Diagnosis and management of precocious sexual maturation: an updated review.

The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. It is classified as central precocious puberty when premature maturation of the hypothalamic-pituitary-gonadal axis occurs, and as peripheral precocious puberty when there is excessive secretion of sex hormones, independent of gonadotropin secretion. Precocious sexual maturation is more common in girls, generally central precocious puberty of idiopathic origin. In boys, it tends to be linked to central nervous system abnormalities. Clinical evaluation should include a detailed history and physical examination, including anthropometric measurements, calculation of growth velocity, and evaluation of secondary sexual characteristics. The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. Hormonal assessment and imaging are required for diagnosis and identification of the etiology. Genetic testing should be considered if there is a family history of precocious puberty or other clinical features suggestive of a genetic syndrome. Long-acting gonadotropin-releasing hormone analogs are the standard of care for central precocious puberty management, while peripheral precocious puberty management depends on the etiology.Conclusion: The aim of this review is to address the epidemiology, etiology, clinical assessment, and management of precocious sexual maturation. What is Known: • The main sign to suspect the onset of puberty is breast tissue development (thelarche) in girls and testicular enlargement (≥4 mL) in boys. The classic definition of precocious sexual maturation is the development of secondary sexual characteristics before 8 years of age in girls and before 9 years of age in boys. • Long-acting gonadotropin-releasing hormone agonist (GnRHa) is the standard of care for CPP management, and adequate hormone suppression results in the stabilization of pubertal progression, a decline in growth velocity, and a decrease in bone age advancement. What is New: • Most cases of precocious sexual maturation are gonadotropin-dependent and currently assumed to be idiopathic, but mutations in genes involved in pubertal development have been identified, such as MKRN3 and DLK1. • A different preparation of long-acting GnRHa is now available: 6-month subcutaneous injection.

Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults.

BACKGROUND: Late-night salivary cortisol (LNSC) is one of the most reliable tests to screen for endogenous Cushing syndrome. This test is simple, inexpensive and noninvasive and has high sensitivity and specificity. The aim of our study was to analyze the putative influence of age, gender and body mass index (BMI) on LNSC levels in a healthy population. METHODS: Cross-sectional study conducted in healthy adults. Midnight saliva samples were collected at home. Participants refrained from teeth brushing, eating or drinking for 2 h prior to collection. Salivary cortisol measured by electrochemiluminescence immunoassay (ECLIA). The study was approved by the Ethics Committee of the hospital (number 140073). RESULTS: We evaluated 122 nonsmoking healthy volunteers. Mean age was 35±14 years (range, 18-74 years); 63% were women. Mean BMI was 24±3 kg/m2, blood pressure 115/74 mmHg and fasting plasma glucose 4.8±0.5 mmol/L. LNSC presented a non-Gaussian distribution; the median was 3.58 (range, 0.55-8.55) nmol/L (0.13 [range, 0.02-0.31] µg/dL), and the 97.5th percentile (P97.5) was 8.3 nmol/L (0.3 µg/dL). Multiple linear regression disclosed a significant positive association between salivary cortisol levels and age (r2=0.21, p<0.001), but no association with gender (p=0.105) or BMI (p=0.119). Accordingly, participants aged >50 years had significantly higher salivary cortisol as compared to those aged <50 years (5.24 nmol/L [0.19 µg/dL] vs. 3.31 nmol/L [0.12 µg/dL], respectively, p<0.001). CONCLUSIONS: The maximum reference value (P97.5) of LNSC was set at 8.3 nmol/L (0.3 µg/dL) using ECLIA. Advanced age was associated with higher LNSC levels, with no evident influence of gender or BMI.

Maternal-fetal impact of vitamin D deficiency: a critical review.

