Height loss in postmenopausal women predicts multiple fractures in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: In daily practice the diagnostic process for osteoporosis in elderly patients should also include physical assessment. The aim of the study was to verify the hypothesis that height loss (HL) predicts fracture incidence. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women recruited in the RAC-OST-POL study. At baseline, data were collected in 978 postmenopausal women at a mean age of 66.48±7.6 years, and at 10-year follow-up 640 patients remained, with a mean age of 75.04 ± 6.95 years. Current height and HL were established in regard to maximal life height. Data on fracture incidence were gathered throughout the period of observation. RESULTS: During the follow-up period 190 osteoporotic fractures were noted. Ninety-one women had one fracture, and in 38 women, multiple fractures occurred. In the fractured and unfractured subgroups, HL was 5.45 ± 3.28 and 4.8 ± 3.56 cm, respectively, and differed significantly (p < 0.05). HL in subjects without fracture did not differ from those with one fracture (HL 4.8 ± 3.56 vs. 4.8 ± 2.66 cm, respectively). For patients with more than one fracture HL was 7.03 ± 4.06 cm and was significantly higher than in subjects with one or without any fracture (p < 0.01). Based on receiver operating characteristic (ROC) analysis, HL of 6 cm was identified as the cut-off point for high risk of multiple fractures. CONCLUSION: HL of at least 6 cm is the predictor of multiple fractures in a prospective observation of a representative epidemiological female sample. Therefore, the measurement of HL should always be included in patients' assessments.

Development of a tool for predicting HNF1B mutations in children and young adults with congenital anomalies of the kidneys and urinary tract.

BACKGROUND: We aimed to develop a tool for predicting HNF1B mutations in children with congenital abnormalities of the kidneys and urinary tract (CAKUT). METHODS: The clinical and laboratory data from 234 children and young adults with known HNF1B mutation status were collected and analyzed retrospectively. All subjects were randomly divided into a training (70%) and a validation set (30%). A random forest model was constructed to predict HNF1B mutations. The recursive feature elimination algorithm was used for feature selection for the model, and receiver operating characteristic curve statistics was used to verify its predictive effect. RESULTS: A total of 213 patients were analyzed, including HNF1B-positive (mut + , n = 109) and HNF1B-negative (mut - , n = 104) subjects. The majority of patients had mild chronic kidney disease. Kidney phenotype was similar between groups, but bilateral kidney anomalies were more frequent in the mut + group. Hypomagnesemia and hypermagnesuria were the most common abnormalities in mut + patients and were highly selective of HNF1B. Hypomagnesemia based on age-appropriate norms had a better discriminatory value than the age-independent cutoff of 0.7 mmol/l. Pancreatic anomalies were almost exclusively found in mut + patients. No subjects had hypokalemia; the mean serum potassium level was lower in the HNF1B cohort. The abovementioned, discriminative parameters were selected for the model, which showed a good performance (area under the curve: 0.85; sensitivity of 93.67%, specificity of 73.57%). A corresponding calculator was developed for use and validation. CONCLUSIONS: This study developed a simple tool for predicting HNF1B mutations in children and young adults with CAKUT.

Depressive disorders in children with chronic kidney disease treated conservatively.

