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.

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.

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.

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.