Research into the extra-skeletal functions of vitamin D has been expanding in recent years. During pregnancy, maternal vitamin D status may be of concern because of the key role of this vitamin in fetal skeletal development and due to the association between hypovitaminosis D and adverse maternal-fetal outcomes. Therefore, the objective of this manuscript was to review the maternal-fetal impact of gestational vitamin D deficiency and the benefits of vitamin D supplementation during pregnancy. A literature search was performed in PubMed and Embase employing the following keywords: vitamin D deficiency, pregnancy, 25-hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English language published since 1980 were analysed by the two authors. Neonatal complications derived from vitamin D deficiency include low birth weight, growth restriction, and respiratory tract infection. In the mother, vitamin D deficiency has been associated with altered glucose homeostasis and increased incidence of gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However, the current state of the evidence is controversial for some other endpoints and the actual benefit of vitamin D supplementation in pregnancy remains unclear. Additional longitudinal studies may clarify the actual impact of vitamin D deficiency during pregnancy, and randomised trials are required to define the benefits of vitamin D supplementation in reducing the incidence of adverse outcomes in the mother and infant.

Is race adjustment necessary to estimate glomerular filtration rate in South Brazilians?

BACKGROUND AND AIMS: Race coefficients (RC) in equations to estimate glomerular filtration rate (GFR) have been highly questioned. We aimed to evaluate the performance of three equations, namely 2009 Chronic Kidney Disease Epidemiology Collaboration (2009 CKD-EPI), 2021 CKD-EPI, and European Kidney Function Consortium (EKFC) in self-reported Black and White Brazilians. MATERIALS AND METHODS: Our cross-sectional study compared estimated GFR (eGFR) with 51Cr-EDTA measured GFR (mGFR) in healthy adults, patients with type 2 diabetes mellitus with or without chronic kidney disease (CKD), and in non-diabetic individuals with CKD. The performance of these equations was assessed using Bland-Altman plots, Lin's concordance correlation coefficient (CCC), bias, P30, and P15 accuracy. RESULTS: Three hundred six White adults (aged 53 ± 17 years, 55% women, mean mGFR: 83 ± 32 mL/min/1.73 m2) and 48 Black participants (aged 53 ± 17 years, 58% women, mGFR: 90 ± 34 mL/min/1.73 m2) were included. No equation achieved the desirable P30 accuracy value of 90%, neither in White (2009 CKD-EPI:78%, 2021 CKD-EPI:76% and EKFC:77%, p = 0.368) nor in Black volunteers (respective values of 77%, 75%, and 77%; p = 0.882). The 2009 CKD-EPI showed the best performance in Black participants (bias: 4.04; CCC: 0.848), whereas the 2021 CKD-EPI performed better in Whites, with smaller bias (1.45), and better concordance correlation coefficient (0.790). The EKFC presented the worst performance. All equations underdiagnosed advanced CKD in White participants, but not in Black. CONCLUSIONS: The 2021 CKD-EPI does not outperform the 2009 CKD-EPI. Instead, it underestimated the occurrence of CKD in White participants. Thus, we do not recommend replacing the 2009 with the new 2021 CKD-EPI in the Brazilian population.

Reference values for glomerular filtration rate in healthy Brazilian adults.

BACKGROUND: Glomerular filtration rate (GFR) is the best index of renal function, but age, gender and ethnicity can putatively affect its values. The aim of this study was to establish reference values for GFR in healthy Brazilian subjects while taking these factors into account. METHODS: In this cross-sectional study, GFR was measured by the 51Cr-EDTA single-injection method. GFR reference values were developed according to CLSI Guidelines for Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory (CLSI C28 protocol). RESULTS: The age range of the 285 healthy individuals was 19 to 70 years, 57% were females, and GFR was 106 ± 18 mL/min/1.73 m(2). There was no difference between male and female GFRs (108 ± 18 vs. 104 ± 18 mL/min/1.73 m(2) respectively, P = 0.134), and reference values were therefore developed from the pooled sample. GFR values were lower in subjects aged ≥45 years as compared with those younger than 45 years (98 ± 15 vs.112 ± 18 mL/min/1.73 m(2), P < 0.001). Based on mean ± 2 SD, GFR reference values were 76 to 148 mL/min/1.73 m(2) for subjects younger than 45 years and 68 to 128 mL/min/1.73 m(2) for individuals older than 45 years, irrespective of gender. CONCLUSION: The age-adjusted reference intervals reported may be reliably adopted to evaluate kidney function, since they are based on recommended standards.

