Dietary protein and muscle wasting in chronic kidney disease: new insights.

PURPOSE OF REVIEW: Muscle wasting is an important health problem in chronic kidney disease (CKD) patients. Protein restriction in the diet can be one of the main causes of muscle wasting in this population. In this review, we aimed to investigate the relationship between dietary protein intake and muscle wasting in CKD patients according to recent literature. RECENT FINDINGS: The one of the main mechanisms responsible for the muscle wasting is the disturbances in skeletal muscle protein turnover. Muscle wasting primarily occurs when the rates of muscle protein breakdown exceed the muscle protein synthesis. Dietary protein intake represents an important role by causing a potent anabolic stimulus resulting a positive muscle protein balance. Compared to studies made in healthy populations, there are very limited studies in the literature about the relationship between dietary protein intake and muscle wasting in the CKD population. Majority of the studies showed that a more liberal protein intake is beneficial for muscle wasting in especially advanced CKD and hemodialysis population. SUMMARY: Although evaluating muscle wasting in CKD patients, the amount of protein in the diet of patients should also be reviewed. Although excessive protein intake has some negative consequences on this patient group, a more liberated dietary protein intake should be taken into account in this patient group with muscle wasting and especially in dialysis patients.

Effects of adenosine triphosphate on vandetanib induced skin damage in rats.

PURPOSE: Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated it has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5'-triphosphate (ATP) on vandetanib-induced skin damage. MATERIALS AND METHODS: A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats' skin tissues were evaluated with histopathological analyses. RESULTS: MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. CONCLUSION: We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.

Relationship between Serum Vitamin D Levels and Health-Related Quality of Life in Maintenance Hemodialysis Patients.

OBJECTIVES: Aim of the study was investigating the effect of serum vitamin D levels on health-related quality of life in hemodialysis patients. METHOD: One-hundred and twenty-three maintenance hemodialysis patients were enrolled in this cross-sectional study. Patients divided into 2 groups according to serum vitamin D levels. A serum 25-hydroxyvitamin D (25[OH] D) level of < 20 ng/mL was identified as vitamin D deficiency (n = 78), and a serum level of ≥20 ng/mL was identified as normal (n = 45). Kidney Disease Quality of Life 36 (KDQOL-36) survey was used for quality of life measurement. Scores of the all of 5 subscales of KDQOL-36 were calculated. Multiple linear regression analyses were used to define independent risk factors affecting the survey. RESULTS: Mean age of patients was 62 and 56% of patients were male. Mean 25(OH) D levels were 11.86 and 29.57 ng/mL, respectively, in 2 groups. There was statistically significant difference between age and Kt/V levels between 2 groups (p = 0.008 and p = 0.041). Age and gender were found as significant predictors of vitamin D deficiency (p = 0.026 and p = 0.021). In symptom and problem list subscale, gender and comorbidity were detected as independent risk factors (p = 0.050 and p = 0.032). Comorbidity was the only independent risk factor for effect of kidney disease subscale (p < 0.001). Independent risk factors associated with burden of kidney disease subscale were comorbidity and serum 25 (OH) D levels (p = 0.003 and p = 0.023). Serum 25(OH) D, gender, and comorbidity were independently associated with physical component summary (PCS) subscale (p < 0.001, p = 0.008, and p = 0.011). The only independently associated factor with mental component summary (MCS) was serum 25(OH) D (p < 0.001). CONCLUSION: We first showed the relationship between serum vitamin D levels and KDQOL-36 in hemodialysis patients. Lower serum vitamin D levels were negatively associated with burden of kidney disease, PCS, and MCS subscales.

The Relationship of Fluid Overload as Assessed by Bioelectrical Impedance Analysis with Pulmonary Arterial Hypertension in Hemodialysis Patients.

BACKGROUND Pulmonary arterial hypertension (PAH) is common disease among hemodialysis (HD) patients and is associated with increased morbidity and mortality. However, its pathogenesis has not been completely elucidated. We aimed to evaluate the frequency of PAH in HD patients, as well as the relationship between fluid status and PAH. MATERIAL AND METHODS We enrolled 77 HD patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status. BIA was performed before and 30 min after the midweek of HD. Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Echocardiographic examinations were performed before and after the HD. Pulmonary arterial hypertension was defined as systolic pulmonary artery pressure at rest (sPAP) higher than 35 mmHg. RESULTS PAH was found in 33.7% of the HD patients. OH/ECW and the frequency of fluid overload were significantly higher in HD patients with PAH than those without PAH, whereas serum albumin and hemoglobin levels were significantly lower. sPAP level was significantly higher in HD patients with fluid overload than in those without fluid overload after hemodialysis session. Furthermore, sPAP, OH/ECW levels, and the frequency of PAH were significantly reduced after HD. We also found a significant positive correlation between sPAP and OH/ECW. Multivariate logistic regression analysis demonstrated fluid overload to be an independent predictor of PAH after HD. CONCLUSIONS PAH is prevalent among HD patients. This study demonstrated a strong relationship between fluid overload and PAH in HD patients.

