Comparison between total thyroidectomy and hemithyroidectomy in TIR3B thyroid nodules management.

PURPOSE: Thyroid nodules classified as TIR3B according to SIAPEC 2014 are considered a clinical challenge due to the risk to be malignant. This retrospective study aimed to compare the performances of total thyroidectomy (TT) and hemithyroidectomy (HT) in the surgical management of a consecutive cohort of patients affected by TIR3B thyroid nodule in terms of side effects and the rate of malignancy detected. METHODS: From 2011 to 2019, 136 (111 women, 25 men; average age of 53.5 years) patients having a thyroid nodule with a cytological diagnosis of TIR3B who underwent TT or HT were retrospectively included. RESULTS: Out of 136 patients, 106 (78%) received TT, while the remaining 30 (22%) HT. The final diagnosis was malignant in 65 patients (48%), with follicular variant of papillary carcinoma as the most frequent. The diagnosis of malignancy was significantly more common in the TT group with 56 patients (53%) compared to the HT group with 9 cases (30%) (p = 0.001). Patients who underwent TT were significantly older, had larger nodules and the time between diagnosis and surgery was significantly longer compared to HT (p = 0.001; p0.003; p = 0.002). No main post-surgical complications were registered, except for one case of transient hypocalcemia in a patient who underwent TT. CONCLUSIONS: Our data showed a malignancy rate of TIR3B lesions higher than expected (48%). Both TT and HT seem to be effective approaches for the treatment of TIR3B nodules with a very low rate of post-surgical comorbidities. In the choice of surgical approach, it is crucial to consider the presence of risk factors (clinical and ultrasound characteristics), nodule size, patients' opinion, and surgeon's skills and experience.

Bioelectrical impedance vector analysis and brain natriuretic peptide in the evaluation of patients with chronic kidney disease in hemodialitic treatment.

INTRODUCTION: Setting dry weight (DW) in haemodialysis (HD) patients is still an hard issue. Several clinical, haematochimical and instrumental parameters have been considered. In the last years bioelectrical impedance vector analysis (BIVA) became the main method to evaluate body composition and water body percentage. However it is still difficult to assess the nutritional status and identify a correct DW in HD patients. AIM: to set DW and nutritional status, combining BIVA with phase angle (PhA) and serum brain natriuretic peptide (BNP) in HD patients. METHODS: we evaluated PhA and BNP modifications before (T0), after HD section (T1) and after 60 days (T2), in all patients treated in our HD centre. RESULTS: A total of 50 patients (36 males) with a mean age of 70.1 ± 8.85 years, were recruited. We did not report significant changes in BNP and PhA between T0 and T1, while they were significantly different between T0 and T2. We also reported a significant difference between T0 and T2 in ECW / TBW, while we did not show significant variations in ECM / BMC between T0, T1 and T2 indicating a stability of the nutritional status. PhA, BNP and ECW / TBW, returned to a normal value in patients in which we reached a DW, also considering clinical parameters such as blood pressure and antihypertensive therapy. The weight loss obtained with the evaluation of the BIVA and the BNP was 1.2-5.7 kg, greater than that calculated empirically which stood at around 0.9-4.3 Kg. CONCLUSION: We suggest to carry out BIVA with PhA combined with BNP to assess an adequate DW and evaluate a correct nutritional status in HD patients.

The role of Hashimoto thyroiditis in predicting radioiodine ablation efficacy and prognosis of low to intermediate risk differentiated thyroid cancer.

