT-751) and sucroferric oxyhydroxide (PA21) are the two iron-based binders that have passed to the clinical field after being found safe and effective in decreasing serum phosphate. Iron from ferric citrate is partially absorbed compared to sucroferric oxyhydroxide. Ferric citrate usage could result in an important reduction in erythropoiesis-stimulating agent (ESA) and IV iron usage, resulting in significant cost savings. Sucroferric oxyhydroxide was effective in lowering serum phosphorus in dialysis patients with similar efficacy to sevelamer carbonate, but with lower pill burden, and better adherence. Ferric citrate may be more suited for the treatment of chronic hyperphosphatemia in CKD patients requiring iron supplements but its use may have been hampered by potential aluminum overload, as citrate facilitates its absorption; sucroferric oxyhydroxide may be more suited for hyperphosphatemic CKD patients not requiring iron supplementation, with low pill burden.
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Introducción: existen pocos datos acerca de la variación en el tiempo de los trastornos del metabolismo mineral y óseo (TMO) relacionado a la IRC en los pacientes prevalentes en diálisis crónica en Argentina. Material y métodos: Tomamos los datos del trienio 2011-2013 del Registro Argentino de Diálisis Crónica SAN-INCUCAI. Se analizaron la demografía, etiología de la IRC y las variables bioquímicas del metabolismo mineral y óseo de los pacientes prevalentes en DC, así como su tratamiento. Resultados: La población prevalente creció desde 26.572 pacientes en el año 2011 hasta 27.966 pacientes en el año 2013. Este aumento de la población prevalente fue debida, fundamentalmente, al crecimiento de los incidentes en DC. La edad promedio de esta población aumentó de 57,2 (±17,0) a 57,5 (±16,9) años entre 2011 y 2013. Aumentó la tasa de prevalentes de 65 o más años de ambos sexos entre 2011 y 2013, pero más en hombres. La nefropatía diabética se constituyó en la primera etiología con el 27,2%. En 2013, se logran valores adecuados de calcemia en el 54,5%, de fosfatemia en el 55% de los pacientes prevalentes en DC. Conclusiones: En el año 2013 el 25,5 % tuvo valores de iPTH entre 150 a 300 pg/ml, el 22,9 % 600 pg/ml. Los valores más bajos de iPTH se obsevan a mayor edad, en varones, en pacientes diabéticos y en los primeros años de DC (nuevos pacientes)...
Introduction: There are few data concerning variation over time of mineral and bone metabolism disorder (MBD) in prevalent chronic dialysis patients (CD) in Argentina. Methods: 3-years-period time 2011-2013 data from Argentine Registry of Chronic Dialysis was used. Demography, Chronic Renal failure etiology (CRF) and MBD biochemical variables in CD prevalent patients, were analyzed. Results: Prevalent population grew from 26572 to 27966 patients between 2011 and 2013, basically as a consequence of incidents growth. Age increased from 57.2 (± 17.0) to 57.5 (±16.9). In both sexs =65 years old rate increased, more in men. Diabetic Nephropathy is the first etiology (27.2%). Between 2011 and 2013 there is a significant decrease of PTHi (p=0.001) average values. In 2013, 25.5% showed between 150 to 300 pg/ml values, 22.9% 600 pg/ml values. The lowest PTHi values can be observed in elderly, males, diabetic pattiens and in the first years under CD treatment. Conclusions: Average PTHi, as well as patients with over 600 pg/ml percentage decreased, but the adequate range patients percentage (150-300) remained unchanged. Average PTHi decrease is due to the progressive increase of sub-populations less likely to develop hyperparathyroidism: elderlypeople, males, diabetics and new patients...