BACKGROUND: Children with chronic kidney disease (CKD) experience a lot of mental and emotional stress, which can lead to the development of depressive disorders. The prevalence of depressive disorders in CKD children is estimated to be between 7% and 35%. OBJECTIVES: The aim of our study was to analyze the prevalence and characteristics of depression and depressive symptoms in children and adolescents with CKD treated conservatively. MATERIAL AND METHODS: The cross-sectional, multicenter study was conducted in 73 CKD children aged 8-18 and in 92 of their parents. To assess the mental wellbeing of CKD children, Kovacs's Children's Depression Inventory 2 (CDI2) was used as CDI2: Self-Report and CDI2: Parent Form. RESULTS: The majority of CKD children acquired medium scores in CDI2, 11% of participants reported symptoms suggesting depressive disorder, and among them 8.2% met the criteria for depression. A significant relationship was found between age and interpersonal problems, age at CKD diagnosis, and total score and ineffectiveness, CKD duration and total score/emotional problems. Depressive symptoms were associated with the stage of CKD, and they differed significantly between stages III and IV. We noticed the child-parent disagreement on reported depressive symptoms. Parents perceive their children's mental state as worse than the children themselves. CONCLUSIONS: There is a problem of depression in children with CKD treated conservatively. Variables associated with depressive symptoms in CKD children treated conservatively require further study. Key factors predisposing to the development of depression seem to be age at the time of diagnosis, disease duration, and progression of CKD from stage III to IV. Disparities between depressive symptoms self-reported by CKD children and their parents' assessment require further analysis. However, these disparaties indicate that the final diagnosis of the occurrence of depressive disorders should be based on a multidimensional assessment of the patient's situation.

Nutritional Status of Children with Newly Diagnosed Food Allergies.

BACKGROUND: Most published pediatric guidelines on food allergy highlight the importance of nutritional counseling and dietary adequacy to avoid either growth retardation or nutritional deficiencies. The aim of the study was an assessment of the nutritional status of children with IgE-mediated food allergies. MATERIAL AND METHOD: 45 patients with newly diagnosed food allergy (FA) and 33 healthy controls were analyzed (aged 6 to 72 months, 60.2% boys). The nutritional status was assessed using anthropometric measurements (body weight and length) and serum laboratory tests. The results were analyzed with the Statistica 12 software (Tulsa, OK, USA). RESULTS: 82%, 40%, 8.8%, and 6.6% of the studied children demonstrated allergy to hen's egg, cow's milk, pork meat, and wheat/rye, respectively. Z-score BMI < -2SD was more often found in the FA subjects under 30 months of age than in the controls (p = 0.04). As many as 77.8% of the FA subjects and 78.8% of the controls were of normal height (hSDS: -0.23 ± 1.74 and -0.31 ± 1.49, respectively, p = 0.8). Retinol binding protein four serum concentration was significantly lower in the FA group (17.01 ± 3.84 mg/L) than in the controls (20.47 ± 4.87 mg/L, p < 0.001). No statistically significant differences were observed between the FA group and the controls (either in the younger or the older age group) (p > 0.05) for the serum concentrations of total protein, total cholesterol, thyroxin-binding prealbumin (TBPA), 25(OH)D, hemoglobin level or white blood cells. CONCLUSIONS: In patients under 30 months of age, one of the symptoms of food allergy may be body weight deficiency, while short stature is less common at the time of diagnosis.

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

BACKGROUND: The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. METHODS: The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. RESULTS: Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. CONCLUSIONS: Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

Functional status as a predictor of the incidence of falls in 10-year follow-up: results from the RAC-OST-POL study.

INTRODUCTION: The aim of this prospective study was to establish the influence of baseline functional status on the incidence of falls. MATERIAL AND METHODS: The study was performed in an epidemiological sample of postmenopausal women from the RAC-OST-POL study. At baseline there were 978 postmenopausal women with a mean age of 65.9 ± 7.6 years, and at the end of 10-year follow-up 640 patients with a mean age of 65.04 ± 6.95 years remained in observation. Functional status was established at baseline using a stand up and go test (SAG) and the Lawton Instrumental Activities of Daily Living (IADL) scale. Afterwards, data on fall incidence were updated annually using phone interviews. RESULTS: In a 10-year period of observation, in 384 (60%) women at least one fall occurred. At baseline, 90% of subjects achieved maximal value in the IADL scale (24 points). Although the difference between mean IADL score in those who fell and did not fall was noticeable (23.50 ± 1.68 vs. 23.65 ± 1.47, respectively), the category of any IADL score below 24 points was significantly more frequent in women with falls (71.9% vs. 28.1%; chi-square 4.2, p < 0.05). The SAG score in the subgroup with falls was (10.75 ± 3.39) and did not differ in comparison to subgroup without falls (10.27 ± 2.72). CONCLUSION: The baseline result of the IADL scale but not that of the SAG test are related to the incidence of falls in a 10-year prospective observation. Adequate correction of functional status may benefit patients and reduce the fall rate.

