Bone Disease in Chronic Kidney Disease and Kidney Transplant.

Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) comprises alterations in calcium, phosphorus, parathyroid hormone (PTH), Vitamin D, and fibroblast growth factor-23 (FGF-23) metabolism, abnormalities in bone turnover, mineralization, volume, linear growth or strength, and vascular calcification leading to an increase in bone fractures and vascular disease, which ultimately result in high morbidity and mortality. The bone component of CKD-MBD, referred to as renal osteodystrophy, starts early during the course of CKD as a result of the effects of progressive reduction in kidney function which modify the tight interaction between mineral, hormonal, and other biochemical mediators of cell function that ultimately lead to bone disease. In addition, other factors, such as osteoporosis not apparently dependent on the typical pathophysiologic abnormalities resulting from altered kidney function, may accompany the different varieties of renal osteodystrophy leading to an increment in the risk of bone fracture. After kidney transplantation, these bone alterations and others directly associated or not with changes in kidney function may persist, progress or transform into a different entity due to new pathogenetic mechanisms. With time, these alterations may improve or worsen depending to a large extent on the restoration of kidney function and correction of the metabolic abnormalities developed during the course of CKD. In this paper, we review the bone lesions that occur during both CKD progression and after kidney transplant and analyze the factors involved in their pathogenesis as a means to raise awareness of their complexity and interrelationship.

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis.

BACKGROUND: The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial. STUDY DESIGN: Cross-sectional retrospective diagnostic test study. SETTING & PARTICIPANTS: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20 °C) serum. INDEX TESTS: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). REFERENCE TEST: Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/BS]) and receiver operating characteristic curves for discriminating diagnostic ability. RESULTS: The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but < 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was <103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was <33.1 U/L, and for high from nonhigh BFR/BS, 42.1U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively. LIMITATIONS: Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries. CONCLUSIONS: The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions.

Bone disease after renal transplantation.

It has been well established that a rapid decrease in bone mineral density (BMD) occurs in the first 6 to 12 mo after a successful renal transplantation and persists, albeit at a lower rate, for many years. This rapid BMD loss significantly increases the fracture risk of these patients to levels that are even higher than those of patients who have chronic kidney disease stage 5 and are on dialysis. The presence of low BMD in renal transplant patients as a predictor of risk fracture is controversial. Indeed, as has been suggested also for patients with postmenopausal osteoporosis, there is not a compelling correlation between the decline in BMD and skeletal fractures. However, bone disease after renal transplantation probably represents a unique bone disorder that must encompass underlying renal osteodystrophy. In fact, this syndrome results from multiple factors that include pretransplantation bone status, use of glucocorticoids and other immunosuppressive drugs, hypophosphatemia, and alterations of the calcium-vitamin D axis. Recent studies have demonstrated decreased osteoblast number, reduced bone formation rate, delayed mineralization, and increased osteoblast and osteocyte apoptosis. Bisphosphonates and vitamin D metabolites may be valuable in preventing or diminishing early bone loss. However, clinicians should be careful with the use of bisphosphonates and oversuppression of bone, especially in patients with low bone turnover. New prospective, controlled trials are required to confirm the real efficacy of these drugs, particularly in long-term renal transplant patients.

Bone remodeling after renal transplantation.

Several studies have indicated that bone alterations after transplantation are heterogeneous. Short-term studies after transplantation have shown that many patients exhibit a pattern consistent with adynamic bone disease. In contrast, patients with long-term renal transplantation show a more heterogeneous picture. Thus, while adynamic bone disease has also been described in these patients, most studies show decreased bone formation and prolonged mineralization lag-time faced with persisting bone resorption, and even clear evidence of generalized or focal osteomalacia in many patients. Thus, the main alterations in bone remodeling are a decrease in bone formation and mineralization up against persistent bone resorption, suggesting defective osteoblast function, decreased osteoblastogenesis, or increased osteoblast death rates. Indeed, recent studies from our laboratory have demonstrated that there is an early decrease in osteoblast number and surfaces, as well as in reduced bone formation rate and delayed mineralization after transplantation. These alterations are associated with an early increase in osteoblast apoptosis that correlates with low levels of serum phosphorus. These changes were more frequently observed in patients with low turnover bone disease. In contrast, PTH seemed to preserve osteoblast survival. The mechanisms of hypophosphatemia in these patients appear to be independent of PTH, suggesting that other phosphaturic factors may play a role. However, further studies are needed to determine the nature of a phosphaturic factor and its relationship to the alterations of bone remodeling after transplantation.

The pathogenesis of osteodystrophy after renal transplantation as detected by early alterations in bone remodeling.

