Ezequiel Bellorin-Font

Magnesium and phosphorus

A summary of new findings regarding alterations of magnesium (Mg2+) and phosphorus (P) metabolism are reviewed for the clinician caring for patients in general wards. Alterations in serum concentrations of Mg2+ and P are frequently observed in acute or very ill patients in emergency rooms or intensive-care areas. A significant proportion of these alterations are iatrogenic. Most of the symptoms related are non-specific, and usually they are associated with changes in concentration of other ions. The need to measure Mg2+ and P routinely and to define better the real abnormal values is stressed. Correction of the abnormalities must be early in the course of the alterations.

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.

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.

Estrogen Receptor (ER) Gene Polymorphism May Predict the Bone Mineral Density Response to Raloxifene in Postmenopausal Women on Chronic Hemodialysis

The estrogen receptor (ER) gene has been considered as a candidate genetic marker for osteoporosis, and PvuII and XbaI polymorphisms of the ERα gene have been associated with low bone mineral density (BMD). We investigated whether ER polymorphism could predict the response of BMD in 28 postmenopausal women on hemodialysis with marked osteopenia or osteoporosis, randomized to receive raloxifene, a selective estrogen receptor modulator (SERM), or placebo for 1 year. BMD was assessed by dual X-ray absorptiometry and PvuII and XbaI restriction fragment-length polymorphism of the ER gene was determined using polymerase chain reaction. Baseline lumbar spine or femoral neck BMD parameters were not different between patients presenting either homozygous PP or xx when compared with heterozygous Pp or Xx genotypes. After 1 year, patients on raloxifene, presenting with PP or xx genotypes (but not those with Pp or Xx), showed a significantly higher mean lumbar spine BMD (0.942 ± 0.18 vs. 0.925 ± 0.17 g/cm2, p < .01) and lower serum pyridinoline (19.7 ± 9.7 vs. 30.6 ± 16.5 nmol/L, p < .02) when compared with baseline values. No changes were detected in the placebo-treated patients or in the femur neck sites. In conclusion, after 1 year on raloxifene, postmenopausal osteoporotic women on chronic hemodialysis, homozygous for the P or x (PP or xx) alleles of the ER, exhibited a better lumbar spine BMD response and decreased serum pyridinoline values when compared with heterozygous women (Pp or Xx), suggesting that ERα allelic variants may explain, at least in part, the different outcomes after treatment of osteoporosis with SERM.

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.

Increased Osteoblastic Activity and Expression of Receptor Activator of NF-κB Ligand in Nonuremic Nephrotic Syndrome

Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-kappaB ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 +/- 26 ml/min per 1.73 m2) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 +/- 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

Insulin Binding and Glycolytic Activity in Erythrocytes from Dialyzed and Nondialyzed Uremic Patients

Insulin resistance in uremia has been attributed to impaired hormone-receptor binding or to postbinding defects. Oral glucose tolerance tests, insulin binding, and in vitro glycolytic activity were studied in purified red blood cells from normal control subjects (C) and from uremic patients belonging to three groups: nondialyzed (U), on chronic hemodialysis (HD), and on continuous ambulatory peritoneal dialysis (CAPD). Glucose intolerance and hyperinsulinemia were demonstrated in all groups of patients. Maximal specific binding of 125I-insulin to erythrocytes, kinetically derived receptor numbers per cell, and affinity constants for insulin binding did not differ between control and patient groups. No correlation was found between the degree of glucose intolerance and insulin binding parameters. Basal lactate production by erythrocytes incubated in vitro was significantly higher in U and HD patients than in C, whereas CAPD patients did not differ from C in this respect. Addition of 1 mM dibutyryl-cAMP and 0.5 mM isobutyl-methyl-xanthine during incubation of erythrocytes caused an increase in the rate of lactate production that was similar in magnitude in the U, HD and C groups, whereas cells from CAPD subjects showed a significantly larger absolute response to these compounds after 1 h of incubation. There was no evidence of impairment of glycolytic capacity in red blood cells from uremic patients. In addition, no correlation was found between the degree of glucose intolerance and basal or stimulated lactate production by erythrocytes. Our results obtained in human erythrocytes suggest that the insulin resistance observed in uremia does not involve a defect in hormone binding or in the intracellular capacity to utilize glucose through glycolysis.