POL-RISK: an algorithm for 10-year fracture risk prediction in postmenopausal women from the RAC-OST-POL study.

INTRODUCTION: Fragility fractures are the major consequence of osteoporosis. Thus, fracture risk assessment is an essential part of the diagnostic process in osteoporosis. OBJECTIVES: The aim of the study was to develop an algorithm for fracture risk prediction. PATIENTS AND METHODS: Bone status was evaluated in a population­basedcohort of postmenopausal women at a mean (SD) age of 66.4 (7.8) years. Subsequently, all participants were contacted by phone once a year (for 10 consecutive years) to update their history of fractures. At the end of the 10­year follow­up, the number of the study participants was 640, of whom 129 had a history of 190 osteoporotic fractures recorded during the study period. Statistical analysis included multistep data preprocessing, feature selection, identification of fracture risk factors, and design of the final model. Logistic regression models were fitted and used for the evaluation of variables from determined feature sets, including global fit measures, as well as individual parameters, such as the Wald statistic and P value, odds ratio, and 95% CI. RESULTS: The 10­year risk for any fracture depended on the age of the patient, the number of recorded fractures after the age of 40 years, femoral neck bone mass, and the occurrence of falls during the previous year. The achieved equation was incorporated into an algorithm, available at the www.fracture­risk.pl webpage. CONCLUSION: A fracture prediction algorithm was developed in a longitudinal study to enable calculation of the 10­year fracture risk. Identification of patients at a high risk of fracture should be followed by implementation of appropriate treatment strategy to reduce the number of future fractures.

Impaired Functional Status Increases Fracture Incidence in 10-year Follow-Up: The Results from RAC-OST-POL Study.

INTRODUCTION: The aim of study was to establish the influence of baseline functional status on fracture incidence. METHODOLOGY: In a prospective 10-years observation in epidemiological sample of postmenopausal women from RAC-OST-POL Study a thesis that affected functional status enhance fracture incidence was verified. At baseline, data were collected in 978 women at mean age 66.48±7.6 years and after 10 years of follow-up 640 subjects at mean age 75.04±6.95 years remained in the study. Functional status at baseline was established using Stand up and Go test (SAG) and Activity of Daily Living (IADL). Afterwards, annually data on fracture incidence were collected by phone interviews. RESULTS: In the period of observation 190 low-energy fractures in 129 women were noted. The whole group was divided into subgroups: without fracture (n=511), with one fracture (n=91) and those ones who had more than one fracture (n=38). In fractured and unfractured subgroup mean SAG results were 11.36±4.28 and 10.36±2.76, respectively and differed significantly (p<0.01). With increasing number of fractures the SAG time was longer - it was 11.15±4.49 in one fracture subgroup and 11.87±3.73 in multiple fractures subgroup, with both values significantly higher than in no fracture subjects. The mean value of IADL was 23.56±1.60. In 576 (90%) women IADL reached maximal value of 24 points. In the rest of them (n=64) IADL score was between 11 and 23 points. Mean value of IADL in fractured and unfractured subgroup were 23.27±1.97 and 23.64±1.47, respectively and differed significantly (p<0.01). CONCLUSION: The measures of functional status predict fractures in a prospective observation of representative epidemiological female sample.

X-linked variations in SHROOM4 are implicated in congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems.