Long-Term Changes in Bone Density and Bone Metabolism After Gastric Bypass Surgery: a Retrospective Cohort Study.

PURPOSE: Patients with severe obesity submitted to Roux-en-Y gastric bypass (RYGB) are at risk of developing long-term hypovitaminosis D and secondary hyperparathyroidism (SHPT) as well as osteometabolic disease. This study aimed to evaluate calcium-vitamin D-PTH axis and bone mineral density (BMD) changes from post-RYGB patients who were followed-up until a median of 5 years. MATERIALS AND METHODS: Vitamin D deficiency was defined as 25-hydroxyvitamin D <20 ng/mL and SHPT as PTH >68 pg/mL, in patients with normal serum creatinine and calcium. BMD was estimated by dual-energy X-ray absorptiometry (DXA, g/cm2). RESULTS: We included 127 post-RYGB patients (51±10.6 years, 87.4% self-declared White, 91.3% female, 52.8% postmenopausal). Vitamin D deficiency prevalence was the highest (41.5%) in the second year and the lowest (21.2%) in the third year (p<0.05). SHPT prevalence was 65.4% in the second year and increased to 83.7% in the sixth year (p<0.05). Patients with low BMD in lumbar, femoral neck, and total proximal femur were older and presented menopausal status more frequently than normal BMD group (p<0.05). Older age was a risk marker for altered BMD in femoral neck (OR=1.185; 95% CI 1.118-1.256) and in total proximal femur (OR=1.158; 95% CI 1.066-1.258), both after adjusting for follow-up and excess weight loss. CONCLUSION: After 5 years, most bariatric patients presented calcium-vitamin D-PTH axis disruption, in which SHPT was more frequent than hypovitaminosis D. Older patients and menopausal women presented higher rates of low BMD, and older age was a risk marker, especially for low BMD in femoral sites.

Accuracy of doppler assessment of the uterine arteries for the diagnosis of pubertal onset in girls: a scoping review.

The uterine artery pulsatility index (PI) assessed by Doppler ultrasound reflects the impedance to the blood flow in the vessel distal to the sampling point. We aimed to assess the accuracy of the uterine artery PI for the diagnosis of puberty in girls. A PRISMA-ScR-compliant scoping review was performed in the MEDLINE and Embase databases with the search terms "puberty" and "Doppler ultrasonography". Studies that included girls aged 0-18 years who underwent pelvic Doppler ultrasound with calculation of uterine artery PI were eligible. Ten studies comprising 1385 girls aged 1.2-18 years were included. The selected studies included participants from Italy, Brazil, Iran, Belgium and Denmark, and were published between 1996 and 2021. Six studies selected girls who were referred for evaluation of pubertal disorders, while four studies included only healthy girls. Nine studies found a significant difference in Doppler signal pattern and PI according to pubertal stage, with PI cutoff points ranging from 2.5 to 4.6 for the diagnosis of puberty, with a sensitivity of 77%-94%, specificity of 85%-100%, and accuracy of 79%-98%. Doppler assessment of the uterine arteries with PI calculation is a useful noninvasive tool in the diagnosis of pubertal onset in girls.

2009 CKD-EPI glomerular filtration rate estimation in Black individuals outside the United States: a systematic review and meta-analysis.