Global overview of health systems oversight and financing for kidney care

Reliable governance and health financing are critical to the abilities of health systems in different countries to sustainably meet the health needs of their peoples, including those with kidney disease. A comprehensive understanding of existing systems and infrastructure is therefore necessary to globally identify gaps in kidney care and prioritize areas for improvement. This multinational, cross-sectional survey, conducted by the ISN as part of the Global Kidney Health Atlas, examined the oversight, financing, and perceived quality of infrastructure for kidney care across the world. Overall, 125 countries, comprising 93% of the worlds population, responded to the entire survey, with 122 countries responding to questions pertaining to this domain. National oversight of kidney care was most common in high-income countries while individual hospital oversight was most common in low-income countries. Parts of Africa and the Middle East appeared to have no organized oversight system. The proportion of countries in which health care system coverage for people with kidney disease was publicly funded and free varied for AKI (56%), nondialysis chronic kidney disease (40%), dialysis (63%), and kidney transplantation (57%), but was much less common in lower income countries, particularly Africa and Southeast Asia, which relied more heavily on private funding with out-of-pocket expenses for patients. Early detection and management of kidney disease were least likely to be covered by funding models. The perceived quality of health infrastructure supporting AKI and chronic kidney disease care was rated poor to extremely poor in none of the high-income countries but was rated poor to extremely poor in over 40% of low-income countries, particularly Africa. This study demonstrated significant gaps in oversight, funding, and infrastructure supporting health services caring for patients with kidney disease, especially in low- and middle-income countries.

Global coverage of health information systems for kidney disease: availability, challenges, and opportunities for development

Development and planning of health care services requires robust health information systems to define the burden of disease, inform policy development, and identify opportunities to improve service provision. The global coverage of kidney disease health information systems has not been well reported, despite their potential to enhance care. As part of the Global Kidney Health Atlas, a cross-sectional survey conducted by the International Society of Nephrology, data were collected from 117 United Nations member states on the coverage and scope of kidney disease health information systems and surveillance practices. Dialysis and transplant registries were more common in high-income countries. Few countries reported having nondialysis chronic kidney disease and acute kidney injury registries. Although 62% of countries overall could estimate their prevalence of chronic kidney disease, less than 24% of low-income countries had access to the same data. Almost all countries offered chronic kidney disease testing to patients with diabetes and hypertension, but few to high-risk ethnic groups. Two-thirds of countries were unable to determine their burden of acute kidney injury. Given the substantial heterogeneity in the availability of health information systems, especially in low-income countries and across nondialysis chronic kidney disease and acute kidney injury, a global framework for prioritizing development of these systems in areas of greatest need is warranted.

Global access of patients with kidney disease to health technologies and medications: findings from the Global Kidney Health Atlas project

Access to essential medications and health products is critical to effective management of kidney disease. Using data from the ISN Global Kidney Health Atlas multinational cross-sectional survey, global access of patients with kidney disease to essential medications and health products was examined. Overall, 125 countries participated, with 118 countries, composing 91.5% of the worlds population, providing data on this domain. Most countries were unable to access eGFR and albuminuria in their primary care settings. Only one-third of low-income countries (LICs) were able to measure serum creatinine and none were able to access eGFR or quantify proteinuria. The ability to monitor diabetes mellitus through serum glucose and glycated hemoglobin measurements was suboptimal. Pathology services were rarely available in tertiary care in LICs (12%) and lower middle-income countries (45%). While acute and chronic hemodialysis services were available in almost all countries, acute and chronic peritoneal dialysis services were rarely available in LICs (18% and 29%, respectively). Kidney transplantation was available in 79% of countries overall and in 12% of LICs. While over one-half of all countries publicly funded RRT and kidney medications with or without copayment, this was less common in LICs and lower middle-income countries. In conclusion, this study demonstrated significant gaps in services for kidney care and funding that were most apparent in LICs and lower middle-income countries.