Applications of external cavity diode laser-based technique to noninvasive clinical diagnosis using expired breath ammonia analysis: chronic kidney disease, epilepsy.

An external cavity laser (ECL)-based off-axis cavity-enhanced absorption spectroscopy was applied to noninvasive clinical diagnosis using expired breath ammonia analysis: (1) the correlation between breath ammonia levels and blood parameters related to chronic kidney disease (CKD) was investigated and (2) the relationship between breath ammonia levels and blood concentrations of valproic acid (VAP) was studied. The concentrations of breath ammonia in 15 healthy volunteers, 10 epilepsy patients (before and after taking VAP), and 27 patients with different stages of CKD were examined. The range of breath ammonia levels was 120 to 530 ppb for healthy subjects and 710 to 10,400 ppb for patients with CKD. There was a statistically significant positive correlation between breath ammonia concentrations and urea, blood urea nitrogen, creatinine, or estimated glomerular filtration rate in 27 patients. It was demonstrated that taking VAP gave rise to increasing breath ammonia levels. A statistically significant difference was found between the levels of exhaled ammonia (NH3) in healthy subjects and in patients with epilepsy before and after taking VAP. The results suggest that our breath ammonia measurement system has great potential as an easy, noninvasive, real-time, and continuous monitor of the clinical parameters related to epilepsy and CKD.

Associations between serum hepcidin level, FGF-21 level and oxidative stress with arterial stiffness in CAPD patients.

BACKGROUND: Patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis have accelerated atherosclerosis associated with an increase in cardiovascular morbidity and mortality. Atherosclerosis is associated with increased arterial stiffness (AS), endothelial dysfunction and elevated oxidative stress (OS) and inflammation. We aimed to investigate the relationship between oxidative stress status, arterial stiffness, hepcidin and fibroblast growth factor-21 (FGF-21) levels in CAPD patients. METHODS: As a prospective observational study, we analyzed 56 CAPD patients, aged between 30 and 63 years. Serum hepcidin, FGF-21 levels, OS status and AS were determined. Arterial stiffness was measured by flow-mediated dilatation (FMD). Oxidative stress status was determined by total antioxidant status, total oxidant status (TOS) and oxidative stress index (OSI). RESULTS: FMD was negatively correlated with TOS, OSI, hepcidin and FGF-21 (r: -0.313, p: 0.020; r: -0.0331, p: 0.014; r: -0.498, p < 0.001; r: -0.403, p: 0.002, respectively). OSI was positively correlated with hepcidin, parathormone and negatively correlated with FMD (r: 0.278, p: 0.040; r: 0.462, p < 0.001; r: -0.0331, p: 0.014, respectively). CONCLUSION: There are many factors affecting arterial stiffness in CAPD patients. In our study, higher levels of OS status, hepcidin and FGF-21 were independent determinants of arterial stiffness in PD patients. Therefore, definition and improvement of these new parameters will be helpful to reduce the cardiovascular disease risk and mortality in CAPD patients.

Generalized Aggressive Periodontitis in a Patient With Nephrotic Syndrome Associated With Primary Renal Amyloidosis: A Case Report.

INTRODUCTION: Renal amyloidosis may lead to renal disease, and then nephrotic syndrome may develop. To the best of the authors' knowledge, this is the first case report in which a patient presents with generalized aggressive periodontitis (GAgP) and nephrotic syndrome in conjunction with renal amyloidosis. CASE PRESENTATION: An 18-year-old male presented to the periodontology department for generalized gingival recessions. He was diagnosed as having primary renal amyloidosis by his physician. The patient presented with severe gingival inflammation and alveolar bone loss. Biochemical tests were within normal limits except for serum albumin level. No amyloid deposition was found in a gingival biopsy, and the patient was diagnosed as having GAgP. Non-surgical periodontal treatment, in combination with antibiotic treatment, was performed. After 3 years, his systemic and periodontal conditions showed deterioration. CONCLUSIONS: The effects of systemic factors related to nephrotic syndrome in conjunction with renal amyloidosis and deterioration in oral hygiene may play a significant role in the progression of periodontal disease. Even if there is no amyloid deposition in periodontal tissues, clinicians should consider that nephrotic syndrome associated with systemic amyloidosis may provide an important contribution to the periodontal breakdown by the modifying conditions that affect the host response to the accumulation of dental biofilm.

