New-onset diabetes after kidney transplantation: Assessing urinary Wilm's tumor-1 protein to predict renal allograft dysfunction.

PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 â€‹mL/min/1.73 â€‹m2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.

Impact of overweight and obesity on disease activity and remission in systemic lupus erythematosus: A systematic review and meta-analysis protocol.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease that requires treatment with hydroxychloroquine and glucocorticoids. Glucocorticoids are responsible for adverse effects such as increased weight, which can modify the severity and chronicity of autoimmune pathologies. AIM: To summarize scientific evidence regarding the impact of overweight and obesity on disease activity and remission in SLE. METHODS: The protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocol (PRISMA-P) and published in the International Prospective Register of Systematic Reviews database (PROSPERO-CRD42021268217). PubMed, Scopus, Embase, and Google Scholar will be searched for observational studies including adult patients with SLE who were overweight and obese or not, that included disease activity or remission as outcomes. The search is planned for May 2023. Three independent authors will select the eligible articles and extract their data. Subsequently, three authors will independently extract data from each included study using an extraction form created by the researchers. Methodological quality analyses will be performed using the modified Newcastle-Ottawa scale. The results will be presented as a narrative synthesis according to the synthesis without a meta-analysis reporting guideline (SWiM). Meta-analysis will be conducted where appropriate using random-effects models. EXPECTED RESULTS: This review will identify the impact of overweight and obesity on the clinical features of SLE, helping clinicians manage disease activity and remission, both important to optimize disease outcomes and patient quality of life.

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study / Estado de la vitamina D y biomarcadores de función del injerto renal después del trasplante de riñón: un estudio longitudinal

Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies. (AU)

Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio, y 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además,los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debeexplorarse en estudios adicionales. (AU)

Vitamin D status and biomarkers of renal graft function after kidney transplantation: a longitudinal study.

Introduction: Introduction: Low 25-hydroxyvitamin D [25(OH)D] levels occur after kidney transplantation (KTx), and can be associated with increase the risk of graft loss. This longitudinal study aimed to evaluate the vitamin D status and association with biomarkers of the renal graft function after KTx. Methods: this longitudinal study included 42 patients evaluated at baseline, 3 and 6 months after KTx. Biodemographic, clinical, and biochemical parameters such as 25(OH)D and parathyroid hormone (PTH), and biomarkers of renal graft function, such as creatinine, estimated glomerular filtration rate (eGFR), and albumin/creatinine ratio (ACR), were assessed. Sun exposure was also evaluated. Patients were categorized according to their 25(OH)D levels. Results: at baseline, 25(OH)D levels < 30 ng/mL were found in 43 % patients, and 38 % of these patients failed to improve their 25(OH)D levels by 6 months after KTx. Low 25(OH)D levels occurred regardless of sun exposure. Further, 44 % patients developed albuminuria at 6 months. An increased ACR was observed in patients with 25(OH)D levels < 30 ng/mL (p = 0.002) compared to that in patients with 25(OH)D > 30 ng/mL. Additionally, 25(OH)D levels were negatively correlated with ACR at 6 months post-KTx (r = -0.444; p = 0.003). Twelve (28.6 %) patients with 25(OH)D levels < 30 ng/mL showed no eGFR recovery until 6 months after KTx. Conclusion: low vitamin D levels and increased albuminuria were observed at 6 months after KTx, even in a region with high sun exposure. The association between vitamin D status and biomarkers of renal graft function after KTx should be explored in further studies.

