Carlo Vulpio

Correlates of symptoms of depression and anxiety in chronic hemodialysis patients

OBJECTIVE Little is known about the demographic, clinical and laboratory variables which may be correlated with symptoms of depression and anxiety in hemodialysis (HD) patients. The present study aimed at evaluating such correlation in HD patients treated at a single HD center in a Mediterranean country. METHODS Eighty HD patients were assessed for depression and anxiety with the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HARS). The scores of BDI and HARS were correlated with demographic, clinical and laboratory variables. RESULTS Based on the Beck Depression Inventory, 38 patients had no symptoms of depression and 42 had symptoms of depression. Based on the HARS, three patients had no symptoms of anxiety and 38 had mild symptoms of anxiety, whereas moderate or severe symptoms of anxiety were present in 39 patients. In univariate analysis, BDI score correlated significantly with age, the Charlson Comorbidity Index, SF-36 Vitality Subscale, Mini-Mental Status Examination, creatinine, albumin, plasma 25-hydroxy vitamin D and interleukin-6 (IL-6) levels. HARS score correlated significantly with age, Charlson Comorbidity Index, SF-36 Vitality Subscale and parathyroid hormone (PTH) levels. In the multivariate analysis, a direct and an inverse correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01-1.71)] and creatinine [P=.050, OR=0.73 (95% CI=0.54-1.00)] was observed. With regard to HARS, only a direct correlation with Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)] was found. CONCLUSION Although numerous demographic, clinical and laboratory variables correlated with BDI and HARS in univariate analysis, the multivariate regression analysis showed only a direct correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01-1.71)] and an inverse correlation between BDI and creatinine [P=.050, OR=0.73 (95% CI=0.54-1.00)] and a direct correlation between HARS and the Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)].

USEFULNESS OF THE COMBINATION OF ULTRASONOGRAPHY AND 99MTC-SESTAMIBI SCINTIGRAPHY IN THE PREOPERATIVE EVALUATION OF UREMIC SECONDARY HYPERPARATHYROIDISM

The usefulness of the combination of technetium‐99m‐methoxyisobutylisonitrile (99mTc‐MIBI) parathyroid scintigraphy and ultrasonography to detect parathyroid glands (PTGs) in secondary hyperparathyroidism (SHPT) is still controversial.

Switch from calcitriol to paricalcitol in secondary hyperparathyroidism of hemodialysis patients: Responsiveness is related to parathyroid gland size

Paricalcitol is more effective than calcitriol in hemodialysis patients (HD) with secondary hyperparathyroidism (SHPT), but it is not effective in some of them. We have investigated the relationship between paricalcitol responsiveness and parathyroid gland (PTG) size. Thirty HD with SHPT treated previously with calcitriol for at least 6 months were switched to paricalcitol (1:4 conversion ratio). Parathyroid gland number and size (maximum longitudinal diameter [MLD] of largest PTG) was measured by ultrasonography. Patients were divided into 2 groups: group A (MLD ≤9.0 mm [17 HD]); and group B (MLD >9.0 mm [13 HD]). They were defined responder if both the last 2 monthly determinations of inhibit parathyroid hormone (iPTH) were within the target (<300 pg/mL) according to National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommendations. Twenty‐six and 20 HD completed 6‐month and 12‐month paricalcitol therapy, respectively. After 6 months of paricalcitol treatment, 23.5% HD of group A and 7.7% of group B were responders. At 12 months, 41.2 % of group A and 7.7% of group B were responders. Throughout paricalcitol therapy, serum calcium and phosphorus concentrations slightly increased in all HD but more significantly in group B. The baseline iPTH and MLD of the largest PTG were significantly correlated with final iPTH levels. Paricalcitol is more effective than calcitriol in SHPT, but the responsiveness to paricalcitol and hypercalcemia are related to PTG size. The measurement of MLD by ultrasonography may be useful for predicting responsiveness to paricalcitol, avoiding an unnecessary and expensive therapy.