OBJECTIVE: The baseline treatment of differentiated thyroid cancer (DTC) consists of thyroidectomy followed by postoperative risk-adapted radioiodine therapy (RAIT) when indicated. The choice of most appropriate RAI activities to administer with the aim to reach an efficient remnant ablation and reduce the risk of recurrence is yet an open issue and the detection of basal factors that may predict treatment response seems fundamental. The aim of this study was to investigate the potential role of Hashimoto thyroiditis (HT) in predicting 1-year and 5-year treatment response after RAIT and prognosis. METHODS: We retrospectively included 314 consecutive patients (174 low-risk and 140 intermediate-risk) who received thyroidectomy plus RAIT. One-year and 5-year disease status was evaluated according to 2015 ATA categories response based upon biochemical and structural findings. RESULTS: HT was reported histopathologically in 120 patients (38%). DTC patients with concomitant HT received a higher number of RAITs and cumulative RAI activities. Initial RAIT reached an excellent response in 63% after one year and 84% after 5 years. The rate of excellent response one year and 5-year after first RAIT was significantly lower in HT groups, compared to not HT (p < 0.001). Instead, HT did not have a prognostic role considering PFS and OS; while stimulate thyroglobulin (sTg) at ablation was significantly related to survival. CONCLUSIONS: HT may affect the efficacy of RAIT in low to intermediate risk DTC, particularly reducing the successful rate of excellent response after RAIT. Instead, HT did not have a prognostic impact such as stimulated sTg.

Atypical parathyroid adenoma: clinical and anatomical pathologic features.

BACKGROUND: Primary hyperparathyroidism is an endocrine pathology that affects calcium metabolism. Patients with primary hyperparathyroidism have high concentrations of serum calcium or high concentrations of parathyroid hormone, or incorrect parathyroid hormone levels for serum calcium values. Primary hyperparathyroidism is due to the presence of an adenoma/single-gland disease in 80-85%. Multiple gland disease or hyperplasia accounts for 10-15% of cases of primary hyperparathyroidism. Atypical parathyroid adenoma and parathyroid carcinoma are both responsible for about 1.2-1.3% and 1% or less of primary hyperparathyroidism, respectively. METHODS: We performed a retrospective cohort study and enrolled 117 patients with primary hyperparathyroidism undergoing minimally invasive parathyroidectomy. Histological and immunohistochemical examination showed that 107 patients (91.5%) were diagnosed with typical adenoma (group A), while 10 patients (8.5%) were diagnosed with atypical parathyroid adenoma (group B). None of the patients were affected by parathyroid carcinoma. RESULTS: Significant statistical differences were found in histological and immunohistochemical parameters as pseudocapsular invasion (p <  0.001), bands of fibrosis (p <  0.001), pronounced trabecular growth (p <  0.001), mitotic rates of > 1/10 high-power fields (HPFs) (p <  0.001), nuclear pleomorphism (p = 0.036), thick capsule (p <  0.001), Ki-67+ > 4% (p <  0.001), galectin-3 + (p = 0.002), and protein gene product (PGP) 9.5 + (p = 0.038). CONCLUSIONS: Atypical parathyroid adenoma is a tumor that has characteristics both of typical adenoma and parathyroid carcinoma. The diagnosis is reached by excluding with strict methods the presence of malignancy criteria. Atypical parathyroid adenoma compared to typical adenoma showed significant clinical, hematochemical, histological, and immunohistochemical differences. We did not find any disease relapse in the 10 patients with atypical parathyroid adenoma during 60 months of follow-up time.

Thyroid Cancer and Nodules in Graves' Disease: A Single Center Experience.

BACKGROUND: The existence of a link between Graves' Disease (GD) and Thyroid Cancer (TC) has long been investigated, however a clear pathogenic correlation is yet to be found. OBJECTIVE: We verified the presence of TC in patients submitted to surgery for GD, both with and without thyroid nodules (TN). METHODS: In this study we analyzed retrospectively a cohort of 151 patients treated at our clinic with total thyroidectomy between 2013 and 2018. All the patients were symptomatic at the time of surgery, preoperatively ultrasonographic (US) study was performed to evaluate the presence of nodules and their distribution. All patients reached euthyroid state before surgery. RESULTS: Nodules were detected in 53% of cases, above 60 years of age, at least one nodule was found; however, younger patients were mostly nodules free. Bilateral diffusion of nodules appeared with increasing age. Cancer was found in 19 of 151 subjects (12.5%), all were papillary carcinomas, and among them 93% were microcarcinomas. Among cancer-proven patients, 14 had thyroid nodules while 5 were nodule-free. During the follow up period, no cancer recurrence was recorded. The most common complication after surgery was transient hypocalcemia (36%). CONCLUSIONS: Graves' patients are burdened by major incidence of TC in the context of their TN. Pre-operative assessment in GD patients should consider the risk of cancer, US scan can help in rapid evaluation of nodules and new rising frontiers in molecular biomarkers analysis may help defining pathogenic basis of Graves' neoplastic development.