Pulmonary Function in Patients with End-Stage Renal Disease: Effects of Hemodialysis and Fluid Overload.

BACKGROUND Respiratory system disorders are one of the most prevalent complications in end-stage renal disease patients on hemodialysis. However, the pathogenesis of impaired pulmonary functions has not been completely elucidated in these patients. We designed a study to investigate acute effects of hemodialysis treatment on spirometry parameters, focusing on the relationship between pulmonary function and fluid status in hemodialysis patients. MATERIAL AND METHODS We enrolled 54 hemodialysis patients in this study. Multifrequency bioimpedance analysis (BIA) was used to assess fluid status before and 30 min after the midweek of hemodialysis (HD). Overhydration (OH)/extracellular water (ECW)% ratio was used as an indicator of fluid status. Fluid overload was defined as OH/ECW ≥7%. Spirometry was performed before and after hemodialysis. RESULTS Forced vital capacity (FVC), FVC%, and forced expiratory volume in the first second (FEV1) levels were significantly increased after hemodialysis. FVC, FVC%, FEV1, FEV1%, mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75), FEF25-75%, peak expiratory flow rate (PEFR), and PEFR% were significantly lower in patients with fluid overload than in those without. OH/ECW ratio was negatively correlated with FVC, FVC%, FEV1, FEV1%, FEF25-75, FEF25-75%, PEFR, and PEFR%. Stepwise multiple regression analysis revealed that male sex and increased ultrafiltration volume were independently associated with higher FVC, whereas increased age and OH/ECW ratio were independently associated with lower FVC. CONCLUSIONS Fluid overload is closely associated with restrictive and obstructive respiratory abnormalities in HD patients. In addition, hemodialysis has a beneficial effect on pulmonary function tests, which may be due to reduction of volume overload.

The relationship between serum uric acid level and carotid intima-media thickness in hemodialysis patients.

INTRODUCTION: We aimed to evaluate the relationship between carotid intima-media thickness (CIMT), which is a known indicator of cardiovascular risk and atherosclerosis, and uric acid level, which may be an easy marker for cardiovascular diseases due to its antioxidant and pro-oxidant properties in hemodialysis patients. METHODS: In this cross-sectional study, we evaluated 77 hemodialysis patients. The mean CIMT of these patients was measured and recorded by Doppler ultrasonography. Patients were divided into two groups according to their serum uric acid levels. Correlation analysis and linear regression analysis were used to define the relationship between study parameters. FINDINGS: The mean CIMT levels in the normouricemic group and the hyperuricemic group were 0.95 ± 0.15 and 1.07 ± 0.15, respectively. There was a statistically significant difference between the two groups (p = 0.001). There was a statistically significant and moderate linear correlation between serum uric acid level and mean CIMT (r = 0.402; p = 0.002). Univariate and multivariate linear regression analyses were performed to identify variables that could independently affect the mean CIMT value. According to analysis, uric acid (p < 0.001), hypertension (p = 0.008), albumin (p = 0.029), and C-reactive protein (p = 0.042) were found independent risk factors for mean CIMT value. DISCUSSION: We found a significant relationship between serum uric acid level and CIMT, which indicates carotid atherosclerosis. Serum uric acid level is a low-cost laboratory parameter that can be measured in almost all laboratories, and it may be valuable in the hemodialysis patient group to identify patients at high risk of carotid atherosclerosis.

Diagnosis of Latent Tuberculosis Infection in Hemodialysis Patients: TST versus T-SPOT.TB.