Introducción: Introducción: los bajos niveles de 25-hidroxivitamina D [25(OH)D] ocurren después del procedimiento de trasplante de riñón (KTx) y pueden estar asociados con un aumento del riesgo de pérdida del injerto. Este estudio longitudinal tuvo como objetivo evaluar el estado de la vitamina D y la asociación con los biomarcadores de función del injerto renal después del KTx. Métodos: este estudio longitudinal incluyó a 42 pacientes que fueron evaluados al inicio del estudio y, 3 y 6 meses después del KTx. Se evaluaron los parámetros biodemográficos, clínicos y bioquímicos, como 25(OH)D y hormona paratiroidea (PTH), y los biomarcadores de función del injerto renal, como creatinina, tasa de filtración glomerular estimada (eGFR) y relación albúmina/creatinina (ACR). También se evaluó la exposición al sol. Los pacientes se clasificaron según sus niveles de 25(OH)D. Resultados: al inicio del estudio se encontraron niveles de 25(OH)D < 30 ng/ml en el 43 % de los pacientes, mientras que el 38 % de estos pacientes no lograron mejorar sus niveles de 25(OH)D a los 6 meses después del KTx. También se produjeron niveles bajos de 25(OH)D independientemente de la exposición al sol. Asimismo, el 44 % de los pacientes desarrollaron albuminuria a los 6 meses. Se observó un aumento de la ACR en los pacientes con niveles de 25(OH)D < 30 ng/mL (p = 0,002) en comparación con los pacientes con 25(OH)D > 30 ng/mL. Además, los niveles de 25(OH)D se correlacionaron negativamente con la ACR a los 6 meses después del KTx (r = -0,444; p = 0,003). Doce (28,6 %) pacientes con niveles de 25(OH)D < 30 ng/ml no mostraron recuperación de la TFGe hasta 6 meses después del KTx. Conclusión: se observaron niveles bajos de vitamina D y un aumento de la albuminuria a los 6 meses después del KTx, incluso en una región con alta exposición solar. La asociación entre el estado de la vitamina D y los biomarcadores de función del injerto renal después del KTx debe explorarse en estudios adicionales.

Effects of an individualized nutritional intervention on kidney function, body composition, and quality of life in kidney transplant recipients: Study protocol for a randomized clinical trial.

BACKGROUND: Proteinuria after kidney transplantation (KTx) has been a frequent problem due to several factors, high protein intake being one of them. Individualized nutritional intervention in the late post-KTx period can promote the improvement or the reduction of risks associated with the parameters of evaluation of kidney function, body composition, and quality of life in individuals submitted to KTx. METHODS: This is a single-center, randomized and stratified clinical trial. The study will be conducted in a university hospital in northeastern Brazil with 174 individuals aged ≥19 years submitted to KTx and followed up for 12 months. Assessments will take place at 3-month intervals (T0, T3, T6, T9, and T12). The patients will be allocated to intervention and control groups by random allocation. The intervention group will receive individualized nutritional interventions with normoproteic diets (1.0 g/kg) after 60 days of KTx whereas the controls will receive the standard nutritional guidance for the post-KTx period. The primary efficacy variable is the change from baseline in log proteinuria assessed with the urinary albumin/creatinine ratio. Secondary efficacy variables include body composition, anthropometry, quality of life assessment and physical activity, lipid profile and glycemic control. Ninety-two subjects per group will afford 70% power to detect a difference of 25% between groups in log proteinuria. Primary efficacy analysis will be on the modified intention-to-treat population with between-groups comparison of the change from baseline in log proteinuria by analysis of covariance. DISCUSSION: The study will assess the effects of an individualized nutritional intervention on proteinuria 12 months after KTx. TRIAL REGISTRATION: REBEC (RBR-8XBQK5).

The low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism: candidate for susceptibility to type 1 diabetes mellitus.

OBJECTIVE: The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. SUBJECTS AND METHODS: A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were studied. Glycated hemoglobin and glucose levels were determined. Genotyping of LRP5 4037C>T (rs3736228) was performed. RESULTS: T1DM patients showed poor glycemic control. Genotypes in the codominant (CT: OR = 2.99 [CI 95%: 1.71-5.24], p < 0.001; TT: OR = 5.34 [CI 95%: 1.05-2702], p < 0.001), dominant (CT + TT: OR = 3.16 [CI 95%: 1.84-5.43], p < 0.001) and log-additive (OR = 2.78 [CI 95%: 1.70-4.52], p < 0.001) models, and LRP5 4037T allele (OR = 2.88, [CI 95%: 1.78-4.77], p < 0.001) were associated with an increased risk of developing T1DM. LRP5 4037CT and CT+TT carriers in T1DM group showed higher concentrations of serum glucose and glycated hemoglobin when compared with CC carriers. CONCLUSION: The LRP5 4037C>T may represent a candidate for T1DM susceptibility, as well as poor glycemic control.

The low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism: candidate for susceptibility to type 1 diabetes mellitus

ABSTRACT Objective: The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. Subjects and methods: A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were studied. Glycated hemoglobin and glucose levels were determined. Genotyping of LRP5 4037C>T (rs3736228) was performed. Results: T1DM patients showed poor glycemic control. Genotypes in the codominant (CT: OR = 2.99 [CI 95%: 1.71-5.24], p < 0.001; TT: OR = 5.34 [CI 95%: 1.05-2702], p < 0.001), dominant (CT + TT: OR = 3.16 [CI 95%: 1.84-5.43], p < 0.001) and log-additive (OR = 2.78 [CI 95%: 1.70-4.52], p < 0.001) models, and LRP5 4037T allele (OR = 2.88, [CI 95%: 1.78-4.77], p < 0.001) were associated with an increased risk of developing T1DM. LRP5 4037CT and CT+TT carriers in T1DM group showed higher concentrations of serum glucose and glycated hemoglobin when compared with CC carriers. Conclusion: The LRP5 4037C>T may represent a candidate for T1DM susceptibility, as well as poor glycemic control.