Background: The 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is the most used equation to estimate glomerular filtration rate (GFR), with race being a factor thereof, increasing GFR by 16% in self-identified Black persons compared with non-Black persons. However, recent publications indicate that it might overestimate GFR for Black adults outside the USA. In this meta-analysis, we assessed the accuracy, evaluated by the percentage of estimated GFR within 30% of measured GFR (P30), of the 2009 CKD-EPI equation in estimating GFR with and without the race coefficient in Black individuals outside the United States of America (USA). Methods: We searched MEDLINE and Embase from inception to 9 July 2022, with no language restriction, supplemented by manual reference searches. Studies that assessed the CKD-EPI P30 accuracy with or without the race coefficient in Black adults outside the USA with an adequate method of GFR measurement were included. Data were extracted by independent pairs of reviewers and were pooled using a random-effects model. Results: We included 11 studies, with a total of 1834 Black adults from South America, Africa and Europe. The race coefficient in the 2009 CKD-EPI equation significantly decreased P30 accuracy {61.9% [95% confidence interval (CI) 53-70%] versus 72.9% [95% CI 66.7-78.3%]; P = .03}. Conclusions: Outside the USA, the 2009 CKD-EPI equation should not be used with the race coefficient, even though the 2009 CKD-EPI equation is not sufficiently accurate either way (<75%). Thus we endorse the Kidney Disease: Improving Global Outcomes guidelines to use exogenous filtration markers when this may impact clinical conduct.

Telephone calls and glycemic control in type 2 diabetes: A PRISMA-compliant systematic review and meta-analysis of randomized clinical trials.

AIMS: In-depth and updated systematic reviews evaluating telephone calls in type 2 diabetes (T2DM) management are missing. This study aimed to assess the effect of this intervention on glycemic control in T2DM patients when compared with usual care. METHODS: We systematically searched for randomized controlled trials (RCT) on T2DM using Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and LILACS, up to March 2021. The Risk of Bias 2.0 (Rob 2.0) tool and GRADE were used for the quality evaluation. The intervention effect was estimated by the change in glycated hemoglobin (HbA1c). PROSPERO registry CRD42020204519. RESULTS: 3545 references were reviewed and 32 were included (8598 patients). Telephone calls, all approaching education, improved HbA1c by 0.33% [95% CI, -0.48% to -0.18%; I2 = 78%; p < 0.0001] compared to usual care. A greater improvement was found when the intervention included pharmacologic modification (-0.82%, 95% CI, -1.42% to -0.22%; I2 = 92%) and when it was applied by nurses (-0.53%, 95% CI, -0.86% to -0.2%; I2 = 87%). Meta-regression showed no relationship between DM duration and HbA1c changes. CONCLUSION: The telephone call intervention provided a benefit regarding T2DM glycemic control, especially if provided by nurses, or if associated with patient education and pharmacological treatment modification.

Accuracy evaluation of 2021 Chronic Kidney Disease Epidemiology Collaboration, Full Age Spectrum and European Kidney Function Consortium equations for estimating glomerular filtration rate in type 2 diabetes mellitus and healthy adults.

BACKGROUND AND AIMS: Estimated glomerular filtration rate (eGFR) equations accuracy has been questioned in diabetes mellitus (DM). We aimed to evaluate the performance of three equations - European Kidney Function Consortium (EKFC), Full Age Spectrum (FAS), and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) - in healthy and type 2 DM participants. MATERIAL AND METHODS: This cross-sectional studycompared eGFR equations withareference method: measured GFR (mGFR) by 51Cr-EDTA. The equations performance was assessed usingBland-Altman plot,concordance correlation coefficient (CCC), bias,P30 andP15 accuracy. RESULTS: In the 100 healthy adults included (aged 39 ± 15 years, 67% women, mean mGFR 107 ± 15, 2021 CKD-EPI 109 ± 14, FAS 107 ± 18 and EKFC 101 ± 12 mL/min/1.73 m2), all equations reached P30 accuracy above the desirable benchmark of 90%. In the 122 patients with type 2 DM (aged 61 ± 10 years, 55% women, mGFR97 ± 22, 2021 CKD-EPI 86 ± 20, FAS 83 ± 25 and EKFC 79 ± 18 mL/min/1.73 m2), the equations presented larger biases, worst agreement with mGFR and inferior accuracy, with 2021 CKD-EPI (83%) and EKFC (82%) presenting greater P30 than FAS (77%). CONCLUSION: In healthy Brazilian adults, 2021 CKD-EPI, FAS and EKFC are suitable to estimate GFR. However, all equations underperform in people with type 2 DM.