Hemodialysis (HD) patients should be screened for latent tuberculosis (TB) infection. We aimed to determine the frequency of latent TB infection in HD patients and to compare the effectiveness of the tests used. The files of 56 HD patients followed between 1 January 2021 and 1 October 2022 were retrospectively analyzed. Demographic data, the presence of the Bacillus Calmette-Guerin (BCG) vaccine, whether or not the patients had previously received treatment for TB before, the status of encountering a patient with active TB of patients over 18 years of age, without active tuberculosis and who had a T-SPOT.TB test or a Tuberculin Skin Test (TST) were obtained from the patient files. The presence of previous TB in a posterior-anterior (PA) chest X-ray was obtained by evaluating PA chest X-rays taken routinely. Of the patients, 60.7% (n = 34) were male and their mean age was 60.18 ± 14.85 years. The mean duration of dialysis was 6.43 ± 6.03 years, and 76.8% (n = 43) had 2 BCG scars. The T-SPOT.TB test was positive in 32.1% (n = 18). Only 20 patients (35.7%) had a TST and all had negative results. While the mean age of those with positive T-SPOT.TB results was higher (p = 0.003), the time taken to enter HD was shorter (p = 0.029). T-SPOT.TB test positivity was higher in the group that had encountered active TB patients (p = 0.033). However, no significant difference was found between T-SPOT.TB results according to BCG vaccine, albumin, urea and lymphocyte levels. Although T-SPOT.TB test positivity was higher in patients with a previous TB finding in a PA chest X-ray, there was no statistically significant difference (p = 0.093). The applicability of the TST in the diagnosis of latent TB infection in HD patients is difficult and it is likely to give false-negative results. The T-SPOT.TB test is not affected by the BCG vaccine and immunosuppression. Therefore, using the T-SPOT.TB test would be a more appropriate and practical approach in the diagnosis of latent TB in HD patients.

Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model.

Pazopanib is a tyrosine kinase inhibitor that is generally used for the treatment of metastatic renal cell cancer and advanced soft tissue sarcoma. It can cause various degrees of hepatotoxicity. Our study aimed to investigate the effect of taxifolin on pazopanib-induced liver toxicity. A total of 18 rats were divided into three groups: the pazopanib (PP), pazopanib plus taxifolin (TPP), and control (C) group. Taxifolin was administered to the TPP (n=6) group with a dose of 50 mg/kg. Distilled water was orally admnistered to the C (n=6) and PP (n=6) groups as a solvent. Subsequently, pazopanib 200 mg/kg was administered to the TPP and PP groups via the stomach. This procedure was repeated once a day for four weeks. Then, all rats were sacrificed, and their livers were removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), and total antioxidant status (TAS) levels were evaluated. MDA and TOS levels were higher in the PP group compared with the levels of the other parameters (P<0.001). tGSH and TAS levels were lower in the PP group than in the TPP and C groups (P<0.001), and the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were higher. Furthermore, liver tissue damage, including hemorrhage, hydropic degeneration, and necrosis was observed in the PP group. Administration of taxifolin before pazopanib significantly improved degenerative changes. Our study demonstrated that the administration of taxifolin is significantly effective in preventing pazopanib-induced hepatotoxicity in rats.

Effects of anakinra on the small intestine mucositis induced by methotrexate in rats.

Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1ß and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.

The relationship between vitamin D and inflammatory markers in maintenance hemodialysis patients.

PURPOSE: The aim of this study was to investigate the relationship between vitamin D and novel inflammatory markers in hemodialysis patients. METHODS: In total, 129 eligible maintenance hemodialysis patients were enrolled in this cross-sectional study. Patients were divided into two groups according to their serum vitamin D levels. A serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml was identified as vitamin D deficiency and a serum level ≥ 20 ng/ml was identified as normal. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated from the complete blood cell count. Spearman correlation analysis and both logistic and linear regression analyses were used to define the relationships between the study parameters. RESULTS: The two groups showed statistically significant differences for gender and for C-reactive protein (CRP) and NLR values (p = 0.017, p = 0.010, and p = 0.013). Age and gender were independently associated with vitamin D deficiency (p = 0.003 and p = 0.030). Serum 25(OH)D levels showed significant but weak inverse correlations with CRP (r = - 0.205, p = 0.020) and with NLR (r = - 0.219, p = 0.013). Serum 25(OH)D levels also showed a significant but very weak correlation with PLR (r = - 0.182, p = 0.039). Serum 25(OH)D levels showed no correlation with mean platelet volume (p = 0.660). Gender was the only variable significantly associated with serum vitamin D levels, as determined by linear regression analysis (p = 0.003). CONCLUSION: CRP levels and NLR values were significantly higher in the vitamin D deficiency group. A significant inverse correlation was found between serum vitamin D levels and CRP levels, and NLR and PLR values.