Risk factors and comorbidities in Brazilian patients with orofacial clefts.

Considering that environmental risk factors substantially contribute to the etiology of orofacial clefts and that knowledge about the characteristics and comorbidities associated with oral clefts is fundamental to promoting better quality of life, this study aimed to describe the risk factors, main characteristics, and comorbidities of a group of patients with cleft lip and/or cleft palate (CL/P) from Rio Grande do Norte (RN), Brazil. Data were obtained from 173 patients with CL/P using a form from the Brazilian database on Orofacial Clefts. Most patients were male with cleft lip and palate and had a normal size and weight at birth; presented few neonatal intercurrent events; and had anemia and respiratory and cardiovascular diseases as main associated comorbidities. They also required timely surgical rehabilitation and multidisciplinary care to stimulate their neuropsychomotor development. In addition, a high frequency of familial recurrence and of parental consanguinity was evidenced in the studied population, especially for the cleft lip and cleft palate type. Other relevant findings were the considerable maternal exposure to alcohol, infections, smoking, and hypertension, as well as low supplementation with vitamins and minerals and deliberate consumption of analgesics, antibiotics, and antihypertensives during pregnancy. Characterization of the CL/P patient profile is essential for the planning of health services and integration among the health professionals involved in the diagnosis and treatment of these malformations. Our results reinforce the need for additional research to confirm the association between environmental factors and the development of orofacial clefts.

Risk factors and comorbidities in Brazilian patients with orofacial clefts

Abstract: Considering that environmental risk factors substantially contribute to the etiology of orofacial clefts and that knowledge about the characteristics and comorbidities associated with oral clefts is fundamental to promoting better quality of life, this study aimed to describe the risk factors, main characteristics, and comorbidities of a group of patients with cleft lip and/or cleft palate (CL/P) from Rio Grande do Norte (RN), Brazil. Data were obtained from 173 patients with CL/P using a form from the Brazilian database on Orofacial Clefts. Most patients were male with cleft lip and palate and had a normal size and weight at birth; presented few neonatal intercurrent events; and had anemia and respiratory and cardiovascular diseases as main associated comorbidities. They also required timely surgical rehabilitation and multidisciplinary care to stimulate their neuropsychomotor development. In addition, a high frequency of familial recurrence and of parental consanguinity was evidenced in the studied population, especially for the cleft lip and cleft palate type. Other relevant findings were the considerable maternal exposure to alcohol, infections, smoking, and hypertension, as well as low supplementation with vitamins and minerals and deliberate consumption of analgesics, antibiotics, and antihypertensives during pregnancy. Characterization of the CL/P patient profile is essential for the planning of health services and integration among the health professionals involved in the diagnosis and treatment of these malformations. Our results reinforce the need for additional research to confirm the association between environmental factors and the development of orofacial clefts.

Relationship between glycemic control and OPG gene polymorphisms with lower bone mineral density in patients with type 1 Diabetes mellitus

ABSTRACT The aim of the present study was to investigate the bone mineral density (BMD) of patients with type 1 Diabetes mellitus (T1DM). We also assessed the association between osteoprotegerin (OPG) genetic polymorphisms and BMD. Genotyping was performed for 1181G>C and 163A>G OPG polymorphisms by allelic discrimination in 119 patients with T1DM and 161 normoglycemic (NG) individuals, aged 6 to 20 years old. Glycemic control, serum parameters of bone metabolism and BMD were evaluated. T1DM patients showed low BMD, poor glycemic control and decreased total calcium values when compared to controls (p < 0.05). For all the polymorphisms studied, the genotype and allele frequencies in patients with T1DM were not significantly different from the controls. In patients with T1DM, carriers of OPG 1181CC showed higher concentrations of ionized calcium compared to patients with GG+GC genotypes. These results suggest that low BMD is associated with poor glycemic control in T1DM. Despite the lack of a detected association between OPG polymorphisms and BMD in these patients, the increased ionized calcium in those carrying OPG 1181CC suggests a possible increase in osteoclastogenesis, a conclusion that may be supported by the lower BMD observed in these subjects.