The upper extremity musculoskeletal complications in dialysis patients: comparison between hemodialysis and peritoneal dialysis.

OBJECTIVES: The aim of this study was to compare the upper extremity musculoskeletal complications in the patients who had been receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). MATERIAL AND METHODS: The patients who had been receiving HD (n=17) or CAPD (n=15) were included to the study. The age, gender, duration of dialysis were recorded. The physical findings related to musculoskeletal system in the upper extremity were researched. The cervical, shoulder, hand standard radiographies and shoulder magnetic resonance imaging were investigated. RESULTS: The mean duration of HD and CAPD were 53.60 ± 36.03 and 49.17 ± 33.14 months, respectively (p=0.720). Only 6.3% of the CAPD group had signs of carpal tunnel syndrome (CTS). There were not any differences in the frequency of cervical destructive spondyloarthropathy, decreased height of vertebral corpus in the examination of cervical radiography (p=0.579) and also in the frequency of erosions in the humeral head and bones of hand, cyst in the clavicula, erosive osteoarthropathy and osteoporosis detected in the bones of hands (p> 0.005). In the examination of shoulder MR imaging, 80% of the HD group and 47.1% of the CAPD group had supraspinatus tendinitis (p=0.059). The frequency of subscapularis, biceps and infraspinatus tendinitis were not different in HD and CAPD groups (p> 0.05). CONCLUSION: The musculoskeletal system complications of the upper extremity were common in the patients undergoing dialysis therapy. The most common complications were osteoporosis of the hand region and supraspinatus tendinitis. LEVEL OF EVIDENCE: Prospective, Level 2b.

The relationship of amelogenesis imperfecta and nephrocalcinosis syndrome.

AIM: To analyze the prevalence and associated oral findings of nephrocalcinosis in a group of patients affected with amelogenesis imperfecta (AI). The relationship between types of AI and nephrocalcinosis were also evaluated. DESIGN: This study examines patients who were referred to Pediatric Dentistry Department of SDU between the years of 2002-2007 and who, upon clinical and radiological examination, were diagnosed with AI and treated. Patients were offered information about the possibility of nephrocalcinosis syndrome. Patients who agreed to have tests carried out on their renal system were advised to visit the department of nephrology at the clinic. RESULTS: Suspicious radiopacity was observed during renal ultrasonography of a controlled number of patients with hypoplastic type AI. Laboratory results revealed low Ca values (100-300 mg/days) and normal P values (0.4-1.3 g/days). Delayed eruption, gingival hyperplasia, pulp stones and orthodontic problems were also observed in the same patient groups. CONCLUSION: Although renal findings were observed in a few patients, pediatric dentists are the doctors who are the first to have early contact with this patient group. Because of the potential risk of nephrocalcinosis, early diagnosis may offer good prognosis.

Comparison of sleep quality between hemodialysis and peritoneal dialysis patients.

AIM: Sleep disorders are common in patients with end-stage renal disease. Although studies have been conducted on the type and frequency of sleep disturbances in hemodialysis and peritoneal dialysis patients, there has been no study comparing the sleep quality between these two groups. Therefore, we aimed to compare sleep quality between hemodialysis and peritoneal dialysis patients. METHODS: A total of 102 patients (52 hemodialysis and 50 peritoneal dialysis) were included in the study. The Pittsburgh sleep quality index (PSQI) was used for the assessment of sleep quality. Two groups were compared for seven components of the PSQI questionnaire and global score as well as for clinical and laboratory findings. We also assessed the independent predictors of sleep quality. RESULTS: There were 51 male and 51 female patients (29 male and 23 female in hemodialysis group versus 22 male and 28 female in peritoneal dialysis group). The mean age was 55.5+/-14.6 years in the hemodialysis and 51.5+/-18.1 years in the peritoneal dialysis group. The median dialysis duration was 36 (77.0) months. The sleep quality was poor in 88.5% of the hemodialysis patients and 78.0% of the peritoneal dialysis patients. However, this difference in sleep quality was not significant between the two groups (P>0.05). There was a significant association between the sleep quality and the age, presence of diabetes mellitus, and serum albumin. Among these variables, only age was found to be an independent predictor of sleep quality. CONCLUSIONS: Hemodialysis and peritoneal dialysis patients had a similar high rate of poor sleep quality. Further studies are necessary to investigate the causes of poor quality of sleep and to investigate methods to improve sleep quality in this population.

