The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection.

Immunity in the urinary tract has distinct and poorly understood pathophysiological characteristics and urinary tract infections (UTIs) are important causes of morbidity and mortality. We investigated the role of the soluble pattern recognition molecule pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, in UTIs. PTX3-deficient mice showed defective control of UTIs and exacerbated inflammation. Expression of PTX3 was induced in uroepithelial cells by uropathogenic Escherichia coli (UPEC) in a Toll-like receptor 4 (TLR4)- and MyD88-dependent manner. PTX3 enhanced UPEC phagocytosis and phagosome maturation by neutrophils. PTX3 was detected in urine of UTI patients and amounts correlated with disease severity. In cohorts of UTI-prone patients, PTX3 gene polymorphisms correlated with susceptibility to acute pyelonephritis and cystitis. These results suggest that PTX3 is an essential component of innate resistance against UTIs. Thus, the cellular and humoral arms of innate immunity exert complementary functions in mediating resistance against UTIs.

Neurological counterparts of hyponatremia: pathological mechanisms and clinical manifestations.

Hyponatremia, defined as a serum sodium concentration <135 mEq/L, represents the most frequent electrolyte disorder in older hospitalized patients. Early recognition of hyponatremia is mandatory, since it represents an independent risk factor that increases hospital mortality by 40 %. Delayed correction of hyponatremia may worsen brain edema, resulting in different degrees of neural damage. However, an overly rapid correction of serum sodium levels can lead to osmotic demyelination syndrome (ODS), a dreadful neurological picture. In recent years, hyponatremia and ODS have received growing attention both in terms of clinical management and pathophysiology, leading to the discovery of new drugs and treatment algorithms. In this review, we recapitulate the pathogenetic background, clinical manifestations, and treatment guidelines of hyponatremia, focusing on the neurological alterations. Neurological symptoms may be neglected when they manifest as early signs of mild hyponatremia, while brain damage can irremediably affect patients' conditions in the context of ODS.

Renal dysfunction in acute congestive heart failure: a common problem for cardiologists and nephrologists.

The term acute heart failure (AHF) refers to a clinical syndrome with typical symptoms and signs, in which a structural or functional heart abnormality leads to defective oxygen delivery. The term cardiorenal syndrome has been proposed to outline the strict interplay between cardiac and renal function. In the setting of acute cardiac decompensation, acute kidney injury (AKI) is generally referred to as cardiorenal syndrome type 1. In this review, we summarize the fundamental pathophysiological aspects of both AHF and AHF-related AKI. We also review the latest therapeutic options, including both pharmacological ones, such as loop diuretics, potassium-sparing diuretics and vaptans, and non-pharmacological ones, such as ultrafiltration, and their impact on patients' outcome. We discuss the pathophysiology of diuretic resistance, a common occurrence in these patients, reviewing the available strategies to treat it and highlighting how a close collaboration between cardiologists and nephrologists is frequently crucial for the management of this complication. Finally, we discuss three new promising non-pharmacological tools for the prevention of AHF recurrence, including two methods that exploit sympathetic denervation and one technique that acts by increasing vagal tone.

The dialysis scenario in patients with systemic lupus erythematosus.

Although prognosis of lupus nephritis has improved over time, a substantial amount of lupus patients still reach end-stage renal disease and require dialysis. Treatment of these patients can be challenging, since the disease poses a number of problems that can portend a poor prognosis, such as infections, lupus reactivations, vascular access thrombosis and cardiovascular complications. Consensus is lacking among investigators about the real incidence of these complications and related diagnosis and treatment. Moreover, the choice of the type of dialysis treatment and the overall prognosis are still a matter of debate. In this paper, we have reviewed the currently available literature in an attempt to answer the most controversial issues about the topic.

CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans histiocytosis, with noncodified therapeutic management and high mortality. No treatment has yet been shown to improve survival in these patients. We conducted a multicenter prospective observational cohort study to assess whether extraskeletal manifestations and interferon-α treatment would influence survival in a large cohort of ECD patients. To achieve this goal, we thoroughly analyzed the clinical presentation of 53 patients with biopsy-proven ECD, and we performed a survival analysis using Cox proportional hazard model. Fifty-three patients (39 men and 14 women) with biopsy-proven ECD were followed up between November 1981 and November 2010. Forty-six patients (87%) received interferon-α and/or PEGylated interferon-α. Multivariate survival analysis using Cox proportional hazard model revealed that central nervous system involvement was an independent predictor of death (hazard ratio = 2.51; 95% confidence interval, 1.28-5.52; P = .006) in our cohort. Conversely, treatment with interferon-α was identified as an independent predictor of survival (hazard ratio = 0.32; 95% confidence interval, 0.14-0.70; P = .006). Although definitive confirmation would require a randomized controlled trial, these results suggest that interferon-α improves survival in ECD patients. This may be seen as a significant advance, as it is the first time a treatment is shown to improve survival in this multisystemic disease with high mortality.