BACKGROUND: Loss of bone mass after transplantation begins in the early periods after transplantations and may persist for several years, even in patients with normal renal function. While the pathogenesis of these abnormalities is still unclear, several studies suggest that preexisting bone disease, glucocorticoid therapy, and alterations in phosphate metabolism may play important roles. Recent studies indicate that osteoblast apoptosis and impaired osteoblastogenesis play important roles in the pathogenesis of glucocorticoid-induced osteoporosis. OBJECTIVES: To examine the early alterations in osteoblast number and surfaces during the period following renal transplantation. METHODS: Twenty patients with a mean age of 36.5 +/- 12 years were subjected to bone biopsy 22 to 160 days after renal transplantation. In 12 patients, a control biopsy was performed on the day of transplantation. Bone sections were evaluated by histomorphometric analysis and cell DNA fragmentation by the methods of terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL), using immunoperoxidase and direct immunofluorescence techniques. RESULTS: The main alterations in posttransplant biopsies were a decrease in osteoid and osteoblast surfaces, adjusted bone formation rate, and prolonged mineralization lag time. Peritrabecular fibrosis was markedly decreased. None of the pretransplant biopsies revealed osteoblast apoptosis. In contrast, TUNEL-positive cells in the proximity of osteoid seams or in the medullary space were observed in nine posttransplant biopsies of which four had mixed bone disease, two had adynamic bone disease, one had osteomalacia, one had osteitis fibrosa, and one had mild hyperparathyroid bone disease. Osteoblast number in posttransplant biopsies with apoptosis was lower as compared with posttransplant biopsies without apoptosis. In addition, most of them showed a marked shift toward quiescence from the cuboidal morphology of active osteoblasts. Serum phosphorus levels were lower in patients showing osteoblast apoptosis and correlated positively with osteoblast number and negatively with the number of apoptotic osteoblasts. In addition, posttransplant osteoblast surface correlated positively with parathyroid hormone (PTH) levels and negatively with glucocorticoid cumulative dose. CONCLUSION: The data suggest that impaired osteoblastogenesis and early osteoblast apoptosis may play important roles in the pathogenesis of posttransplant osteoporosis. The possible mechanisms involved in the pathogenesis of theses alterations include posttransplant hypophosphatemia, the use of glucocorticoids, and the preexisting bone disease. PTH seems to have a protective effect by preserving osteoblast survival.

Pénfigo foliaceo var. brasilera (fuego salvaje) con glomerulonefritis focal y segmentaria: presentación de un caso / Penphigus foliaceus var. brazil. (fogo selvagem) with focal and segmentary glomerulonefritis: report of a case

El pénfigo es un enfermedad auto-inmune intraepidérmica que compromete piel y mucosas. Su etiopatogenia está relacionada con la producción de anticuerpos IgG dirigidos contra un antígeno en la epidermis (4). El pénfigo var brazilera ocurre en forma endémica en Brasil (7). Afecta en mayor proporción al sexo femenino y los casos infantiles reportados están entre los 5 y 12 años (4). Describimos el caso de una indígena de 11 años, procedente del Territorio Federal Amazonas, quie ingresa con lesiones eritemato-costrosas-pábulo-vesiculosas, hiperqueratosis, pigmentación y olor desagradable con toque del estado general. Por clínica, histopatología e Inmunoflorescencia de piel se diagnostica pénfigo foliáceo. Concomitantemente microhematuria persistente con proteinuria. Se realiza biópsia renal que reportan como Glomerulonefritis focal y segmentaria. Tratamiento: hidroterapia, cremas saliciladas y esteroideas y prednisona por vía oral con respuestas favorable. Egresa con corticoterapia

Síndrome netrófico secundario a amiloidosis en un niño de 11 años / Nephrotic syndrome secondary to any amyloidosis in a 11 year old bay

Presentamos el caso de un niño de 11 años de edad, que ingresa en Noviembre de 1981 al Servicio de Pediatría del Hospital, con edema generalizado y fiebre. Tenía como antecendete importante accidente automovilístico cinco años antes que dejó como secuela paraplejía con un nivel sensitivo de D5 y dos años antes de su ingreso amputación de miembro inferior derecho por osteomielitis. El examen físico de ingreso demostró como datos positivos: Edema generalizado, normotensión, escaras sacras múltiples infectadas secundariamente, vejiga neurogénica. Funcionalismo renal normal, hipalbuminemia, proteinuria en rango nefrótico, urocultivo positivo para E. Coli y Pseudomonas ae. La biopsia renal y rectal fueron positivas para miloidosis. Seis meses más tarde el paciente desarrolla insuficiencia renal, falleciendo en uremia seis meses después. El presente caso ilustra la asociación de amiloide generalizada como probable complicación de pareplejía en infecciones crónicas en un niño. Este tipo de relación aunque relativamente frecuente en adutlos es sumamente rara en edad pediátrica

Antagonista-agonista de opiáceo após morfina peridural / Opiate antagonist-agonist after peridural morphine

Utilizamos antagonista agonista do opiáceo, nalorfina 10 30/microng. kg-1, no tratamento do prurido, náuseas e vômitos e retençäo urinária, quando se tornaram insuportáveis, após 2 mg de morfina peridural pós-operatória, havendo melhora dos sintomas, näo ocorrendo regressäo da analgesia espinhal