Association between Multidimensional Prognostic Index and Hospitalization and Mortality among Older Adults with Chronic Kidney Disease on Conservative or on Replacement Therapy.

The prevalence of renal disease is constantly increasing in older adults and a prognostic evaluation by a valid tool may play a key role in treatment management. We aimed to assess the association(s) between the multidimensional prognostic index (MPI) and both the hospitalization and mortality among older adults with renal disease. Patients with chronic kidney disease (CKD) (stage 3-5 KDOQI) and on dialysis were considered. Clinical parameters were registered at baseline and after 2 years. In all the patients, the MPI was calculated and divided into grade 0 (low risk), 1 (moderate risk), and 2 (severe risk). Hospitalizations and mortality were recorded during the follow-up and analyzed according to MPI grade. A total of 173 patients, with a median age of 76 years, on conservative (n = 105) and replacement therapy (32 patients on hemodialysis, 36 patients on peritoneal dialysis) were enrolled. Of them, 60 patients were in MPI grade 0, 102 in grade 1, and 11 in grade 2. The median duration of all the hospitalizations was 6 days and the number of deaths was 33. MPI significantly correlated with days of hospitalization (r = 0.801, p < 0.00001) and number of hospitalizations per year (r = 0.808, p < 0.00001), which was higher in MPI grade 2 compared to grade 1 (p < 0.001) and to grade 0 (p < 0.001). We found a significant association between MPI grades and mortality (p < 0.001). Our results indicate that MPI was associated with outcomes in patients with renal disease, suggesting that a multidimensional evaluation should be implemented in this clinical setting.

Prebiotic Therapy with Inulin Associated with Low Protein Diet in Chronic Kidney Disease Patients: Evaluation of Nutritional, Cardiovascular and Psychocognitive Parameters.

A relationship between dysbiotic gut microbiome and chronic kidney disease (CKD) has been recently documented; it contributes to CKD-related complications, including cardiovascular disease. Aim: We tested how a low-protein diet (LPD)-with or without oral inulin supplementation as a prebiotic-modulates some inflammatory, atherosclerosis and endothelial dysfunction indices and nutritional markers, as well as psychocognitive functions in CKD patients. We conducted a prospective, case-control study on CKD patients on conservative therapy, divided in two groups: the intervention group treated with LPD (0.6 g/kg/day) plus inulin (19 g/day) and a control group treated with LPD without inulin, for six consecutive months. Clinical and hematochemical parameters as well as instrumental, and psychocognitive assessments (by SF-36 survey and MMSE, HAM-D, BDI-II) were recorded in all the participants at baseline (T0), at three months (T1) and at six months (T2). A total of 41 patients were enrolled: 18 in the intervention group and 23 in the control group. At T2, in both groups, we observed a significant reduction of serum nitrogen and phosphorus (p ≤ 0.01) and serum uric acid (p ≤ 0.03), and an improvement in metabolic acidosis (bicarbonates, p ≤ 0.01; base excess, p ≤ 0.02). Moreover, at T2 the intervention group showed a reduction in serum insulin (p = 0.008) and fasting glucose levels (p = 0.022), HOMA-IR (p = 0.004), as well as lower total serum cholesterol (p = 0.012), triglycerides (p = 0.016), C-reactive protein (p = 0.044) and homocysteine (p = 0.044) and higher HDL (p < 0.001) with respect to baseline. We also observed a significant amelioration of some quality of life and functional status indices (SF-36 survey) among the intervention group compared to controls, without a significant improvement in the cognitive state (MMSE). On the other hand, an amelioration in mood (by HAM-D and BDI-II) was found in the intervention group and in controls (only by BID-II). In conclusion, LPD in association with oral inulin supplementation improved glycemic and lipid metabolism and ameliorated the systemic inflammatory state, likely reducing cardiovascular risk in CKD patients and this may represent a promising therapeutic option, also improving quality of life and mood.

Effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular risk indices in renal cell carcinoma.

BACKGROUND: Sunitinib is a standard treatment for metastatic renal cell carcinoma (RCC). Currently, the data available on the effects of sunitinib on endothelial dysfunction, metabolic changes, and cardiovascular (CV) risk factors are limited, and we aimed to evaluate these aspects in patients with RCC after a short period of treatment. METHODS: Patients affected by metastatic RCC were enrolled and evaluated before starting sunitinib (T0) and after 40 days of treatment (T1) by the flow-mediated dilation (FMD), carotid intima media thickness (IMT), ankle-brachial pressure index (ABI), and 24-hour proteinuria. We also assessed serum metabolic and nutritional parameters at T0 and T1. RESULTS: Twenty patients (7 female), with a mean age of 61.4 ± 12.0 years, were studied. Overtime, we observed a reduction in estimated glomerular filtration rate (P = .002), FMD (P = .001) and in fasting plasma glucose levels (P = .04), as well as an increase in plasma insulin (P < .001), HOMA-IR (P < .01), and serum total cholesterol levels (P = .01). Moreover at T1 we found a significant increase in systolic and diastolic blood pressure (P ≤ .001) and 24-hour proteinuria (P < .001) compared to baseline, whereas no changes in IMT and ABI were detected. CONCLUSION: The changes observed overtime after sunitinib treatment in terms of markers of early endothelial dysfunction, blood pressure, as well as in glucose/insulin metabolism and proteinuria may contribute to increase CV risk in RCC patients and suggest a strict follow-up in this setting. Larger evidences are mandatory to confirm our observations.

α-lipoic acid in patients with autosomal dominant polycystic kidney disease.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls. METHODS: This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2). RESULTS: Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P <0.001; respectively) and significantly higher values of base excess (P < 0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P < 0.001), and a significant reduction of C-reactive protein (P <0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P < 0.001, P < 0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1ß, and tumor necrosis factor-α concentrations in either group. CONCLUSIONS: We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.

Chronic kidney disease and urological disorders: systematic use of uroflowmetry in nephropathic patients.

BACKGROUND: Chronic kidney disease (CKD) is a highly prevalent condition. Urologic disorders are known causes of CKD, but often remain undiagnosed and underestimated also for their insidious onset and slow progression. We aimed to evaluate the prevalence of urological unrecognized diseases in CKD patients by uroflowmetry. METHODS: We enrolled consecutive stable CKD outpatients. The patients carried out two questionnaires, the International Prostate Symptom Score and Incontinence Questionnaire-Short Form, and they also underwent uroflowmetry, evaluating max flow rate (Q max), voiding time and voided volume values. RESULTS: A total of 83 patients (43 males, mean age of 59.8 ± 13.3 years) were enrolled. Our study showed 28 males and 10 females with a significant reduction of Q max (P < 0.001) while 21 females reported a significant increase of Q max (P < 0.001) with a prevalence of 49.5% of functional urological disease. Moreover, we showed a significant association between Q max and creatinine (P = 0.013), estimated glomerular filtration rate (P = 0.029) and voiding volume (P = 0.05). We have not shown significant associations with age (P = 0.215), body mass index (P = 0.793), systolic blood pressure (P = 0.642) or diastolic blood pressure (P = 0.305). Moreover, Pearson's chi-squared test showed a significant association between Q max altered with CKD (χ2 = 1.885, P = 0.170) and recurrent infection (χ2 = 8.886, P = 0.012), while we have not shown an association with proteinuria (χ2 = 0.484, P = 0.785), diabetes (χ2 = 0.334, P = 0.563) or hypertension (χ2 = 1.885, P = 0.170). CONCLUSIONS: We showed an elevated prevalence of urological diseases in nephropathic patients; therefore, we suggest to include uroflowmetry in CKD patient assessment, considering the non-invasiveness, repeatability and low cost of examination. Uroflowmetry could be used to identify previously unrecognized urological diseases, which may prevent the onset of CKD or progression to end-stage renal disease and reduce the costs of management.