Wave dispersion in moderate channel turbulence.

We study channel turbulence by interpreting its vorticity as a random sea of ocean wave packet analogues. In particular, we investigate the ocean-like properties of vortical packets applying stochastic methods developed for oceanic fields. Taylor's hypothesis of frozen eddies does not hold when turbulence is not weak, and vortical packets change shape as they are advected by the mean flow, altering their own speed. This is the physical manifestation of a hidden wave dispersion of turbulence. Our analysis at the bulk Reynolds number Reb = 5600 suggests that turbulent fluctuations behave dispersively as gravity-capillary waves, with capillarity being dominant near the wall region.

How Free Swimming Fosters the Locomotion of a Purely Oscillating Fish-like Body.

The recoil motions in free swimming, given by lateral and angular rigid motions due to the interaction with the surrounding water, are of great importance for a correct evaluation of both the forward locomotion speed and efficiency of a fish-like body. Their contribution is essential for calculating the actual movements of the body rear end whose prominent influence on the generation of the proper body deformation was established a long time ago. In particular, the recoil motions are found here to promote a dramatic improvement of the performance when damaged fishes, namely for a partial functionality of the tail or even for its complete loss, are considered. In fact, the body deformation, which turns out to become oscillating and symmetric in the extreme case, is shown to recover in the water frame a kind of undulation leading to a certain locomotion speed though at the expense of a large energy consumption. There has been a deep interest in the subject since the infancy of swimming studies, and a revival has recently arisen for biomimetic applications to robotic fish-like bodies. We intend here to apply a theoretical impulse model to the oscillating fish in free swimming as a suitable test case to strengthen our belief in the beneficial effects of the recoil motions. At the same time, we intend to exploit the linearity of the model to detect from the numerical simulations the intrinsic physical reasons related to added mass and vorticity release behind the experimental observations.

Syndrome of inappropriate secretion of antidiuretic hormone in traumatic brain injury: when tolvaptan becomes a life saving drug.

OBJECTIVE: To outline the role of a new drug, tolvaptan, in treating severe and chronic hyponatraemia. Tolvaptan decreases aquaporin expression in renal collecting ducts, by inhibiting antidiuretic hormone (ADH)-V2 receptors, to promote free water clearance. Given its mechanism of action, this drug seems the ideal treatment for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) when the osmotic imbalance leads to life threatening complications. DATA SOURCES: A case is described of severe hyponatraemia deriving from SIADH secondary to meningoencephalitis in a patient admitted to hospital for traumatic brain injury. DATA EXTRACTION: Clinical, laboratory and radiological data at presentation and for a 1 year of follow-up were analysed. DATA SYNTHESIS: Tolvaptan ameliorated hyponatraemia, brain oedema and consciousness, and drug withdrawal led to recurrence of hyponatraemia and coma. CONCLUSIONS: In patients with SIADH, which is not self-limited, and is associated with severe cognitive impairment, the use Tolvaptan may prove life saving and should be rigorously evaluated.

Proteinuria after kidney transplantation.

The prevalence of proteinuria at 1 year after renal transplantation ranges between 11% and 45% and is even higher in patients treated with inhibitors of the mammalian target of rapamycin (mTOR). Two main mechanisms can lead to proteinuria: an inadequate reabsorption of small proteins from proximal tubular cells damaged by ischemia-reperfusion injury, rejection, or toxic agents (tubular proteinuria) or an increased passage of albumin and/or protein with higher molecular weight (MW) because of a disruption of glomerular barrier caused by recurrent or de novo glomerulonephritis, transplant glomerulopathy, chronic rejection, or CNI toxicity (glomerular proteinuria). Proteinuric patients have worse patient and graft survival rates in comparison to non proteinuric patients. The amount of proteinuria is a reliable predictor of the allograft outcome. However, even microalbuminuria may be associated with a poor outcome. Treatment of proteinuria mainly rests on the management of the etiologic cause. Inhibitors of renin-angiotensin system (RAS) are useful in reversing microalbuminuria and can reduce proteinuria, but their efficacy in interfering with patient or graft survival is not demonstrated.

