Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Atypical hemolytic uremic syndrome in Brazil: clinical presentation, genetic findings and outcomes of a case series in adults and children treated with eculizumab.

Background: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and kidney injury caused by a dysregulation of the alternative complement pathway.

Methods: We conducted a multicenter nonregistry study aimed at collecting clinical, laboratory and genetic information of patients with aHUS in Brazil. Demographic data, genetic findings, treatments and outcomes are presented.

Diacylglycerol kinase epsilon nephropathy: late diagnosis and therapeutic implications.

A 17-year-old male presented thrombotic microangiopathy (TMA) at 6 months of age with arterial hypertension, anemia, thrombocytopenia and kidney injury improving with plasma infusions. Fourteen years later, he was diagnosed with severe arterial hypertension, increase in serum creatinine and chronic TMA on kidney biopsy. Eculizumab was started and after 18 months of treatment, he persisted with hypertension, decline in renal function and proteinuria.

Reversal of pulmonary hypertension in children after adenoidectomy or adenotonsillectomy.

Introduction: Adenotonsillar hypertrophy is a common condition in pediatric patients with upper respiratory airways complaints, and pulmonary arterial hypertension (PAH) may be one complication of that condition.

Objectives: To study the occurrence of PAH (mean pulmonary artery pressure higher than or equal to 25 mmHg) in a group of children with adenotonsillar hypertrophy and upper respiratory complaints (snoring or oral breathing), and to verify the pulmonary arterial pressure (PAP) changes after adenotonsillectomy.

Study Design: Case-control prospective study.

Renal oxygen content is increased in healthy subjects after angiotensin-converting enzyme inhibition.

Objective: The association between renal hypoxia and the development of renal injury is well established. However, no adequate method currently exists to non-invasively measure functional changes in renal oxygenation in normal and injured patients.

Method: R2* quantification was performed using renal blood oxygen level-dependent properties.

Fluid overload and changes in serum creatinine after cardiac surgery: predictors of mortality and longer intensive care stay. A prospective cohort study.

Introduction: Fluid overload is a clinical problem frequently related to cardiac and renal dysfunction. The aim of this study was to evaluate fluid overload and changes in serum creatinine as predictors of cardiovascular mortality and morbidity after cardiac surgery.

Methods: Patients submitted to heart surgery were prospectively enrolled in this study from September 2010 through August 2011.

C-terminal fragments of the alpha 1C (CaV1.2) subunit associate with and regulate L-type calcium channels containing C-terminal-truncated alpha 1C subunits.

L-type Ca(2+) channels in native tissues have been found to contain a pore-forming alpha(1) subunit that is often truncated at the C terminus. However, the C terminus contains many important domains that regulate channel function. To test the hypothesis that C-terminal fragments may associate with and regulate C-terminal-truncated alpha(1C) (Ca(V)1.

Beta-adrenergic and cholinergic modulation of inward rectifier K+ channel function and phosphorylation in guinea-pig ventricle.

1. To clarify the nature of the inhibition of whole-cell inwardly rectifying K+ current (IK1) by isoprenaline (Iso) and its antagonism by acetylcholine (ACh), we studied the effects of Iso and ACh and their surrogates on single channel currents (iK1) carried by inwardly rectifying K+ channels in cell-attached and excised inside-out patches obtained from guinea-pig ventricular myocytes. 2.

beta-adrenergic and cholinergic modulation of the inwardly rectifying K+ current in guinea-pig ventricular myocytes.

1. Whole-cell patch-clamp technique was used to study the beta-adrenergic and cholinergic regulation of the inwardly rectifying K+ conductance (gK1) in isolated guinea-pig ventricular myocytes. 2.

Alteration of the sodium current in cat cardiac ventricular myocytes during primary culture.

To determine the response of cardiac Na current (INa) in adult cardiac ventricular myocytes to culture, single isolated ventricular myocytes from collagenase-perfused adult cat hearts were placed in primary culture for up to 2 wk on a two-dimensional (2D) surface (laminin-coated coverslips), which allowed the morphology of the myocytes to change markedly, or in a three-dimensional matrix (3D) of alginate, in which cell shape changed only minimally. Action potentials and INa were recorded from groups of 1) freshly isolated myocytes serving as the control (day 0),2) cells maintained in 2D culture for 9-14 days (2D, day 9-14), and 3) cells cultured in alginate for 9-14 days (3D, day 9-14) with use of a conventional whole cell patch technique. Maximal upstroke velocity (Vmax) of the action potential was reduced by approximately 50% in 2D- and 3D-cultured cells relative to controls.

Electrophysiology of adult cat cardiac ventricular myocytes: changes during primary culture.

To investigate the nature of electrophysiological changes in adult cat cardiac ventricular myocytes that may occur when cells are maintained in primary culture for 1-2 wk, the electrophysiology of cells freshly isolated from collagenase-perfused hearts (day 0 controls) was compared with that of cells maintained in primary culture for up to 14 days 1) on a two-dimensional (2D) surface (laminin-coated coverslips), which allowed for changes in cellular morphology, or 2) in a three-dimensional (3D) alginate matrix, which minimized changes in cell shape. Action potentials and whole cell ionic currents were recorded using a conventional whole cell patch technique. Whereas cellular resting potential and the depth of the "notch" terminating phase 1 were diminished relative to controls in 2D- and 3D-cultured cells, the action potential duration and the incidence of early afterdepolarizations (EADs) were increased relative to controls in 2D- but not in 3D-cultured cells.

Comparison of the effects of internal [Mg2+] on IK1 in cat and guinea-pig cardiac ventricular myocytes.

