RESUMEN

CONTEXT: The optimal circulating concentration of 25(OH) vitamin D is controversial. OBJECTIVE: The aim was to investigate if FGF-23 and 24,25(OH)2D can guide cholecalciferol replacement. DESIGN: Oral cholecalciferol (10,000 IU weekly) administered to subjects with 25(OH)D levels < 20 ηg/mL and eGFR > 60 mL/min/1.73 m(2) (n = 25), chronic kidney disease (CKD) (n = 27), or end stage renal disease (ESRD) (n = 14). SETTING: The study was conducted at the Veterans Affairs clinics. MAIN OUTCOME MEASURE: Serum FGF-23, PTH, 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, calcium, and phosphorous concentrations, and urinary excretion of calcium and phosphorus at baseline and after 8 weeks of treatment. RESULTS: Cholecalciferol treatment increased concentrations of serum 25(OH)D by (19.3 ± 8 ηg/mL, P = .001; 12.2 ± 9 ηg/mL, P = .0001) and 24,25(OH)2D (1.14 ± 0.89 ηg/mL, P = .0024; 1.0 ± 0.72 ηg/mL P = .0002), and reduced serum PTH (-11 ± 21 pg/mL, P = .0292; -42 ± 68 pg/mL, P = .0494) in normal and CKD subjects, respectively. Cholecalciferol increased serum FGF-23 levels only in normal subjects (44 ± 57 ηg/mL, P = .01). Increments in serum 25(OH)D positively correlated with serum FGF-23 and 24,25(OH)2D and negatively correlated with PTH. In ESRD, cholecalciferol administration increased 25(OH)D by (16.6 ± 6.6 ηg/mL P ≤ .05) without changing 24,25(OH)2D, FGF-23 or PTH levels. CONCLUSION: Modest elevations of serum 25(OH)D levels after cholecalciferol treatment are sufficient to induce compensatory degradative pathways in patients with sufficient renal reserves, suggesting that optimal circulating 25(OH)D levels are approximately 20 ηg/mL. In addition, catabolism of 25(OH)D may also contribute to the low circulating vitamin D levels in CKD, since elevations of FGF-23 in CKD are associated with increased 24,25(OH)2D after cholecalciferol administration.

Asunto(s)

24,25-Dihidroxivitamina D 3/sangre , Colecalciferol/administración & dosificación , Monitoreo de Drogas/métodos , Factores de Crecimiento de Fibroblastos/sangre , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/análogos & derivados , 24,25-Dihidroxivitamina D 3/orina , Anciano , Colecalciferol/metabolismo , Factor-23 de Crecimiento de Fibroblastos , Humanos , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Análisis Multivariante , Hormona Paratiroidea/sangre , Estudios Prospectivos , Insuficiencia Renal Crónica/metabolismo , Vitamina D/sangre , Vitamina D/orina , Deficiencia de Vitamina D/sangre , Vitaminas/administración & dosificación , Vitaminas/metabolismo

RESUMEN

Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23-parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease.

Asunto(s)

Enfermedades Óseas Metabólicas/etiología , Trasplante de Riñón/efectos adversos , Minerales/metabolismo , Insuficiencia Renal Crónica/cirugía , Anciano , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/terapia , Femenino , Humanos

RESUMEN

BACKGROUND: 25-Hydroxyvitamin D [25(OH)D] is a marker of nutritional status; however, chronic kidney disease (CKD) results in alterations in vitamin D metabolism, including the loss of vitamin D-binding proteins and alterations in CYP27B1 and CYP24 enzymes that metabolize 25(OH)D. This study was designed to determine the predictors of responsiveness to correction of vitamin D deficiency with oral vitamin D2 (ergocalciferol) in adults. METHODS: A retrospective study of 183 veterans with 25(OH)D level <30 ng/mL, who were treated with 50,000 IU per week of vitamin D2, was performed. Logistic regression models were developed to determine the factors predicting the response to treatment, defined as either the change in serum 25(OH)D level/1000 IU of vitamin D2 or the number of vitamin D2 doses (50,000 IU per dose) administered. RESULTS: The mean age of the patients was 63 ± 12 years. About 87% were men and 51% diabetic, and 29% had an estimated glomerular filtration rate of <60 mL/min/1.73 m. The average number of vitamin D2 doses was 10.91 ± 5.95; the average increase in 25(OH)D level was 18 ± 10.80 ng/mL. 25(OH)D levels remained <30 ng/mL in 61 patients after treatment. A low estimated glomerular filtration rate and the presence of diabetes mellitus were significant independent predictors for inadequate response to vitamin D2 treatment in logistic regression models. Patients with CKD required greater amounts of vitamin D2 to achieve similar increases in 25(OH)D levels, versus non-CKD patients. CONCLUSIONS: The presence of CKD and diabetes mellitus is associated with resistance to correction of 25(OH)D deficiency with vitamin D2 therapy. The underlying mechanism needs to be evaluated in prospective studies.

