Sustainable Development Goals relevant to kidney health: an update on progress.

Globally, more than 5 million people die annually from lack of access to critical treatments for kidney disease - by 2040, chronic kidney disease is projected to be the fifth leading cause of death worldwide. Kidney diseases are particularly challenging to tackle because they are pathologically diverse and are often asymptomatic. As such, kidney disease is often diagnosed late, and the global burden of kidney disease continues to be underappreciated. When kidney disease is not detected and treated early, patient care requires specialized resources that drive up cost, place many people at risk of catastrophic health expenditure and pose high opportunity costs for health systems. Prevention of kidney disease is highly cost-effective but requires a multisectoral holistic approach. Each Sustainable Development Goal (SDG) has the potential to impact kidney disease risk or improve early diagnosis and treatment, and thus reduce the need for high-cost care. All countries have agreed to strive to achieve the SDGs, but progress is disjointed and uneven among and within countries. The six SDG Transformations framework can be used to examine SDGs with relevance to kidney health that require attention and reveal inter-linkages among the SDGs that should accelerate progress.

Determinant factors for chronic kidney disease after partial nephrectomy.

The objective of this review is to evaluate the factors that determine the development or deterioration of Chronic Kidney Disease (CKD) after partial nephrectomy (PN). When current literature is reviewed, it is found that factors that influence renal function after partial nephrectomy, are multifactorial. Those are divided into pre-surgical factors, such as hypertension, diabetes mellitus, urolithiasis, obesity, metabolic syndrome among others; intra-surgical factors, like the surgical technique used, the remaining healthy tissue, the experience of the surgeon, the time and type of ischemia among others. Lastly, post-surgical factors, also impose some influence on the post-surgical renal performance. It was also found that minimally invasive surgery, in addition to its known advantages, seems to offer a greater field of action in the future that will allow more nephrons preservation in any future surgical scenario. Finally, the current trend is to perform PN on all patients, in whom surgery is technically feasible regardless of the approach used, without risking oncological outcomes, patient safety, and without being exposed to any additional complications.

The First Report of The Latin American Society of Nephrology and Hypertension (SLANH) Anemia Committee in Chronic Hemodialysis Patients

Background: Anemia almost invariably occurs in patients with chronic kidney disease. Limited data are available regarding anemia management in Latin American (LA) hemodialysis (HD) patients. Objective: To evaluate the results of the first anemia survey of the Anemia Committee of the SLANH. Methods: This is a multinational, voluntary survey that collected anemia management data from adult HD patients from independent, non-chain owned HD units, between 09/2009 and 03/2010. T-test, ANOVA, chi-square test and multivariate logistic regression were used for statistical analysis. Results: The survey received responses from 134 HD units of 16 countries providing data from 9,025 patients. Mean values of Hb, ferritin, and transferrin saturation (TSAT) were 10.5±1.8g/dL, 570±539μg/l, and 29.8±15%, respectively. Only 32.7% of patients were within the Hb target of 10.5-12.0g/dL (46.3% were below and 21.1% above). Erythropoietin-stimulating agents (ESAs) were administered to 84.3% patients and 68.3% received intravenous iron (IV). Iron deficiency (TSAT≤20%) was present in 27.5% patients and among those receiving erythropoietin, 47% did not achieve Hb target. The independent variables associated with the lowest Hb level (<10.5g/dL) were: female gender, TSAT<25% and age<50 years. Conclusions: According to these results, nearly half of LA chronic HD patients did not achieve the recommended Hb target despite wide use of ESAs and IV iron (AU)

