Raul G. Carlini

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.

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.

Endothelin-1 release by erythropoietin involves calcium signaling in endothelial cells

We investigated the effects of recombinant human erythropoietin (rHuEPO) on intracellular calcium ([Ca2+]i) and whether these changes regulate both endothelin-1 (ET-1) protein release and ET-1 messenger RNA (mRNA) production in bovine pulmonary arterial endothelial cells (BPAEC). rHuEPO (3.3 U/ml) induced [Ca2+]i increases from a basal level of 54 +/- 12.2 (SE) to 147 +/- 21.1 nM (p < 0.001), in fura-2-loaded BPAEC. In the presence of nifedipine (10 microM), the increases in [Ca2+]i were significantly reduced. Furthermore, when extracellular calcium ([Ca2+]o) was reduced (200 microM), there was a significant reduction in [Ca2+]i increase after stimulation with rHuEPO. Incubation of BPAEC with rHuEPO for 4 h increased ET-1 levels in the culture supernatant from 44.7 +/- 5.3 to 85 +/- 7.6 pg/ml (p < 0.001). However, when the cells were treated with rHuEPO and nifedipine, the ET-1 levels were decreased, as compared to levels resulting from treatment with rHuEPO alone (41 +/- 6.1 vs. 85 +/- 7.6 pg/ml, p < 0.001, respectively). rHuEPO also induced a fourfold increase in the level of the preproET-1 mRNA as compared with control. PreproET-1 mRNA was diminished in the presence of nifedipine and rHuEPO and rHuEPO can increase [Ca2+]i in BPAEC, and this increase may be related to the stimulation of ET-1 synthesis and release.

Guías de práctica clínica para la prevención, diagnóstico, evaluación y tratamiento de los trastornos minerales y óseos en la enfermedad renal crónica (TMO-ERC) en adultos

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.

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.