The New TNM Staging System for Thyroid Cancer and the Risk of Disease Downstaging.

In October 2016 the American Joint Committee on Cancer (AJCC) published the 8th edition of the AJCC/TNM cancer staging system and it has been introduced in clinical practice since 1st January 2018. The effect of most of the changes in the new edition was the downstaging of a significant number of patients into lower stages, reflecting their low risk of thyroid cancer-related death. One of the most relevant modification refers to the role of the microscopic extra-thyroidal tumor invasion, which is no longer considered as criterion for the classification of T3 tumors. With the present study we want to assess the impact of the changes of the new staging system and therefore we analyzed or casistic of 84 T1-T3 thyroid-cancer patients. The results of our analysis show that he downstaging of patients according to the 8th TNM edition does not necessarily reflect less aggressive disease: we actually reported 2 lymph-nodal recurrences (40%) in the five patients that were downstaged from pT3 to pT2 and the lypmh-nodal recurrence rate for stage I rises from 0% with the 7th TNM edition to 5.3% with the 8th edition.

Total Parathyroidectomy with Subcutaneous Parathyroid Forearm Autotransplantation in the Treatment of Secondary Hyperparathyroidism: A Single-Center Experience.

INTRODUCTION: Secondary hyperparathyroidism is common in chronic kidney disease. Parathyroidectomy is indicated in refractory hyperparathyroidism when medical treatments and so the parathyroid hormone levels cannot be lowered to acceptable values without causing significant hyperphosphatemia or hypercalcemia. The aim of this study is to compare the efficacy and safety of total parathyroidectomy with subcutaneous forearm autotransplantation with total parathyroidectomy with intramuscular forearm autotransplantation. MATERIALS AND METHODS: A single-center retrospective cohort study of total parathyroidectomy with forearm autotransplantation from January 2002 to February 2013 was performed. According to the surgical technique, patients were divided into an intramuscular group (Group 1) and a subcutaneous group (Group 2). 38 patients with secondary hyperparathyroidism were enrolled; 23 patients were subjected to total parathyroidectomy with parathyroid tissue replanting in the subcutaneous forearm of the upper nondominant limb, while 15 patients were subjected to replanting in the intramuscular seat. RESULTS: A total of 38 patients (56 ± 13 years) were enrolled. In both groups, the preoperative iPTH value was markedly high, 1750 ± 619 pg/ml in the intramuscular autotransplantation group and 1527 ± 451 pg/ml in the subcutaneous autotransplantation group (p = 0.079). Transient hypoparathyroidism was shown in 7 patients, and 1 patient showed persistent hypoparathyroidism (p = 0.387). 2 patients showed persistent hyperparathyroidism (p = 0.816), and in 2 others was found recurrent hyperparathyroidism (p = 0.816); 3 of them underwent autograftectomy. The anterior compartment of the forearm nondominant limb was sacrificed in 1 case of intramuscular autotransplantation with functional arm deficit. CONCLUSIONS: The efficacy and safety of parathyroid tissue autotransplantation in the subcutaneous forearm of the upper nondominant limb is confirmed with a good rate of tissue engraftment and with a comparable number of postsurgical transient and persistent hypoparathyroidism and hyperparathyroidism incidence in both techniques. Furthermore, this technique preserves arm functionality in the case of autograftectomy. Consequently, it is our opinion that total parathyroidectomy with subcutaneous forearm autotransplantation is currently the best choice.

Neurological and Psychological Changes in Hemodialysis Patients Before and After the Treatment.

