Rosilene M. Elias

Rostral overnight fluid shift in end-stage renal disease: relationship with obstructive sleep apnea

BACKGROUND In both healthy male subjects and men with heart failure, the severity of obstructive sleep apnea (OSA) is related to the amount of fluid displaced from their legs into the neck overnight. Whether overnight rostral fluid shift contributes to the pathogenesis of OSA in patients with end-stage renal disease (ESRD) is unknown. We hypothesized that the change in neck circumference (NC) and severity of OSA are related to the extent of overnight change in leg fluid volume (LFV) in patients with ESRD. METHODS We studied 26 patients with ESRD (14 men) on conventional hemodialysis. All subjects underwent polysomnography. LFV was measured by bioelectric impedance at bedtime and repeated in the next morning on awakening. RESULTS Our cohorts overall apnea-hypopnea index was 22.8±26.8 episodes/h of sleep. Their overnight change in LFV was -243±278 mL. The change in LFV correlated with apnea-hypopnea time (AHT) (P=0.001) and NC (P=0.0016). Other independent factors associated with AHT included age (P=0.005), baseline neck (P=0.0002), sitting time (P=0.008) and male gender. Stepwise multiple regression analysis revealed that age, change in LFV and male gender remained independent related to AHT. CONCLUSIONS Nocturnal rostral fluid shift is associated with the severity of OSA in ESRD. Prospective evaluation of the effect of reducing fluid overload and severity of OSA in ESRD patients warrants further examination.

Relationship of pharyngeal water content and jugular volume with severity of obstructive sleep apnea in renal failure

BACKGROUND In patients with end-stage renal disease (ESRD), fluid overload may contribute to their high prevalence of obstructive sleep apnea (OSA) by increasing the amount of fluid displaced from the legs into the neck overnight, and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the amount of overnight rostral fluid displacement from the legs is related to the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI). We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the AHI. METHODS We studied 20 patients with ESRD on thrice weekly hemodialysis who had undergone diagnostic polysomnography (age 41.0 ± 12.3 years, with a body mass index (BMI) of 25.8 ± 6.3 kg/m(2) and an AHI of 20.2 ± 26.8). The leg fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were measured by UA magnetic resonance imaging (MRI). RESULTS The only significant independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC (r = 0.720, P = 0.0005) which together explained 72% of its variability. CONCLUSIONS These data suggest that fluid overload via increased IJVVol, and UA-MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings help us to explain the high prevalence of OSA in ESRD patients, and attenuation of OSA in association with nocturnal dialysis. They also suggest the need for randomized trials to determine whether more aggressive fluid removal in ESRD patients will alleviate OSA.

Parathyroidectomy Improves Survival In Patients with Severe Hyperparathyroidism: A Comparative Study

Background and objectives Secondary hyperparathyroidism (SHPT) in CKD is associated with an increased risk for mortality, but definitive data showing that parathormone control decreases mortality is still lacking. This study aimed to compare the mortality of patients with severe SHPT submitted to parathyroidectomy(PTX) with those who did not have access to surgery. Methods This is a retrospective study in a cohort of 251 CKD patients with severe SHPT who were referred to a CKD-MBD Center for PTX from 2005 until 2012. Results Most of our patients had indication of PTX, but only 49% of them had access to this surgical procedure. After a mean follow-up of 23 months, 72 patients had died. Non-survivors were older; more often had diabetes, lower serum 25 vitamin D and mostly had not been submitted to surgery. The relative risk of death was lower in the PTX patients (0.428; 95% CI, 0.28 to 0.67; p<0.0001). After adjustments, mortality risk was dependent on age (1.04; 95% CI, 1.01 to 1.07; p = 0.002), 25 vitamin D (0.43; 95% CI, 0.24 to 0.81; p = 0.006) and no access to PTX (4.13; 95% CI, 2.16 to 7.88; p<0.0001). Results remained the same in a second model using the PTX date as the study start date for the PTX group. Conclusions Our data confirms the benefit of PTX on mortality in patients with severe SHPT. The high mortality encountered in our population is significant and urges the need to better treat these patients.

Effects of bone remodelling on calcium mass transfer during haemodialysis

BACKGROUND During haemodialysis, calcium balance can affect, or be affected by, mineral metabolism. However, when dialysate calcium concentration (d[Ca]) is chosen or kinetic models are employed to calculate calcium balance, bone remodelling is rarely considered. In this study, we examined whether bone remodelling affects calcium mass transfer during haemodialysis. METHODS We dialysed 23 patients using a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L. Calcium mass transfer was measured and associated with remodelling bone factors. RESULTS Calcium balance varied widely depending on the d[Ca]. Calcium removal was -578 +/- 389, -468 +/- 563, +46 +/- 400 and +405 +/- 413 mg when a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L was used, respectively (1.0 and 1.25 vs 1.5 and 1.75 mmol/L, P < 0.001; 1.5 vs 1.75 mmol/L, P < 0.05). Univariate analysis showed that calcium balance correlated with calcium gradient, parathyroid hormone (PTH), osteocalcin and dialysis vintage. Multivariate analysis revealed that calcium balance was dependent on calcium gradient, PTH and osteocalcin. CONCLUSIONS These results suggest that bone remodelling could affect calcium mass transfer during haemodialysis.