The fish ability to accelerate and suddenly turn in fast maneuvers.

Velocity burst and quick turning are performed by fish during fast maneuvers which might be essential to their survival along pray-predator encounters. The parameters to evaluate these truly unsteady motions are totally different from the ones for cruising gaits since a very large acceleration, up to several times the gravity, and an extreme turning capability, in less than one body length, are now the primary requests. Such impressive performances, still poorly understood, are not common to other living beings and are clearly related to the interaction with the aquatic environment. Hence, we focus our attention on the water set in motion by the body, giving rise to the relevant added mass and the associated phenomena in transient conditions, which may unveil the secret of the great maneuverability observed in nature. Many previous studies were almost exclusively concentrated on the vortical wake, whose account, certainly dominant at steady state, is not sufficient to explain the entangled transient phenomena. A simple two-dimensional impulse model with concentrated vorticity is used for the self-propulsion of a deformable body in an unbounded fluid domain, to single out the potential and the vortical impulses and to highlight their interplay induced by recoil motions.

Hypertension in kidney transplant recipients.

Arterial hypertension is frequently observed in renal transplant recipients. Its pathogenesis is multifactorial in most cases. Calcineurin inhibitors (CNI) can increase peripheral vascular resistance by inducing arteriolar vasoconstriction and can cause extracellular fluid expansion by reducing the glomerular filtration rate (GFR), activating the renin-angiotensin system (RAS), and by inactivating the atrial natriuretic peptide. Glucocorticoids can impair urinary water and salt excretion. Poor graft function can lead to increased extracellular volume and inappropriate production of renin. Native kidneys, older age of the donor and transplant renal artery stenosis (TRAS) may also contribute to the development of hypertension. Arterial hypertension not only can increases the risk for cardiovascular events but can also deteriorate renal allograft function. A number of studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure. On the other hand, a good control of blood pressure may prevent many cardiovascular and renal complications. Appropriate lifestyle modification is the first step for treating hypertension. Calcium channel blockers (CCB) and renin-angiotensin system (RAS) inhibitors are the most frequently used antihypertensive agents, but in many cases, a combination of these and other drugs is required to obtain good control of hypertension.

Chyluria associated with nephrotic-range proteinuria: pathophysiology, clinical picture and therapeutic options.

Chyluria denotes the urinary excretion of chyle, which is a lymphatic fluid rich in chylomicrons. Chyle flows from the intestinal lacteals to the left subclavian vein through the thoracic duct. When an abnormal connection between these structures and the urinary tract develops, chyluria appears. The syndrome is often associated with a nephrotic-range proteinuria, and this could be a wrong indication to perform renal biopsy. Chyluria is classified as parasitic or nonparasitic, the former being induced by lymphatic filariasis, whereas the latter is caused by medical, traumatic or inherited diseases. The patient usually reports excretion of milky urines, monolateral flank pain, malnutrition, weight loss and weakness. Urinalysis demonstrates lymphocyturia associated with chylomicrons and triglycerides in the supernatant. The diagnostic approach is aimed to define the site of lymphourinary fistula. A selective ureteral catheterization allows to collect urine samples from each kidney, demonstrating a monolateral source of proteins and lipids and making renal biopsy superfluous. Other diagnostic tools include nuclear magnetic resonance urography and lymphoangiography. Many therapeutic options have been proposed. Sclerosing solution instillation into the renal pelvis and laparoscopic renal pedicle disconnection are the invasive procedures most commonly employed. Among the medical alternatives, a low-fat diet supplemented with medium-chain triglycerides is often followed by complete clinical and biochemical remission.

The performance of a flapping foil for a self-propelled fishlike body.

Several fish species propel by oscillating the tail, while the remaining part of the body essentially contributes to the overall drag. Since in this case thrust and drag are in a way separable, most attention was focused on the study of propulsive efficiency for flapping foils under a prescribed stream. We claim here that the swimming performance should be evaluated, as for undulating fish whose drag and thrust are severely entangled, by turning to self-propelled locomotion to find the proper speed and the cost of transport for a given fishlike body. As a major finding, the minimum value of this quantity corresponds to a locomotion speed in a range markedly different from the one associated with the optimal efficiency of the propulsor. A large value of the feathering parameter characterizes the minimum cost of transport while the optimal efficiency is related to a large effective angle of attack. We adopt here a simple two-dimensional model for both inviscid and viscous flows to proof the above statements in the case of self-propelled axial swimming. We believe that such an easy approach gives a way for a direct extension to fully free swimming and to real-life configurations.