The effects of internal Mg2+ (Mg2+i) on processes underlying the inward rectification of the cardiac IK1 in enzymatically isolated cardiac ventricular myocytes (CVM) obtained from cat, guinea pig and rabbit were compared using the whole-cell and excised inside-out patch configurations of the voltage-clamp technique. In confirmation of the findings of other investigators, Mg(2+)i-sensitive outward IK1 currents could be elicited from guinea pig CVM at 15 degrees C when Mg2+i was reduced from 1 mM to less than 1 microM, suggesting that Mg2+i has an important role in the inward rectification of IK1 in guinea pig CVM at unphysiologically low temperatures. However, as temperature was raised to more physiological levels (e.

Protein kinase-dependent Cl- currents in feline ventricular myocytes.

A Cl- current (ICl) induced by isoproterenol (ISO) has been identified in isolated guinea pig ventricular myocytes. This ISO-induced ICl can be inhibited by propranolol and mimicked by forskolin (FSK), suggesting that beta-receptors, cAMP, and protein kinase A (PKA) are involved in regulating the involved Cl- channel. Because activation of protein kinase C (PKC) mediated via alpha-adrenergic receptor stimulation is also known to regulate several ion channels, the idea that activation of PKC also can induce ICl was investigated by using isolated feline ventricular myocytes and the whole-cell patch-clamp technique.

A 3,4-diaminopyridine-insensitive, Ca(2+)-independent transient outward K+ current in cardiac ventricular myocytes.

A previously unrecognized current that initially is not present and requires at least 25 min of intracellular access to develop can be found in approximately 75% of cardiac myocytes isolated from cat ventricle within 90 min after intracellular access is obtained with conventional suction patch pipette electrodes. We refer to this patch-duration-dependent (PDD) current as IK(PDD). IK(PDD) can be elicited with depolarizing test steps (Vt) ranging between -40 and +60 mV applied after a hyperpolarizing conditioning step to -140 mV for 200 ms from a holding potential of -40 mV.

Enhancement of ATP-sensitive potassium current in cat ventricular myocytes by beta-adrenoreceptor stimulation.

1. To address the questions of whether beta-adrenoreceptor stimulation can augment ATP-sensitive potassium current (IK(ATP)), and what the mechanism of such an effect might be, action potentials and whole-cell ionic currents were recorded from adult cat cardiac ventricular myocytes using a conventional whole-cell patch technique. 2.

Effect of osmotic swelling and shrinkage on Na(+)-K+ pump activity in mammalian cardiac myocytes.

The effect on the sarcolemmal Na(+)-K+ pump of exposure to anisosmolar solutions was examined using whole cell patch clamping and ion-selective microelectrodes. Na(+)-K+ pump currents were measured in single ventricular myocytes by using pipette Na+ concentrations ([Na]pip) of 0-70 mM. The relationship between [Na]pip and pump current was well described by the Hill equation.

Enhanced functional expression of transient outward current in hypertrophied feline myocytes.

Cardiac hypertrophy can decrease myocardial contractility and alter the electrophysiological activity of the heart. It is well documented that action potentials recorded from hypertrophied feline ventricular cells can exhibit depressed plateau voltages and prolonged durations. Similar findings have been made by others in rabbit, rat, guinea pig, and human heart.

Connections: heart disease, cellular electrophysiology, and ion channels.

Our purpose in this article is to examine the hypothesis that both myocardial disease and ischemia can alter the electrophysiologic function of the ion channels responsible for the cellular electrical activity of the heart. Changes in the intracellular and extracellular milieus occur during ischemia and can alter the electrophysiology of several species of ionic channels and the cellular electrophysiologic activity of cardiac myocytes. Included are 1) changes in extracellular [K+] and pH and in intracellular [Na+], [Ca2+], and pH; 2) accumulation of noxious metabolic products such as lysophosphatidylcholine; and 3) depletion of intracellular ATP.

Dependence of Na-K pump current on internal Na+ in mammalian cardiac myocytes.

Na-K pump current (Ipump) is a function of the intracellular Na+ concentration [( Na+]i). We examined the quantitative relationship between Ipump and [Na+]i in isolated guinea pig ventricular myocytes under steady-state conditions. [Na+]i was controlled and "clamped" at several selected concentrations using wide-tipped pipette microelectrodes, and membrane current was measured using the whole cell patch voltage-clamp technique.

Characterization of the electrophysiological effects of metoprolol on isolated feline ventricular myocytes.

Metoprolol is considered to be a class II antiarrhythmic agent that is highly specific for cardiac beta-1 adrenergic receptors, yet long-term administration can produce prolongation of the rate-corrected Q-T interval in humans. Action potentials and sodium (INa), "L"-type calcium (ICa) and transient outward (Ito) or inward rectifying potassium (IKl) currents were recorded from isolated cat ventricular myocytes using the whole-cell-patch technique to determine if metoprolol can directly affect cellular electrophysiological activity. External and pipette solutions, holding potentials and voltage-clamp protocols appropriate to isolate and examine INa, IKl, Ito and ICa were used.

Inhibition of electrogenic Na(+)-pumping in isolated atrial tissue from patients treated with digoxin.

The effect on the cardiac sarcolemmal Na+,K(+)-pump of therapeutic concentrations of cardiac glycosides administered long-term to humans in a clinical setting is uncertain. We therefore examined Na+,K(+)-pump activity in atrial tissue from two groups of patients undergoing cardiac surgery. Fourteen patients received digoxin long-term until the time of surgery and 12 "controls" never received digoxin.