BACKGROUND: SHROOM4 is thought to play an important role in cytoskeletal modification and development of the early nervous system. Previously, single-nucleotide variants (SNVs) or copy number variations (CNVs) in SHROOM4 have been associated with the neurodevelopmental disorder Stocco dos Santos syndrome, but not with congenital anomalies of the urinary tract and the visceral or the cardiovascular system. METHODS: Here, exome sequencing and CNV analyses besides expression studies in zebrafish and mouse and knockdown (KD) experiments using a splice blocking morpholino in zebrafish were performed to study the role of SHROOM4 during embryonic development. RESULTS: In this study, we identified putative disease-causing SNVs and CNVs in SHROOM4 in six individuals from four families with congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems (CNS). Embryonic mouse and zebrafish expression studies showed Shroom4 expression in the upper and lower urinary tract, the developing cloaca, the heart and the cerebral CNS. KD studies in zebrafish larvae revealed pronephric cysts, anomalies of the cloaca and the heart, decreased eye-to-head ratio and higher mortality compared with controls. These phenotypes could be rescued by co-injection of human wild-type SHROOM4 mRNA and morpholino. CONCLUSION: The identified SNVs and CNVs in affected individuals with congenital anomalies of the urinary tract, the anorectal, the cardiovascular and the central nervous systems, and subsequent embryonic mouse and zebrafish studies suggest SHROOM4 as a developmental gene for different organ systems.

Fracture risk and fracture prevalence in women from outpatient osteoporosis clinic and subjects from population-based sample: A comparison between GO Study and RAC-OST-POL cohorts.

BACKGROUND: The method of recruiting the study subjects is an important element of the study design. It can have a strong influence on the results. Different recruitment schedules can give a different picture of the studied phenomenon. OBJECTIVES: The aim of the study was to compare bone health in a group of female patients treated for osteoporosis with a population-based sample. MATERIAL AND METHODS: A cohort of women from GO Study from 1 outpatient osteoporotic clinic (n = 1442, mean age 65.8 ±6.7 years) and population-based female sample of RAC-OST-POL Study (n = 963, mean age 65.8 ±7.5 years) were studied. Mean age did not differ between groups. Mean weight, height and body mass index (BMI) in subjects from GO Study and RAC-OST-POL Study were 69.5 ±13.1 kg, 157.8 ±6.1 cm and 27.9 ±5.1 kg/m2, and 74.2 ±13.7 kg, 156.0 ±6.0 cm and 30.5 ±5.4 kg/m2, respectively, and differed significantly (p < 0.0001 for each variable). Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a Prodigy or Lunar DPX device (GE Healthcare, Waukesha, USA). Fracture risk was established using FRAX, Garvan and POL-RISK. RESULTS: Mean values of T-score for femoral neck in subjects from GO Study and RAC-OST-POL Study were -1.67 ±0.91 and -1.27 ±0.91 and differed significantly (p < 0.0001). In GO Study and RAC-OST-POL Study, there were 518 (35.9%) and 280 (29.1%) subjects with fractures, respectively. The fracture frequency was significantly higher in the GO Study group (p < 0.001). Among clinical risk factors, only rheumatoid arthritis (p < 0.0001) secondary osteoporosis (p < 0.0001) and falls (p < 0.0001) were more frequent in RAC-OST-POL Study. Fracture risk established using FRAX, Garvan and POL-RISK calculators was significantly greater in patients enrolled in the GO Study than in subjects from the RAC-OST-POL population-based sample (p < 0.0001 for each variable). CONCLUSIONS: Differences noted between female patients treated for osteoporosis and population-based sample, especially in regard to fracture risk, reveal a strong influence of recruitment criteria on study results in the field of bone health and osteoporosis.

Pulmonary Function in Paediatric Patients with Inflammatory Bowel Disease.

BACKGROUND: Among the extraintestinal manifestations of inflammatory bowel disease (IBD), those involving the lungs are relatively rare and often overlooked. There are only scarce data on the prevalence of IBD-associated lung involvement in children. OBJECTIVES: The aim of our study was to assess pulmonary function in IBD children by different methods and to evaluate the influence of immunosuppressive therapy on disease severity. METHODS: Seventy-two children with IBD (mean age of 14.45 ± 2.27 years) and 40 age-matched healthy controls (mean age of 14.17 ± 2.82) were included in the study. Pulmonary function tests (PFTs) were carried out by means of spirometry, oscillometry (IOS) and fractional exhaled nitric oxide (FeNO) to assess the pulmonary involvement. RESULTS: Certain differences were observed between the study group and the control group, regarding the spirometric and oscillometry parameters. The fractions of exhaled nitric oxide did not differ between the group with IBD patients and the control group with regards to disease activity, the duration of illness and the administered immunosuppressive treatment. CONCLUSIONS: The mean spirometry results were significantly different in the study group compared to the controls, although they were still within the normal limits. The pulmonary function abnormalities did not depend on either the disease activity or the immunosuppressive therapy. Oscillometry could be a supplementary method to assess pulmonary resistance. In turn, FeNO does not appear to be useful either in screening IBD children for pulmonary involvement or for the evaluation of disease activity. It appears then that only general screening of asymptomatic patients is a suitable method and a necessary recommendation in this population, prompting a revision of the current diagnostic approach.

Changes in osteoporosis therapy in postmenopausal women from the RAC­OST­POL study: a 10­year follow­up.

INTRODUCTION: Therapeutic regimens for osteoporosis are the key elements in the management of osteoporotic patients. OBJECTIVE: The aim of the study was to present data on changes in osteoporosis therapy in women during a 10­year follow­up. PATIENTS AND METHODS: We analyzed a population­based sample recruited in the RAC­OST­POL study. At baseline, the cohort included 978 women, of whom 541 remained in the follow­up. Mean (SD) age of the patients was 74.7 (6.6) years. RESULTS: The number of untreated women and those on alendronate decreased, while the number of patients receiving other forms of the antiresorptive therapy or calcium / vitamin D supplementation increased during the study. The percentage of untreated women in the rural areas and the urban areas was, respectively, 85% and 74.1% at baseline, and 74.3% and 63.3% at the end of the follow­up. The percentage of untreated women decreased significantly, both in rural and urban cohorts. It was accompanied by a significant increase in calcium / vitamin D supplementation in both subgroups. Regarding the antiresorptive therapy, there was a significant increase in the frequency of its use only in the rural cohort. The use of therapeutic strategies was determined by the level of education. The frequency of calcium and / or vitamin D supplementation increased significantly in all education-related categories during the follow­up. CONCLUSION: Changes in the therapy of postmenopausal women with osteoporosis, observed in a 10­year follow­up of the RAC­OST­POL study, indicated that the level of care did not improve in this group of patients.

One year of the COVID-19 pandemic in Poland-the incidence of osteoporotic forearm, arm, and hip fractures.

The study attempts to analyse whether the COVID-19 pandemic affected the incidence of forearm, arm, and hip fractures during a 1-year observation period. Additionally, changes in the overall treatment costs of those fractures were estimated. During the COVID-19 pandemic, the incidence of forearm, arm, and hip fractures remained statistically unchanged, neither were any significant changes observed in the expenditure, incurred for the treatment of the fracture cases. PURPOSE: The purpose of the study was to find out and evaluate if the consequences of COVID-19 pandemic (including lockdown and the fear of infection) influenced the incidence of osteoporotic forearm, arm, and hip fractures and to estimate the changes in the costs of their management during one-year observation period. METHODS: The incidence of forearm, arm, and hip fractures was collected for the population, aged ≥ 50, residing at the district of Tarnowskie Góry and the Town of Piekary Slaskie, Poland, during 1 year of COVID-19 pandemic (from March 16th 2020 to March 15th 2021). The obtained results were compared with the number of corresponding limb fractures, recorded before the pandemic during five consecutive yearly periods, each starting from 16th March and ending on the 15th March of a subsequent year, the entire period covering the years 2015-2020. The rates of the analysed fractures were calculated per 100,000 inhabitants together with their economic impact. RESULTS: The mean numbers and the incidence rates of upper extremity fractures were slightly lower during the COVID-19 pandemic than in the previous 5 years, whereas hip fracture figures remained almost stable. The observed changes were not statistically significant. That annual observation revealed a slight decrease in expenditure volumes, when compared to the analysed period before the pandemic (-0.33%). CONCLUSION: The decreased incidence rate of forearm, arm, and hip fractures, observed during the first months of the COVID-19 pandemic, was not statistically significant in the 1-year observation. After several weeks/months under the shock, caused by government limitations and the fear of infection, the number of patients remained unchanged during the one-year observation.