Different cardiovascular responses to hemodialysis-induced fluid depletion and blood pressure compliance.

BACKGROUND: On the basis of cardiovascular compliance, hemodialysis (HD) patients can be classified as hypotension prone (HP) or hypotension resistant (HR). METHODS: We compare the hemodynamic behavior and myocardial performances in 6 HP and 6 HR patients before and after an isolated ultrafiltration (IU) session removing 3% of total body water. RESULTS: HP show higher basal plasma angiotensin II levels during IU (p<0.01), whereas angiotensin II remained unchanged in HR patients (p<0.001 between groups). The percentage changes of plasma volume (PV) was similar in the 2 groups. A significant reduction of cardiac index was observed only in the HP group (p<0.001 between groups). The mean values of heart rate remained significantly higher, whereas total peripheral resistances significantly fell in the HP in comparison with the HR group (p<0.001 between groups). During IU, the mean arterial pressure (MAP) changes were -10 +/- 3 mm Hg in the HP vs. -3.3 +/- 2 mm Hg in the HR group (p<0.001). Echocardiography data were collected before and after IU. All enrolled patients presented left ventricular hypertrophy; following IU, HP patients showed a reduction of mean left ventricular diameter (p<0.01), left atrial diameters and right atrial diameter, and a change in percentage of right atrium ejection fraction (p<0.001, p<0.01). CONCLUSIONS: In comparison with HR patients, HP patients before and after IU showed a defective arteriovenous tone adjustment to the PV changes, with a hemodynamic picture of abnormal sympathetic stimulation. Moreover, a reduced cardiac preload with both atrial and ventricular underfilling in these patients is at risk for a sudden drop in MAP.

Ureteral endometriosis: a rare and underdiagnosed cause of kidney dysfunction.

Little attention has been paid by the renal literature to ureteral endometriosis, a rare and silent disorder that can eventually lead to renal failure. In endometriosis, the ureteral involvement can be limited to a single ureter, more often the left one, or both ureters with consequent urine tract obstruction and ureterohydronephrosis. In most cases, the ureteral obstruction is caused by endometrial tissue surrounding the ureter (extrinsic ureteral endometriosis). In the remaining cases, endometrial cells are located within the ureter (intrinsic ureteral endometriosis). Progressive ureteral obstruction can be insidious in onset and can ultimately lead to renal failure if a correct diagnosis is missed. The true incidence of renal failure caused by endometriosis is completely unknown, although cases have been reported in the literature. The diagnosis of ureteral endometriosis is difficult since the disease may be clinically silent or associated with non-specific symptoms. Only a high index of suspicion and radiological support may help to obtain an early diagnosis. However, while renal imaging is useful in the cases of extrinsic endometriosis, the diagnosis of intrinsic endometriosis often requires ureteroscopy or laparoscopy. The prognosis of ureteral endometriosis depends on the time of diagnosis. In too many cases of bilateral obstruction, the patient is referred to the nephrologist because of an advanced, irreversible renal failure. Although some patients may benefit from progestin or anti-arotamase therapy, in most cases of ureteral endometriosis surgery is needed, laparoscopy surgery being preferred today to laparatomy.

On the feasibility of the Rayleigh cycle for dynamic soaring trajectories.

Dynamic soaring is a flight technique used by albatrosses and other birds to cover large distances without the expenditure of energy, which is extracted from the available wind conditions, as brightly perceived five centuries ago by Leonardo da Vinci. Closed dynamic soaring trajectories use spatial variations of wind speed to travel, in principle, indefinitely over a prescribed area. The application of the concept of closed dynamic soaring trajectories to aerial vehicles, such as UAVs, may provide a solution to improve the endurance in certain missions. The main limitation of dynamic soaring is its dependence on the wind characteristics. More than one century ago, Lord Rayleigh proposed a very simple model, based on the repeated crossing of a step wind profile, presently known as Rayleigh cycle, that provides a clear explanation of the physical phenomenon. The present paper studies the feasibility of closed, single-loop, energy-neutral trajectories for a broad set of wind and vehicle conditions. Through the use of trajectory optimization methods, it was possible to see how the shape of the wind profile, the initial flight conditions and the vehicle constraints influence the required wind strength to perform dynamic soaring trajectories and consequently their feasibility. It was possible to conclude that there are optimal values for the initial airspeed and initial height of the vehicle, that minimize the required wind strength. In addition, it was seen how the structural and aerodynamic constraints of the vehicle affect dynamic soaring at high and low airspeeds respectively. Finally, some new trajectories that can be performed in conditions of excess wind are proposed. The purpose is to maximize the time spent aloft and the path length while maintaining the concept of single-loop, energy-neutral trajectories, making them especially useful for aerial vehicles surveillance applications.