Neurological, psychological, and cognitive disorders in chronic kidney disease may contribute to poor quality of life in these patients. The aim of this study was to assess the electroencephalographic, psychological, and cognitive changes before and after hemodialysis (HD) compared with healthy controls (HC). Sixteen HD patients and 15 HC were enrolled. Electroencephalogram (EEG), Minnesota multiphasic personality inventory (MMPI-2) Satisfaction profile (SAT-P), and Neuropsychological test Global z-scores (NPZ5) were performed before (T0) and after (T1) HD treatment and in HC. Renal function, inflammatory markers and mineral metabolism indexes were also evaluated. Patients did not show significant differences before and after HD in the absolute and relative power of band of EEG, except in Theta/Alpha index (P < 0.001). At T1, HD patients showed significant differences in Beta, Delta and Theta band, in addition to Theta/alpha index, with respect to HC. Moreover, HD patients showed significant differences in specific MMPI-2 clinical and content scales, SAT-P domains and NPZ5 tests of memory and concentration with respect to HC. We also observed significant correlations between renal function, mineral metabolism, inflammatory markers and psychocognitive alterations. In our sample EEG abnormalities tend to reduce, but not significantly, after HD treatment and differences remain present with respect to HC. In HD patients cognitive and psychological alterations were associated with reduced quality of life and correlated with mineral metabolism and inflammation. Modification in EEG and in psychological and cognitive parameters should be assessed in a larger HD population to confirm our observation.

Vascular Endothelial Growth Factor Inhibitor Therapy and Cardiovascular and Renal Damage in Renal Cell Carcinoma.

BACKGROUND: Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. AIM: To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. MATERIALS AND METHODS: Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment. RESULTS: Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), hemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001), IVS (p=0.03) and proteinuria (p<0.001), while we showed no significant differences in glycosuria, phosphaturia, serum uric acid, intact parathormone, and LVMI. CONCLUSION: We observed the development of renal damage and worsening of CV indices in patients treated with sunitinib. We suggest to consider a careful assessment of renal function and CV risk factors, before initiation and during administration of this drug.

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND/AIMS: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. METHODS: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O2 uptake (V'O2max), and O2 uptake at lactic acid threshold (V'O2@LT). RESULTS: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V'O2max, V'O2max/Kg and V'O2max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V'O2@LT, V'O2 @LT%, V'O2@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). CONCLUSION: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

Neurological, psychological, and cognitive disorders in patients with chronic kidney disease on conservative and replacement therapy.

Chronic kidney disease (CKD) is a highly prevalent condition in the world. Neurological, psychological, and cognitive disorders, related to CKD, could contribute to the morbidity, mortality, and poor quality of life of these patients. The aim of this study was to assess the neurological, psychological, and cognitive imbalance in patients with CKD on conservative and replacement therapy.Seventy-four clinically stable patients affected by CKD on conservative therapy, replacement therapy (hemodialysis (HD), peritoneal dialysis (PD)), or with kidney transplantation (KT) and 25 healthy controls (HC), matched for age and sex were enrolled. Clinical, laboratory, and instrumental examinations, as renal function, inflammation and mineral metabolism indexes, electroencephalogram (EEG), psychological (MMPI-2, Sat P), and cognitive tests (neuropsychological tests, NPZ5) were carried out.The results showed a significant differences in the absolute and relative power of delta band and relative power of theta band of EEG (P = 0.008, P < 0.001, P = 0.051), a positive correlation between relative power of delta band and C-reactive protein (CRP) (P < 0.001) and a negative correlation between estimated glomerular filtration rate (eGFR) (P < 0.001) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) (P < 0.001), in all the samples. Qualitative analysis of EEG showed alterations of Grade 2 (according to Parsons-Smith classification) in patients on conservative therapy, and Grade 2-3 in KT patients. The scales of MMPI-2 hysteria and paranoia, are significantly correlated with creatinine, eGFR, serum nitrogen, CRP, 1,25-(OH)2D3, intact parathyroid hormone (iPTH), phosphorus, and cynical and hysterical personality, are correlated with higher relative power of delta (P = 0.016) and theta band (P = 0.016). Moreover, all NPZ5 scores showed a significant difference between the means of nephropathic patients and the means of the HC, and a positive correlation with eGFR, serum nitrogen, CRP, iPTH, and vitamin D.In CKD patients, simple and noninvasive instruments, as EEG, and cognitive-psychological tests, should be performed and careful and constant monitoring of renal risk factors, probably involved in neuropsychological complications (inflammation, disorders of mineral metabolism, electrolyte disorders, etc.), should be carried out. Early identification and adequate therapy of neuropsychological, and cognitive disorders, might enable a better quality of life and a major compliance with a probable reduction in the healthcare costs.