Ultrasound Patterns of Parathyroid Glands in Chronic Hemodialysis Patients with Secondary Hyperparathyroidism

Background: The role ofparathyroid glands (PTG) ultrasonography (US) in hemodialysis patients with secondary hyperparathyroidism (SHPT) is still controversial. The present study aimed at evaluating the relationship between US findings and SHPT degree as well as therapeutic outcome. Methods: Twenty hemodialysis patients with moderate SHPT and 15 with severe SHPT underwent US to assess the PTG number, maximum longitudinal diameter (MLD), structural (1 – hypoechoic, 2 – slight heterogeneous, 3 – high heterogeneous, 4 – nodular) and vascular patterns (1 – slight, 2 – medium and 3 – high). Results: PTG number, MLD and US patterns were correlated with iPTH levels. MLD of patients with moderate or severe SHPT was 7.2 ± 2.3 and 15 ± 5.1 mm (p < 0.001). Most patients with moderate SHPT showed a single PTG with an MLD <9 mm associated with 1–2 structural and vascular pattern, whereas patients with severe SHPT exhibited more than one PTG with MLD >9 mm and 3–4 structural and vascular patterns. Thirteen patients were responders to treatment and 22 nonresponders. In nonresponders, a higher number of PTG was observed as well as higher echostructural and vascular patterns. In 14 patients who underwent parathyroidectomy, no differences were found between PTG US MLD and pathology diameter. All PTG with evidence of 3–4 structural and vascular score at ultrasound showed nodular hyperplasia at pathological examination. Conclusions: The adopted classification of US findings is correlated with SHPT degree and therapeutic outcome and might be an adjunctive predictive method useful to assess the SHPT severity and to plan the therapeutic strategy.

Serum Albumin, Body Weight and Inflammatory Parameters in Chronic Hemodialysis Patients: A Three-Year Longitudinal Study

Backgrounds and Aims: The present study aimed at making prospective longitudinal measurements of nutritional and inflammatory parameters to determine whether nutritional and inflammatory status decline or increase over time in a cohort of prevalent hemodialysis patients, and to evaluate which factors influence eventual changes. Patients: 64 hemodialysis patients were followed at 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months. At each follow-up visit, dry body weight, serum albumin, serum total cholesterol, total white blood cells, total lymphocyte count, serum glucose, C-reactive protein, ferritin, fibrinogen, hemoglobin, and weekly erythropoietin dose were assessed. Main Outcome Measures: Changes in nutritional and inflammatory parameters over time. Results: 43 patients completed the study at 36 months. Mean serum albumin levels (g/dl) improved significantly between baseline (3.76 ± 0.24) and 36 months (3.93 ± 0.27) (F = 4.005; p = 0.0009). Dialytic age was significantly associated with changes of serum albumin (F = 2.797; p = 0.028). The mean dry weight slightly remained stable over time (F = 1.473; p = 1.0) as well as the level of total cholesterol (p = 0.77) and lymphocyte count (F = 1.539; p = 0.186). Over time, the levels of C-reactive protein tended to decrease, although the differences were not statistically significant (F = 1.332; p = 0.19). Over time, the serum level of fibrinogen (F = 0.422; p = 0.17) and ferritin (F = 0.314; p = 0.52) remained stable. The number of white blood cells significantly decreased over time (F = 4.691; p = 0.0079) and dialytic age (F = 3.214; p = 0.015) was the variable significantly associated with such decline. The hemoglobin levels (F = 1.423; p = 0.14) and the weekly erythropoietin dose did not change significantly during the study (F = 1.019; p = 0.61), nor did the serum glucose levels (F = 1.231; p = 0.10). Conclusion: These results support the hypothesis that end-stage renal disease and HD are not necessarily associated with deterioration of the nutritional status over time.

Dietary intake of macronutrients and fiber in Mediterranean patients on chronic hemodialysis.