The effect of serum albumin level on iron-induced oxidative stress in chronic renal failure patients.

BACKGROUND: Intravenous iron (IVIR) administration is widely used to treat anemia in chronic renal failure (CRF) patients and causes oxidative stress. Despite the fact that proteins are extremely susceptible to oxidative stress, there have been no studies investigating the relationship between the severity of iron-induced acute oxidative stress and serum albumin. Therefore, we wanted to investigate the relation between the severity of iron-induced acute oxidative stress and serum albumin level in CRF patients. METHODS: A total of 68 patients (22 on hemodialysis, 24 on continuous ambulatory peritoneal dialysis and 22 predialytic CRF) with absolute iron deficiency were included to the study. Patients with acute inflammatory status, serum ferritin level > or = 100 ng/mL, transferrin saturation > or = 20%, hemoglobin level > or = 12 g/dL or serum C-reactive protein (CRP) level > or = 10 mg/dL were excluded. Serum direct 8-isoprostoglandin F2 alpha (IsoPG-F2 alpha) level was used as an oxidative stress marker. After baseline sampling, 100 mg ferric sucrose was infused within 30 minutes. Blood samples were drawn to assess changes in oxidative stress marker at the end of the IVIR infusion and at 240 minutes. Patients with serum albumin level <4 g/dL were defined as hypoalbuminemic and > or = 4 g/dL as normoalbuminemic. RESULTS: There were 34 hypoalbuminemic and 34 normoalbuminemic patients. Serum IsoPG-F2 alpha level increased in all patients after the administration of IVIR. The severity of iron-induced acute oxidative stress was more prominent in patients with a low serum albumin level. Serum albumin level, presence of diabetes mellitus (DM) and hemoglobin level were found as significant predictors of time-dependent changes in serum IsoPG-F2 alpha level. When the analyses were repeated in nondiabetic patients, serum albumin level was similarly found to be a significant predictor of time-dependent changes in serum IsoPG-F2 alpha level. CONCLUSION: This study demonstrated a negative interaction between iron-induced acute oxidative stress and serum albumin level in CRF patients. Because CRF patients with low serum albumin level are at greater risk for iron-induced acute oxidative stress, new strategies are necessary in this population.

Insulin resistance in critically ill patients with acute renal failure.

Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 +/- 508 vs. 234 +/- 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 +/- 30.0 vs. 11.7 +/- 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 +/- 498 vs. 1,470 +/- 581 microg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

Effect of renal transplantation on biomarkers of inflammation and oxidative stress in end-stage renal disease patients.

BACKGROUND: Chronic kidney disease patients have a high prevalence of inflammation and oxidative stress, and this has been associated with the excess cardiovascular morbidity and mortality observed in this population. Because maintenance hemodialysis is ineffective in controlling these factors, we hypothesized that restoration of kidney function by transplantation would be required to improve uremic inflammation and oxidative stress. METHODS: This was a prospective cohort study evaluating time-dependent changes in biomarkers of inflammation and oxidative stress before and after renal transplantation. Nineteen end-stage renal disease (ESRD) patients (age 38.3+/-13.7 years, 58% male, 95% white, 21% diabetic) undergoing living-donor renal transplantation were enrolled. C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha, protein-associated carbonyl content, and F2-isoprostanes were assessed at 1 week pretransplantation and at 1 week and 2 months posttransplantation. RESULTS: Pretransplant levels of the pro-inflammatory proteins IL-6, TNF-alpha, and CRP, as well as the oxidative stress markers plasma protein carbonyls and F2-isoprostanes, were significantly elevated in ESRD patients compared with healthy control subjects. We observed rapid and significant declines in all of these biomarkers after transplantation that persisted for 2 months. CONCLUSIONS: Our findings indicate that restoration of renal function by transplantation improves the chronic inflammation and increased oxidative stress associated with uremia, which may contribute to the improved survival afforded to ESRD patients by renal transplantation.