Asunto(s)

Complicaciones de la Diabetes/tratamiento farmacológico , Ergocalciferoles/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Vitaminas/uso terapéutico , Anciano , Complicaciones de la Diabetes/complicaciones , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Progressive elevations of fibroblastic growth factor 23 (FGF23) in chronic kidney disease may reduce serum 25-hydroxyvitamin D (25(OH)) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) levels, via stimulation of 24-hydroxylase (Cyp24a1)-mediated catabolism of these vitamin D metabolites. To test this possibility, we measured serum concentrations of 24,25-dihydroxyvitamin D (24,25(OH)(2)D), a product of Cyp24a1 hydroxylation of 25(OH)D, in the Col4a3 knockout mouse, a model of Alport syndrome-derived chronic kidney disease, and in patients with chronic kidney disease of variable severity. There was an inverse correlation between serum FGF23 and both 25(OH)D and 1,25(OH)(2)D in the mouse model, but no significant relationship was observed in the cross-sectional patient cohort. The FGF23-dependent increase in Cyp24a1 mRNA expression in the mouse kidneys was consistent with the possibility that FGF23 induces vitamin D catabolism. There was, however, a reduction in serum 24,25(OH)(2)D levels, rather than the expected elevation, in both the mice and patients with chronic kidney disease. Low 25(OH)D and elevated FGF23 and parathyroid hormone levels were correlated with the reduced serum 24,25(OH)(2)D concentrations of these patients. Thus, we failed to find support for FGF23-mediated catabolism of vitamin D metabolites in chronic kidney disease assessed by 24,25(OH)(2)D levels.

Asunto(s)

Dihidroxicolecalciferoles/sangre , Factores de Crecimiento de Fibroblastos/sangre , Nefritis Hereditaria/sangre , Insuficiencia Renal Crónica/sangre , 25-Hidroxivitamina D3 1-alfa-Hidroxilasa/metabolismo , Anciano , Animales , Autoantígenos/genética , Biomarcadores/sangre , Distribución de Chi-Cuadrado , Colágeno Tipo IV/deficiencia , Colágeno Tipo IV/genética , Estudios Transversales , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Hidroxilación , Riñón/enzimología , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Nefritis Hereditaria/enzimología , Hormona Paratiroidea/sangre , ARN Mensajero/metabolismo , Insuficiencia Renal Crónica/enzimología , Índice de Severidad de la Enfermedad , Esteroide Hidroxilasas/genética , Esteroide Hidroxilasas/metabolismo , Regulación hacia Arriba , Vitamina D/análogos & derivados , Vitamina D/sangre , Vitamina D3 24-Hidroxilasa

RESUMEN

Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE), which is associated with significant morbidity and mortality. Renal involvement in SLE is heterogeneous; therefore, the treatment of LN is determined by the pathological type of LN and ranges from nonspecific measures such as maintenance of adequate blood pressure control and blockade of renin-angiotensin-aldosterone system to the use of immunosuppressive medications. Cyclophosphamide in combination with prednisone has been the standard of care for the treatment of proliferative forms of LN. However, the high rates of progression to end-stage renal disease coupled with adverse side effects from cyclophosphamide and prednisone administration have lead to an intensive search for more effective and less toxic therapies for LN. The authors review available treatment options for proliferative and membranous LN and summarize the results of recently published clinical trials that add new perspectives to the management of kidney disease in SLE.

Asunto(s)

Nefritis Lúpica/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Quimioterapia de Mantención , Inducción de Remisión

RESUMEN

This report describes a novel presentation of chloride resistant metabolic alkalosis in a patient with hypercalcemia related to Multiple Myeloma (MM). A 51-year-old male with newly diagnosed MM presented with widespread skeletal involvement, calcium (Ca(+2)) of 18 mg/dL, phosphorous (PO4) of 6 mg/dL, serum bicarbonate (HCO3) of 37 mEq/L, and serum creatinine (Cr) of 2.6 mg/dL Other causes of metabolic alkalosis such as vomiting, diuretics, alkali ingestion, mineralocorticoid excess and hypokalemia were excluded. Hypercalcemia and metabolic alkalosis were only partially corrected after rehydration, calcitonin and steroids. Subsequent treatment with zoledronic acid resulted in resolution of hypercalcemia and correction of metabolic alkalosis.The chloride resistant component of metabolic alkalosis was most likely related to extensive release of Ca(+2), carbonate and phosphate from bone by activated osteoclasts with inhibited osteoblastic activity. The additional reduction in glomerular filtration rate due to MM, contributed to a triad mimicking Calcium-Alkali syndrome.