Antecedentes: La anemia representa una complicación frecuente en pacientes con enfermedad renal crónica. En Latinoamérica (LA) la prevalencia y características de la anemia en pacientes en hemodiálisis (HD) no ha sido bien estudiada. Objetivo: Evaluar los resultados del primer registro de anemia del Comité de Anemia de la Sociedad Latinoamericana de Nefrología e Hipertensión. Métodos: Esta es una encuesta multinacional, voluntaria, que recolectó datos sobre el tratamiento de la anemia en pacientes en HD de unidades independientes en LA entre septiembre de 2009 y marzo de 2010. Para el análisis estadístico se utilizaron los siguientes métodos: t-test, ANOVA, χ2 y el análisis de regresión logística multivariante. Resultados: La encuesta fue respondida por 134 unidades de HD de 16 países, recibiéndose datos de 9025 pacientes. Las medias ± desviación estándar de Hb, ferritina y del índice de saturación de transferrina (IST) fueron respectivamente: 10,5 ± 1,8 g/dl, 570 ± 539 μg/l y 29,8 % ± 15. Se administró agentes estimulantes de la eritropoyesis (AEE) al 84,3 % de los pacientes y hierro intravenoso (FeIV) al 68,3 %. Solamente el 32,7 % de los pacientes tuvieron una Hb blanco de 10,5-12,0 g/dl. En pacientes con Hb < 10,5 g/dl, el 85,2 % estaban recibiendo AEE y un 68 % FeIV. Las variables independientes asociadas con nivel Hb < 10,5 g/dl fueron: género femenino, IST < 25 % y edad < 50 años. En la muestra de pacientes analizada, a pesar del amplio uso de los AEE y FeIV, casi la mitad de los pacientes no alcanzó la Hb blanco (AU)

The first report of The Latin American Society of Nephrology and Hypertension (SLANH) Anemia Committee in chronic hemodialysis patients.

BACKGROUND: Anemia almost invariably occurs in patients with chronic kidney disease. Limited data are available regarding anemia management in Latin American (LA) hemodialysis (HD) patients. OBJECTIVE: To evaluate the results of the first anemia survey of the Anemia Committee of the SLANH. METHODS: This is a multinational, voluntary survey that collected anemia management data from adult HD patients from independent, non-chain owned HD units, between 09/2009 and 03/2010. T-test, ANOVA, chi-square test and multivariate logistic regression were used for statistical analysis. RESULTS: The survey received responses from 134 HD units of 16 countries providing data from 9,025 patients. Mean values of Hb, ferritin, and transferrin saturation (TSAT) were 10.5 ± 1.8 g/dL, 570 ± 539 µg/l, and 29.8 ± 15%, respectively. Only 32.7% of patients were within the Hb target of 10.5-12.0 g/dL (46.3% were below and 21.1% above). Erythropoietin-stimulating agents (ESAs) were administered to 84.3% patients and 68.3% received intravenous iron (IV). Iron deficiency (TSAT≤20%) was present in 27.5% patients and among those receiving erythropoietin, 47% did not achieve Hb target. The independent variables associated with the lowest Hb level (<10.5 g/dL) were: female gender, TSAT<25% and age<50 years. CONCLUSIONS: According to these results, nearly half of LA chronic HD patients did not achieve the recommended Hb target despite wide use of ESAs and IV iron.

Clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of mineral and bone disorders in chronic kidney disease (CKD-MBD) in adults.

The clinical practice guidelines for the prevention, diagnosis, evaluation and treatment of chronic kidney disease mineral and bone disorders (CKD-BMD) in adults, of the Latin American Society of Nephrology and Hypertension (SLANH) comprise a set of recommendations developed to support the doctor in the management of these abnormalities in adult patients with stages 3-5 kidney disease. This excludes changes associated with renal transplantation. The topics covered in the guidelines are divided into four chapters: 1) Evaluation of biochemical changes, 2) Evaluation of bone changes, 3) Evaluation of vascular calcifications, and 4) Treatment of CKD-MBD. The guidelines are based on the recommendations proposed and published by the Kidney Disease: Improving Global Outcomes (KDIGO) for the prevention, diagnosis, evaluation and treatment of CKD-MBD (KDIGO Clinical practice guidelines for the diagnosis, evaluation, prevention and treatment of Chronic Kidney Disease Mineral and Bone Disorder [CKD-MBD]), adapted to the conditions of patients, institutions and resources available in Latin America, with the support of KDIGO. In some cases, the guidelines correspond to management recommendations directly defined by the working group for their implementation in our region, based on the evidence available in the literature. Each chapter contains guidelines and their rationale, supported by numerous updated references. Unfortunately, there are few controlled studies with statistically sufficient weight in Latin America to support specific recommendations for the region, and as such, most of the references used correspond to studies carried out in other regions. This highlights the need to plan research studies designed to establish the current status of mineral and bone metabolism disorders in Latin America as well as defining the best treatment options for our population.

Latin American Dialysis and Transplant Registry: 2008 prevalence and incidence of end-stage renal disease and correlation with socioeconomic indexes.