Plasma cytokine levels predict mortality in patients with acute renal failure.

BACKGROUND: Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness. RESULTS: When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients. CONCLUSION: There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

Urea space and total body water measurements by stable isotopes in patients with acute renal failure.

BACKGROUND: Knowledge of urea volume of distribution (Vurea) in patients with acute renal failure (ARF) is critical in order to prescribe and monitor appropriate dialytic treatment. We have recently shown that in ARF patients, Vurea estimation by urea kinetic modeling is significantly higher than total body water (TBW) by anthropometric estimation. However, these estimates of Vurea and TBW have not been validated by isotopic methods, considered as reference measurement standards. METHODS: In this study, we measured Vurea by [13C]urea and TBW by deuterium oxide (D2O) in 21 patients with ARF (14 males, 7 females, age 62.0 +/- 10.6 years old, 83% Caucasian, 17% African American) at three different centers. These measurements were compared to TBW estimates from anthropometric and bioelectrical impedance (BIA) measurements. RESULTS: Our results show that Vurea by [13C]urea (51.0 +/- 11.7 L) is significantly higher than TBW estimated by all other methods (TBW by D2O: 38.3 +/- 9.8 L, P < 0.001; TBW by BIA: 45.7 +/- 15.7 L, P= 0.08; TBW by Watson formula: 38.3 +/- 7.3 L, P < 0.001; TBW by Chertow formula: 39.3 +/- 7.8 L, P= 0.002, all versus Vurea). Despite significant overestimation of the absolute value and considerable variation, Vurea significantly correlated with TBW by BIA (r= 0.66, P < 0.01) and TBW by D2O (r= 0.5, P= 0.04). There was also significant correlation between D2O and BIA determined TBW (r= 0.8, P < 0.001). CONCLUSION: In terms of useful guidelines to prescribe a specific dose of dialysis in patients with ARF, conventional estimates of TBW as surrogates for Vurea should be used with caution. We propose that these conventional estimates of TBW should be increased by approximately 20% (a factor of 1.2) to avoid significant underdialysis.

Psychological symptoms are greater in caregivers of patients on hemodialysis than those of peritoneal dialysis.

BACKGROUND: The purpose of this study was to evaluate and compare psychosocial characteristics in caregiving relatives (caregivers) of hemodialysis (HD) and peritoneal dialysis (PD) patients. METHODS: Thirty-three caregivers (17 women, 16 men) of HD patients, 27 caregivers (11 women, 16 men) of PD patients, and a control group of 49 subjects who do not care for family members with chronic illness (23 women, 26 men) are included in this study. The brief symptom inventory (BSI), social disability schedule (SDS), and brief disability questionnaire (BDQ) were used for the psychosocial evaluation. RESULTS: The mean age, men-to-women ratios, duration of education, and distribution of marital status did not differ significantly among the three groups. In addition, dialysis duration and distribution of caregiver type were not different between the HD and PD groups. Although the mean global severity index scores of the three groups were similar, somatization and depression scores from BSI subitems were greater in the HD group than the scores of the PD and control groups. Although the mean SDS and BDQ scores were higher in the HD group, the differences did not achieve statistical significance. BSI subitems such as somatization, obsession-compulsion, interpersonal sensitivity, depression, and anxiety were positively correlated among themselves. Hostility and somatization were negatively correlated with age and education, respectively. Nevertheless, somatization was positively correlated with age. Social disability was negatively correlated with duration of education. CONCLUSION: Somatization and depression are greater in the caregivers of center HD patients compared to PD and control groups. According to the findings of this study, we suggest that caregiving family members of dialysis patients especially on HD also should be evaluated for psychosocial problems and supported as needed. Further studies are needed to explore whether psychosocial parameters of caregivers predict outcomes for caregivers and patients.