The 2021-2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD.

BACKGROUND: Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021-2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice. METHODS: The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease]. RESULTS: The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75-89% of agreement; IIb 50-74% of agreement, and III, when most of the panelist recommends against a defined treatment. CONCLUSIONS: To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin-angiotensin-aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients' survival.

Accuracy of Doppler assessment of the uterine arteries in healthy girls for the diagnosis of pubertal onset.

PURPOSE: To evaluate the accuracy of the uterine artery pulsatility index (PI) for the diagnosis of pubertal onset in girls. METHODS: Cross-sectional study of girls with normal pubertal development. Puberty was diagnosed by the presence of Tanner breast development score ≥2. All girls underwent pelvic ultrasound and Doppler imaging of the uterine arteries. We evaluated the uterine artery PI and uterine, endometrial, and ovarian measurements. We used ROC curves with cutoffs determined by Youden index for data analysis. RESULTS: We included 169 girls aged 5-16 years who underwent 202 pelvic ultrasound examinations. Prepubertal girls had a significantly higher mean PI (6.70 ± 2.15) than girls in initial puberty (4.14 ± 1.55) and in late puberty (2.81 ± 1.05) (P < 0.001 for all comparisons), which reflects a progressive increase in blood flow to the uterus with the progression of puberty. ROC curve analysis showed that the PI was able to identify the onset of puberty with a mean area under the curve of 0.838 ± 0.04 (P < 0.001), and the PI cutoff point of 5.05 had a sensitivity of 77%, specificity of 85%, positive predictive value (PPV) of 92%, and accuracy of 79%. The combination of PI < 5.05 plus uterine volume >3.75 cm³ had a sensitivity of 73%, specificity of 95%, PPV of 97%, and accuracy of 79% to detect initial puberty. CONCLUSIONS: We found a significant reduction in the PI during pubertal development, which can possibly be a valuable noninvasive tool in the evaluation of pubertal disorders, alone or in combination with uterine and ovarian volumes.

Glomerular filtration rate estimation: performance of serum cystatin C-based prediction equations.

Serum creatinine measurement is a mainstay in the routine laboratory evaluation of renal function, despite of having several disadvantages. Cystatin C, on the other hand, suffers less influence of gender and muscle mass and has been proposed as a more sensitive marker for glomerular filtration rate. However, serum endogenous markers should not be used alone to assess glomerular filtration rate. Creatinine-based equations such as the modification of diet in renal disease (MDRD) and Cockcroft-Gault are widely used despite their limitations. A large number of cystatin C-based prediction equations were developed in recent years, in diverse populations, with different laboratory assays and methods. Several studies demonstrated that cystatin C-based equations are reliable markers of glomerular filtration rate and can be used for diagnosis, evaluation and follow-up of kidney disease. They are simpler than creatinine-based equations and have at least the same accuracy and precision for glomerular filtration rate estimation. In conclusion, diabetes mellitus, cystic fibrosis, kidney transplantation, HIV-infection, and cirrhosis are clinical situations where cystatin C-based equations can be useful. Extremes of age such as childhood and advanced age have also been evaluated with favorable results.

Glycated Hemoglobin and Blood Pressure Levels in Adults With Type 2 Diabetes: How Many Patients Are on Target?

