Histologic evolution of bone disease 6 months after successful kidney transplantation

Background: the histologic patterns of bone disease, as well as the evolution of renal osteodystrophy after kidney transplantation (Tx), are not well defined. Information in this regard is scarce and contradictory. Methods: Before and 6 months after Tx, analysis of biochemical, hormonal, and bone histomorphometric parameters were performed. Twenty patients (14 men and 6 women) entered the study. Median age was 36.5 (range, 20 to 55) years, and median time on dialysis was 22 (9 to 88) months. Results: Bone histomorphometric diagnoses at pre-Tx were adynamic bone disease, 12; mixed bone disease, 3; mild disease, 3; and osteitis fibrosa, 2. After Tx, 11 had adynamic bone disease; 8, mild disease; and 1, osteomalacia. As a whole, dynamic parameters improved significantly in patients who had adynamic bone. Five of the 12 with this diagnosis completely recovered their bone turnover. Pre-Tx hyperparathyroldism bone features improved or resolved, but 5 of the 8 patients had low-turnover bone disease (adynamic disease, 4; osteomalacia, 1). Three of them had persistence of aluminum and/or iron deposits on bone surface, and the other 2 had hypophosphatemia and high intact parathyroid hormone levels. Overall, biochemical parameters tended toward normalization. Serum intact parathyroid hormone before Tx was correlated negatively with post-Tx trabecular thickness. Conclusion: Six months after Tx, bone histology remained abnormal. the high turnover bone disease improved in all cases, but in most of them low turnover bone disease emerged. Nearly half of the cases with pre-Tx adynamic bone disease recovered their bone turnover completely with some improvement observed in the majority of the remaining cases.Univ Fed Fluminense, Div Nephrol, Dept Internal Med, Rio de Janeiro, BrazilUniv São Paulo, Div Nephrol, Dept Internal Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Internal Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Internal Med, São Paulo, BrazilWeb of Scienc

Relationship between damage and mortality in juvenile-onset systemic lupus erythematosus: Cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

To identify patterns (clusters) of damage manifestation within a large cohort of juvenile SLE (jSLE) patients and evaluate their possible association with mortality. This is a multicentre, descriptive, cross-sectional study of a cohort of 345 jSLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestation were identified and compared. Mean age (years) ± S.D. at diagnosis was 14.2 ± 2.89; 88.7% were female and 93.4% were Caucasian. Mean SLICC/ACR DI ± S.D. was 1.27 ± 1.63. A total of 12 (3.5%) patients died. Three damage clusters were identified: Cluster 1 (72.7% of patients) presented a lower number of individuals with damage (22.3% vs. 100% in Clusters 2 and 3, P  In a large cohort of jSLE patients, renal and musculoskeletal damage manifestations were the two dominant forms of damage by which patients were sorted into clinically meaningful clusters. We found two clusters of jSLE with important clinical damage that were associated with higher rates of mortality, especially for the cluster of patients with predominant renal damage. Physicians should be particularly vigilant to the early prevention of damage in this subset of jSLE patients with kidney involvement

Associated factors to serious infections in a large cohort of juvenile-onset systemic lupus erythematosus from Lupus Registry (RELESSER).

To assess the incidence of serious infection (SI) and associated factors in a large juvenile-onset systemic lupus erythematosus (jSLE) retrospective cohort. All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria and disease onset A total of 353 jSLE patients were included: 88.7% female, 14.3 years (± 2.9) of age at diagnosis, 16.0 years (± 9.3) of disease duration and 31.5 years (±10.5) at end of follow-up. A total of 104 (29.5%) patients suffered 205 SI (1, 55.8%; 2-5, 38.4%; and ≥6, 5.8%). Incidence rate was 3.7 (95%CI: 3.2-4.2) SI per 100 patient years. Respiratory location and bacterial infections were the most frequent. Higher number of SLE classification criteria, SLICC/ACR DI score and immunosuppressants use were associated to the presence of SI. Associated factors to shorter time to first infection were higher number of SLE criteria, splenectomy and immunosuppressants use. The risk of SI in jSLE patients is significant and higher than aSLE. It is associated to higher number of SLE criteria, damage accrual, some immunosuppressants and splenectomy

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55-98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04-117·73]) than in those in the lowest risk category (aged 18-38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57-38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67-104·02) for those with obesity in the highest risk category and OR 20·07 (12·73-31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron