Gastrointestinal cell injury and perceived symptoms after running the Boston Marathon.

Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. Our aim was to study intestinal cell injury [via intestinal fatty acid binding protein (I-FABP)] and perceived GI distress symptoms among marathon runners. We also examined potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners. This was a parallel mixed-methods study design. 2019 Boston Marathon participants were recruited via email and subjects completed surveys before the race describing demographics and training history. Participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample at three time points (immediately pre-race, post-race, and 24-h post-race). Due to weather, blood samples were only collected immediately and 24-h post-race. A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/mL) to 24-h post-race (1657.3 ± 950.7 pg/mL, t (39) = -4.228, p < .001, d = -.669). There was a significant difference in overall GI symptom scores across the three time points (F (2, 39) = 41.37, p < .001). The highest average score occurred post-race (.84 ± .68), compared to pre-race (.09 ± .12) and 24-h post-race (.44 ± .28). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. Our study provides further support to the individualized nature of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise.

Comparison of female breast cancer between Russia and Germany: A population-based study on time trends and stage at diagnosis.

OBJECTIVES: While a mammography-screening program (MSP) is being offered systematically in Germany since 2009, the dispanserizatsiya has been implemented in Russia since 2013. This study examined trends of stage at breast cancer diagnosis in two Russian regions and compared the results with the development in Germany. In addition, we aimed to gain further insights into the early detection of breast cancer in Russia. METHODS: Incidence data from two cancer registries in Russia and 12 population-based cancer registries in Germany were used to analyse breast cancer incidence rates among women above age 30 over time. Further, we calculated rate ratios to compare the age group-specific incidence rates after the implementation of MSP in Germany (2010-2014) with the period before implementation (2003-2005) separately for each tumour stage and all stages combined. RESULTS: During the study period from 2003 to 2014, age-standardised rates for breast cancer were 54.6 and 116.7 per 100,000 for Russia and Germany, respectively. The proportion of the T1 stage at diagnosis among Russian women aged 50 + is half than that in Germany. Nevertheless, we observed an increasing trend of early-stage alongside the reduction of advanced-stage incidence rates of breast cancer in Russia. CONCLUSIONS: The observed trend in Russia may reflect overall positive changes in early detection of breast cancer, with actual proportion of T1 stage still far behind Germany. Advances in breast cancer screening efforts through the dispanserizatsiya may help to further reduce the breast cancer burden.

Long-Term Outcomes of in Utero Ramadan Exposure: A Systematic Literature Review.

Health outcomes of in utero Ramadan exposure have been reported in a systematic literature review; however, the available literature on long-term effects were not fully covered. Our study aims to specifically review the long-term outcomes of in utero Ramadan exposure. We searched for original research articles analyzing any long-term outcome of in utero Ramadan exposure, excluding maternal and perinatal outcomes. Sixteen studies from 8304 non-duplicate search results were included. Most studies suggest negative consequences from in utero Ramadan exposure on health, as well as on economic outcomes later in adulthood. Higher under-five mortality rate, higher mortality under three months, and under one year, shorter stature, lower body mass index, increased incidence of vision, hearing and learning disabilities, lower mathematics, writing and reading scores, as well as a lower probability to own a home were associated with Ramadan exposure during conception or the first trimester of pregnancy. Furthermore, age and sex seem to play a pivotal role on the association. Existing studies suggest that in utero Ramadan exposure may adversely impact long-term health and economic well-being. However, evidence is limited. Meanwhile, increasing awareness of the potential risks of Ramadan fasting during pregnancy should be raised among pregnant women and clinicians and other antenatal care workers should promote better maternal healthcare.

The reliability of the slopes and y-intercepts of the motor unit firing times and action potential waveforms versus recruitment threshold relationships derived from surface electromyography signal decomposition.

PURPOSE: Changes in motor unit (MU) activity pre- to post-interventions is of high interest. However, there is minimal information regarding day-to-day changes or the reliability of measuring MU activity. This study examined the reliability of relationships calculated via the MU action potential (AP) trains derived from surface electromyography signal decomposition. A comparison between reliability statistics was made between MUAP trains verified with only the reconstruct-and-test versus verification including reconstruct-and-test with spike trigger average (STA) procedures. METHODS: Twenty-one individuals performed isometric muscle actions at 50% of maximal voluntary contraction of the first dorsal interosseous on two separate visits. MUs included for reliability analyses initially met the > 90% accuracy from the reconstruct-and-test. STA was applied as an additional exclusionary procedure. Linear regressions were applied to the firing rate and AP amplitude versus recruitment threshold relationships with and without MUs that met the STA criteria. Reliability statistics were also performed on relationships that met a strict range of recruitment thresholds. Reliability was established with intraclass correlation coefficients (ICC) along with other traditional parameters. RESULTS: The firing rate versus recruitment threshold relationships were reliable (ICC > 0.56) and improved (ICC > 0.84) when recruitment ranges were controlled. The slopes of the MUAP amplitude versus recruitment threshold relationships were reliable (ICC > 0.78) while the y-intercepts were reliable (ICC > 0.81) once corrections were made to combat negative scores. CONCLUSIONS: Electromyographic signal decomposition without the secondary STA verification procedures can be used to detect intervention-related changes in neural drive with confidence when recorded MU recruitment thresholds are similar across days.

Examination of eating disorder risk among university marching band artists.

BACKGROUND: Marching band artists are a physically active population, composed of approximately 27,000 people in the United States. University marching band artists face many of the same physically active demands and mental stressors as student athletes, potentially predisposing them to injury, illness, and risk for eating disorders (EDs). The purpose of this study was to examine ED risk across sex in university marching band artists, and to determine the type of risk based on the Eating Disorder Inventory-3 (EDI-3) and Eating Disorder Inventory-3 Symptom Check List (EDI-3 SC). A secondary aim examined marching band artists and pathogenic weight control behavior use across sex. METHODS: This was a cross-sectional study. A total of 150 marching band artists (female: n = 84, male: n = 66, age = 19.9 ± 1.1 years) from three National Collegiate Athletic Association Division I university marching bands participated in the study. We screened for ED risk using the EDI-3, and the EDI-3 SC. RESULTS: Overall, marching band artists were at risk for EDs, using only the EDI-3, 45.3% (n = 68) were at risk, with females at significant higher risk than males [χ2 = 5.228, p = .022]; using only the EDI-3 SC, 54% (n = 81) were at risk and no significant differences were found across sex. Overall, 48% of all participants reported dieting and 20.7% engaged in excessive exercise to control weight. Significant differences were found between sex and purging to control weight [χ2 = 3.94, p = .047] and laxative use [χ2 = 4.064, p = .044], with females engaging in behavior more than males. CONCLUSIONS: Eating disorder risk was prevalent for both female and male marching band artists, with females displaying higher risk for EDs than males. Furthermore, marching band artists are engaging in pathogenic behaviors to control their weight. Healthcare providers (e.g., physicians, athletic trainers, physical therapist, dietitians, etc.) working in this setting should be aware of the risk factors displayed in marching band artists, and be able to provide education, prevention, and clinical interventions to this population. Additionally, marching band administrators should be aware of all medical risk factors and the benefit of having a healthcare provider (e.g., athletic trainer) to oversee the healthcare and wellness of marching band artists.

Non-steroidal anti-inflammatory drugs on core body temperature during exercise: A systematic review.