BACKGROUND We aimed to measure the dietary intake of calories, proteins, carbohydrates, lipids and fiber in patients on chronic hemodialysis (HD) at 3 centers in 1 metropolitan and 2 urban areas of Italy, and to evaluate whether it met the dietary guidelines for cardiovascular risk reduction. METHODS Daily dietary intake was assessed through a 3-day diet diary in 128 HD patients at the hemodialysis units of the Catholic University of Rome, Hospital A. Murri of Jesi and Hospital Principe di Piemonte of Senigallia, Italy. RESULTS Mean dietary calorie and protein intakes were 22.9 ± 9.1 kcal/kg per day and 0.95 ± 0.76 g protein/kg per day, respectively. Daily carbohydrate and lipid intakes as a percentage of total calorie intake were 51.8% ± 8.9% and 32.1% ± 7.1%. Mean daily dietary cholesterol intake was 206.6 ± 173.6 mg. Mean daily dietary intakes of omega-3 and omega-6 fatty acids were 0.49 ± 0.28 g and 5.1 ± 2.5 g, respectively, while the mean ratio of omega-6 to omega-3 intake was 11.5 ± 4.8. Forty-eighty percent of patients had an omega-6 to omega-3 ratio =10. Mean daily dietary intakes of saturated fatty acids (SFAs), monounsaturated fatty acids and polyunsaturated fatty acids were 5.5 ± 3.3 g, 28.9 ± 9.1 g and 3.1 ± 1.7 g, respectively. Ninety-six percent of HD patients had an SFA intake <10% of total calories. Most unsaturated fatty acids intakes were under the value of =30%. Mean daily dietary fiber intake was 11.8 ± 6.1 g. CONCLUSION In HD patients from a Mediterranean country (Italy), daily intakes of calories, proteins and fiber were lower than the recommended values, whereas the intake of lipids was closer to being adequate.

Parathyroid-gland ultrasonography in clinical and therapeutic evaluation of renal secondary hyperparathyroidism

PurposeThis study evaluated the relationship between ultrasonographic (US) parameters of parathyroid glands (PTGs) in haemodialysis patients (HDP) and degree of secondary hyperparathyroidism (SHPT), therapeutic responsiveness and type of PTG hyperplasia (diffuse or nodular).Materials and methodsIn 85 HDP, we evaluated the following US parameters of all and of the largest PTGs: number, maximum longitudinal diameter (MLD), structural (hypoechoic, heterogeneous, nodular) and vascular (nonhypovascular, intermediate, hypervascular) echo-pattern scores. Sixty-nine HDP underwent medical therapy (vitamin D, 39; vitamin D/cinacalcet, 30) and 16 underwent parathyroidectomy. The 69 HDP were classified as responders [median intact parathyroid hormone (iPTH) ≤300 pg/ml during follow-up) or nonresponders (iPTH >300 pg/ml).ResultsNumber, MLD and structural and vascular echo patterns of PTGs were significantly correlated with iPTH and calcium concentrations. In the 41 (59%) responders, number (0–1), MLD (<10 mm) and structural and vascular scores (1–2) of the largest PTG were significantly lower than in nonresponders. Receiver operating curve (ROC) curve analysis showed high sensitivity and specificity (90% and 73%, respectively) of the MLD (<10mm) of the largest PTG in the predicting therapeutic outcome. US and histological MLD are significantly correlated and predict the type of hyperplasia.ConclusionsUS parameters of PTGs are correlated to the degree of SHPT and type of hyperplasia and predict responsiveness to medical therapy.RiassuntoObiettivoScopo del presente lavoro è stato valutare le relazioni tra i parametri ecografici (US) paratiroidei (PTG) nei pazienti emodializzati (HDP) con la severità dell’iperparatiroidismo secondario (SHPT), la risposta alla terapia, il tipo d’iperplasia ghiandolare (diffusa o nodulare).Materiali e metodiIn 85 HDP sono stati valutati i seguenti parametri US di tutte le PTG e di quella maggiore: diametro longitudinale massimo (MLD) gli ecopatterns strutturali (ipoecogeno, eterogeneo, nodulare] e vascolari (a-/ipo-vascolarizzato, intermedio, ipervascolarizzato). Sessantanove HDP sono stati sottoposti a terapia medica (39 con vitamina D; 30 con vitamina D/ cinacalcet) e 16 a paratiroidectomia. I 69 HDP sono stati classificati responders (R) [mediana ormone paratiroideo intatto (iPTH)≤300 pg/ml durante follow-up] o nonresponders (NR) (iPTH>300 pg/ml).RisultatiIl numero di PTG, il MLD e gli eco-patterns strutturali e vascolari sono significamente correlati con calcemia e iPTH. In 41 (59%) R il numero (0–1), il MLD (<10 mm) e gli score strutturali e vascolari (1–2) della PTG maggiore erano significativamente inferiori rispetto ai NR. L’analisi della curva receiver operating curve (ROC) dimostra un’elevata sensibilità e specificità del MLD [90%/73%] della PTG maggiore (<10 mm) nel predire la risposta terapeutica. Il MLD ecografico ed istologico sono significativamente correlati e predicono il tipo di iperplasia.ConclusioniI parametri ecografici delle PTG sono correlati alla gravità del SHPT ed al tipo di iperplasia paratiroidea e predicono la risposta alla terapia medica.