Depression in hemodialysis patients: the role of dialysis shift

OBJECTIVE: Depression is the most important neuropsychiatric complication in chronic kidney disease because it reduces quality of life and increases mortality. Evidence demonstrating the association between dialysis shift and depression is lacking; thus, obtaining such evidence was the main objective of this study. METHOD: This cross-sectional study included patients attending a hemodialysis program. Depression was diagnosed using Becks Depression Inventory. Excessive daytime sleepiness was evaluated using the Epworth Sleepiness Scale. RESULTS: A total of 96 patients were enrolled (55 males, age 48±14 years). Depression and excessive daytime sleepiness were observed in 42.7% and 49% of the patients, respectively. When comparing variables among the three dialysis shifts, there were no differences in age, dialysis vintage, employment status, excessive daytime sleepiness, hemoglobin, phosphorus levels, or albumin levels. Patients in the morning shift were more likely to live in rural areas (p<0.0001), although patients in rural areas did not have a higher prevalence of depression (p = 0.30). Patients with depression were more likely to be dialyzed during the morning shift (p = 0.008). Independent risk factors for depression were age (p<0.03), lower levels of hemoglobin (p<0.01) and phosphorus (p<0.01), and dialysis during the morning shift (p = 0.0009). The hospitalization risk of depressive patients was 4.5 times higher than that of nondepressive patients (p<0.008). CONCLUSION: These data suggest that depression is associated with dialysis shift, higher levels of phosphorus, and lower levels of hemoglobin. The results highlight the need for randomized trials to determine whether this association occurs by chance or whether circadian rhythm disorders may play a role.

Pruritus in hemodialysis patients: The problem remains

Pruritus is still one of the most common and disturbing symptoms of end‐stage renal disease. The objective of this study is to analyze the prevalence of pruritus in hemodialysis patients and the possible factors implicated in its genesis. In a cross‐sectional study, 101 patients on hemodialysis at our center were screened for pruritus. The relationship of various factors with pruritus was evaluated. Of the 101 patients included, 31(30.7%) had pruritus at the time of examination. Patients with pruritus were significantly older than those without pruritus (P=0.0027). Pruritus tended to be more prevalent in patients undergoing dialysis 3 times a week than in those undergoing daily dialysis, but the difference did not reach statistical significance (P=0.0854). Lower transferrin saturation levels were found in patients with pruritus than in those without pruritus (P=0.0144). C‐reactive protein levels were significantly higher in patients with pruritus than in those without pruritus (P=0.0013). There was no significant difference between the groups in the levels of the other inflammatory biomarkers measured. However, there was a tendency toward a correlation between the levels of α‐1‐glycoprotein and the intensity of pruritus (P=0.0834). Our results suggest a possible relationship of the inflammatory response upregulation to pruritus. Additionally, there was a positive relationship between pruritus and iron deficiency, possibly associated with inflammatory elevation of hepcidin. A better understanding of the factors implicated in the genesis of pruritus related to end‐stage renal disease is crucial in the development of more effective treatments for this symptom.

The complexity of chronic kidney disease–mineral and bone disorder across stages of chronic kidney disease

Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed. Additionally, there was a gradual increase in bone resorption associated with a decrease in bone formation and impairment in bone mineralization. Bone expression of sclerostin and parathyroid hormone receptor-1 seemed to be increased in earlier stages of CKD, whereas FGF-23 and phosphorylated β-catenin had increased expression in the late stages of CKD, although all these proteins were elevated relative to healthy individuals. Immunohistochemical studies showed that FGF-23 and sclerostin did not co-localize, suggesting that distinct osteocytes produce these proteins. Moreover, there was a good correlation between serum levels and bone expression of FGF-23. Thus, our studies help define the complex mechanism of bone and mineral metabolism in patients with CKD. Linkage of serum markers to bone expression of specific proteins may facilitate our understanding and management of this disease.

Obstructive sleep apnea in patients on conventional and short daily hemodialysis.

Obstructive sleep apnea (OSA) is common among patients on maintenance hemodialysis. However, the factors associated with the origin of OSA as well as the cardiovascular consequences in this population are not completely understood. We evaluated, by standard overnight polysomnography, 24-hour ambulatory blood pressure (BP) monitoring and echocardiography in 30 patients (14 males, age 34 ± 11 years, BMI 23.2 ± 5.2) – 15 on short daily hemodialysis (SDH) and 15 matched patients on conventional hemodialysis (CHD). The hemodialysis dose (standard Kt/V) was higher in patients on SDH than on CHD (p = 0.001). OSA (apnea-hypopnea index >5 events/h) was present in 13 patients (43%). Patients with OSA were predominantly males (77 vs. 44%), presented a higher BMI (25.5 ± 6.2 vs. 21.5 ± 3.6), a larger neck circumference (38 ± 1 vs. 34 ± 1 cm) and a lower Kt/V (2.6 ± 0.3 vs. 2.2 ± 0.1) than patients with no OSA (p < 0.05). Neck circumference and lower Kt/V were independently associated with OSA on multivariate analysis. No patient with Kt/V >2.5 (n = 10) presented OSA. On the other hand, hypertensive patients with OSA needed more BP control pills (p = 0.03). Despite similar BP control, patients with OSA presented a higher interventricular septum thickness (11.5 ± 0.5 vs. 9.9 ± 0.3 mm; p = 0.011). In conclusion, among patients on maintenance hemodialysis, the traditional risk factors for OSA are present and interact with hemodialysis efficiency. Among these patients, OSA is associated with difficult BP control and heart remodeling suggesting that OSA may contribute to poor cardiovascular outcome.