Alternative treatment of resistant hypoparathyroidism by intermittent infusion of teriparatide using an insulin pump: A case report.

Hypoparathyroidism usually responds to oral active vitamin D and calcium, but, although rare, some patients do not respond to this treatment. A 47-year-old Caucasian female presented to our medical unit with classical oral treatment-resistant hypocalcemia after thyroidectomy. Teriparatide was infused through the insulin pump with dosage set to 1 unit which equals to 2.5 µg of teriparatide. In conclusion, intermittent subcutaneous infusion of teriparatide using an insulin pump is a safe and effective treatment modality to ensure normocalcemic conditions in patients with classical treatment-resistant hypoparathyroidism. 39th Turkey Congress of Endocrinology and Metabolic Diseases, May 3-7, 2017, Antalya, Turkey.

Effect of Intraperitoneal Etanercept on Oxidative Stress in Rats with Peritonitis.

Our aim was to evaluate effect of etanercept on oxidative stress parameters in rats with experimental peritonitis and investigate the availability of etanercept usage in the treatment of peritonitis in the future. Twenty-eight rats were divided into four groups as control (group 1), peritonitis (group 2), peritonitis + cefazolin sodium (group 3), and peritonitis + cefazolin sodium + etanercept (group 4). Peritoneal tissue and blood samples were taken from all of the rats for histopathological and biochemical examination. The oxidative stress parameters were examined in blood and tissue samples. It was observed that rats with peritonitis benefit from cefazolin sodium treatment. Evaluating the effectiveness of etanercept was our main objective for this study. In this perspective, we compared group 3 and group 4 and found statistically significant decreases in oxidative parameters and statistically significant increases in antioxidants in serum and tissue samples in group 4. It is observed that there was a significant contribution of etanercept on biochemical and also histopathological results. As a result, the TNF-α inhibitor, etanercept, in addition to antibiotics given in the early treatment of peritonitis results in more significant improvement of histopathological and oxidative parameters as compared to antibiotics alone.

Evaluation of Anthropometric and Metabolic Parameters in Obstructive Sleep Apnea.

AIMS: Sleep disorders have recently become a significant public health problem worldwide and have deleterious health consequences. Obstructive sleep apnea (OSA) is the most common type of sleep-related breathing disorders. We aimed to evaluate anthropometric measurements, glucose metabolism, and cortisol levels in patients with obstructive sleep apnea (OSA). MATERIALS AND METHODS: A total of 50 patients with a body mass index ≥30 and major OSA symptoms were included in this study. Anthropometric measurements of the patients were recorded and blood samples were drawn for laboratory analysis. A 24-hour urine sample was also collected from each subject for measurement of 24-hour cortisol excretion. Patients were divided equally into 2 groups according to polysomnography results: control group with an apnea-hypopnea index (AHI) <5 (n = 25) and OSA group with an AHI ≥5 (n = 25). RESULTS: Neck and waist circumference, fasting plasma glucose, HbA1c, late-night serum cortisol, morning serum cortisol after 1 mg dexamethasone suppression test, and 24-hour urinary cortisol levels were significantly higher in OSA patients compared to control subjects. Newly diagnosed DM was more frequent in patients with OSA than control subjects (32% versus 8%, p = 0.034). There was a significant positive correlation between AHI and neck circumference, glucose, and late-night serum cortisol. CONCLUSIONS: Our study indicates that increased waist and neck circumferences constitute a risk for OSA regardless of obesity status. In addition, OSA has adverse effects on endocrine function and glucose metabolism.

Primary antiphospholipid syndrome associated with pneumonia: a case report of a 16-year-old male patient.

Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterial and/or venous thrombosis and/or recurrent pregnancy loss in the presence of antiphospholipid (APL) antibodies. It is evaluated as APS when it develops associated with other systemic autoimmune diseases or primary APS if there is no concomitant disorder. In this study, we present a case of a 16-year-old male patient with primary APS. The patient was admitted with presumptive diagnosis of pneumonia, but multiple pulmonary thromboembolism (PTE) was observed on computerized tomography (CT) pulmonary angiography. APL antibodies positivity and thrombocytopenia developed in our patient. The patient was evaluated as primary APS since another etiology that could explain PTE was not found. Primary APS is a rare disease in children along with adolescents, compared with APS associated with other systemic autoimmune diseases. We present here a young male patient with primary APS and PTE to contribute to the literature. The patient initially had pneumonia but later developed PTE and thrombocytopenia.