[The CROFF pavilion at the Policlinico Hospital in Milan: the beginnings].

This article collects the personal stories of the young doctors who in the early sixties contributed to the birth and development of the Croff pavilion at the Policlinico Hospital in Milan. Inaugurated on October 19, 1964, this has been the first institute in Italy entirely devoted to patients with kidney diseases. Since its inception, it has significantly contributed to the progress of nephrology thanks to important and pioneering investigations in the main fields of our specialty, which still continue nowadays. The different stories reported here follow the chronological order in which the young doctors arrived at Croff, each story representing a personal narrative that interweaves and integrates that of others. This gives rise to a vivid many-voiced account, from which emerge not only the figures of these young doctors, but also those of patients, nurses, and laboratory technicians.

Nephrogenic systemic fibrosis an unsolved riddle.

Nephrogenic systemic fibrosis (NSF) is an emergent scleroderma-like disease progressively inducing a skin and joint severe dermal fibrosis. Until now there have been about 215 cases reported in NSF registry, linked to the use of Gadolinium as contrast agent for Magnetic Resonance. The pathogenesis of NSF is unexplained, and the factor or factors triggering the onset of the disease are a matter of debate. The toxic Gd effect on tissues of uremic patients may be linked to the long Gd half-life. Alternatively, according to the transmetallation theory, Gd may easily be released from linear versus cyclic chelating agents exchanged with other metals. Despite many studies indicating exposure to Gd in end-stage renal disease (ESRD) or hemodialysis as a trigger of NSF, a certain cause-effect relationship has still not been found. Other epidemiological studies report cases of NSF without previous Gd infusion. Another intriguing hypothesis is the possible role of lanthanum carbonate, which like Gd is a rare earth element. The lanthanum toxicity theory may explain the diffusion of Gd-induced NSF only in countries where the use of lanthanum carbonate was introduced some years ago (e.g., United States and northern Europe). In spite of the tight linkage reported between Gd infusion and NSF occurrence in ESRD and HD patients,the prevalence of this dermal severe disease ranges from 0.4 to 0.7%. Therefore the nephrologist, must keep this in mind and advise patients that the risk of renal impairement induced by iodinated contrast media infusion, is exceedingly more elevated than the occurrence of Gd-induced NSF which is below 1%.

Pilot study to assess increased dialysis efficiency in patients with limited blood flow rates due to vascular access problems.

In the last few years, the number of hemodialysis patients with inadequate blood flow (Qb) rates has increased due to vascular access problems. To avoid a clinical status of underdialysis, these patients need long-lasting dialysis sessions. However, other factors aimed to optimize the dialysis dose have to be considered. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to high-flux hemodialysis (HF-HD) in improving the dialysis efficacy, but treatment efficacy is strongly related to blood flow rate and infusion volumes. Online mid-dilution (HDF-MD) with the Nephros OL-pure MD190 represents a new HDF concept to increase the removal of middle molecules. In a cross-over clinical trial, 8 patients, with Qb eff <300 mL/min, received either online HDF-MD or HF-HD; Qd was 700 mL/min, the time duration was 240 min, and the filtration volume in HDF-MD was 112+/-7 mL/min. No differences were found for Kt/V, urea, and creatinine clearances. Clearance of both small phosphate (P) large beta(2)-microglobulin (beta(2)m), and leptin (L) solutes was significantly greater for MD (P 217+/-32, beta(2)m 85.5+/-10, L 42.6+/-18 mL/min) than for HF-HD (P 178+/-32, beta(2)m 71.9+/-13, L 32.1+/-12 mL/min). The results of this study indicate that HDF remains the best means of providing increased removal of large-molecular weight solutes even in patients with vascular access problems.