Association of chemotactic cytokine receptor 5 (CCR5) gene polymorphism (59029 A/G, rs1799987) with diabetic kidney disease in patients with type 2 diabetes from Poland.

INTRODUCTION: Diabetic kidney disease (DKD) pathogenesis is multifactorial and is a combination of metabolic, genetic, and environmental factors. Due to a long period of asymptomatic course, it is often diagnosed late when advanced stages of the disease are present. Among patients with diabetes, the presence of chemotactic cytokine receptor 5 (CCR5) gene polymorphism is suspected to be associated with the risk of DKD occurrence; however, the results of the research conducted so far are inconclusive. The aim of this study was to evaluate the CCR5 gene polymorphism (rs1799987, 59029 A/G) association with DKD among patients with type 2 diabetes mellitus (T2DM), who are residents of the Upper Silesia region of Poland. MATERIAL AND METHODS: CCR5 gene polymorphism (rs1799987, 59029 A/G) was assessed among consecutive patients with type 2 diabetes mellitus (T2DM) treated in a single outpatient diabetology clinic in Upper Silesia, Poland. Its association with DKD was examined. Additionally, selected clinical and demographic data were included in the analysis. RESULTS: Among 467 eligible study patients, there was no association between examined CCR5 gene polymorphism and the presence of DKD in relation both to the American Diabetes Association definition (p = 0.6) and to the National Kidney Foundation definition (p = 0.3) of this complication. CONCLUSION: The presented study did not confirm the association between the examined gene polymorphism and the risk of DKD; further studies in this area are needed in order to establish or explicitly exclude this association.

Glucocorticoids Increase Fracture Risk and Fracture Prevalence Independently from Bone Mineral Density and Clinical Risk Factors: Results from the Gliwice Osteoporosis (GO) Study.

The aim of the study was to establish the influence of glucocorticoids (GC) on fracture risk, probability, and prevalence. A set of 1548 postmenopausal women were divided into study group - treated with GC (n=114, age 66.48±7.6 years) and controls (n=1434, age 66.46±6.83 years). Data on clinical risk factors for osteoporosis and fractures were collected. Hip bone densitometry was performed using a device Prodigy (GE, USA). Fracture probability was established by FRAX, and fracture risk by Garvan algorithm and POL-RISK. Fracture risk and fracture probability were significantly greater for GC-treated women in comparison to controls. In the study group, there were 24, 3, 24, and 6 fractures noted at spine, hip, forearm, and arm, respectively. The respective numbers of fractures reported in controls at those skeletal sites were: 186, 23, 240, and 25. The use of GCs increased significantly prevalence of all major, spine and arm fractures. Also the number of all fractures was affected by GC use. Following factors significantly increased fracture probability: age (OR 1.04 per each year; 95% CI: 1.03-1.06), GC use (OR 1.54; 95% CI: 1.03-2.31), falls (OR 2.09; 95% CI: 1.60-2.73), and FN T-score (OR 0.62 per each unit; 95% CI: 0.54-0.71). In conclusion, in patients treated with GCs the fracture risk, probability, and prevalence were increased. This effect was evident regardless of whether GC therapy is included in the algorithm as a risk factor (FRAX, POL-RISK) or not taken into consideration (Garvan nomogram).

Tumour necrosis factor alpha (TNFα) and alpha-Klotho (αKL) in children and adolescents with chronic kidney disease (CKD).

INTRODUCTION: Chronic kidney disease (CKD) in children, despite the progress in science and technology, is still a serious challenge. Early CKD detection gives a chance of early therapeutic intervention and lowering the progression of the disease. According to several publications indicating the possible use of alpha-Klotho (αKL) and tumour necrosis factor alpha (TNFα) for the early detection of the disease in adults, an attempt was made to evaluate their usefulness in the paediatric population. MATERIAL AND METHODS: The study group consisted of 42 patients with CKD with a mean age of 10.7 years (18 girls and 24 boys). The control group involved 21 healthy children with a mean age of 8.4 years (11 girls and 10 boys). Anthropometrical parameters and blood pressure were taken and routine biochemical tests were performed in the whole group. The concentrations of TNFα and αKL in serum and urine were determined by enzyme immunoassay. RESULTS: Children from the CKD group showed a statistically significant difference in serum TNFα and αKL in comparison to the control group. There was no significant relationship between the evaluated markers and sex, presence of hypertension, or proteinuria in the children. The mean αKL serum concentration was higher in patients on dialysis compared to the group of conservatively treated children, whereas the values of TNFα in serum and urine, as well as the αKL in urine, did not differ significantly in these groups. A significant positive correlation was found between serum αKL concentration and serum creatinine, but there was no other correlation between serum αKL or TNFα concentration and any of the measured anthropometric and laboratory parameters. CONCLUSIONS: Serum TNFα and αKL levels in children with chronic kidney disease, although being statistically different compared to the group of healthy children, except for the correlation of serum aKL and creatinine, showed no other correlations to the most parameters used for chronic kidney disease evaluation including, eGFR. Their usefulness in the early detection of kidney dysfunction in children was not proven.

Influence of SGLT2 Inhibitor Treatment on Urine Antioxidant Status in Type 2 Diabetic Patients: A Pilot Study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been recognized as potent antioxidant agents. Since SGLT2i are nephroprotective drugs, we aimed to examine the urine antioxidant status in patients with type 2 diabetes mellitus (T2DM). One hundred and one subjects participated in this study, including 37 T2DM patients treated with SGLT2i, 31 T2DM patients not using SGLT2i, and 33 healthy individuals serving as a control group. Total antioxidant capacity (TAC), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD), free thiol groups (R-SH, sulfhydryl groups), and catalase (CAT) activity, as well as glucose concentration, were assessed in the urine of all participants. Urine SOD and MnSOD activity were significantly higher among T2DM patients treated with SGLT2i than T2DM patients without SGLT2i treatment (p = 0.009 and p = 0.003, respectively) and to the healthy controls (p = 0.002 and p = 0.001, respectively). TAC was significantly lower in patients with T2DM treated with SGLT2i when compared to those not treated and healthy subjects (p = 0.036 and p = 0.019, respectively). It could be hypothesized that the mechanism by which SGLT2i provides nephroprotective effects involves improvement of the SOD antioxidant activity. However, lower TAC might impose higher OS (oxidative stress), and elevation of SOD activity might be a compensatory mechanism.

Hyperuricemia Is an Early and Relatively Common Feature in Children with HNF1B Nephropathy but Its Utility as a Predictor of the Disease Is Limited.

BACKGROUND: Hyperuricemia is recognized as an important feature of nephropathy, associated with a mutation in the hepatocyte nuclear factor-1B (HNF1B) gene, and could serve as a useful marker of the disease. However, neither a causal relationship nor its predictive value have been proven. The purpose of this study was to assess this in children with renal malformations, both with (mut+) and without HNF1B mutations (mut-). METHODS: We performed a retrospective analysis of clinical characteristics of pediatric patients tested for HNF1B mutations, collected in a national registry. RESULTS: 108 children were included in the study, comprising 43 mut+ patients and 65 mut- subjects. Mean sUA was higher and hyperuricemia more prevalent (42.5% vs. 15.4%) in HNF1B carriers. The two groups were similar with respect to respect to age, sex, anthropometric parameters, hypertension, and renal function. Renal function, fractional excretion of uric acid and parathyroid hormone level were independent predictors of sUA. The potential of hyperuricemia to predict mutation was low, and addition of hyperuricemia to a multivariate logistic regression model did not increase its accuracy. CONCLUSIONS: Hyperuricemia is an early and common feature of HNF1B nephropathy. A strong association of sUA with renal function and parathyroid hormone limits its utility as a reliable marker to predict HNF1B mutation among patients with kidney anomalies.

Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine.

INTRODUCTION: Thiopurines, such as azathioprine (AZA) and 6-mercaptopurine (6-MP), are immunomodulatory agents, used for the maintenance of remission in children with inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC), as well as with autoimmunological hepatitis (AIH). Measurements of thiopurine metabolites may allow identifying patients at risk for toxicity and nonadherence. It can also provide an explanation for the ineffectiveness of the treatment, observed in some patients. Patients and Methods. A retrospective analysis was carried out of sixty-eight patients (thirty-six patients with CD, eighteen with UC, and fourteen with AIH), treated with AZA. Thiopurine metabolites, 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP), were assayed by high-performance liquid chromatography (HPLC), and the AZA dose was adjusted when 6-TGN concentration was known. RESULT: Only twenty-five (41%) children had therapeutic 6-TGN concentrations, ten (16%) subjects had suboptimal 6-TGN concentrations, and twenty-six subjects (43%) had 6-TGN concentrations above the recommended therapeutic range. 6-MMP was not above the therapeutic range in any case. Seven subjects revealed undetectable 6-TGN and 6-MMP levels, indicating nonadherence. The mean AZA dose after the 6-TGN concentration-related adjustment did not differ, in comparison to the initial dose, either in IBD or AIH groups. The mean AZA dose was lower in AIH than in IBD. The subjects with an optimal 6-TGN level presented with a higher ratio of remission (88%) than the under- or overdosed patients (60% and 69%), respectively (Chi - square test = 3.87, p < 0.05). CONCLUSION: Timely measurements of thiopurine metabolites can be a useful tool to identify nonadherent patients before a decision is taken to switch to another drug. We may also spot the patients who receive either too low or too high doses, compensating dose deviations in an appropriate way. The patients with optimal 6-TGN levels presented a higher percentage of remission than the under- or overdosed patients. In most patients, both initial and adjusted AZA doses, lower than suggested in guidelines, appeared to be sufficient to maintain remission.

Low dietary calcium intake does not modify fracture risk but increases fall frequency: the results of GO Study.

INTRODUCTION: The aim of the study was to verify the thesis that dietary calcium intake influences the risk of osteoporotic fractures established by online available calculators. MATERIAL AND METHODS: The study was performed in 521 postmenopausal women aged over 55 years, recruited in one osteoporotic outpatient clinic. Mean age was 67.7 ± 8.6 years. Fracture risk was established using FRAX (major and hip fractures, 10 years), Garvan calculator (any and hip fractures, 5 and 10 years), and the Polish algorithm available at www.fracture-risk.pl (any fractures, 5 years). Bone densitometry at the femoral neck was performed using a DPX device (Lunar, GE, USA) to calculate fracture risk by each of those calculators. Calcium intake was established based on a dietary questionnaire. RESULTS: Mean values of fracture risk for all three calculators and T-score value for DXA measurement at the femoral neck did not correlate with calcium intake. A tendency to insignificantly lower calcium intake was observed in the subgroup with high hip fracture risk by FRAX (≥ 3%) vs. low hip FRAX (< 3%): 744 ± 328 mg/day vs. 765 ± 299 mg/day. The same analysis for FRAX major fracture risk revealed a similar tendency: 700 ± 299 mg/day and 760 ± 311 mg/day in high (≥ 20%) and low (< 20%) fracture-risk groups, respectively. Calcium intake did not influence the results obtained in the other two calculators at all. Calcium intake did not differ between subjects with prior falls and those without falls. However, if the number of falls was taken into account, the women who reported three and more falls had significantly lower calcium intake (621 ± 275 mg/day) than subjects with no falls (767 ± 304 mg/day; p < 0.05) or those with one fall (766 ± 317 mg/day; p < 0.05). CONCLUSIONS: Calcium intake does not correlate with fracture risk established by calculators available on-line, but low calcium intake may increase the risk of falls.