Parathyroid Gland Ultrasound Patterns and Biochemical Findings After One-year Cinacalcet Treatment for Advanced Secondary Hyperparathyroidism

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium–phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 ± 5.9 and 13.0 ± 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 ± 416.3 and 556.8 ± 480.8 mm3, respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.

Histology and immunohistochemistry of the parathyroid glands in renal secondary hyperparathyroidism refractory to vitamin D or cinacalcet therapy.

BACKGROUND Cinacalcet is a new effective treatment of secondary hyperparathyroidism (SHPT) in hemodialysis patients (HP), but the alterations of parathyroid gland (PTG) hyperplasia determined by cinacalcet and vitamin D have not been extensively investigated in humans. METHODS We performed histological analyses of 94 PTGs removed from 25 HP who underwent parathyroidectomy (PTx) because of SHPT refractory to therapy with vitamin D alone (group A=13 HP and 46 PTGs) or associated with cinacalcet (group B=12 HP and 48 PTGs). The number, weight, the macroscopic cystic/hemorrhagic changes, and type of hyperplasia of PTG (nodular=NH, diffuse=DH) were assessed. In randomly selected HP of group A (4 HP and 14 PTGs) and group B (4 HP and 15 PTGs), the labeling index of cells positive to Ki-67 and TUNEL and the semiquantitative score of immunohistochemistry staining of vitamin D receptor, calcium-sensing receptor, and vascular endothelial growth factor-α (VEGF-α) were measured in the entire PTGs and in the areas with DH or NH. RESULTS The number and weight of single and total PTG of each HP were similar in the two groups as well as the number of PTG with macroscopic cystic/hemorrhagic areas. TUNEL, Ki-67, and VEGF-α scores were higher in NH than in DH areas. CONCLUSION This observational study of a highly selected population of HP, submitted to PTx because SHPT refractory to therapy, shows that the macroscopic, microscopic, and immunochemistry characteristics of PTG in HP who received or did not receive cinacalcet before PTx did not differ significantly.

Reactive oxygen metabolites (ROMs) are associated with cardiovascular disease in chronic hemodialysis patients

Abstract Background: The aim of our study was to measure reactive oxygen metabolites (ROMs) in chronic hemodialysis (HD) patients and evaluate the possible association with cardiovascular disease (CVD) and mortality. Methods: We measured ROMs in 76 HD patients and correlated with CVD, cardiovascular (CV) events in the follow-up and all-cause and CVD-related mortality. Results: The levels of ROMs presented a median value of 270 (238.2–303.2) CARR U (interquartile range). We created a ROC curve (ROMs levels vs. CVD) and we identified a cut-off point of 273 CARR U. Patients with ROMs levels ≥273 CARR U were significantly older, had higher C-reactive protein levels and lower creatinine concentrations. The prevalence of CVD was higher in patients with ROMs levels ≥273 (87.1%) than in those with ROMs levels <273 CARR U (17.7%; p<0.0001). ROMs levels were significantly higher in patients with CVD (317±63.8) than in those without (242.7±49.1; p<0.0001). At multiple regression analysis, age, creatinine and C-reactive protein were independent factors associated with ROMs. At multiple logistic regression analysis the association between ROMs and CVD was independent (OR: 1.02, 95% CI: 1.00–1.05; p=0.03). Twenty six patients developed cardiovascular (CV) events during the follow-up. Of these, seven were in the group with ROMs levels <273 CARR U and 19 in the group with ROMs levels ≥273 CARR U. The logistic regression analysis showed that both age (OR: 1.06, 95% CI: 1.01–1.12; p=0.013) and ROMs levels (OR: 1.10, 95% CI: 1.00–1.02; p=0.045) were independently associated with CV events in the follow-up. Conclusions: ROMs are independently associated with CVD and predict CV events in chronic HD patients.