Asunto(s)

Alcalosis/etiología , Hipercalcemia/etiología , Mieloma Múltiple/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Cloruro de Sodio/uso terapéutico , Insuficiencia del Tratamiento

RESUMEN

INTRODUCTION: Hypernatremia is a common problem in hospitalized patients and is associated with high morbidity and mortality. This study was designed to evaluate whether physicians follow the recommended guidelines for the rate of correction of hypernatremia of ≤0.5 mEq/L/hr and to evaluate the effect of the rate of correction of severe hypernatremia on the mortality of hospitalized patients. METHODS: A retrospective chart review of 131 consecutively hospitalized patients with severe hypernatremia (serum sodium ≥155 mEq/L) was performed. Primary outcomes were 30-day patient mortality and 72-hour hypernatremia correction. The first 24-hour serum sodium (Na(+)) correction rate was tested as a categorical variable; slow rate (<0.25 mEq/L/hr) and fast rate (≥0.25 mEq/L/hr). RESULTS: The mean admission serum Na level was 159 ± 3 mEq/L. Ninety percent of patients received the recommended <0.5 mEq/L/hr serum Na(+) correction rate; however, hypernatremia was corrected only in 27% of patients after 72 hours of treatment. Thirty-day patient mortality rate was 37%. In multivariable analysis, do not resuscitate status [hazards ratio (HR), 3.85; P < 0.0001], slower correction rate of hypernatremia (HR, 2.63; P = 0.02) and high heart rate (>100 beats/min; HR, 1.99; P = 0.03) were the independent predictors of 30-day mortality. CONCLUSION: In patients with severe hypernatremia, the rate of correction of hypernatremia was slow and resulted in inadequate correction in majority of the patients. Both slow rate of hypernatremia correction during the first 24 hours and do not resuscitate status were found to be significant predictors of 30-day patient mortality.

Asunto(s)

Fluidoterapia , Mortalidad Hospitalaria , Hipernatremia/mortalidad , Hipernatremia/terapia , Índice de Severidad de la Enfermedad , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Adhesión a Directriz , Humanos , Hipernatremia/sangre , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Sodio/sangre , Factores de Tiempo , Resultado del Tratamiento

RESUMEN

Severe lactic acidosis has been reported in patients struggling against restraints, especially in association with the use of stimulant drugs, such as cocaine. Profound acidosis occurring under these conditions can lead to cardiac arrhythmias, autonomic instability and cardiac arrest, a syndrome known as restraint associated asphyxia. Early recognition of this condition and removing the stimulus for lactic acid production (excessive muscle activity) by aggressive sedation and ventilatory assistance, coupled with fluid administration to improve tissue perfusion and lactate metabolism, can be life-saving. The current report describes a case of restraint associated severe lactic acidosis in a cocaine intoxicated patient that was successfully treated by sedation, muscular paralysis and mechanical ventilation. Public safety personnel must be aware of this potentially life threatening complication. Avoiding hobble and prone restraint positions may eliminate some of the problems that contribute to the pathophysiology of this condition.

Asunto(s)

Acidosis Láctica/etiología , Trastornos Relacionados con Cocaína/complicaciones , Restricción Física , Acidosis Láctica/terapia , Humanos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Posición Prona , Respiración Artificial , Factores de Riesgo , Adulto Joven

RESUMEN

INTRODUCTION: Although membranoproliferative glomerulonephritis has been reported to occur in association with non-Hodgkin's lymphoma, information concerning the long term effects of treatment of non-Hodgkin's lymphoma on the associated membranoproliferative glomerulonephritis is limited. CASE PRESENTATION: The current report describes a patient who presented with the abrupt onset of hypertension, mixed nephritic/nephrotic syndrome and acute renal failure. Kidney biopsy was consistent with membranoproliferative glomerulonephritis, type 1. Bone marrow biopsy performed in the evaluation of periaortic lymphadenopathy, hepatosplenomegaly, and thrombocytopenia confirmed the diagnosis of low grade B-cell non-Hodgkin's lymphoma. The patient's renal function improved and proteinuria resolved after initial treatment of non-Hodgkin's lymphoma with chemotherapy. During eleven years of follow up, membranoproliferative glomerulonephritis has remained in remission, as confirmed by repeatedly negative urinalyses, normal blood pressure and absence of clinical signs and symptoms suggestive of nephritic/nephrotic syndrome. CONCLUSION: Membranoproliferative glomerulonephritis has been known to be associated with both chronic lymphocytic leukemia and non-Hodgkin's lymphoma, particularly with B cell lymphocytic type non-Hodgkin's lymphoma. There is limited information available concerning the effects of treatment of non-Hodgkin's lymphoma on the progression of non-Hodgkin's lymphoma associated membranoproliferative glomerulonephritis. In the few reported cases we found, long term follow up after initial resolution of the membranoproliferative glomerulonephritis was lacking. This report presented a rare case of non-Hodgkin's lymphoma associated membranoproliferative glomerulonephritis, that continued to be in remission during eleven years of follow up after initial chemotherapy treatment of lymphoma.