Hypothyroidism and nephrotic syndrome: why, when and how to treat

Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free tri-iodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine-binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition. In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies

Pharmacological effects of raas blockade in ischemic nephropathy

Background: The management of ischemic nephropathy due to atherosclerotic renal artery stenosis has become increasingly conservative in the modern era, with current guidelines recommending optimized medical therapy as the initial step. The doubts raised by the recently published trials of revascularization strategies have led to a renewed focus on pharmacological strategies promoting blood pressure control and renal protection. It is essential to further elucidate the pathophysiological mechanisms underlying hypoperfusion induced renal microvascular dysfunction with subsequent tissue injury and fibrogenesis. The role of renin angiotensin aldosterone system as a mediator of the main pathophysiological consequences of ischemic nephropathy is well known. However, more recent experimental evidence on the adrenergic system and intrarenal tubular feedback mechanisms has stimulated new interest towards a multi-target therapeutic approach. Methods: This review focuses on the pharmacology of the principle therapeutic drug classes currently used in the treatment of atherosclerotic renal artery stenosis with an analysis of their metabolic aspects and use in clinical practice based on evidence from clinical trials. Results and Conclusions: An optimal pharmacologic approach is crucial for a successful prevention of renal injury and cardiovascular events in this high-risk population. Antihypertensive treatment should include renin angiotensin aldosterone system blockade medication not only for their antihypertensive properties, but especially for those cardio and renoprotectiv

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients

Background: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. Methods: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. Results: The serum UA showed a significant positive correlation with sCr (r = 0.33, p < 0.0001) and PAPs (r = 0.38, p < 0.01) > and negative correlation with CKD-EPI (r = -0.35, p < 0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7 mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p < 0.05) in SSc patients with low normal or high normal serum UA. Conclusions: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies

Left ventricular mass and intrarenal arterial stiffness as early diagnostic markers in cardiorenal syndrome type 5 due to systemic sclerosis

Background: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. Methods: Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. Results: Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. Conclusions: SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression

MicroRNA-155 influences B-cell function through PU.1 in rheumatoid arthritis

MicroRNA-155 (miR-155) is an important regulator of B cells in mice. B cells have a critical role in the pathogenesis of rheumatoid arthritis (RA). Here we show that miR-155 is highly expressed in peripheral blood B cells from RA patients compared with healthy individuals, particularly in the IgD-CD27- memory B-cell population in ACPA+ RA. MiR-155 is highly expressed in RA B cells from patients with synovial tissue containing ectopic germinal centres compared with diffuse synovial tissue. MiR-155 expression is associated reciprocally with lower expression of PU.1 at B-cell level in the synovial compartment. Stimulation of healthy donor B cells with CD40L, anti-IgM, IL-21, CpG, IFN-α, IL-6 or BAFF induces miR-155 and decreases PU.1 expression. Finally, inhibition of endogenous miR-155 in B cells of RA patients restores PU.1 and reduces production of antibodies. Our data suggest that miR-155 is an important regulator of B-cell activation in RA

Learning selective top-down control enhances performance in a visual categorization task.

We model the putative neuronal and synaptic mechanisms involved in learning a visual categorization task, taking inspiration from single-cell recordings in inferior temporal cortex (ITC). Our working hypothesis is that learning the categorization task involves both bottom-up, ITC to prefrontal cortex (PFC), and top-down (PFC to ITC) synaptic plasticity and that the latter enhances the selectivity of the ITC neurons encoding the task-relevant features of the stimuli, thereby improving the signal-to-noise ratio. We test this hypothesis by modeling both areas and their connections with spiking neurons and plastic synapses, ITC acting as a feature-selective layer and PFC as a category coding layer. This minimal model gives interesting clues as to properties and function of the selective feedback signal from PFC to ITC that help solving a categorization task. In particular, we show that, when the stimuli are very noisy because of a large number of nonrelevant features, the feedback structure helps getting better categorization performance and decreasing the reaction time. It also affects the speed and stability of the learning process and sharpens tuning curves of ITC neurons. Furthermore, the model predicts a modulation of neural activities during error trials, by which the differential selectivity of ITC neurons to task-relevant and task-irrelevant features diminishes or is even reversed, and modulations in the time course of neural activities that appear when, after learning, corrupted versions of the stimuli are input to the network

Renal parenchymal resistance in patients with biopsy proven glomerulonephritis: correlation with histological findings

Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis (P <0.01, r = 0.26), conversely a negative correlation exists between glomerular filtrate rate and percentage of glomerular sclerosis(P <0.0001, r = -0.35). The percentage of glomerular sclerosis correlate positively with pulsatile index (PI) (P <0.05, r = 0.21) and renal resistive index (RI) (P <0.05, r = 0.20). The percentage of crescents correlates positively with PI(P <0.05, r = 0.21) and RI (P <0.05, r = 0.20). Classifying arteriolosclerosis in four groups according to a severity scale, from absence to severe, PI (P <0.05) and RI (P <0.01) were significantly different. In the post hoc analysis, the median values of PI and RI are significantly different in patients with severe arteriolosclerosis than others. Ultrasound examination is a non-invasive diagnostic technique used on patients with suspected or established renal disease. Our study shows a close correlation between kidney function, ultrasound parameters, and histological findings. Measurement of renal parenchymal resistance by ultrasound could be used in association with biopsy and glomerular function for the evaluation of renal damage in patients with glomerulonephritis

A new tool to assess the occurrence of personality traits: the Phenomenological Personality Factor questionnaire

Personality traits are patterns of thoughts, feelings and actions that are usually assessed by means of psychometric questionnaires. In the present study we described the Phenomenological Personality Factor (PPF), a short questionnaire assessing the personality traits, taking into account the different interpretative models of personality

Validation of a guideline to reduce variability in diagnosing cervical dystonia

Background: Cervical dystonia is characterized by a variable pattern of neck muscle involvement. Due to the lack of a diagnostic test, cervical dystonia diagnosis is based on clinical examination and is therefore subjective. The present work was designed to provide practical guidance for clinicians in confirming or refuting suspected cervical dystonia. Methods: Participants were video recorded according to a standardized protocol to assess 6 main clinical features possibly contributing to cervical dystonia diagnosis: presence of repetitive, patterned head/neck movements/postures inducing head/neck deviation from neutral position (item 1); sensory trick (item 2); and red flags related to conditions mimicking dystonia that should be absent in dystonia (items 3-6). Inter-/intra-rater agreement among three independent raters was assessed by k statistics. To estimate sensitivity and specificity, the gold standard was cervical dystonia diagnosis reviewed at each site by independent senior neurologists. Results: The validation sample included 43 idiopathic cervical dystonia patients and 41 control subjects (12 normal subjects, 6 patients with isolated head tremor, 4 with chorea, 6 with tics, 4 with head ptosis due to myasthenia or amyotrophic lateral sclerosis, 7 with orthopedic/rheumatologic neck diseases, and 2 with ocular torticollis). The best combination of sensitivity and specificity was observed considering all the items except for an item related to capability to voluntarily suppress spasms (sensitivity: 96.1%; specificity: 81%). Conclusions: An accurate diagnosis of cervical dystonia can be achieved if, in addition to the core motor features, we also consider some clinical features related to dystonia mimics that should be absent in dystonia