Hemodynamic Behavior During Hemodialysis: Effects of Dialysate Concentrations of Bicarbonate and Potassium

Background/Aims: Ultrafiltration that occurs during hemodialysis (HD) promotes profound alterations in a relatively short period of time. The dialysate content of bicarbonate (DBic) and potassium (DK) may have impact over intradialytic hemodynamics, which goes beyond ultrafiltration, and its impact was evaluated in a prospective cohort. Methods: 30 patients under HD were submitted to hemodynamic assessment (HA) at the beginning and at the end of HD sessions, through a non-invasive method. Serum minus dialysate potassium concentration was expressed as K-Gap. Cardiac index (CI) and peripheral arterial resistance (PAR) variation (post-HD minus pre-HD) were expressed as ΔCI and ΔPAR. Dialysate content of sodium and calcium were expressed as DNa and DCa, respectively. Results: Mean DNa, DK and DBic were, respectively, 136.4 ± 1.1, 2.1 ± 0.6 and 38.2 ± 2.1 mEq/L. In 15 patients, DCa was >1.5 mmol/L and in the other 15 patients ≤ 1.5 mmol/L. The K-Gap ranged from 1.4 to 5.1 mEq/l (median 3.0 mEq/L). There was a reduction in post-HD CI and systolic blood pressure (ΔCI = -0.72l/min/m2 and -11.3±15.1mmHg, respectively, p<0.001 for both). Conversely, PAR increased (ΔPAR = 272dyn.s/cm5, p<0.001). Lower post-HD CI was was associated to higher DBic (p=0.0013) and lower K-Gap (p=0.026). In multivariate analysis, ΔCI was dependent on DBic and K-Gap, whereas ΔPAR was dependent on dialysate calcium during HD. Conclusion: We confirmed that Na and Ca dialysate content exerts and important role on hemodynamic during HD. In addition, our findings pointed out that higher dialysate concentrations of bicarbonate and potassium promote lower cardiac performance at the end of hemodialysis session.

Insuficiência e deficiência de vitamina D em pacientes portadores de doença renal crônica

INTRODUCAO: Hipovitaminose D e bem documentada em pacientes portadores de doenca renal cronica (DRC). Espera-se niveis inferiores em habitantes de regioes nao tropicais em relacao aos habitantes de regioes tropicais, pela infericao de uma maior exposicao solar e maior producao de vitamina D. OBJETIVO: Analisar os niveis sericos de vitamina D, como 25-hidroxivitamina D - 25(OH)D, de 125 pacientes brasileiros portadores de DRC em fase pre-dialitica. METODOS: Foram estudados 125 pacientes (57,4 ± 16,2 anos, 78 brancos e 55,2% homens), com creatinina de 2,67 ± 1,73 mg/dL e o clearance estimado 43,7 ± 34,5 mL/min. O indice de massa corporal era de 27,4 ± 4,7 kg/m² e a circunferencia abdominal de 95,0 ± 14,0 cm. O calcio era de 9,3 ± 0,6 mg/dL, o paratormonio intacto (PTHi) 212,6 ± 221,2 pg/mL e a albumina serica 4,2 ± 0,6 g/dL. A media de 25(OH)D era de 23,9 ± 10,7 ng/mL. RESULTADOS: Dos 125 pacientes, 92 (72,6%) apresentavam niveis de 25(OH)D < 30 ng/mL, sendo que 65 (52%) apresentavam insuficiencia (15-29 ng/mL); 27 (21,5%) apresentavam deficiencia (5-14 ng/mL) e apenas um paciente apresentava deficiencia severa < 5 ng/mL. Nao foram observadas diferencas entre os niveis de 25(OH)D nos pacientes estratificados quanto ao estagio de DRC. Os niveis de 25(OH)D foram maiores nos homens (38,1 ± 20,6 versus 22,4 ± 9,7 ng/ml; p < 0,0001), havendo tambem uma correlacao inversa entre os niveis de 25(OH)D e de PTHi, proteinuria e circunferencia abdominal, e uma correlacao positiva entre 25(OH)D e calcio total e albumina serica. Na analise multivariada, encontrou-se apenas correlacao inversa entre 25(OH)D e circunferencia abdominal e PTHi. CONCLUSAO: A despeito de a populacao do Brasil estar em um clima tropical, a maioria dos pacientes analisados apresentou niveis sericos subotimos de vitamina D, podendo este achado estar relacionado ao desenvolvimento de hiperparatireoidismo.