OBJECTIVES: Achieving glycated hemoglobin (A1C) and blood pressure targets is an important strategy for preventing chronic vascular complications in diabetes. Our aim in this study was to determine the proportion of type 2 diabetes patients who meet the recommended A1C and arterial blood pressure targets and to identify the determinants of failure to do so. METHODS: A cross-sectional study was conducted in an outpatient endocrine clinic at a university hospital. The A1C goal was 7% in general and 8% for patients with advanced chronic complications. Regarding blood pressure, the overall expected target was 140/90 mmHg. RESULTS: A total of 602 type 2 diabetes patients were analyzed: 62% were female, 14% self-reported as black, mean age was 63±11 years, mean diabetes duration was 17±9 years and median A1C was 8.0% (interquartile range, 7.0% to 9.5%). Macrovascular disease was present in 33% of the patients, diabetic retinopathy in 47%, peripheral neuropathy in 43% and diabetic kidney disease in 56%. Regarding metabolic control, 403 (67%) patients were not at the adjusted target A1C level, and being female, black, young and an insulin user were the main determinants of poor glycemic control. Regarding blood pressure, 348 (58%) patients were not at the recommended targets, and a more advanced age was the main associated factor. CONCLUSIONS: Because more than half of type 2 diabetes outpatients do not meet the recommended A1C and blood pressure target values, there is a major call to overcome the therapeutic inertia and target treatment of patients on an individual basis.

Monitoring and management of hyperglycemia in patients with advanced diabetic kidney disease.

Diabetes mellitus is the leading cause of end-stage renal disease, and uncontrolled hyperglycemia is directly related to the increased mortality in this setting. As kidney function decreases, it becomes more challenging to control blood glucose since the risk of hypoglycemia increases. Decreased appetite, changes in glycaemia homeostasis, along with reduced renal excretion of anti-hyperglycemic drugs tend to facilitate the occurrence of hypoglycemia, despite the paradoxical occurrence of insulin resistance in advanced kidney disease. Thus, in patients using insulin and/or oral anti-hyperglycemic agents, dynamic adjustments with drug dose reduction or drug switching are often necessary. Furthermore, in addition to consider these pharmacokinetics alterations, it is of utmost importance to choose drugs with proven cardio-renal benefits in this setting, such as sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists. In this review, we summarize the indications and contraindications, titration of doses and side effects of the available anti-hyperglycemic agents in the presence of advanced diabetic kidney disease (DKD) and dialysis, highlighting the risks and benefits of the different agents. Additionally, basic renal function assessment and monitoring of glycemic control in DKD will be evaluated in order to guide the use of drugs and define the glycemic targets to be achieved.

Gender does not influence cystatin C concentrations in healthy volunteers.

BACKGROUND: Current data are conflicting about the influence of gender on cystatin C concentrations. The goal of this study was to determine the reference interval for serum cystatin C in normal Brazilian subjects, taking into account the influence of gender. METHODS: Ninety-seven healthy volunteers, aged 18-70 years, 44% male, had glomerular filtration rate (GFR) measured using a (51)Cr-EDTA method and estimated with the Modification of Diet in Renal Disease (MDRD) study equation. Serum cystatin C was measured using a turbidimetric method, and creatinine by the Jaffe method. RESULTS: Mean serum cystatin C was not significantly different between males and females, 0.62 +/- 0.12 vs. 0.65 +/- 0.12 mg/L, respectively (p = 0.26). However, median serum creatinine was significantly higher in men [97 (80-115) vs. 80 (53-88) micromol/L; p = 0.0001]. There were also no significant differences between genders with respect to GFR measured using (51)Cr-EDTA (103 +/- 14 for males and 106 +/- 19 mL/min/1.73 m(2) for females, p = 0.47), and estimated with the MDRD equation (86 +/- 12 vs. 83 +/- 16 mL/min/1.73 m(2), respectively, p = 0.24). CONCLUSIONS: There was no effect of gender on serum cystatin C, as well as on measured and estimated GFR.

Lower serum 25-hydroxyvitamin D levels are associated with impaired glomerular filtration rate in type 2 diabetes patients.