In 2008, 563,294,000 people were living in Latin America (LA), of which 6.6% were older than 65. The region is going through a fast demographic and epidemiologic transition process, in the context of an improvement in socio-economic indices. The Latin American Dialysis and Renal Transplant Registry has collected data since 1991, through an annual survey completed by 20 affiliated National Societies. Renal replacement treatment (RRT) prevalence and incidence showed an increase year by year. The prevalence rate (in all modalities) correlated with the World Bank country classification by income and the epidemiologic transition stage the countries were experiencing. RRT prevalence and kidney transplantation rates correlated significantly with gross national income (GNI), health expenditure in constant dollars (HeExp), % older than 65, life expectancy at birth, and % of the population living in urban settings. Kidney transplantation increased also, year by year, with more than 50% of transplants performed using kidneys from deceased donors. Double transplants were performed in six countries. RRT prevalence and incidence increased in LA, and are associated with indexes reflecting higher and more evenly distributed national wealth (GNI and HeExp), and the stage of demographic and epidemiological transition.

Apoptotic stress pathway activation mediated by iron on endothelial cells in vitro.

BACKGROUND: Iron sucrose (Fe-S) and low-molecular-weight iron dextran (Fe-D) have been used successfully in the treatment of anaemia in chronic kidney disease patients. However, some side effects, such as endothelial cell dysfunction have been reported. Mechanisms by which iron can induce endothelial cell damage have not been completely understood. This study was designed to examine the effect of Fe-S and Fe-D on bovine aortic endothelial cells in vitro. METHODS: Cell proliferation was determined by [3H] thymidine incorporation, cytotoxicity by lactate dehydrogenase, pro-Caspase-3 by immunoblotting; and Caspase-3 activity using a colorimetric assay. Expression of the apoptosis stress pathway proteins Bcl-2 and Bax and cycle arrest proteins p53 and p21WAF/CIP1 were examined by immunoblot. Cell apoptosis was tested by terminal deoxynucleotidyltransferase-mediated nick-end labelling (TUNEL) and DNA fragmentation. RESULTS: Both iron preparations inhibited cell proliferation. This effect was more important and occurred at lower concentrations in Fe-S than Fe-D cultured cells. Expression of p53 and p21WAF/CIP1 increased in cells incubated with Fe-S, but not with Fe-D. Bcl-2 expression was significantly down-regulated in cells incubated with Fe-S in comparison with Fe-D, while Bax expression was not modified by the iron compounds. Pro-Caspase-3 expression and Caspase-3 activity increased only in cells treated with Fe-S. Apoptosis was present in cells treated with Fe-S. CONCLUSIONS: Our results demonstrate that Fe-S exerts a greater inhibitory effect on endothelial cell proliferation than Fe-D. The mechanisms involved in this process may be related, at least in part, to over expression of proteins related to the cell cycle arrest and apoptosis stress pathway.

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.

Access to and coverage of renal replacement therapy in minorities and ethnic groups in Venezuela.

Access to and coverage of renal replacement therapy in minorities and ethnic groups in Venezuela. Numerous studies have documented the presence of racial and minority disparities regarding the impact of renal disease and access to renal replacement therapy (RRT). This problem is less well documented in Latin America. Venezuela, like most countries in the region, is subject to severe constraints in the allocation of resources for high-cost chronic diseases, which limits the access of patients with chronic kidney disease to RRT. Although access to health care is universal, there is both a deficit in coverage and disparity in the access to RRT, largely as a result of socioeconomic limitations and budget constrains. With current rising trends of the incidence of end-stage renal disease (ESRD) and costs of medical technology, the long-term goal of complete RRT coverage will become increasingly out of reach. Current evidence suggests that prevention of progression of renal disease is possible at relatively low cost and broad coverage. Based on this evidence, the Ministry of Health has redesigned its policy with respect to renal disease based on 4 elements: 1. Prevention by means of early detection and referral to multidisciplinary health teams, as well as promotion of health habits in the community. 2. Prevention of progression of renal disease by pharmacologic and nonpharmacologic means. 3. An increase in the rate of coverage and reduction of disparities in the access to dialysis. 4. An increase in the rates of renal transplantation through better organ procurement programs and reinforcement of transplant centers. However, the projected increase in the number of patients with ESKD receiving RRT will represent a serious burden to the health care system. Therefore, implementation of these policies will require the involvement of international agencies as well as an adequate partnership between nephrologists and health care planners, so that meeting the increasing demands of ESKD programs may be balanced with other priorities of our national health system.