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Masculino , Feminino , Humanos , Distúrbios do Metabolismo do Cálcio , Registros de Doenças , Distúrbios do Metabolismo do Fósforo , Prevalência , Diálise Renal/estatística & dados numéricos , Diálise Renal/tendências , ArgentinaRESUMO
Association of dysregulated calcium homeostasis and granulomatous disease is well established. There exist reports in the literature of granulomatous reactions produced by silicones associated with hypercalcemia. In this case series we report four young women that underwent methacrylate injections in gluteus, thighs and calves that developed granulomas with posterior appearance of hypercalcemia. This complication presented as subacute around 6 months after the procedure. The four patients have as common elements the presence of moderate to severe renal insufficiency, suppressed PTH and elevated calcitriol levels for the degree of renal function. In the image studies, two patients presented in the nuclear magnetic resonance of the gluteus hypodense nodular images compatible with granulomas. Two patients had a positron emission tomography performed showing increased metabolic activity in the muscles of the gluteal region compatible with granulomas. Two patients had a partial surgical resection of the gluteal lesions with the finding of methacrylate associated to foreign body granulomas. In these patients hypercalcemia was treated with oral or local injections of corticoids, intravenous bisphosphonates or ketoconazole with good response. Although the prevalence of this complication with methacrylate injection is not common, hypercalcemia secondary to granulomas should be considered in the differential diagnosis of patients with hypercalcemia when there is a history of this procedure, and especially if they have a reduction in their renal function.
RESUMO
Los pacientes con enfermedad renal crónica (ERC) sometido a hemodiálisis de mantenimiento (HD) tienen un riesgo de mortalidad cardiovascular y general muy elevado. La uremia se ha asociado a inflamación sistémica. Esta inflamación ha sido relacionada con la mortalidad general y cardiovascular de estos pacientes. La elevación de la proteína C reactiva, uno de los marcadores de inflamación más comunes es predictiva de mortalidad cardiovascular en la población en diálisis. Otros marcadores de: inflamación predictivos de eventos adversos en diálisis son la interleukina -6 y el factor de necrosis tumoral alfa. Recientemente otro marcador de inflamación, la pentraxina 3 (PTX3) ha demostrado ser un predictor de mortalidad, y en pacientes en HD se ha relacionado con enfermedad cardiovascular y malnutrición calóricoproteica. Varios estudios han demostrado que contaminaciones con muy pequeñas cantidades de endotoxinas bacterianas producen una respuesta inflamatoria subclínica. En los pacientes en HD hay varias fuentes de endotoxemia, como fluidos, tejidos y cuerpos extraños. Los líquidos de diálisis están contaminados con bacterias Gram-negalivas y sustancias inductoras de citoquinas derivadas de estos microorganismos. La presencia de biofilms incrementa el riesgo de una contaminación continua de estos líquidos. La periodontitis severa está asociada a incrementos en las concentraciones séricas de hs-CRP y es frecuente en pacientes en HD y trasplantados. Las uremia per se puede ser una causa de translocación de endotoxina desde el intestino. Finalmente otras fuentes de infección oculta que pueden llevar a una respuesta inflamatoria subclínica son la presencia de catéteres para diálisis, las fístulas arteriovenosas no funcionantes y los injertos no funcionantes.(AU)
Patients with chronic renal failure on maintenance hemodialysis (HD) have a very high risk of total and cardiovascular mortality. Uremia is associated with systemic inflammation. This inflammation is related to the general and cardiovascular mortality of these patients. Elevation of C reactive protein (CRP), one of the most common inflammation rnarkers is predictive of cardiovascular rnortality in the dialysis population. Other inflammation markers that are predictive of adverse events in dialysis are interleukin -6 and Tumor necrosis factor alfa. Recently another inflammation marker, pentraxin 3 (PTX3) have shown to be a predictor of rnortality, and in HD patients it has been related to cardiovascular disease and calorie ûprotein malnutrition. Several studies have shown that