BACKGROUND: 25-Hydroxyvitamin D [25(OH)D] deficiency has been implicated as a possible risk factor for the onset and progression of diabetes kidney disease (DKD). The aim of this study was to evaluate the interaction between levels of 25(OH)D and DKD in type 2 diabetes mellitus (DM) patients. METHODS: Cross-sectional design, outpatient type 2 DM. Glomerular filtration rate (GFR) was measured by 51Cr-EDTA and estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), urinary albumin excretion (UAE) by immunoturbidimetry, and 25(OH)D by chemiluminescence. Receiver operating characteristic (ROC) curve analysis and generalized linear model (Poisson robust regression estimator) were used to assess the interaction between 25(OH)D levels and renal function. RESULTS: A total of 114 type 2 DM patients aged 60 ± 10 years, 49 males (43%), DM duration 22 ± 10 years, with GFR > 60 ml/min/1.73 m2 were evaluated. Patients with GFRs 60-90 (n = 50) had significantly lower 25(OH)D levels than individuals with GFRs > 90 ml/min/1.73 m2 (n = 64), respectively 40 ± 20 versus 48 ± 20 nmol/l, p = 0.027. This difference was more pronounced for older individuals (39 ± 20 versus 54 ± 23 nmol/l, respectively), and Poisson robust regression disclosed that lower 25(OH)D [Poisson regression (PR) = 0.989, confidence interval (CI): 0.978-0.999, p = 0.034], and advanced age (PR = 1.050, CI: 1.007-1.096, p = 0.023) were significantly associated with the lower GFR category, adjusted for seasons. ROC curve analysis showed that the cutoff point of 25(OH)D of 41 nmol/l was associated with lower GFR [area under the curve (AUC) = 0.694, p = 0.009]. CKD-EPI estimated GFR (eGFR) was not associated with 25(OH)D in any analysis. There was no difference in 25(OH)D levels between patients with elevated UAE as compared with normoalbuminuric ones (44 ± 21 versus 46 ± 19 nmol/l, p = 0.587). CONCLUSION: Lower levels of 25(OH)D are associated with decreased GFR in patients with type 2 DM, especially in older patients, with no evidence of interaction with UAE levels.

Urinary peptidomics and bioinformatics for the detection of diabetic kidney disease.

The aim of this study was to establish a peptidomic profile based on LC-MS/MS and random forest (RF) algorithm to distinguish the urinary peptidomic scenario of type 2 diabetes mellitus (T2DM) patients with different stages of diabetic kidney disease (DKD). Urine from 60 T2DM patients was collected: 22 normal (stage A1), 18 moderately increased (stage A2) and 20 severely increased (stage A3) albuminuria. A total of 1080 naturally occurring peptides were detected, which resulted in the identification of a total of 100 proteins, irrespective of the patients' renal status. The classification accuracy showed that the most severe DKD (A3) presented a distinct urinary peptidomic pattern. Estimates for peptide importance assessed during RF model training included multiple fragments of collagen and alpha-1 antitrypsin, previously associated to DKD. Proteasix tool predicted 48 proteases potentially involved in the generation of the 60 most important peptides identified in the urine of DM patients, including metallopeptidases, cathepsins, and calpains. Collectively, our study lightened some biomarkers possibly involved in the pathogenic mechanisms of DKD, suggesting that peptidomics is a valuable tool for identifying the molecular mechanisms underpinning the disease and thus novel therapeutic targets.

Glomerular filtration rate measurement and prediction equations.

Chronic kidney disease (CKD) is defined as the presence of kidney damage or a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for three or more months. Measurement of serum creatinine is the most commonly used method to evaluated kidney function, but it must be included in formulas to estimate GFR, adjusting for age, gender and ethnicity, such as the Modification of Diet in Renal Disease (MDRD) study equation. The performance of this equation is acceptable for patients with CKD but appears to under-estimate GFR in populations with unknown kidney status. A new formula has been developed recently. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation appears to perform better than the MDRD equation. Cystatin C has been widely evaluated as a marker for GFR and seems to be more sensitive than creatinine. The aim of this review is to discuss the recommendations for detecting CKD, emphasizing the characteristics and limitations of GFR estimating equations and pitfalls in the evaluation of urinary albumin excretion.