Cardio-Renal Syndrome Type 4: The Correlation Between Cardiorenal Ultrasound Parameters.

Bakground/Aims: Cardiovascular diseases represent the leading causes of morbidity and mortality in patients with cronich kidney disease (CKD). The pathogenesis includes a complex, bidirectional interaction between heart and kidney termed cardiorenal syndrome type 4. The aim of study was to evaluate the association between renal and cardiovascular ultrasonographic parameters and identify early markers of cardiovascular risk. METHODS: A total of 35 patients with CKD and 25 healthy controls, were enrolled and we have evaluated inflammatory indexes, mineral metabolism, renal function, renal and cardiovascular ultrasonographic parameters. RESULTS: Tricuspid anular plane systolic excursion (TAPSE) and estimated pulmonary artery systolic pressure (ePAPs) showed a statistically significant difference between CKD patients and healthy controls (p<0.001, p=0.05). Also 25 hydroxyvitaminD (25-OH-VitD), parathyroid hormone (iPTH), posphorus, serum uric acid, renal resistive index (RRI) and C-reactive protein (CRP) showed a significant difference between the two groups (p=0.002, p<0.001, p<0.001, p<0.001, p<0.001, p<0.001). Moreover the TAPSE correlated positively with estimated glomerula filtration rate (eGFR) and negatively with RRI (p=0.05, p=0.008), while ePAPs correlated negatively with eGFR and positively with RRI (p=0.029, p<0.001). CONCLUSION: CKD can contribute to the development and progression of right ventricle dysfunction with endothelial dysfunction, inflammation and mineral metabolism disorders. Accurate assessment of right ventricular function is recommended in patients with CKD. RRI and echocardiographic parameters can be an important instrument for the diagnosis, prognosis and therapeutic assessment of cardio-renal syndrome in these patients.

Hyperaldosteronism and cardiovascular risk in patients with autosomal dominant polycystic kidney disease.

Hypertension is commonly associated with autosomal dominant polycystic kidney disease (ADPKD), often discovered before the onset of renal failure, albeit the pathogenetic mechanisms are not well elucidated. Hyperaldosteronism in ADPKD may contribute to the development of insulin resistance and endothelial dysfunction, and progression of cardiorenal disease. The aim of study was to evaluate the prevalence of primary aldosteronism (PA) in ADPKD patients and identify some surrogate biomarkers of cardiovascular risk.We have enrolled 27 hypertensive ADPKD patients with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, evaluating the renin-angiotensin-aldosterone system (RAAS), inflammatory indexes, nutritional status, homocysteine (Hcy), homeostasis model assessment-insulin resistance (HOMA-IR), mineral metabolism, microalbuminuria, and surrogate markers of atherosclerosis [carotid intima media thickness (cIMT), ankle/brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI) and left ventricular mass index (LVMI)]. Furthermore, we have carried out the morpho-functional magnetic resonance imaging (MRI) with high-field 3 T Magnetom Avanto.We have divided patients into group A, with normal plasma aldosterone concentration (PAC) and group B with PA, present in 9 (33%) of overall ADPKD patients. Respect to group A, group B showed a significant higher mean value of LVMI, HOMA-IR and Hcy (P = 0.001, P = 0.004, P = 0.018; respectively), and a lower value of FMD and 25-hydroxyvitamin D (25-OH-VitD) (P = 0.037, P = 0.019; respectively) with a higher prevalence of non-dipper pattern at Ambulatory Blood Pressure Monitoring (ABPM) (65% vs 40%, P < 0.05) at an early stage of the disease.In this study, we showed a high prevalence of PA in ADPKD patients, associated to higher LVMI, HOMA-IR, Hcy, lower FMD, and 25-OH-VitD, considered as surrogate markers of atherosclerosis, compared to ADPKD patients with normal PAC values. Our results indicate a higher overall cardiovascular risk in ADPKD patients with inappropriate aldosterone secretion, and a screening for PA in all patients with ADPKD is recommended.