contaminations very small quantities of bacterial endotoxins produce a subclinical inflammatory response. In patients on HD there are several] sources of endetoxin, as fluids, tissues and foreign bodies. Dialysis fluids are contaminated with Gram-negative bacteria and substances that can induce cytokine production derived from theses microorganisms. The presence of biofilms increases the risk of a continuous contamination of these fluids. Severe periodontitis is associated with increased serurn concentrations uf high sensitivity-CRP and this is frequent in patients in HD and transplanted patients. Uremia per se can be a cause of endotoxin translocation from the intestine. Finally other sources of occult infection that can lead to a subclinical inflammatory response are the presence of catheters for dialysis, nonfunctioning grafts or fistulas and non-Functioning kidney grafts.(AU)
Assuntos
Insuficiência Renal Crônica , Inflamação , Doenças Cardiovasculares/mortalidadeRESUMO
Los pacientes con enfermedad renal crónica (ERC) sometido a hemodiálisis de mantenimiento (HD) tienen un riesgo de mortalidad cardiovascular y general muy elevado. La uremia se ha asociado a inflamación sistémica. Esta inflamación ha sido relacionada con la mortalidad general y cardiovascular de estos pacientes. La elevación de la proteína C reactiva, uno de los marcadores de inflamación más comunes es predictiva de mortalidad cardiovascular en la población en diálisis. Otros marcadores de: inflamación predictivos de eventos adversos en diálisis son la interleukina -6 y el factor de necrosis tumoral alfa. Recientemente otro marcador de inflamación, la pentraxina 3 (PTX3) ha demostrado ser un predictor de mortalidad, y en pacientes en HD se ha relacionado con enfermedad cardiovascular y malnutrición calóricoproteica. Varios estudios han demostrado que contaminaciones con muy pequeñas cantidades de endotoxinas bacterianas producen una respuesta inflamatoria subclínica. En los pacientes en HD hay varias fuentes de endotoxemia, como fluidos, tejidos y cuerpos extraños. Los líquidos de diálisis están contaminados con bacterias Gram-negalivas y sustancias inductoras de citoquinas derivadas de estos microorganismos. La presencia de biofilms incrementa el riesgo de una contaminación continua de estos líquidos. La periodontitis severa está asociada a incrementos en las concentraciones séricas de hs-CRP y es frecuente en pacientes en HD y trasplantados. Las uremia per se puede ser una causa de translocación de endotoxina desde el intestino. Finalmente otras fuentes de infección oculta que pueden llevar a una respuesta inflamatoria subclínica son la presencia de catéteres para diálisis, las fístulas arteriovenosas no funcionantes y los injertos no funcionantes.
Patients with chronic renal failure on maintenance hemodialysis (HD) have a very high risk of total and cardiovascular mortality. Uremia is associated with systemic inflammation. This inflammation is related to the general and cardiovascular mortality of these patients. Elevation of C reactive protein (CRP), one of the most common inflammation rnarkers is predictive of cardiovascular rnortality in the dialysis population. Other inflammation markers that are predictive of adverse events in dialysis are interleukin -6 and Tumor necrosis factor alfa. Recently another inflammation marker, pentraxin 3 (PTX3) have shown to be a predictor of rnortality, and in HD patients it has been related to cardiovascular disease and calorie protein malnutrition. Several studies have shown that contaminations very small quantities of bacterial endotoxins produce a subclinical inflammatory response. In patients on HD there are several] sources of endetoxin, as fluids, tissues and foreign bodies. Dialysis fluids are contaminated with Gram-negative bacteria and substances that can induce cytokine production derived from theses microorganisms. The presence of biofilms increases the risk of a continuous contamination of these fluids. Severe periodontitis is associated with increased serurn concentrations uf high sensitivity-CRP and this is frequent in patients in HD and transplanted patients. Uremia per se can be a cause of endotoxin translocation from the intestine. Finally other sources of occult infection that can lead to a subclinical inflammatory response are the presence of catheters for dialysis, nonfunctioning grafts or fistulas and non-Functioning kidney grafts.