BACKGROUND: Because of their anti-pyretic effects, some individuals prophylactically use non-steroidal anti-inflammatory drugs (NSAIDs) to blunt core temperature (Tc) increases during exercise, thus, potentially improving performance by preventing hyperthermia and/or exertional heat illness. However, NSAIDs induce gastrointestinal damage, alter renal function, and decrease cardiovascular function, which could compromise thermoregulation and increase Tc. The aim of this systematic review was to evaluate the effects of NSAIDs on Tc in exercising, adult humans. METHODS: We conducted searches in MEDLINE, PubMed, Cochrane Reviews, and Google Scholar for literature published up to November 2020. We conducted a quality assessment review using the Physiotherapy Evidence Database scale. Nine articles achieved a score ≥ seven to be included in the review. RESULTS: Seven studies found aspirin, ibuprofen, and naproxen had no effect (p > .05) on Tc during walking, running, or cycling for ≤ 90 min in moderate to hot environments. Two studies found significant Tc changes. In one investigation, 81 mg of aspirin for 7-10 days prior to exercise significantly increased Tc during cycling (p < .001); final Tc at the end of exercise = 38.3 ± 0.1 °C vs. control = 38.1 ± 0.1 °C. In contrast, participants administered 50 mg rofecoxib for 6 days experienced significantly lower Tc during 45 min of cycling compared to placebo (NSAID Tc range ≈ 36.7-37.2 °C vs control ≈ 37.3-37.8 °C, p < 0.05). CONCLUSIONS: There are limited quality studies examining NSAID effects on Tc during exercise in humans. The majority suggest taking non-selective NSAIDs (e.g., aspirin) 1-14 days before exercise does not significantly affect Tc during exercise. However, it remains unclear whether Tc increases, decreases, or does not change during exercise with other NSAID drug types (e.g., naproxen), higher dosages, chronic use, greater exercise intensity, and/or greater environmental temperatures.

Core Body Temperatures in Collegiate Marching Band Artists During Rehearsals and Performances.

CONTEXT: To our knowledge, no researchers have investigated thermoregulatory responses and exertional heat illness (EHI) risk factors in marching band (MB) artists performing physical activity in high environmental temperatures. OBJECTIVE: To examine core temperature (Tc) and EHI risk factors in MB artists. DESIGN: Descriptive epidemiology study. SETTING: Three rehearsals and 2 football games for 2 National Collegiate Athletic Association Division I institution's MBs. PATIENTS OR OTHER PARTICIPANTS: Nineteen volunteers (females = 13, males = 6; age = 20.5 ± 0.9 years, height = 165.1 ± 7.1 cm, mass = 75.0 ± 19.1 kg) completed the study. MAIN OUTCOME MEASURE(S): We measured Tc, wet bulb globe temperature, and relative humidity preactivity, during activity, and postactivity. Other variables were activity time and intensity, body surface area, hydration characteristics (fluid volume, sweat rate, urine specific gravity, percentage of body mass loss), and medical history (eg, previous EHI, medications). The statistical analysis consisted of descriptive information (mean ± standard deviation), comparative analyses that determined differences within days, and correlations that identified variables significantly associated with Tc. RESULTS: The mean time for rehearsals was 102.8 ± 19.8 minutes and for games was 260.5 ± 47.7 minutes. Mean maximum Tc was 39.1 ± 1.1°C for games and 38.4 ± 0.7°C for rehearsals; the highest Tc (41.2°C) occurred during a game. Fluid consumption did not match sweat rates (P < .001). Participants reported to games in a hypohydrated state 63.6% of the time. The maximum Tc correlated with the maximum wet bulb globe temperature (r = 0.618, P < .001) and was higher in individuals using mental health medications (rpb = -0.254, P = .022) and females (rpb = 0.330, P = .002). Body surface area (r = -0.449, P < .001) and instrument mass (r = -0.479, P < .001) were negatively correlated with Tc. CONCLUSIONS: Marching band artists experienced high Tc during activity and should have access to athletic trainers who can implement EHI-prevention and -management strategies.

Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon.

The purpose of our field study was to investigate the effects of running the Boston Marathon on acute kidney injury (AKI) biomarkers. We hypothesized that biomarker values would be elevated immediately post-marathon but would resolve in the 24-h post-marathon. Secondarily, we sought to identify sex differences related to renal stress. Participants were 65 runners who completed the Boston Marathon (46 ± 9 years, 65.4 ± 10.8 kg). Urine samples were collected at three different time points (pre-marathon, post-marathon, and 24-h post-marathon). Blood samples were collected post-marathon and 24-h post-marathon. Urine specific gravity (USG) and AKI biomarkers were evaluated. Pre-marathon USG (1.012 ± 0.007) was significantly less than post-marathon (1.018 ± 0.008) and 24-h post-marathon (1.020 ± 0.009; P < 0.001). Male USG (1.024 ± 0.009) was significantly greater 24-h post-marathon than females (1.017 ± 0.008; P = 0.019). Urinary neutrophil gelatinase-associated lipocalin values were significantly greater over time (P < 0.001), and there was a main effect of sex with female urinary creatinine (UCr) greater than males at all three time points (P = 0.040). Post-marathonUCr (366.24 ± 295.16 mg/dl) was significantly greater than pre-marathon (206.65 ± 145.28.56 mg/dl; p < 0.001) and 24-h post-marathon was significantly lower than other time-points (93.90 ± 125.07 mg/dl; P < 0.001). FemaleUCr values were significantly greater than males 24-h post-marathon (P < 0.001). There was no difference in serum cystatin C (SCys) values post- or 24-h post-marathon (P = 0.178). Serum creatinine (SCr) significantly decreased between post-marathon and 24-h post-marathon, (P < 0.001). We can infer that the characteristics unique to the Boston Marathon may have attributed to prolonged elevations in AKI biomarkers. Sex differences were observed during the Boston Marathon warranting further investigation.

Collegiate Marching Band Artists Experience High Core Body Temperatures during Rehearsals and Performances.

CONTEXT: No research has investigated thermoregulatory responses and exertional heat illness (EHI) risk factors in marching band (MB) artists performing physical activity in high environmental temperatures. OBJECTIVE: Examine core temperature (Tc) and EHI risk factors in MB artists. DESIGN: Descriptive epidemiology study. SETTING: Three rehearsals and 2 football games for 2 NCAA Division I MBs. PARTICIPANTS: Nineteen volunteers completed the study (female = 13, males = 6; age = 20.5 ± 0.9 years; weight = 75.0 ± 19.1 kg; height = 165.1 ± 7.1 cm). MAIN OUTCOME MEASURES: We measured Tc pre-, post-, and every 15 minutes during activity and recorded wet-bulb globe temperature (WBGT) and relative humidity (RH) every 15 minutes. Other variables included activity time and intensity, ground surface, hydration characteristics (fluid volume, sweat rate, urine specific gravity, percent body mass loss [%BM]), and medical history (eg, previous EHI, medications). Statistical analysis included descriptives (mean ± standard deviation), comparative analyses determined differences within and between days, and linear regression identified variables that significantly explained Tc. RESULTS: Mean rehearsal time = 102.8 ± 19.8 minutes and game time = 260.5 ± 47.7 minutes. Max game Tc (39.1 ± 1.1°C) was significantly higher than rehearsal (38.4 ± 0.7°C, P = .003). The highest max game Tc = 41.2°C. Participants consumed significantly more fluid than their sweat rates (P < .003), which minimized %BM loss, particularly during rehearsals (-0.4 ± 0.6%). Mean game %BM loss = -0.9 ± 2.0%; however, 63.6% of the time, participants reported hypohydrated to game day. Max Tc was significantly predicted by max WBGT, max RH, ground surface, using mental health medications, and hours of sleep (adjusted R2 = 0.542, P < .001). CONCLUSIONS: Marching band artists experience high Tc during activity and should have access to athletic trainers who can implement EHI prevention and management strategies.

Measuring the accuracies of motor unit firing times and action potential waveforms derived from surface electromyographic decomposition.

This study included spike trigger averaging (STA) procedures to examine the acceptability of the Precision Decomposition (PD) III derived motor unit action potential (MUAP) trains that met the >90% accuracy criteria from the reconstruct-and-test. MUs met the >90% accuracy criteria from the reconstruct-and-test with STA procedures then applied. Y-intercepts and slopes were calculated for the firing rate- and MUAP amplitude-recruitment threshold relationships. Gaussian noise (1% of the SD of the mean interspike interval) was added to the firing times with the changes in MUAPs quantified. A total of 455 MUs were decomposed with 155 MUs removed as a result of the reconstruct-and-test. Five additional MUs were excluded via the STA criteria. The MUAP waveforms deteriorated with the inclusion of Gaussian noise. There were differences in the derived action potentials amplitudes of higher-threshold MUs between the PD III algorithm and the STA procedure. There was excellent agreement among the slopes and y-intercepts between the relationships that included or excluded MUs that did not meet the STA criteria. There was good agreement between the MUAP amplitude-recruitment threshold relationships derived from the PD III and STA procedure. The addition of the STA procedures did not alter the MU-derived relationships.

Quality of life after surgery in secondary hyperparathyroidism, comparing subtotal parathyroidectomy with total parathyroidectomy with immediate parathyroid autograft: Prospective randomized trial.

BACKGROUND: No prospective randomized data exist about the impact of various strategies of parathyroidectomy in secondary hyperparathyroidism patients on quality of life and its possible relationship with metabolic status after the operation. METHOD: In a prospective randomized trial, the Short Form 36 Health Survey Questionnaire was applied to 69 patients undergoing parathyroidectomy through various approaches: subtotal parathyroidectomy (n = 23), total parathyroidectomy (PTx) with autotransplantation of 45 fragments (n = 25) and PTx with autotransplantation of 90 fragments (n = 21). The questionnaire was completed at three moments: (1) preoperatively, (2) 6 months after surgery, and (3) 12 months after surgery. RESULTS: Quality of life improved significantly in the physical component summary score in all three groups. Subtotal parathyroidectomy scores changed from 30.6 preoperatively to 51.7 6 months after surgery and 53.7 12 months after surgery. Total arathyroidectomy with autotransplantation of 45 fragments scores changed from 33.8 preoperatively to 52.6 6 months after surgery and 55.2 12 months after surgery. Total parathyroidectomy with autotransplantation of 90 fragments scores changed from 31.8 preoperatively to 50.5 6 months after surgery and 55.2 12 months after surgery (all groups P < .0001). No significant difference was detected in the physical component summary score change among the three groups. The physical component summary score was negatively correlated to age, parathormone, and alkaline phosphatase preoperatively. CONCLUSION: Parathyroidectomy significantly improves quality of life in hemodialysis patients with secondary hyperparathyroidism, regardless of the type of operation.

The unexpected presence of iron in bone biopsies of hemodialysis patients.

PURPOSE: Bone biopsy defines classical diseases that constitute the renal osteodystrophy. There is a recent concern regarding other histological findings that are not appreciated by using the turnover, mineralization, and volume (TMV) classification. Iron (Fe) overload has been considered a new challenge and the real significance of the presence of this metal in bones is not completely elucidated. Therefore, the main goal of the current study was to not only to identify bone Fe, but also correlate its presence with demographic, and biochemical characteristics. METHODS: This is a cross-sectional analysis of bone biopsies performed in 604 patients on dialysis from 2010 to 2014 in a tertiary academic Hospital. RESULTS: Histomorphometric findings revealed the presence of Fe in 29.1%. Fe was associated with higher levels of serum ferritin and serum calcium. No TMV status was related to Fe bone overload. CONCLUSION: Our study has highlighted that the presence of Fe in one-third of bone samples has unknown clinical significance. The lack of other contemporary bone biopsy study reporting Fe prevents us from comparison. The findings presented here should be specifically addressed in a future research and will require attention prior to implementation of any clinical guideline. If any proposed treatment, however, would change the bone Fe-related morbidity is undetermined.

The effect of vitamin D and zoledronic acid in bone marrow adiposity in kidney transplant patients: A post hoc analysis.

PURPOSE: Osteoblasts and adipocytes are derived from mesenchymal stem cells. An imbalance in the differentiation of these lineages could affect the preservation of bone integrity. Several studies have suggested the importance of this imbalance in the pathogenesis of osteoporosis after kidney transplant (KT), but the role of bone marrow adiposity in this process is not well known, and if the treatment with the anti-absorptive (zoledronic acid-ZA) drugs could attenuate bone loss. Thus, our objective was compare bone marrow adiposity, osteoblasts and osteocytes before and after KT, verify an association between bone remodeling process (Turnover, Volume, and Mineralization-TMV classification), the osteocyte sclerostin expression to evaluate if there is a role of Wnt pathway, as well as the effect of ZA on these cells. METHODS: We studied 29 new living-donor KT patients. One group received ZA at the time of KT plus cholecalciferol for twelve months, and the other group received only cholecalciferol. Bone biopsies were performed at baseline and after 12 months of treatment. Histomorphometric evaluation was performed in bone and bone marrow adipocytes. Sclerostin (Scl) expression in osteocytes was evaluated by immunohistochemistry. RESULTS: Some bone marrow adiposity parameters were increased before KT. After KT, some of them remained increased and they worsened with the use of ZA. In the baseline, lower bone Volume and Turnover, were associated with increased bone marrow adiposity parameters (some of them). After KT, both groups showed the same associations. Osteocyte Scl expression after KT decreased with the use of ZA. We observed also an inverse association between bone adiposity parameters and lower osteocyte sclerostin expression 12 months after KT. CONCLUSION: In conclusion, the present study suggests that KT fails to normalize bone marrow adiposity, and it even gets worse with the use of ZA. Moreover, bone marrow adiposity is inversely associated with bone Volume and Turnover, which seems to be accentuated by the antiresorptive therapy.

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure.

OBJECTIVES:: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS:: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS:: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS:: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

Hypovitaminosis D in patients undergoing kidney transplant: the importance of sunlight exposure

OBJECTIVES: Recent studies have shown a high prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D level less than 30 ng/ml, in both healthy populations and patients with chronic kidney disease. Patients undergoing kidney transplant are at an increased risk of skin cancer and are advised to avoid sunlight exposure. Therefore, these patients might share two major risk factors for hypovitaminosis D: chronic kidney disease and low sunlight exposure. This paper describes the prevalence and clinical characteristics of hypovitaminosis D among patients undergoing kidney transplant. METHODS: We evaluated 25-hydroxyvitamin D serum levels in a representative sample of patients undergoing kidney transplant. We sought to determine the prevalence of hypovitaminosis D, compare these patients with a control group, and identify factors associated with hypovitaminosis D (e.g., sunlight exposure and dietary habits). RESULTS: Hypovitaminosis D was found in 79% of patients undergoing kidney transplant, and the major associated factor was low sunlight exposure. These patients had higher creatinine and intact parathyroid hormone serum levels, with 25-hydroxyvitamin D being inversely correlated with intact parathyroid hormone serum levels. Compared with the control group, patients undergoing kidney transplant presented a higher prevalence of 25-hydroxyvitamin D deficiency and lower serum calcium, phosphate and albumin but higher creatinine and intact parathyroid hormone levels. CONCLUSIONS: Our results confirmed the high prevalence of hypovitaminosis D in patients undergoing kidney transplant. Therapeutic strategies such as moderate sunlight exposure and vitamin D supplementation should be seriously considered for this population.

Persistence of bone and mineral disorders 2 years after successful kidney transplantation.

BACKGROUND: Studies that have conducted bone biopsies after kidney transplantation are scarce, and the results are conflicting. METHODS: We evaluate the bone histomorphometry, in vitro proliferation, and alkaline phosphatase expression in osteoblasts isolated from bone biopsies from 27 kidney transplant patients. The patients had preserved renal function and were treated with the same immunosuppressive therapy, receiving a minimum dose of corticosteroids. RESULTS: The biochemical analysis revealed that 41% of the patients presented with hypercalcemia, 26% presented with hypophosphatemia, and hypovitaminosis D was detected in 63%. The histomorphometric analysis showed a reduced trabecular number and increased trabecular separation, mineral apposition rate, and mineralization lag time, as well as higher osteoid surface, osteoblastic surface, resorption surface, and osteoclastic surface and a lower mineralizing surface, compared with the controls. Based on the TMV classification, bone turnover was normal in 48%, high in 26%, and low in 26% of patients. Bone mineralization was delayed in 48% of the patients, and 58% of the patients with hypovitaminosis D presented with delayed bone mineralization. Bone volume was low in 37% of the patients. The osteoblasts from patients exhibited a higher degree of proliferation compared with those from controls. CONCLUSION: Eight-two percent of our patients presented with alterations in at least one of the TMV parameters. Persistence of hyperparathyroidism, hypovitaminosis D, and immunosuppressive drugs may have influenced osteoblast function, which would explain many of the bone alterations found in these patients.

Impact of cholecalciferol treatment on biomarkers of inflammation and myocardial structure in hemodialysis patients without hyperparathyroidism.

INTRODUCTION: Vitamin D (25-hydroxyvitamin D, 25(OH)D) deficiency, hypovitaminosis D, is highly prevalent in chronic kidney disease patients and is potentially involved with complications in the hemodialysis (HD) population. The aim of this study was to evaluate the impact of cholecalciferol supplementation on biomarkers of mineral metabolism, inflammation, and cardiac function in a group of HD patients presenting with hypovitaminosis D and low intact parathyroid hormone (iPTH) levels. MATERIAL AND METHODS: HD patients with iPTH levels of <300 pg/mL, not receiving vitamin D therapy, and presenting with 25(OH)D levels of <30 ng/mL were enrolled in this prospective study. Oral cholecalciferol was prescribed once a week in the first 12 weeks (50,000 IU) and in the last 12 weeks (20,000 IU) of the study. High-sensitivity C-reactive protein, interleukin-6, and serum albumin were used as inflammatory markers. Echocardiograms were performed on a midweek interdialytic day at baseline and after 6 months of cholecalciferol supplementation. RESULTS: In all, 30 patients were included in the final analysis. We observed a significant increase in serum 25(OH)D levels after 3 months (46.2 ± 14.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) and after 6 months (40.4 ± 10.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) of cholecalciferol supplementation. There were no significant changes in alkaline phosphatase, iPTH, phosphorus, and serum albumin levels, but there was a slight but significant increase in calcium levels after 6 months of cholecalciferol supplementation (9.4 ± 0.6 mg/dL vs. 9.0 ± 0.6 mg/dL; P = .02). Additionally, we observed a significant reduction in high-sensitivity C-reactive protein levels after 3 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.32 [0.02 to 3.13] mg/L; P = .02) and after 6 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.50 [0.02 to 5.66] mg/L; P = .04) of cholecalciferol supplementation, as well as a significant reduction in interleukin-6 levels (median: 6.44 pg/mL vs. 3.83 pg/mL; P = .018) after 6 months of supplementation. Left ventricular mass index was significantly reduced at the end of supplementation (159 ± 55 g/m(2) vs. 175 ± 63 g/m(2); P = .03). CONCLUSIONS: Cholecalciferol supplementation in HD patients was found to be safe and efficient to correct hypovitaminosis D and established little impact on mineral metabolism markers. Additionally, we observed a reduction in important surrogate markers of cardiovascular risk, namely systemic inflammation and left ventricular hypertrophy, suggesting an anti-inflammatory action and possibly an improvement of cardiac dysfunction.

Parathyroid hormone and phosphorus overload in uremia: impact on cardiovascular system.

BACKGROUND: Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. METHODS: Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V+normal-phosphorus diet (np)) and 'Nx+PTx': G2 (nPTH+pP), G3 (nPTH+rP), G4 (hPTH+pP) and G5 (hPTH+rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-ß) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. RESULTS: Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-ß, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. CONCLUSION: In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.