Selective estrogen receptor modulators in chronic renal failure.

BACKGROUND: In addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. Hormone replacement therapy (HRT) could have beneficial effects as well as potentially serious risks, especially in uremic women, due to the pharmacokinetics of estradiol in renal failure. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone and serum lipid levels, without its adverse effects on the breast and endometrium, in nonuremic women. METHODS: Recent data on the effect of the SERM raloxifene in bone and lipid metabolism in osteoporotic postmenopausal women on dialysis is reviewed. Since the estrogen receptor (ER) gene has been suggested as a candidate marker for osteoporosis, we investigated whether ER polymorphism could have predicted the BMD response to raloxifene. RESULTS: Hemodialyzed women on raloxifene demonstrated increased trabecular bone mineral density (BMD) and decreased bone resorption markers. Similarly, LDL-cholesterol values dropped significantly. ER gene polymorphism analysis of baseline BMD parameters did not differ between PP/xx or Pp/Xx groups. Nevertheless, patients on raloxifene with PP/xx genotypes, but not those with Pp/Xx, showed a higher trabecular BMD after one year on treatment, suggesting that homozygous women for P or x alleles of the ER have a better BMD response to raloxifene. CONCLUSION: Raloxifene and, most likely, other SERMs, could represent a good alternative to HRT in postmenopausal uremic women.

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.

Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis.

BACKGROUND: Premature amenorrhea and hypoestrogenism and lack of hormone replacement therapy after menopause have been frequently reported in uremic women on dialysis. Therefore, in addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. In addition, these patients are at higher risk for hyperlipidemia, arteriosclerosis, and subsequent coronary heart disease and stroke. Recent evidence has suggested that hormone replacement therapy (HRT) in postmenopausal women could have several beneficial effects as well as potentially serious risks. Great efforts have been made to identify therapeutic alternatives that would have the benefits of estrogen on brain and bone without its adverse effects on breast and endometrium. In the present study, we evaluated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. METHODS: We performed a prospective, blind, placebo-controlled, and randomized study. Fifty postmenopausal women on chronic hemodialysis with proven severe osteopenia or osteoporosis by bone densitometry were selected. After a written informed consent, patients were randomized into two groups: 25 women on placebo and 25 women on the study drug, raloxifene hydrochloride, at a dose of 60 mg/day. In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks). BMD was reassessed after 1 year of therapy. Bone resorption markers were determined every 3 months for 1 year. RESULTS: After 1 year on raloxifene therapy, lumbar spine BMD (trabecular bone) significantly improved, whereas femoral neck BMD (cortical bone) did not change significantly. No changes in BMD were observed at trabecular or cortical sites in the placebo group. Serum pyridinoline levels showed a significant decrease after 6 months on raloxifene that persisted thereafter. Low-density lipoprotein (LDL)-cholesterol decreased significantly in the raloxifene group with no changes in serum triglycerides, total cholesterol, or HDL cholesterol. No significant side effects were observed in the raloxifene group. CONCLUSION: The study demonstrates that after one year on raloxifene, postmenopausal women on hemodialysis have a significant increase in trabecular BMD, decrease in bone resorption markers and LDL-cholesterol values, suggesting that SERMs could constitute a therapeutic alternative to improve bone metabolism and control of hyperlipidemia in these patients. The possible long-term effects of raloxifene remain to be determined.

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.

Insuficiencia renal aguda secundaria a rabdomiolisis no traumática: presentación de dos casos / Acute renal failure secondary a rhabdomyolysis non-traumatic: presentation of two cases

La rabdomiolisis además de complicar muchas enfermedades críticas, puede requerir manejo intensivo debido a su frecuente asociación a complicaciones que amenazan la vida. La insuficiencia renal aguda (IRA) es una complicación frecuente de rabdomiolisis y puede presentarse después de daño muscular de origen traumático o no traumático y es una complicación frecuente del uso de cocaína. Nosotros presentamos dos casos de rabdomiolisis no traumática con IRA, uno de ellos secundaria a la ingestión compulsiva de alcohol y cocaína dentro de las 12 horas antes de su admisión a la UCI, el otro fue presumiblemente secundaria a una infección viral tipo influenza. Ambos casos sobrevivieron y requirieron diálisis