Cardiac, Inflammatory and Metabolic Parameters: Hemodialysis versus Peritoneal Dialysis.

INTRODUCTION: Mortality in dialysis patients is higher than in the general population, and cardiovascular disease represents the leading cause of death. Hypertension and volume overload are important risk factors for the development of left ventricular hypertrophy (LVH) in hemodialysis (HD) and peritoneal dialysis (PD) patients. Other factors are mainly represented by hyperparathyroidism, vascular calcification, arterial stiffness and inflammation. The aim of this study was to compare blood pressure (BP) and metabolic parameters with cardiovascular changes [cardiothoracic ratio (CTR), aortic arch calcification (AAC) and LV mass index (LVMI)] between PD and HD patients. MATERIALS AND METHODS: 45 patients (23 HD and 22 PD patients) were enrolled. BP measurements, echocardiography and chest X-ray were performed in each patient to determine the LVMI and to evaluate the CTR and AAC. Inflammatory indexes, intact parathyroid hormone (iPTH) and arterial blood gas analysis were also evaluated. RESULTS: LVMI was higher in PD than HD patients (139 y 19 vs. 104 y 22; p = 0.04). In PD patients, a significant correlation between iPTH, C-reactive protein and the presence of LVH was observed (r = 0.70, p = 0.04; r = 0.70, p = 0.03, respectively). The CTR was increased in PD patients as compared to HD patients, while no significant differences in cardiac calcifications were determined. CONCLUSIONS: Our data indicate that HD patients present more effective BP control than PD patients. Adequate fluid and metabolic control are necessary to assess the adequacy of BP, which is strongly correlated with the increase in LVMI and with the increased CTR in dialysis patients. PD is a home therapy and allows a better quality of life, but PD patients may present a further increased cardiovascular risk if not adequately monitored.

Early markers of cardiovascular risk in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) present a markedly increased cardiovascular (CV) morbidity and mortality since the early stages and have a high prevalence of accelerated atherosclerosis, inflammation and endothelial dysfunction. Nontraditional cardiovascular risk factors and serum cardiac biomarkers would contribute to explain this increased morbidity. AIM: The aim is to investigate the relation among serum cardiac biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), nontraditional cardiovascular risk factors (serum uric acid, homocysteine), inflammatory indexes (C-reactive protein (CRP) serum ferritin, fibrinogen) and noninvasive predictors of atherosclerosis (carotid intima-media thickness (cIMT), brachial artery flow mediated dilation (baFMD), and left ventricular mass index (LVMI)) in CKD patients. MATERIALS AND METHODS: In 50 patients with CKD in stage 2/3 kidney disease outcomes quality initiative (KDOQI) and 18 age- and sex-matched healthy controls, the following parameters were measured: cardiac markers (cTnT and NT-proBNP), renal function, inflammatory markers (CRP, serum ferritin and fibrinogen), serum uric acid and homocysteine. We have also evaluated LVMIs, cIMT and baFMD. RESULTS: In our study, we showed an increase of NT-proBNP and the serum cTnT, of serum uric acid and homocysteine with a positive correlation with the increase of cIMT and LVMI and reduced baFMD compared with the controls. CONCLUSIONS: Serum cardiac biomarkers and nontraditional cardiovascular risk factors increase already in the stage 2/3 KDOQI contributing to explain the high cardiovascular morbidity and mortality of these patients. The NT-proBNP seems to have a rise earlier compared with serum cTnT; however, both seemed to be a useful clinical biomarker for evaluating noninvasive predictors of atherosclerosis in CKD patients.