Papel del hueso en la fisiopatologia de la hipercalciuria idiopatica: efecto del aminobisfosfonato alendronato / Role of the bone in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate

Estudios previos de nuestro laboratorio han demonstrado una disminución del contenido mineral del hueso y una correlación entre la disminución del contenido mineral y la producción de distintas citoquinas que intervienen en el proceso de resorción ósea. Al mismo tiempo, observamos que el tratamiento a corto plazo con alendronato produce una disminución del calcio urinario en pacientes con hipercalciuria idiopática. En el presente estudio analizamos los efectos del alendronato a largo plazo (10 mg/día por un año) sobre el calcio y la hidroxiprolina urinaria y el contenido mineral óseo en 18 hipercalciúricos y 8 normocalciúricos con litiasis urinaria. Las características clínicas, así como la distribución por edades y sexo fue similar en ambos grupos. En calcio urinario disminuyó significativamente al final del primer mes y continuó bajo posteriormente (277 + 28, antes vs. 202 + 26 mg/g creatinina, después de 12 meses con alendronato, p<0.01). La hidroxiprolina urinaria disminuyó significativamente durante el estudio (125,5 + 32.1 vs. 39.66 + 17.5 mg/g creatinina, p<0.05). El calcio sérico, la filtración glomerular y el sodio urinario no se modificaron durante el estudio. La densidad mineral ósea en columna lumbar, determinada por densitometría por rayos X, se incremento significativamente el primer año de 1.162 + 0.231 a 1.197 + 0.248 g/cm2 (p<0.01). No se observaron cambios en la densidad mineral del cuello de fémur. Estos cambios se asociaron a una disminución en la transcripción del mRNA para IL-1 alpha, determinados por la reacción en cadena de polimerase (PCR), en células mononucleares no estimuladas. Los sujetos normocalciúricos no demostraron cambios significativos en la excreción urinaria de calcio. En resumen, los cambios observados en el calcio urinario y otros parámetros metabólicos óseos sugieren un papel importante del hueso en la fisiopatología de la hipercalciuria idiopática.

Papel del hueso en la fisiopatologia de la hipercalciuria idiopatica: efecto del aminobisfosfonato alendronato / Role of the bone in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate

Estudios previos de nuestro laboratorio han demonstrado una disminución del contenido mineral del hueso y una correlación entre la disminución del contenido mineral y la producción de distintas citoquinas que intervienen en el proceso de resorción ósea. Al mismo tiempo, observamos que el tratamiento a corto plazo con alendronato produce una disminución del calcio urinario en pacientes con hipercalciuria idiopática. En el presente estudio analizamos los efectos del alendronato a largo plazo (10 mg/día por un año) sobre el calcio y la hidroxiprolina urinaria y el contenido mineral óseo en 18 hipercalciúricos y 8 normocalciúricos con litiasis urinaria. Las características clínicas, así como la distribución por edades y sexo fue similar en ambos grupos. En calcio urinario disminuyó significativamente al final del primer mes y continuó bajo posteriormente (277 + 28, antes vs. 202 + 26 mg/g creatinina, después de 12 meses con alendronato, p<0.01). La hidroxiprolina urinaria disminuyó significativamente durante el estudio (125,5 + 32.1 vs. 39.66 + 17.5 mg/g creatinina, p<0.05). El calcio sérico, la filtración glomerular y el sodio urinario no se modificaron durante el estudio. La densidad mineral ósea en columna lumbar, determinada por densitometría por rayos X, se incremento significativamente el primer año de 1.162 + 0.231 a 1.197 + 0.248 g/cm2 (p<0.01). No se observaron cambios en la densidad mineral del cuello de fémur. Estos cambios se asociaron a una disminución en la transcripción del mRNA para IL-1 alpha, determinados por la reacción en cadena de polimerase (PCR), en células mononucleares no estimuladas. Los sujetos normocalciúricos no demostraron cambios significativos en la excreción urinaria de calcio. En resumen, los cambios observados en el calcio urinario y otros parámetros metabólicos óseos sugieren un papel importante del hueso en la fisiopatología de la hipercalciuria idiopática. (AU)